atrasentan profile

Atrasentan: A pyrrolidine and benzodioxole derivative that acts a RECEPTOR, ENDOTHELIN A antagonist. It has therapeutic potential as an antineoplastic agent and for the treatment of DIABETIC NEPHROPATHIES. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

ID Source	ID
PubMed CID	159594
CHEMBL ID	9194
CHEBI ID	135810
SCHEMBL ID	34654
MeSH ID	M0393223

Synonym
(2r,3r,4s)-4-benzo[1,3]dioxol-5-yl-1-dibutylcarbamoylmethyl-2-(4-methoxy-phenyl)-pyrrolidine-3-carboxylic acid
bdbm50051007
atrasentan
(+)-a-127722
xinlay
a-147627
nsc720763
abt-627
2r-(4-methoxyphenyl)-4s(1,n-di(n-butyl)aminocarbonyl-methyl)-pyrrolidine-3r-carboxylic acid
nsc-720763
3-pyrrolidinecarboxylic acid, 4-(1,3-benzodioxo-5-yl)-1-(2-(dibutylamino)-2-oxoethyl)-2-(4-methoxyphenyl)-, (2r,3r,4s)-
atrasentan [inn]
3-pyrrolidinecarboxylic acid, 4-(1,3-benzodioxol-5-yl)-1-(2-dibutylamino)-2-oxoethyl)-2-(4-methoxyphenyl)-, (2r-(2alpha,3beta,4alpha))-
(+)-a 127722
abt 627
a-127722
a 127722
CHEBI:135810
CHEMBL9194 ,
(2r,3r,4s)-4-(1,3-benzodioxol-5-yl)-1-[2-(dibutylamino)-2-oxoethyl]-2-(4-methoxyphenyl)pyrrolidine-3-carboxylic acid
173937-91-2
unii-v6d7vk2215
v6d7vk2215 ,
abt 147627
gtpl3487
SCHEMBL34654
MOTJMGVDPWRKOC-QPVYNBJUSA-N
(2r,3r,4s)-(+)-2-(4-methoxyphenyl)-4-(1,3-benzodioxol-5-yl)-1-(n,n-di(n-butyl)aminocarbonylmethyl)-pyrrolidine-3-carboxylic acid
atrasentan [vandf]
atrasentan [who-dd]
(2r,3r,4s)-1-((dibutylcarbamoyl)methyl)-2-(p-methoxyphenyl)-4-(3,4-(methylenedioxy)phenyl)-3-pyrrolidinecarboxylic acid
atrasentan [mi]
3-pyrrolidinecarboxylic acid, 4-(1,3-benzodioxol-5-yl)-1-(2-(dibutylamino)-2-oxoethyl)-2-(4-methoxyphenyl)-, (2r-(2.alpha.,3.beta.,4.alpha.))
AKOS030255123
NCGC00378853-03
NCGC00378853-01
EX-A7929
DB06199
rel-(2r,3r,4s)-4-(benzo[d][1,3]dioxol-5-yl)-1-(2-(dibutylamino)-2-oxoethyl)-2-(4-methoxyphenyl)pyrrolidine-3-carboxylic acid
195704-72-4
rel-(2r,3r,4s)-4-(1,3-benzodioxol-5-yl)-1-[2-(dibutylamino)-2-oxoethyl]-2-(4-methoxyphenyl)-3-pyrrolidinecarboxylic acid
Q125083
A-455
(2r,3r,4s)-4-(1,3-benzodioxol-5-yl)-1-[2-(dibutylamino)-2-oxoethyl]-2-(4-methoxyphenyl)pyrrolidine-3-carboxylic acid.
(2s,3r,4s)-4-(1,3-benzodioxol-5-yl)-1-[2-(dibutylamino)-2-oxoethyl]-2-(4-methoxyphenyl)pyrrolidine-3-carboxylic acid
3-pyrrolidinecarboxylic acid, 4-(1,3-benzodioxol-5-yl)-1-[2-(dibutylamino)-2-oxoethyl]-2-(4-methoxyphenyl)-, (2r,3r,4s)-

Excerpt	Reference	Relevance
"Atrasentan is a selective endothelin A receptor antagonist that reduces urinary albumin-to-creatinine ratio (UACR), with a large variability between patients."	( Rationale and protocol of the Study Of diabetic Nephropathy with AtRasentan (SONAR) trial: A clinical trial design novel to diabetic nephropathy. Andress, DL; Bakris, G; Brennan, JJ; Correa-Rotter, R; de Zeeuw, D; Dey, J; Heerspink, HJL; Hou, FF; Kitzman, DW; Kohan, D; Makino, H; McMurray, J; Parving, HH; Perkovic, V; Tobe, S; Wigderson, M, 2018)	1.44
"Atrasentan is a selective pharmacologic ETA blocker that preferentially inhibits ETA activation."	( Endothelin receptor a blockade is an ineffective treatment for adriamycin nephropathy. Lin, L; Liu, Y; Tan, RJ; Zhou, D; Zhou, L, 2013)	1.11
"Atrasentan is a promising therapy for treating diabetic nephropathy (DN). "	( Atrasentan increased the expression of klotho by mediating miR-199b-5p and prevented renal tubular injury in diabetic nephropathy. Kang, WL; Xu, GS, 2016)	3.32
"Atrasentan is a potent, oral, selective endothelin-A (ET(A)) receptor antagonist that has clinical activity in patients with hormone-refractory prostate cancer (HRPC). "	( Phase 3, randomized, controlled trial of atrasentan in patients with nonmetastatic, hormone-refractory prostate cancer. Carducci, M; Chin, JL; Love, W; Nelson, JB; Qian, J; Saad, F; Schulman, CC; Sleep, DJ; Steinberg, J, 2008)	2.05
"Atrasentan is a potent and selective endothelin (ETA) receptor antagonist that lowers blood pressure and affects tumor growth."	( ETA receptor blockade with atrasentan prevents hypertension with the multitargeted tyrosine kinase inhibitor ABT-869 in telemetry-instrumented rats. Albert, DH; Banfor, PN; Cox, BF; Davidsen, SK; Franklin, PA; Fryer, RM; Gintant, GA; Segreti, JA; Widomski, DL, 2009)	1.37
"Atrasentan is a highly potent and selective endothelin receptor A (ET(A)) antagonist under development for the treatment of prostate cancer. "	( Interaction potential of the endothelin-A receptor antagonist atrasentan with drug transporters and drug-metabolising enzymes assessed in vitro. Haefeli, WE; Weiss, J, 2011)	2.05
"Atrasentan is a selective endothelin ET(A) receptor antagonist under development by Abbott for the potential treatment of cancer, particularly prostate cancer, for which it is in phase III trials [413197]. "	( Atrasentan Abbott. Norman, P, 2002)	3.2
"Atrasentan is an oral, targeted therapy with favorable tolerability and the potential to delay progression of HRPCa."	( Effect of endothelin-A receptor blockade with atrasentan on tumor progression in men with hormone-refractory prostate cancer: a randomized, phase II, placebo-controlled trial. Breul, J; Carducci, MA; Daliani, DD; Humerickhouse, RA; Nabulsi, AA; Nelson, JB; Padley, RJ; Schmitt, JL; Schulman, CC; Vogelzang, NJ; Weinberg, MA; Zonnenberg, BA, 2003)	2.02
"Atrasentan (ABT-627) is a highly potent, selective ET(A) receptor antagonist."	( Phase I dose-escalation study of the safety and pharmacokinetics of atrasentan: an endothelin receptor antagonist for refractory prostate cancer. Carr, RA; Groenewegen, G; Humerickhouse, RA; Isaacson, JD; Janus, TJ; Leahy, TW; Voest, E; Zonnenberg, BA, 2003)	1.28
"Atrasentan is an orally bioavailable selective antagonist of the endothelin receptor ET(A). "	( Dose-ranging study of the safety and pharmacokinetics of atrasentan in patients with refractory malignancies. André, AK; Carr, RA; Humerickhouse, R; Kindler, HL; Ratain, MJ; Ryan, CW; Undevia, SD; Vogelzang, NJ; Vokes, EE; Wang, Q, 2004)	2.01
"Atrasentan is a novel agent that effectively targets this pathway and is able to inhibit and/or reverse several of those events."	( Atrasentan: targeting the endothelin axis in prostate cancer. Carducci, M; Jimeno, A, 2004)	2.49
"Atrasentan (A-147627) is an endothelin antagonist receptor being developed at Abbott Laboratories for the treatment of prostate cancer. "	( High-throughput determination of atrasentan in human plasma by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry. Chang, M; El-Shourbagy, T; Wang, PG; Wei, J, 2005)	2.05
"Atrasentan is a novel agent that effectively targets this pathway and is able to inhibit and/or reverse several of those events."	( Atrasentan: a novel and rationally designed therapeutic alternative in the management of cancer. Carducci, M; Jimeno, A, 2005)	2.49
"Atrasentan is a novel and selective inhibitor of ET-1 and ET-A."	( Endothelin receptor antagonists: rationale, clinical development, and role in prostate cancer therapeutics. Choueiri, TK; Garcia, JA; Thakkar, SG, 2006)	1.06
"Atrasentan is a novel agent that effectively targets this pathway and is able to inhibit and/or reverse several of these events."	( Atrasentan: a rationally designed targeted therapy for cancer. Carducci, M; Jimeno, A, 2006)	2.5
"Atrasentan is an investigational agent that inhibits endothelin-1 receptor, resulting in decreased osteoblast activity."	( Randomized phase II study of atrasentan alone or in combination with zoledronic acid in men with metastatic prostate cancer. Kantoff, P; Kaufman, DS; Michaelson, MD; Oh, WK; Smith, MR, 2006)	1.35
"Atrasentan is an oral selective endothelin-A receptor antagonist that may inhibit cell proliferation and interfere with angiogenesis during glioma growth. "	( Phase I safety study of escalating doses of atrasentan in adults with recurrent malignant glioma. Carson, KA; Desideri, S; Fisher, JD; Grossman, SA; Lesser, G; Mikkelsen, T; Olson, J; Phuphanich, S, 2008)	2.05
"Atrasentan is an endothelin antagonist selective for the ET(A) receptor in development at Abbott Laboratories for the treatment of cardiovascular disease and cell proliferation disorders. "	( Determination of atrasentan by high performance liquid chromatography with fluorescence detection in human plasma. Bryan, PD; El-Shourbagy, TA; Padley, RJ; Sapochak, LB; Tames, MM, 2001)	2.09

Excerpt	Reference	Relevance
"Atrasentan (Atr) has potential therapeutic values for DN."	( Atrasentan alleviates high glucose-induced podocyte injury by the microRNA-21/forkhead box O1 axis. Hong, H; Li, J; Li, X; Shen, L; Wang, H; Wang, J, 2019)	2.68
"Atrasentan has been developed as an oral selective endothelin-A receptor antagonist."	( Phase 1/2 study of atrasentan combined with pegylated liposomal doxorubicin in platinum-resistant recurrent ovarian cancer. Groenewegen, G; Kronemeijer, RH; Los, M; van der Mijn, KJ; Voest, EE; Witteveen, PO, 2010)	1.41
"Atrasentan has been granted Fast Track status, allowing for a rolling NDA [414666], [443479]; the company was planning to begin filing for prostate cancer in late 2003."	( Atrasentan Abbott. Norman, P, 2002)	2.48

Excerpt	Reference	Relevance
"Atrasentan displays additive effects when administered in combination with the cytotoxic drug paclitaxel."	( Growth inhibition of cervix carcinoma cells in vivo by endothelin A receptor blockade. Bagnato, A; Cirilli, A; Muller, A; Natali, PG; Nicotra, MR; Salani, D; Simeone, P; Venuti, A, 2002)	1.04

Excerpt	Reference	Relevance
"3. Atrasentan treatment significantly improved left ventricular systolic and diastolic function in response to exogenous norepinephrine, but there were no differences between genotypes."	( Cardioprotective effects of atrasentan, an endothelin-A receptor antagonist, but not of nitric oxide in diabetic mice with myocyte-specific overexpression of endothelial nitric oxide synthase. Brunner, F; Kirchengast, M; Saad, Z; Stessel, H; Wölkart, G, 2006)	1.14
"Atrasentan treatment was associated with lower cardiac output, PAP (14 +/- 1 mm Hg), and medial wall thickness of pulmonary arteries (diameter: 50-150 microM) compared with placebo [13.6 +/- 3.0% versus 18.1 +/- 4.2%; P < 0.05 (ANOVA)]."	( Atrasentan treatment of pulmonary vascular disease in piglets with increased pulmonary blood flow. Demirakca, S; Dieckmann, R; Gebhard, MM; Gorenflo, M; Hagl, S; Herpel, E; Klimpel, H; Neumayer, S; Ullmann, MV, 2007)	2.5
"Treatment with atrasentan (7.5 mg/kg/day) for 4 weeks reduced urinary albumin-to-creatinine ratios by 26.0 ± 6.5% (P < 0.01) in apoE knockout (KO) mice with streptozotocin-induced diabetes consuming an atherogenic diet, without changes in gross glomerular morphology, systemic blood pressure, and blood glucose concentration."	( Atrasentan Reduces Albuminuria by Restoring the Glomerular Endothelial Glycocalyx Barrier in Diabetic Nephropathy. Avramut, MC; Boels, MG; Dane, MJ; Gröne, HJ; Koster, AJ; Koudijs, A; Lee, DH; Rabelink, TJ; van den Berg, BM; van der Vlag, J; van Faassen, E; van Zonneveld, AJ, 2016)	2.22
"Pretreatment with atrasentan (5 mg/kg for 5 days) prevented and abolished the hypertensive effects of ABT-869."	( ETA receptor blockade with atrasentan prevents hypertension with the multitargeted tyrosine kinase inhibitor ABT-869 in telemetry-instrumented rats. Albert, DH; Banfor, PN; Cox, BF; Davidsen, SK; Franklin, PA; Fryer, RM; Gintant, GA; Segreti, JA; Widomski, DL, 2009)	0.97

Excerpt	Reference	Relevance
" The most common adverse events, such as rhinitis, headache, asthenia, and peripheral edema, were reversible on drug discontinuation and responded to symptom-specific treatment."	( Atrasentan, an endothelin-receptor antagonist for refractory adenocarcinomas: safety and pharmacokinetics. Andre, A; Bowling, MK; Carducci, MA; Carr, RA; Donehower, R; Eisenberger, MA; Hosmane, BS; Isaacson, JD; Janus, TJ; Leahy, TL; Nelson, JB; Padley, RJ; Rogers, T; Sinibaldi, V, 2002)	1.76
" The data provide a basis for further investigation of the impact of ET-R blockade on both the short- and long-term adverse effects of preretrieval warm ischemic injury in cadaveric renal Tx."	( Endothelin receptor blockade during hypothermic perfusion preservation mitigates the adverse effect of preretrieval warm ischemic injury on posttransplant glomerular filtration rate. Antonelli, JA; Burns, TE; Inman, SR; Lewis, RM; Plott, WK; Pomilee, RA, 2002)	0.31
" The most common adverse events were rhinitis, headache, and peripheral edema."	( Phase I dose-escalation study of the safety and pharmacokinetics of atrasentan: an endothelin receptor antagonist for refractory prostate cancer. Carr, RA; Groenewegen, G; Humerickhouse, RA; Isaacson, JD; Janus, TJ; Leahy, TW; Voest, E; Zonnenberg, BA, 2003)	0.55
"Atrasentan is well tolerated, with no dose-limiting adverse events observed up to 95 mg."	( Phase I dose-escalation study of the safety and pharmacokinetics of atrasentan: an endothelin receptor antagonist for refractory prostate cancer. Carr, RA; Groenewegen, G; Humerickhouse, RA; Isaacson, JD; Janus, TJ; Leahy, TW; Voest, E; Zonnenberg, BA, 2003)	2
" The most frequent drug-related adverse events were headache (60%), rhinitis (49%), and peripheral edema (31%)."	( Dose-ranging study of the safety and pharmacokinetics of atrasentan in patients with refractory malignancies. André, AK; Carr, RA; Humerickhouse, R; Kindler, HL; Ratain, MJ; Ryan, CW; Undevia, SD; Vogelzang, NJ; Vokes, EE; Wang, Q, 2004)	0.57
" Atrasentan generally was tolerated well, and the most common adverse events associated with treatment were headache, rhinitis, and peripheral edema, reflecting the vasodilatory and fluid-retention properties of endothelin-A receptor antagonism."	( A phase 3 randomized controlled trial of the efficacy and safety of atrasentan in men with metastatic hormone-refractory prostate cancer. Abrahamsson, PA; Carducci, MA; Dearnaley, DP; Isaacson, JD; Nelson, JB; North, SA; Saad, F; Schulman, CC; Sleep, DJ, 2007)	1.49
" When the animals were pretreated with either ABT-627 or A-192621, given alone or combined, the adverse effects of IAP on GFR, RPF, V, and U(Na)V were significantly augmented."	( Adverse effects of pneumoperitoneum on renal function: involvement of the endothelin and nitric oxide systems. Abassi, Z; Bishara, B; Hoffman, A; Karram, T; Khatib, S; Winaver, J, 2008)	0.35
" The most common adverse effects with atrasentan were nasal stuffiness, headache, and edema."	( Efficacy and safety of atrasentan in patients with cardiovascular risk and early atherosclerosis. Holmes, DR; Kent, B; Lerman, A; Lerman, LO; Mathew, V; Nelson, RE; Prasad, A; Pumper, GM; Raichlin, E, 2008)	0.93

Excerpt	Reference	Relevance
" The present study was designed to investigate the pharmacokinetic and pharmacodynamic effects of the orally active ETA selective receptor antagonist ABT-627 in healthy humans."	( Pharmacokinetics and pharmacodynamic effects of ABT-627, an oral ETA selective endothelin antagonist, in humans. Grahn, AY; Honing, ML; Morrison, PJ; Padley, RJ; Rabelink, TJ; Van Weerdt, AW; Verhaar, MC; Yang, YP, 2000)	0.31
" The terminal elimination half-life was approximately 24 hours, and steady-state plasma concentrations were achieved within 7 days."	( Atrasentan, an endothelin-receptor antagonist for refractory adenocarcinomas: safety and pharmacokinetics. Andre, A; Bowling, MK; Carducci, MA; Carr, RA; Donehower, R; Eisenberger, MA; Hosmane, BS; Isaacson, JD; Janus, TJ; Leahy, TL; Nelson, JB; Padley, RJ; Rogers, T; Sinibaldi, V, 2002)	1.76
" PK are linear and dose-proportional; the half-life is appropriate for once-daily dosing."	( Phase I dose-escalation study of the safety and pharmacokinetics of atrasentan: an endothelin receptor antagonist for refractory prostate cancer. Carr, RA; Groenewegen, G; Humerickhouse, RA; Isaacson, JD; Janus, TJ; Leahy, TW; Voest, E; Zonnenberg, BA, 2003)	0.55
" Analysis of covariance including genotype, study, age, weight, sex, and ethnicity was used to identify factors influencing atrasentan single-dose (n = 44) and steady-state (n = 38) pharmacokinetic parameters."	( Organic anion transporting polypeptide 1B1 activity classified by SLCO1B1 genotype influences atrasentan pharmacokinetics. Allen, A; Carr, R; Doan, T; Edeki, T; Grimm, DR; Han, L; Holley-Shanks, R; Katz, DA; Kim, RB; Leake, B; Mueller, T; Sahelijo, L; Spear, BB; Wang, PG; Wang, Q; Xiong, H, 2006)	0.76
" On average, rifampin increased atrasentan peak plasma concentrations by 150% and reduced its terminal half-life by 77% (P<."	( Dual effects of rifampin on the pharmacokinetics of atrasentan. Achari, R; Carr, RA; Doan, TT; Jankowski, JR; Katz, DA; Locke, CS; Sleep, DJ; Wang, P; Xiong, H, 2007)	0.87

Excerpt	Reference	Relevance
" This study was designed to assess the influence of atrasentan on paclitaxel pharmacokinetics and to determine the safety and efficacy of atrasentan in combination with paclitaxel-carboplatin."	( Phase I/II study of atrasentan, an endothelin A receptor antagonist, in combination with paclitaxel and carboplatin as first-line therapy in advanced non-small cell lung cancer. Antonia, S; Bepler, G; Boulware, D; Burton, M; Chiappori, AA; Haura, E; Kapoor, R; Lush, R; Neuger, AM; Padilla, B; Rodriguez, FA; Simon, G; Sullivan, DM; Williams, C, 2008)	0.92
"Patients with platinum-resistant ovarian cancer were treated with pegylated liposomal doxorubicin (PLD) 50 mg/m(2) on day 1 (and repeated every 4 weeks) in combination with escalating doses of atrasentan once daily."	( Phase 1/2 study of atrasentan combined with pegylated liposomal doxorubicin in platinum-resistant recurrent ovarian cancer. Groenewegen, G; Kronemeijer, RH; Los, M; van der Mijn, KJ; Voest, EE; Witteveen, PO, 2010)	0.88
") three times a week) in combination with atrasentan (2."	( Targeting the endothelin axis with atrasentan, in combination with IFN-alpha, in metastatic renal cell carcinoma. de Gast, B; Giles, R; Groenewegen, G; Haanen, J; Vermaat, J; Voest, E; Walraven, M; Witteveen, E, 2012)	0.92
" In an exploratory analysis, we observed that in the subset of patients with declining vascular endothelial growth factor (VEGF) levels (in combination with rising Endothelin-1 levels), median OS was 22."	( Targeting the endothelin axis with atrasentan, in combination with IFN-alpha, in metastatic renal cell carcinoma. de Gast, B; Giles, R; Groenewegen, G; Haanen, J; Vermaat, J; Voest, E; Walraven, M; Witteveen, E, 2012)	0.66

Excerpt	Reference	Relevance
" In conclusion, A-127722 is ETA-selective, orally bioavailable and efficacious for inhibiting the effects of ET in the rat, and A-127722 is the most potent ET receptor antagonist yet reported."	( Pharmacological characterization of A-127722: an orally active and highly potent ETA-selective receptor antagonist. Adler, AL; Calzadilla, SV; Chiou, WJ; Dayton, BD; Dixon, DB; Gehrke, LJ; Hernandez, L; Magnuson, SR; Marsh, KC; Novosad, EI; Opgenorth, TJ; Von Geldern, TW; Wessale, JL; Winn, M; Wu-Wong, JR, 1996)	0.29
" The compound has 70% oral bioavailability in rats."	( 2,4-Diarylpyrrolidine-3-carboxylic acids--potent ETA selective endothelin receptor antagonists. 1. Discovery of A-127722. Bal, R; Boyd, SA; Chiou, WJ; Dixon, DB; Hernandez, L; Jae, HS; Kester, JA; Mantei, RA; Marsh, KC; Novosad, EI; Opgenorth, TJ; Sorensen, BK; Tasker, AS; von Geldern, TW; Winn, M; Wu-Wong, JR, 1996)	0.29
" EMD 122946 exhibited high bioavailability in rats and monkeys."	( Endothelin antagonists: discovery of EMD 122946, a highly potent and orally active ETA selective antagonist. Anzali, S; Christadler, M; Dorsch, D; Fluck, M; Mederski, WW; Osswald, M; Schelling, P; Schmitges, CJ; Wilm, C, 1998)	0.3
" Adding a fluorine further increases the binding activity and provides a metabolically stable and orally bioavailable ET(A)-selective antagonist."	( Pyrrolidine-3-carboxylic acids as endothelin antagonists. 5. Highly selective, potent, and orally active ET(A) antagonists. Chiou, WJ; Jae, HS; Marsh, KC; Nguyen, B; Opgenorth, TJ; Sorensen, BK; von Geldern, TW; Winn, M, 2001)	0.31
" Here we report an expansion of this work by substituting a variety of electron-withdrawing groups at the ortho position and evaluating their effects on oral bioavailability as well as structure-activity relationships."	( Discovery, modeling, and human pharmacokinetics of N-(2-acetyl-4,6-dimethylphenyl)-3-(3,4-dimethylisoxazol-5-ylsulfamoyl)thiophene-2-carboxamide (TBC3711), a second generation, ETA selective, and orally bioavailable endothelin antagonist. Berens, KL; Blok, N; Bourgoyne, AR; Brock, TA; Bui, H; Decker, ER; Dixon, RA; Holland, GW; Knowles, V; Wang, J; Wu, C; You, TJ, 2004)	0.32
"Atrasentan is an orally bioavailable selective antagonist of the endothelin receptor ET(A)."	( Dose-ranging study of the safety and pharmacokinetics of atrasentan in patients with refractory malignancies. André, AK; Carr, RA; Humerickhouse, R; Kindler, HL; Ratain, MJ; Ryan, CW; Undevia, SD; Vogelzang, NJ; Vokes, EE; Wang, Q, 2004)	2.01
" These results suggest that YM598 has high selectivity for native human ETA against ETB receptors, and that YM598 is superior to atrasentan as an ETA receptor antagonist with regard to pharmacological bioavailability in rats."	( Superiority of YM598 over atrasentan as a selective endothelin ETA receptor antagonist. Fujimori, A; Fujiyasu, N; Miyata, K; Noguchi, Y; Ohtake, A; Sasamata, M; Sato, S; Sudoh, K; Ukai, M; Yuyama, H, 2004)	0.83
" These results suggest that YM598 has a high selectivity for native human ETA receptors against ETB receptors, and that YM598 is superior to atrasentan as an ETA receptor antagonist, with regard to pharmacological bioavailability in rats."	( Pharmacological characterization of YM598, a selective endothelin-A receptor antagonist. Fujimori, A; Miyata, K; Noguchi, Y; Ohtake, A; Sasamata, M; Sato, S; Sudoh, K; Ukai, M; Yuyama, H, 2004)	0.53
" Clinical testing of an orally bioavailable endothelin antagonist has demonstrated benefit in PSA progression, markers of bone turnover, and pain in men with prostate cancer, but has not demonstrated significant improvement in survival or time to cancer progression."	( Endothelin receptor antagonists in cancer therapy. Lalich, M; Liu, G; McNeel, DG; Wilding, G, 2007)	0.34
"The clinical investigation of an orally bioavailable ET antagonist, atrasentan, in prostate cancer, is encouraging."	( Anti-endothelin drugs in solid tumors. Bazan, V; Bronte, G; Di Gaudio, F; Fanale, D; Gebbia, N; Rizzo, S; Russo, A, 2010)	0.6
"The ATP-binding cassette transporter P-glycoprotein (P-gp) is known to limit both brain penetration and oral bioavailability of many chemotherapy drugs."	( A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein. Ambudkar, SV; Brimacombe, KR; Chen, L; Gottesman, MM; Guha, R; Hall, MD; Klumpp-Thomas, C; Lee, OW; Lee, TD; Lusvarghi, S; Robey, RW; Shen, M; Tebase, BG, 2019)	0.51
" We confirmed dominant role of ETA receptors in regulation of blood pressure and renal hemodynamics in normotensive and hypertensive rats and provided novel evidence for the role of ETA in control of intrarenal NO bioavailability in salt-dependent and spontaneous hypertension."	( Effects of systemic and renal intramedullary endothelin-1 receptor blockade on tissue NO and intrarenal hemodynamics in normotensive and hypertensive rats. Bądzyńska, B; Hojná, S; Kompanowska-Jezierska, E; Sadowski, J; Vaneckova, I, 2021)	0.62

Excerpt	Relevance	Reference
") orally, starting 3 days before angioplasty and continuing for 4 weeks; 10 additional pigs were treated with the same dosing regimen of the angiotensin-converting enzyme (ACE) inhibitor captopril (3."	( Selective antagonism of the ET(A) receptor reduces neointimal hyperplasia after balloon-induced vascular injury in pigs. Burke, SE; Dayton, BD; Gagne, GD; Lubbers, NL; Opgenorth, TJ; Wegner, CD; Wessale, JL, 1997)	0.3
" Our results define the dose-response relation for the ET(A)-receptor antagonist ABT-627 in the vasculature of the domestic pig and suggest the presence of an ET(B)-receptor subtype that mediates vasoconstriction in this species."	( Evidence for vasoconstriction mediated by the endothelin-B receptor in domestic swine. Burke, SE; Cox, BF; Ford, TT; Fu, KI; Lubbers, NL; Nelson, RA; Padley, RJ; Wegner, CD, 2000)	0.31
" Five-day oral dosing with the selective ET(A)-receptor antagonist ABT-627 (~2 mg."	( Role of ET(A) receptors in experimental ANG II-induced hypertension in rats. Ballew, JR; Fink, GD, 2001)	0.31
" Plasma concentration profiles for atrasentan were determined after dosing on days 1 and 28."	( Dose-ranging study of the safety and pharmacokinetics of atrasentan in patients with refractory malignancies. André, AK; Carr, RA; Humerickhouse, R; Kindler, HL; Ratain, MJ; Ryan, CW; Undevia, SD; Vogelzang, NJ; Vokes, EE; Wang, Q, 2004)	0.85
" ETB antagonism at either dose had no effect on vasorelaxation in control rats, whereas in diabetes the dose-response curve to ACh was shifted to the right, indicating a decreased relaxation at 15 mg/kg A-192621."	( Effect of chronic and selective endothelin receptor antagonism on microvascular function in type 2 diabetes. Elgebaly, MM; Ergul, A; Harris, AK; Hutchinson, JR; Mezzetti, EM; Portik-Dobos, V; Sachidanandam, K, 2008)	0.35
" At termination, basilar arteries were collected and mounted on a wire myograph and cumulative dose-response curves to endothelin-1 (1-500 nM) and acetylcholine (1 nM-5 μm) were studied."	( Comparison of selective versus dual endothelin receptor antagonism on cerebrovascular dysfunction in diabetes. Ergul, A; Li, W; Sachidanandam, K, 2011)	0.37

Class	Description
pyrrolidines	Any of a class of heterocyclic amines having a saturated five-membered ring.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Protein	Taxonomy	Measurement	Average (µ)	Min (ref.)	Avg (ref.)	Max (ref.)	Bioassay(s)
cytochrome P450 family 3 subfamily A polypeptide 4	Homo sapiens (human)	Potency	1.6933	0.0123	7.9835	43.2770	AID1645841
G	Vesicular stomatitis virus	Potency	21.3174	0.0123	8.9648	39.8107	AID1645842
cytochrome P450 2D6	Homo sapiens (human)	Potency	18.9991	0.0010	8.3798	61.1304	AID1645840
Interferon beta	Homo sapiens (human)	Potency	21.3174	0.0033	9.1582	39.8107	AID1645842
HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)	Potency	21.3174	0.0123	8.9648	39.8107	AID1645842
Inositol hexakisphosphate kinase 1	Homo sapiens (human)	Potency	21.3174	0.0123	8.9648	39.8107	AID1645842
cytochrome P450 2C9, partial	Homo sapiens (human)	Potency	21.3174	0.0123	8.9648	39.8107	AID1645842
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Protein	Taxonomy	Measurement	Average	Min (ref.)	Avg (ref.)	Max (ref.)	Bioassay(s)
Endothelin receptor type B	Rattus norvegicus (Norway rat)	IC50 (µMol)	0.0000	0.0000	1.1744	4.4000	AID104929
Endothelin receptor type B	Homo sapiens (human)	IC50 (µMol)	0.2221	0.0001	0.6565	9.8000	AID66514; AID66534; AID66704
Endothelin-1 receptor	Homo sapiens (human)	IC50 (µMol)	0.0001	0.0000	0.7647	9.9000	AID1631613; AID66198; AID68296; AID68310; AID68311
Endothelin-1 receptor	Homo sapiens (human)	Ki	0.0000	0.0000	0.4300	10.0000	AID1631613; AID68488
Endothelin-1 receptor	Rattus norvegicus (Norway rat)	IC50 (µMol)	0.0002	0.0000	1.7746	10.0000	AID104929; AID66055; AID66060; AID66183; AID66197; AID68500
Endothelin-1 receptor	Rattus norvegicus (Norway rat)	Ki	0.0000	0.0000	0.0021	0.0065	AID66210; AID68501
Endothelin receptor type B	Sus scrofa (pig)	IC50 (µMol)	0.3150	0.1100	0.3233	0.5200	AID66713; AID66717
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Process	via Protein(s)	Taxonomy
cell surface receptor signaling pathway via JAK-STAT	Interferon beta	Homo sapiens (human)
response to exogenous dsRNA	Interferon beta	Homo sapiens (human)
B cell activation involved in immune response	Interferon beta	Homo sapiens (human)
cell surface receptor signaling pathway	Interferon beta	Homo sapiens (human)
cell surface receptor signaling pathway via JAK-STAT	Interferon beta	Homo sapiens (human)
response to virus	Interferon beta	Homo sapiens (human)
positive regulation of autophagy	Interferon beta	Homo sapiens (human)
cytokine-mediated signaling pathway	Interferon beta	Homo sapiens (human)
natural killer cell activation	Interferon beta	Homo sapiens (human)
positive regulation of peptidyl-serine phosphorylation of STAT protein	Interferon beta	Homo sapiens (human)
cellular response to interferon-beta	Interferon beta	Homo sapiens (human)
B cell proliferation	Interferon beta	Homo sapiens (human)
negative regulation of viral genome replication	Interferon beta	Homo sapiens (human)
innate immune response	Interferon beta	Homo sapiens (human)
positive regulation of innate immune response	Interferon beta	Homo sapiens (human)
regulation of MHC class I biosynthetic process	Interferon beta	Homo sapiens (human)
negative regulation of T cell differentiation	Interferon beta	Homo sapiens (human)
positive regulation of transcription by RNA polymerase II	Interferon beta	Homo sapiens (human)
defense response to virus	Interferon beta	Homo sapiens (human)
type I interferon-mediated signaling pathway	Interferon beta	Homo sapiens (human)
neuron cellular homeostasis	Interferon beta	Homo sapiens (human)
cellular response to exogenous dsRNA	Interferon beta	Homo sapiens (human)
cellular response to virus	Interferon beta	Homo sapiens (human)
negative regulation of Lewy body formation	Interferon beta	Homo sapiens (human)
negative regulation of T-helper 2 cell cytokine production	Interferon beta	Homo sapiens (human)
positive regulation of apoptotic signaling pathway	Interferon beta	Homo sapiens (human)
response to exogenous dsRNA	Interferon beta	Homo sapiens (human)
B cell differentiation	Interferon beta	Homo sapiens (human)
natural killer cell activation involved in immune response	Interferon beta	Homo sapiens (human)
adaptive immune response	Interferon beta	Homo sapiens (human)
T cell activation involved in immune response	Interferon beta	Homo sapiens (human)
humoral immune response	Interferon beta	Homo sapiens (human)
positive regulation of T cell mediated cytotoxicity	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
adaptive immune response	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independent	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
regulation of T cell anergy	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
defense response	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
immune response	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
detection of bacterium	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
regulation of interleukin-12 production	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
regulation of interleukin-6 production	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
protection from natural killer cell mediated cytotoxicity	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
innate immune response	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
regulation of dendritic cell differentiation	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
antigen processing and presentation of endogenous peptide antigen via MHC class Ib	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
negative regulation of transcription by RNA polymerase II	Endothelin receptor type B	Homo sapiens (human)
neural crest cell migration	Endothelin receptor type B	Homo sapiens (human)
positive regulation of protein phosphorylation	Endothelin receptor type B	Homo sapiens (human)
renin secretion into blood stream	Endothelin receptor type B	Homo sapiens (human)
regulation of heart rate	Endothelin receptor type B	Homo sapiens (human)
regulation of pH	Endothelin receptor type B	Homo sapiens (human)
cell surface receptor signaling pathway	Endothelin receptor type B	Homo sapiens (human)
negative regulation of adenylate cyclase activity	Endothelin receptor type B	Homo sapiens (human)
phospholipase C-activating G protein-coupled receptor signaling pathway	Endothelin receptor type B	Homo sapiens (human)
positive regulation of cytosolic calcium ion concentration	Endothelin receptor type B	Homo sapiens (human)
nervous system development	Endothelin receptor type B	Homo sapiens (human)
peripheral nervous system development	Endothelin receptor type B	Homo sapiens (human)
posterior midgut development	Endothelin receptor type B	Homo sapiens (human)
positive regulation of cell population proliferation	Endothelin receptor type B	Homo sapiens (human)
gene expression	Endothelin receptor type B	Homo sapiens (human)
negative regulation of neuron maturation	Endothelin receptor type B	Homo sapiens (human)
response to organic cyclic compound	Endothelin receptor type B	Homo sapiens (human)
vein smooth muscle contraction	Endothelin receptor type B	Homo sapiens (human)
calcium-mediated signaling	Endothelin receptor type B	Homo sapiens (human)
cGMP-mediated signaling	Endothelin receptor type B	Homo sapiens (human)
heparin metabolic process	Endothelin receptor type B	Homo sapiens (human)
melanocyte differentiation	Endothelin receptor type B	Homo sapiens (human)
regulation of fever generation	Endothelin receptor type B	Homo sapiens (human)
aldosterone metabolic process	Endothelin receptor type B	Homo sapiens (human)
enteric smooth muscle cell differentiation	Endothelin receptor type B	Homo sapiens (human)
positive regulation of urine volume	Endothelin receptor type B	Homo sapiens (human)
renal sodium excretion	Endothelin receptor type B	Homo sapiens (human)
epithelial fluid transport	Endothelin receptor type B	Homo sapiens (human)
vasoconstriction	Endothelin receptor type B	Homo sapiens (human)
vasodilation	Endothelin receptor type B	Homo sapiens (human)
negative regulation of apoptotic process	Endothelin receptor type B	Homo sapiens (human)
positive regulation of canonical NF-kappaB signal transduction	Endothelin receptor type B	Homo sapiens (human)
macrophage chemotaxis	Endothelin receptor type B	Homo sapiens (human)
response to pain	Endothelin receptor type B	Homo sapiens (human)
enteric nervous system development	Endothelin receptor type B	Homo sapiens (human)
regulation of epithelial cell proliferation	Endothelin receptor type B	Homo sapiens (human)
negative regulation of protein metabolic process	Endothelin receptor type B	Homo sapiens (human)
canonical Wnt signaling pathway	Endothelin receptor type B	Homo sapiens (human)
positive regulation of penile erection	Endothelin receptor type B	Homo sapiens (human)
establishment of endothelial barrier	Endothelin receptor type B	Homo sapiens (human)
renal sodium ion absorption	Endothelin receptor type B	Homo sapiens (human)
calcium ion transmembrane transport	Endothelin receptor type B	Homo sapiens (human)
cellular response to lipopolysaccharide	Endothelin receptor type B	Homo sapiens (human)
protein transmembrane transport	Endothelin receptor type B	Homo sapiens (human)
podocyte differentiation	Endothelin receptor type B	Homo sapiens (human)
endothelin receptor signaling pathway	Endothelin receptor type B	Homo sapiens (human)
renal albumin absorption	Endothelin receptor type B	Homo sapiens (human)
neuroblast migration	Endothelin receptor type B	Homo sapiens (human)
chordate pharynx development	Endothelin receptor type B	Homo sapiens (human)
response to sodium phosphate	Endothelin receptor type B	Homo sapiens (human)
response to endothelin	Endothelin receptor type B	Homo sapiens (human)
developmental pigmentation	Endothelin receptor type B	Homo sapiens (human)
mitotic cell cycle	Endothelin-1 receptor	Homo sapiens (human)
branching involved in blood vessel morphogenesis	Endothelin-1 receptor	Homo sapiens (human)
response to hypoxia	Endothelin-1 receptor	Homo sapiens (human)
in utero embryonic development	Endothelin-1 receptor	Homo sapiens (human)
blood vessel remodeling	Endothelin-1 receptor	Homo sapiens (human)
response to amphetamine	Endothelin-1 receptor	Homo sapiens (human)
regulation of heart rate	Endothelin-1 receptor	Homo sapiens (human)
glomerular filtration	Endothelin-1 receptor	Homo sapiens (human)
cardiac chamber formation	Endothelin-1 receptor	Homo sapiens (human)
left ventricular cardiac muscle tissue morphogenesis	Endothelin-1 receptor	Homo sapiens (human)
atrial cardiac muscle tissue development	Endothelin-1 receptor	Homo sapiens (human)
cardiac neural crest cell migration involved in outflow tract morphogenesis	Endothelin-1 receptor	Homo sapiens (human)
noradrenergic neuron differentiation	Endothelin-1 receptor	Homo sapiens (human)
intracellular calcium ion homeostasis	Endothelin-1 receptor	Homo sapiens (human)
smooth muscle contraction	Endothelin-1 receptor	Homo sapiens (human)
mitochondrion organization	Endothelin-1 receptor	Homo sapiens (human)
signal transduction	Endothelin-1 receptor	Homo sapiens (human)
G protein-coupled receptor signaling pathway	Endothelin-1 receptor	Homo sapiens (human)
activation of adenylate cyclase activity	Endothelin-1 receptor	Homo sapiens (human)
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	Endothelin-1 receptor	Homo sapiens (human)
phospholipase C-activating G protein-coupled receptor signaling pathway	Endothelin-1 receptor	Homo sapiens (human)
positive regulation of cytosolic calcium ion concentration	Endothelin-1 receptor	Homo sapiens (human)
respiratory gaseous exchange by respiratory system	Endothelin-1 receptor	Homo sapiens (human)
regulation of blood pressure	Endothelin-1 receptor	Homo sapiens (human)
cell population proliferation	Endothelin-1 receptor	Homo sapiens (human)
response to wounding	Endothelin-1 receptor	Homo sapiens (human)
gene expression	Endothelin-1 receptor	Homo sapiens (human)
protein kinase A signaling	Endothelin-1 receptor	Homo sapiens (human)
regulation of glucose transmembrane transport	Endothelin-1 receptor	Homo sapiens (human)
neural crest cell fate commitment	Endothelin-1 receptor	Homo sapiens (human)
artery smooth muscle contraction	Endothelin-1 receptor	Homo sapiens (human)
neuron remodeling	Endothelin-1 receptor	Homo sapiens (human)
heparin metabolic process	Endothelin-1 receptor	Homo sapiens (human)
thyroid gland development	Endothelin-1 receptor	Homo sapiens (human)
cellular response to oxidative stress	Endothelin-1 receptor	Homo sapiens (human)
embryonic heart tube development	Endothelin-1 receptor	Homo sapiens (human)
aorta development	Endothelin-1 receptor	Homo sapiens (human)
vasoconstriction	Endothelin-1 receptor	Homo sapiens (human)
norepinephrine metabolic process	Endothelin-1 receptor	Homo sapiens (human)
middle ear morphogenesis	Endothelin-1 receptor	Homo sapiens (human)
positive regulation of canonical NF-kappaB signal transduction	Endothelin-1 receptor	Homo sapiens (human)
cellular response to human chorionic gonadotropin stimulus	Endothelin-1 receptor	Homo sapiens (human)
enteric nervous system development	Endothelin-1 receptor	Homo sapiens (human)
sympathetic nervous system development	Endothelin-1 receptor	Homo sapiens (human)
axon extension	Endothelin-1 receptor	Homo sapiens (human)
embryonic skeletal system development	Endothelin-1 receptor	Homo sapiens (human)
neuromuscular process	Endothelin-1 receptor	Homo sapiens (human)
sodium ion homeostasis	Endothelin-1 receptor	Homo sapiens (human)
canonical Wnt signaling pathway	Endothelin-1 receptor	Homo sapiens (human)
face development	Endothelin-1 receptor	Homo sapiens (human)
axonogenesis involved in innervation	Endothelin-1 receptor	Homo sapiens (human)
establishment of endothelial barrier	Endothelin-1 receptor	Homo sapiens (human)
pharyngeal arch artery morphogenesis	Endothelin-1 receptor	Homo sapiens (human)
renal sodium ion absorption	Endothelin-1 receptor	Homo sapiens (human)
calcium ion transmembrane transport	Endothelin-1 receptor	Homo sapiens (human)
cellular response to follicle-stimulating hormone stimulus	Endothelin-1 receptor	Homo sapiens (human)
cellular response to luteinizing hormone stimulus	Endothelin-1 receptor	Homo sapiens (human)
protein transmembrane transport	Endothelin-1 receptor	Homo sapiens (human)
glomerular endothelium development	Endothelin-1 receptor	Homo sapiens (human)
podocyte differentiation	Endothelin-1 receptor	Homo sapiens (human)
endothelin receptor signaling pathway involved in heart process	Endothelin-1 receptor	Homo sapiens (human)
renal albumin absorption	Endothelin-1 receptor	Homo sapiens (human)
vascular associated smooth muscle cell development	Endothelin-1 receptor	Homo sapiens (human)
mesenchymal cell apoptotic process	Endothelin-1 receptor	Homo sapiens (human)
sympathetic neuron axon guidance	Endothelin-1 receptor	Homo sapiens (human)
semaphorin-plexin signaling pathway involved in axon guidance	Endothelin-1 receptor	Homo sapiens (human)
podocyte apoptotic process	Endothelin-1 receptor	Homo sapiens (human)
meiotic cell cycle process involved in oocyte maturation	Endothelin-1 receptor	Homo sapiens (human)
cranial skeletal system development	Endothelin-1 receptor	Homo sapiens (human)
response to acetylcholine	Endothelin-1 receptor	Homo sapiens (human)
regulation of protein localization to cell leading edge	Endothelin-1 receptor	Homo sapiens (human)
positive regulation of cation channel activity	Endothelin-1 receptor	Homo sapiens (human)
endothelin receptor signaling pathway	Endothelin-1 receptor	Homo sapiens (human)
developmental pigmentation	Endothelin-1 receptor	Homo sapiens (human)
inositol phosphate metabolic process	Inositol hexakisphosphate kinase 1	Homo sapiens (human)
phosphatidylinositol phosphate biosynthetic process	Inositol hexakisphosphate kinase 1	Homo sapiens (human)
negative regulation of cold-induced thermogenesis	Inositol hexakisphosphate kinase 1	Homo sapiens (human)
inositol phosphate biosynthetic process	Inositol hexakisphosphate kinase 1	Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Process	via Protein(s)	Taxonomy
cytokine activity	Interferon beta	Homo sapiens (human)
cytokine receptor binding	Interferon beta	Homo sapiens (human)
type I interferon receptor binding	Interferon beta	Homo sapiens (human)
protein binding	Interferon beta	Homo sapiens (human)
chloramphenicol O-acetyltransferase activity	Interferon beta	Homo sapiens (human)
TAP binding	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
signaling receptor binding	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
protein binding	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
peptide antigen binding	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
TAP binding	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
protein-folding chaperone binding	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
endothelin receptor activity	Endothelin receptor type B	Homo sapiens (human)
protein binding	Endothelin receptor type B	Homo sapiens (human)
peptide hormone binding	Endothelin receptor type B	Homo sapiens (human)
type 1 angiotensin receptor binding	Endothelin receptor type B	Homo sapiens (human)
phosphatidylinositol phospholipase C activity	Endothelin-1 receptor	Homo sapiens (human)
endothelin receptor activity	Endothelin-1 receptor	Homo sapiens (human)
protein binding	Endothelin-1 receptor	Homo sapiens (human)
inositol-1,3,4,5,6-pentakisphosphate kinase activity	Inositol hexakisphosphate kinase 1	Homo sapiens (human)
inositol hexakisphosphate kinase activity	Inositol hexakisphosphate kinase 1	Homo sapiens (human)
inositol heptakisphosphate kinase activity	Inositol hexakisphosphate kinase 1	Homo sapiens (human)
inositol hexakisphosphate 5-kinase activity	Inositol hexakisphosphate kinase 1	Homo sapiens (human)
protein binding	Inositol hexakisphosphate kinase 1	Homo sapiens (human)
ATP binding	Inositol hexakisphosphate kinase 1	Homo sapiens (human)
inositol hexakisphosphate 1-kinase activity	Inositol hexakisphosphate kinase 1	Homo sapiens (human)
inositol hexakisphosphate 3-kinase activity	Inositol hexakisphosphate kinase 1	Homo sapiens (human)
inositol 5-diphosphate pentakisphosphate 5-kinase activity	Inositol hexakisphosphate kinase 1	Homo sapiens (human)
inositol diphosphate tetrakisphosphate kinase activity	Inositol hexakisphosphate kinase 1	Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Process	via Protein(s)	Taxonomy
extracellular space	Interferon beta	Homo sapiens (human)
extracellular region	Interferon beta	Homo sapiens (human)
Golgi membrane	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
endoplasmic reticulum	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
Golgi apparatus	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
plasma membrane	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
cell surface	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
ER to Golgi transport vesicle membrane	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
membrane	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
secretory granule membrane	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
phagocytic vesicle membrane	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
early endosome membrane	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
recycling endosome membrane	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
extracellular exosome	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
lumenal side of endoplasmic reticulum membrane	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
MHC class I protein complex	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
extracellular space	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
external side of plasma membrane	HLA class I histocompatibility antigen, B alpha chain	Homo sapiens (human)
plasma membrane	Endothelin receptor type B	Homo sapiens (human)
nuclear membrane	Endothelin receptor type B	Homo sapiens (human)
plasma membrane	Endothelin receptor type B	Homo sapiens (human)
plasma membrane	Endothelin-1 receptor	Homo sapiens (human)
plasma membrane	Endothelin-1 receptor	Homo sapiens (human)
fibrillar center	Inositol hexakisphosphate kinase 1	Homo sapiens (human)
nucleoplasm	Inositol hexakisphosphate kinase 1	Homo sapiens (human)
cytosol	Inositol hexakisphosphate kinase 1	Homo sapiens (human)
nucleus	Inositol hexakisphosphate kinase 1	Homo sapiens (human)
cytoplasm	Inositol hexakisphosphate kinase 1	Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (48)

Assay ID	Title	Year	Journal	Article
AID68500	Inhibitory activity against human Endothelin A receptor	2001	Journal of medicinal chemistry, Nov-08, Volume: 44, Issue:23	Pyrrolidine-3-carboxylic acids as endothelin antagonists. 5. Highly selective, potent, and orally active ET(A) antagonists.
AID68311	Binding affinity towards human Endothelin A receptor (hET -A)	1999	Journal of medicinal chemistry, Sep-09, Volume: 42, Issue:18	Pyrrolidine-3-carboxylic acids as endothelin antagonists. 4. Side chain conformational restriction leads to ET(B) selectivity.
AID66214	Selectivity for endothelin A receptor over endothelin receptor B	2004	Journal of medicinal chemistry, Apr-08, Volume: 47, Issue:8	Discovery, modeling, and human pharmacokinetics of N-(2-acetyl-4,6-dimethylphenyl)-3-(3,4-dimethylisoxazol-5-ylsulfamoyl)thiophene-2-carboxamide (TBC3711), a second generation, ETA selective, and orally bioavailable endothelin antagonist.
AID66183	Binding affinity towards endothelin A receptor in prolactin secreting rat pituitary cells using [125I]ET1 as radioligand.	1997	Journal of medicinal chemistry, Jan-31, Volume: 40, Issue:3	Potent and selective non-benzodioxole-containing endothelin-A receptor antagonists.
AID66713	Binding affinity towards endothelin B receptor in porcine cerebellar tissue using [125I]-ET-1 as radioligand.	1997	Journal of medicinal chemistry, Jan-31, Volume: 40, Issue:3	Potent and selective non-benzodioxole-containing endothelin-A receptor antagonists.
AID24311	Time taken to decrease the plasma concentration to half of the maximum concentration when compound was administered intravenously in rats	1997	Journal of medicinal chemistry, Jan-31, Volume: 40, Issue:3	Potent and selective non-benzodioxole-containing endothelin-A receptor antagonists.
AID66186	In vitro ability to inhibit specific [125I]ET1 binding to rat aorta membranes Endothelin A receptor	1998	Bioorganic & medicinal chemistry letters, Jul-07, Volume: 8, Issue:13	Endothelin antagonists: discovery of EMD 122946, a highly potent and orally active ETA selective antagonist.
AID66704	Binding affinity against endothelin B receptor in porcine cerebellar tissue	2001	Journal of medicinal chemistry, Nov-08, Volume: 44, Issue:23	Pyrrolidine-3-carboxylic acids as endothelin antagonists. 5. Highly selective, potent, and orally active ET(A) antagonists.
AID66198	Displacement of [125I]ET-1 from Endothelin A receptor	2004	Journal of medicinal chemistry, Apr-08, Volume: 47, Issue:8	Discovery, modeling, and human pharmacokinetics of N-(2-acetyl-4,6-dimethylphenyl)-3-(3,4-dimethylisoxazol-5-ylsulfamoyl)thiophene-2-carboxamide (TBC3711), a second generation, ETA selective, and orally bioavailable endothelin antagonist.
AID196820	Compound was evaluated for the functional assay performed by obtaining ET-1 concentration-response curves [pA2(ETA)] in isolated rat aortic rings	1998	Bioorganic & medicinal chemistry letters, Jul-07, Volume: 8, Issue:13	Endothelin antagonists: discovery of EMD 122946, a highly potent and orally active ETA selective antagonist.
AID68310	Binding ability determined by the displacement of [125I]ET1 from the human endothelin A receptor	1999	Journal of medicinal chemistry, Sep-09, Volume: 42, Issue:18	Design, synthesis, and activity of a series of pyrrolidine-3-carboxylic acid-based, highly specific, orally active ET(B) antagonists containing a diphenylmethylamine acetamide side chain.
AID10518	Area under curve was determined in portal blood of rat when administered intradermally	1997	Journal of medicinal chemistry, Jan-31, Volume: 40, Issue:3	Potent and selective non-benzodioxole-containing endothelin-A receptor antagonists.
AID25743	Compound was evaluated for pharmacokinetic data, area under curve (AUC)	2001	Journal of medicinal chemistry, Nov-08, Volume: 44, Issue:23	Pyrrolidine-3-carboxylic acids as endothelin antagonists. 5. Highly selective, potent, and orally active ET(A) antagonists.
AID229283	Ratio of IC50 of ETA receptor to that of ETB receptor	2001	Journal of medicinal chemistry, Nov-08, Volume: 44, Issue:23	Pyrrolidine-3-carboxylic acids as endothelin antagonists. 5. Highly selective, potent, and orally active ET(A) antagonists.
AID66055	Ability to displace [125I]ET1 from the rat endothelin A receptor expressed in rat aorta smooth muscle cells.	2004	Journal of medicinal chemistry, May-20, Volume: 47, Issue:11	Chemical function based pharmacophore generation of endothelin-A selective receptor antagonists.
AID66534	Inhibitory activity against human endothelin B receptor	2001	Journal of medicinal chemistry, Nov-08, Volume: 44, Issue:23	Pyrrolidine-3-carboxylic acids as endothelin antagonists. 5. Highly selective, potent, and orally active ET(A) antagonists.
AID1631613	Displacement of [125I]ET-1 from human ET-A receptor expressed in CHO cell membrane	2016	Journal of medicinal chemistry, 09-22, Volume: 59, Issue:18	Endothelin-Receptor Antagonists beyond Pulmonary Arterial Hypertension: Cancer and Fibrosis.
AID14054	Maximum concentration of compound in plasma administered orally to rats	1997	Journal of medicinal chemistry, Jan-31, Volume: 40, Issue:3	Potent and selective non-benzodioxole-containing endothelin-A receptor antagonists.
AID68493	Ratio of binding affinity towards human endothelin receptor type A to human endothelin receptor type B (hETA to hETB)	1999	Journal of medicinal chemistry, Sep-09, Volume: 42, Issue:18	Design, synthesis, and activity of a series of pyrrolidine-3-carboxylic acid-based, highly specific, orally active ET(B) antagonists containing a diphenylmethylamine acetamide side chain.
AID66197	Inhibitory activity against the Endothelin A receptor of rat MMQ cells	1996	Journal of medicinal chemistry, Mar-01, Volume: 39, Issue:5	2,4-Diarylpyrrolidine-3-carboxylic acids--potent ETA selective endothelin receptor antagonists. 1. Discovery of A-127722.
AID28099	Compound was evaluated for pharmacokinetic data, Cmax	2001	Journal of medicinal chemistry, Nov-08, Volume: 44, Issue:23	Pyrrolidine-3-carboxylic acids as endothelin antagonists. 5. Highly selective, potent, and orally active ET(A) antagonists.
AID31118	Compound was evaluated for bioavailability	2001	Journal of medicinal chemistry, Nov-08, Volume: 44, Issue:23	Pyrrolidine-3-carboxylic acids as endothelin antagonists. 5. Highly selective, potent, and orally active ET(A) antagonists.
AID66210	Binding affinity towards Endothelin A receptor	2004	Journal of medicinal chemistry, Apr-08, Volume: 47, Issue:8	Discovery, modeling, and human pharmacokinetics of N-(2-acetyl-4,6-dimethylphenyl)-3-(3,4-dimethylisoxazol-5-ylsulfamoyl)thiophene-2-carboxamide (TBC3711), a second generation, ETA selective, and orally bioavailable endothelin antagonist.
AID28872	Compound was evaluated for half life period when administered intravenously	2001	Journal of medicinal chemistry, Nov-08, Volume: 44, Issue:23	Pyrrolidine-3-carboxylic acids as endothelin antagonists. 5. Highly selective, potent, and orally active ET(A) antagonists.
AID28873	Compound was evaluated for half life period when administered orally	2001	Journal of medicinal chemistry, Nov-08, Volume: 44, Issue:23	Pyrrolidine-3-carboxylic acids as endothelin antagonists. 5. Highly selective, potent, and orally active ET(A) antagonists.
AID166817	Compound was evaluated for the functional assay performed by obtaining ET-1 concentration-response curves [pA2(ETB)] in isolated rabbit jugularis vein	1998	Bioorganic & medicinal chemistry letters, Jul-07, Volume: 8, Issue:13	Endothelin antagonists: discovery of EMD 122946, a highly potent and orally active ETA selective antagonist.
AID68501	binding affinity against human Endothelin A receptor	2001	Journal of medicinal chemistry, Nov-08, Volume: 44, Issue:23	Pyrrolidine-3-carboxylic acids as endothelin antagonists. 5. Highly selective, potent, and orally active ET(A) antagonists.
AID66060	Binding affinity against Endothelin A receptor in MMQ cells in rat	2001	Journal of medicinal chemistry, Nov-08, Volume: 44, Issue:23	Pyrrolidine-3-carboxylic acids as endothelin antagonists. 5. Highly selective, potent, and orally active ET(A) antagonists.
AID18610	Oral bioavailability in rat	1997	Journal of medicinal chemistry, Jan-31, Volume: 40, Issue:3	Potent and selective non-benzodioxole-containing endothelin-A receptor antagonists.
AID68488	Inhibitory activity against human Endothelin A receptor in chinese hamster ovary cells	1996	Journal of medicinal chemistry, Mar-01, Volume: 39, Issue:5	2,4-Diarylpyrrolidine-3-carboxylic acids--potent ETA selective endothelin receptor antagonists. 1. Discovery of A-127722.
AID66848	Inhibitory activity measured against Endothelin B receptor binding to porcine cerebellum	1996	Journal of medicinal chemistry, Mar-01, Volume: 39, Issue:5	2,4-Diarylpyrrolidine-3-carboxylic acids--potent ETA selective endothelin receptor antagonists. 1. Discovery of A-127722.
AID66717	In vitro ability to inhibit specific [125I]ET1 binding to porcine kidney (inner medulla) membranes Endothelin B receptor	1998	Bioorganic & medicinal chemistry letters, Jul-07, Volume: 8, Issue:13	Endothelin antagonists: discovery of EMD 122946, a highly potent and orally active ETA selective antagonist.
AID12105	Half life period was evaluated in rat	2004	Journal of medicinal chemistry, Apr-08, Volume: 47, Issue:8	Discovery, modeling, and human pharmacokinetics of N-(2-acetyl-4,6-dimethylphenyl)-3-(3,4-dimethylisoxazol-5-ylsulfamoyl)thiophene-2-carboxamide (TBC3711), a second generation, ETA selective, and orally bioavailable endothelin antagonist.
AID18193	Oral bioavailability in rat	1997	Journal of medicinal chemistry, Sep-26, Volume: 40, Issue:20	Pyrrolidine-3-carboxylic acids as endothelin antagonists. 2. Sulfonamide-based ETA/ETB mixed antagonists.
AID104929	Inhibition of phosphoinositol hydrolysis of MMQ cells.	1996	Journal of medicinal chemistry, Mar-01, Volume: 39, Issue:5	2,4-Diarylpyrrolidine-3-carboxylic acids--potent ETA selective endothelin receptor antagonists. 1. Discovery of A-127722.
AID10517	Area under curve was determined in carotid blood of rat when administered intradermally	1997	Journal of medicinal chemistry, Jan-31, Volume: 40, Issue:3	Potent and selective non-benzodioxole-containing endothelin-A receptor antagonists.
AID68296	Ability to displace endothelin ([125I]ET1) from human Endothelin A receptor	1997	Journal of medicinal chemistry, Sep-26, Volume: 40, Issue:20	Pyrrolidine-3-carboxylic acids as endothelin antagonists. 2. Sulfonamide-based ETA/ETB mixed antagonists.
AID66514	Binding ability determined by the displacement of [125 I]ET-3 from the human Endothelin B receptor	1999	Journal of medicinal chemistry, Sep-09, Volume: 42, Issue:18	Design, synthesis, and activity of a series of pyrrolidine-3-carboxylic acid-based, highly specific, orally active ET(B) antagonists containing a diphenylmethylamine acetamide side chain.
AID12753	Compound was evaluated for oral bioavailability in rats	2004	Journal of medicinal chemistry, Apr-08, Volume: 47, Issue:8	Discovery, modeling, and human pharmacokinetics of N-(2-acetyl-4,6-dimethylphenyl)-3-(3,4-dimethylisoxazol-5-ylsulfamoyl)thiophene-2-carboxamide (TBC3711), a second generation, ETA selective, and orally bioavailable endothelin antagonist.
AID1296008	Cytotoxic Profiling of Annotated Libraries Using Quantitative High-Throughput Screening	2020	SLAS discovery : advancing life sciences R & D, 01, Volume: 25, Issue:1	Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening.
AID1347160	Primary screen NINDS Rhodamine qHTS for Zika virus inhibitors	2020	Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49	Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1347159	Primary screen GU Rhodamine qHTS for Zika virus inhibitors: Unlinked NS2B-NS3 protease assay	2020	Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49	Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1346986	P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen	2019	Molecular pharmacology, 11, Volume: 96, Issue:5	A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1346987	P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen	2019	Molecular pharmacology, 11, Volume: 96, Issue:5	A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1347411	qHTS to identify inhibitors of the type 1 interferon - major histocompatibility complex class I in skeletal muscle: primary screen against the NCATS Mechanism Interrogation Plate v5.0 (MIPE) Libary	2020	ACS chemical biology, 07-17, Volume: 15, Issue:7	High-Throughput Screening to Identify Inhibitors of the Type I Interferon-Major Histocompatibility Complex Class I Pathway in Skeletal Muscle.
AID1345905	Human ETA receptor (Endothelin receptors)	1996	The Journal of pharmacology and experimental therapeutics, Feb, Volume: 276, Issue:2	Pharmacological characterization of A-127722: an orally active and highly potent ETA-selective receptor antagonist.
AID1345905	Human ETA receptor (Endothelin receptors)	1996	Journal of medicinal chemistry, Mar-01, Volume: 39, Issue:5	2,4-Diarylpyrrolidine-3-carboxylic acids--potent ETA selective endothelin receptor antagonists. 1. Discovery of A-127722.
AID1345807	Human ETB receptor (Endothelin receptors)	1996	Journal of medicinal chemistry, Mar-01, Volume: 39, Issue:5	2,4-Diarylpyrrolidine-3-carboxylic acids--potent ETA selective endothelin receptor antagonists. 1. Discovery of A-127722.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Timeframe	Studies, This Drug (%)	All Drugs %
pre-1990	0 (0.00)	18.7374
1990's	37 (10.45)	18.2507
2000's	190 (53.67)	29.6817
2010's	98 (27.68)	24.3611
2020's	29 (8.19)	2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Publication Type	This drug (%)	All Drugs (%)
Trials	41 (11.45%)	5.53%
Reviews	41 (11.45%)	6.00%
Case Studies	1 (0.28%)	4.05%
Observational	0 (0.00%)	0.25%
Other	275 (76.82%)	84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (20)

Trial Overview

Trial	Phase	Enrollment	Study Type	Start Date	Status
RADAR: Reducing Residual Albuminuria in Subjects With Diabetes and Nephropathy With AtRasentan - A Phase 2b, Prospective, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate Safety and Efficacy [NCT01356849]	Phase 2	149 participants (Actual)	Interventional	2011-04-30	Completed
A Phase 2b, Prospective, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate Efficacy and Safety of Atrasentan, Including Thoracic Bioimpedance, in Type 2 Diabetic Subjects With Nephropathy [NCT01399580]	Phase 2	48 participants (Actual)	Interventional	2011-08-31	Completed
A Phase 2a, Prospective, Randomized, Double-blind, Placebo-controlled Multicenter Study to Evaluate the Safety and Efficacy of Atrasentan on Reducing Albuminuria in Type 2 Diabetic Nephropathy Subjects Who Are Currently Being Treated With an Renin-Angiote [NCT00920764]	Phase 2	92 participants (Actual)	Interventional	2009-06-30	Completed
A Phase 3, Randomized, Double-blind, Placebo-controlled Study of Atrasentan in Patients With IgA Nephropathy at Risk of Progressive Loss of Renal Function [NCT04573478]	Phase 3	380 participants (Anticipated)	Interventional	2020-12-11	Active, not recruiting
A Phase II Study of Atrasentan (ABT-627) Plus DOXIL in Patients With Recurrent Ovarian, Fallopian Tube, or Peritoneal Serous Papillary Adenocarcinoma Following Platinum + Taxane Therapy [NCT00653328]	Phase 2	15 participants (Actual)	Interventional	2003-05-31	Terminated(stopped due to Abbott (drug manufacturer) discontinued manufacture of ABT-627)
Phase III Study of Docetaxel and Atrasentan Versus Docetaxel and Placebo for Patients With Advanced Hormone Refractory Prostate Cancer [NCT00134056]	Phase 3	1,038 participants (Actual)	Interventional	2006-08-31	Completed
Reducing Residual Albuminuria in Subjects With Diabetes & Nephropathy With Atrasentan - A Phase 2b, Prospective, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate Safety & Efficacy in Japanese Subjects [NCT01424319]	Phase 2	58 participants (Actual)	Interventional	2011-08-31	Completed
Atrasentan and Zometa for Men With Androgen Independent Prostate Cancer Metastatic to Bone: A Randomized Pilot Study [NCT00181558]	Phase 2	44 participants	Interventional	2001-12-31	Completed
Endothelin in the Coronary Circulation in Early Atherosclerosis in Humans [NCT00271492]	Phase 3	200 participants (Actual)	Interventional	2001-07-31	Completed
A Randomized, Double-blind, Placebo-controlled, Crossover Study of Atrasentan in Subjects With IgA Nephropathy on Sodium-glucose Cotransporter-2 Inhibitors (SGLT2i) [NCT05834738]	Phase 2	52 participants (Anticipated)	Interventional	2023-07-20	Recruiting
A Phase II/III Extension Study to Evaluate the Safety and Tolerability of Atrasentan [NCT00127478]	Phase 2/Phase 3	166 participants (Actual)	Interventional	2001-07-31	Completed
A Phase 2, Open-Label, Basket Study of Atrasentan in Patients With Proteinuric Glomerular Diseases [NCT04573920]	Phase 2	100 participants (Anticipated)	Interventional	2021-02-01	Recruiting
A Phase III, Randomized Study of Atrasentan in Men With Non-Metastatic, Hormone-Refractory Prostate Cancer [NCT00036556]	Phase 3	941 participants (Actual)	Interventional	2001-06-30	Completed
A Phase 2 Study Evaluating the Safety and Efficacy of Atrasentan (ABT-627) in Men With Hormone Naive Prostate Cancer Exhibiting Early Signs of Biochemical Failure [NCT00038662]	Phase 2	200 participants	Interventional	2002-05-31	Completed
A Phase I Evaluation of the Safety and Pharmacokinetics of ABT-627 in Adults With Recurrent Malignant Gliomas [NCT00017264]	Phase 1	0 participants	Interventional	2002-06-30	Completed
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of 10 Mg Atrasentan in Men With Metastatic, Hormone-Refractory Prostate Cancer [NCT00036543]	Phase 3	1,000 participants	Interventional	2001-05-31	Completed
A Phase III Extension Study to Evaluate the Safety of 10 mg Atrasentan in Men With Hormone-Refractory Prostate Cancer [NCT00046943]	Phase 3	0 participants	Interventional	2002-09-30	Completed
A Multicenter, Single-Arm Study of the Effects of Atrasentan on Spermatogenesis and Testicular Function [NCT02118714]	Phase 2	20 participants (Actual)	Interventional	2015-04-06	Completed
A Phase II Trial Evaluating Atrasentan In Patients With Advanced Renal Cell Carcinoma [NCT00039429]	Phase 2	180 participants (Anticipated)	Interventional	2003-07-14	Completed
A Randomized, Multicountry, Multicenter, Double-Blind, Parallel, Placebo-Controlled Study of the Effects of Atrasentan on Renal Outcomes in Subjects With Type 2 Diabetes and Nephropathy. SONAR: Study Of Diabetic Nephropathy With Atrasentan [NCT01858532]	Phase 3	5,107 participants (Actual)	Interventional	2013-05-17	Terminated(stopped due to Strategic considerations)
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

Trial	Outcome
NCT00134056 (7) [back to overview]	Compare Elements of Quality of Life Between Treatment Arms: Pain Palliation Response, as Measured by the Brief Pain Inventory (BPI)
NCT00134056 (7) [back to overview]	Compare Pain Progression Between the Two Study Arms.
NCT00134056 (7) [back to overview]	Compare Progression-free Survival Between a Control or Standard Therapy Arm of Docetaxel + Placebo + Prednisone With Docetaxel + Atrasentan + Prednisone in Patients With Hormone Refractory Prostate Cancer.
NCT00134056 (7) [back to overview]	Compare Prostate Specific Antigen (PSA) Response Rates Between the Experimental Arm and the Standard Arm.
NCT00134056 (7) [back to overview]	Compare Survival Between a Control or Standard Therapy Arm of Docetaxel + Placebo + Prednisone With Docetaxel + Atrasentan + Prednisone in Patients With Hormone Refractory Prostate Cancer.
NCT00134056 (7) [back to overview]	Number of Patients With a Change in Functional Status
NCT00134056 (7) [back to overview]	Compare Qualitative and Quantitative Toxicity Between the Two Study Arms
NCT00653328 (4) [back to overview]	Median Time to Tumor Progression
NCT00653328 (4) [back to overview]	Overall Survival
NCT00653328 (4) [back to overview]	Number of Patients With Objective Response
NCT00653328 (4) [back to overview]	Number of Patients With Worst Grade Toxicities
NCT01858532 (5) [back to overview]	Time to a 50% Estimated Glomerular Filtration Rate Reduction in the Intent-to-Treat (ITT) Responder Set (as Randomized)
NCT01858532 (5) [back to overview]	Time to Cardio-renal Composite Endpoint in the Intent-to-Treat (ITT) Responder Set (as Randomized)
NCT01858532 (5) [back to overview]	Time to First Occurrence of a Component of Composite Renal Endpoint for All Randomized Participants (Pooled)
NCT01858532 (5) [back to overview]	Time to the Cardiovascular Composite Endpoint in the Intent-to-Treat (ITT) Responder Set (as Randomized)
NCT01858532 (5) [back to overview]	Time to the First Occurrence of a Component of the Composite Renal Endpoint in the Intent-to-Treat (ITT) Responder Set (as Randomized)
NCT02118714 (11) [back to overview]	Percentage of Participants Who Entered the Observation Period and Did Not Return to Within 15% of Baseline Sperm Concentration or Above During the 52-Week Observational Period
NCT02118714 (11) [back to overview]	Percentage of Subjects With a Sperm Concentration < 15 Million Per mL by Treatment Week 26
NCT02118714 (11) [back to overview]	Change From Baseline up to Treatment Period Week 26 and Observation Period Week 52 in Estradiol
NCT02118714 (11) [back to overview]	Change From Baseline up to Treatment Period Week 26 and Observation Period Week 52 in in Follicle Stimulating Hormone (FSH)
NCT02118714 (11) [back to overview]	Change From Baseline up to Treatment Period Week 26 and Observation Period Week 52 in Inhibin B
NCT02118714 (11) [back to overview]	Change From Baseline up to Treatment Period Week 26 and Observation Period Week 52 in Lutenizing Hormone (LH)
NCT02118714 (11) [back to overview]	Change From Baseline up to Treatment Period Week 26 and Observation Period Week 52 in Semen Volume
NCT02118714 (11) [back to overview]	Change From Baseline up to Treatment Period Week 26 and Observation Period Week 52 in Serum Testosterone
NCT02118714 (11) [back to overview]	Change From Baseline up to Treatment Period Week 26 and Observation Period Week 52 in Sperm Concentration
NCT02118714 (11) [back to overview]	Change From Baseline up to Treatment Period Week 26 and Observation Period Week 52 in Sperm Morphology
NCT02118714 (11) [back to overview]	Change From Baseline up to Treatment Period Week 26 and Observation Period Week 52 in Sperm Motility

Compare Elements of Quality of Life Between Treatment Arms: Pain Palliation Response, as Measured by the Brief Pain Inventory (BPI)

"Pain palliation is the proportion of patients showing a two-point reduction in the Worst Pain score (WPS) maintained for two consecutive assessments with no increase in analgesic use. Increase in analgesic use is defined as an increase in Analgesic code Level to 2 (weak opioid) or 3 (strong opioid). Patients will be classified as pain palliated or not palliated. Patients with a WPS of 0 will be defined as stable if their WPS remains 0 for Weeks 7 and 10 with no increase in analgesic use, but they will not be categorized as responders. Pain palliation response is measured by BPI short form that has the following: yes/no question about pain today; 4 pain rating questions (worst pain, least pain, average pain, and current pain); pain medications and pain relief; 7 items addressing effect of pain on functioning. For patients who continue to receive treatment beyond 12 treatment cycles, the Worst Pain item is measured by Pain Medication Log and Pain Assessment" (NCT00134056)
Timeframe: up to 18 months study period

Intervention	Participants (Count of Participants)
Arm I: Placebo	75
Arm II: Atrasentan	83

Intervention	Participants (Number)
	ALT, SGPT (serum glutamic pyruvic transaminase)	AST, SGOT	Adult respiratory distress syndrome (ARDS)	Albumin, serum-low (hypoalbuminemia)	Alkaline phosphatase	Allergic reaction/hypersensitivity	Allergy/Immunology-Other (Specify)	Amylase	Anorexia	Arthritis (non-septic)	Aspiration	Auditory/Ear-Other (Specify)	Bilirubin (hyperbilirubinemia)	Blood/Bone Marrow-Other (Specify)	CNS cerebrovascular ischemia	CPK (creatine phosphokinase)	Calcium, serum-low (hypocalcemia)	Cardiac Arrhythmia-Other (Specify)	Cardiac General-Other (Specify)	Cardiac troponin I (cTnI)	Cardiac troponin T (cTnT)	Cardiac-ischemia/infarction	Conduction abnormality NOS	Confusion	Constipation	Cough	Creatinine	Dehydration	Diarrhea	Dizziness	Dry mouth/salivary gland (xerostomia)	Dysphagia (difficulty swallowing)	Dyspnea (shortness of breath)	Edema: head and neck	Edema: limb	Edema: trunk/genital	Erectile dysfunction	Esophagitis	Fatigue (asthenia, lethargy, malaise)	Febrile neutropenia	Fever in absence of neutropenia, ANC lt1.0x10e9/L	Fracture	Glucose, serum-high (hyperglycemia)	Glucose, serum-low (hypoglycemia)	Heartburn/dyspepsia	Hemoglobin	Hemolysis	Hemorrhage, Respiratory tract NOS	Hemorrhage, GI - Rectum	Hemorrhage, GI - Stomach	Hemorrhage, GI - Upper GI NOS	Hemorrhage, GU - Bladder	Hemorrhage/Bleeding-Other (Specify)	Hemorrhoids	Hot flashes/flushes	Hypertension	Hypotension	Hypoxia	INR (of prothrombin time)	Induration/fibrosis (skin and subcutaneous tissue)	Inf (clin/microbio) w/Gr 3-4 neuts - Bladder	Inf (clin/microbio) w/Gr 3-4 neuts - Blood	Inf (clin/microbio) w/Gr 3-4 neuts - Bronchus	Inf (clin/microbio) w/Gr 3-4 neuts - Esophagus	Inf (clin/microbio) w/Gr 3-4 neuts - Lung	Inf (clin/microbio) w/Gr 3-4 neuts - Nerve-periph	Inf (clin/microbio) w/Gr 3-4 neuts - Skin	Inf (clin/microbio) w/Gr 3-4 neuts - Soft tissue	Inf (clin/microbio) w/Gr 3-4 neuts - UTI	Inf (clin/microbio) w/Gr 3-4 neuts - Upper airway	Inf w/normal ANC or Gr 1-2 neutrophils - Blood	Inf w/normal ANC or Gr 1-2 neutrophils - Bronchus	Inf w/normal ANC or Gr 1-2 neutrophils - Colon	Inf w/normal ANC or Gr 1-2 neutrophils - Lung	Inf w/normal ANC or Gr 1-2 neutrophils - Muscle	Inf w/normal ANC or Gr 1-2 neutrophils - Scrotum	Inf w/normal ANC or Gr 1-2 neutrophils - Sinus	Inf w/normal ANC or Gr 1-2 neutrophils - Skin	Inf w/normal ANC or Gr 1-2 neutrophils - Stomach	Inf w/normal ANC or Gr 1-2 neutrophils - Trachea	Inf w/normal ANC or Gr 1-2 neutrophils - UTI	Inf w/normal ANC or Gr 1-2 neutrophils - Ungual	Inf w/unknown ANC - Middle ear (otitis media)	Inf w/unknown ANC - Upper aerodigestive NOS	Infection with unknown ANC - Blood	Infection with unknown ANC - Lung (pneumonia)	Infection with unknown ANC - Upper airway NOS	Infection with unknown ANC - Urinary tract NOS	Infection-Other (Specify)	Insomnia	Left ventricular diastolic dysfunction	Left ventricular systolic dysfunction	Leukocytes (total WBC)	Lipase	Lymphopenia	Magnesium, serum-high (hypermagnesemia)	Metabolic/Laboratory-Other (Specify)	Mood alteration - agitation	Mood alteration - depression	Mucositis/stomatitis (clinical exam) - Oral cavity	Mucositis/stomatitis (clinical exam) - Pharynx	Mucositis/stomatitis (clinical exam) - Stomach	Mucositis/stomatitis (functional/symp) - Esophagus	Mucositis/stomatitis (functional/symp) - Oral cav	Mucositis/stomatitis (functional/symp) - Pharynx	Mucositis/stomatitis (functional/symp) - Rectum	Muscle weakness, not d/t neuropathy - Extrem-lower	Muscle weakness, not d/t neuropathy - body/general	Myocarditis	Nail changes	Nasal cavity/paranasal sinus reactions	Nausea	Neuropathy: motor	Neuropathy: sensory	Neutrophils/granulocytes (ANC/AGC)	Opportunistic inf associated w/gt=Gr 2 lymphopenia	PTT (Partial thromboplastin time)	Pain - Abdomen NOS	Pain - Back	Pain - Bone	Pain - Chest wall	Pain - Chest/thorax NOS	Pain - Extremity-limb	Pain - Joint	Pain - Muscle	Pain - Neuralgia/peripheral nerve	Pain - Pelvis	Pain-Other (Specify)	Phosphate, serum-low (hypophosphatemia)	Platelets	Pneumonitis/pulmonary infiltrates	Pneumothorax	Potassium, serum-high (hyperkalemia)	Potassium, serum-low (hypokalemia)	Pulmonary/Upper Respiratory-Other (Specify)	Rash: hand-foot skin reaction	Renal failure	Renal/Genitourinary-Other (Specify)	Right ventricular dysfunction (cor pulmonale)	SVT and nodal arrhythmia - Atrial fibrillation	SVT and nodal arrhythmia - Atrial flutter	SVT and nodal arrhythmia - Sinus tachycardia	Sodium, serum-low (hyponatremia)	Somnolence/depressed level of consciousness	Speech impairment (e.g., dysphasia or aphasia)	Sudden death	Syncope (fainting)	Thrombosis/embolism (vascular access-related)	Thrombosis/thrombus/embolism	Vasovagal episode	Vomiting	Watery eye (epiphora, tearing)	Weight gain
Arm I: Placebo	2	2	3	3	4	5	0	0	5	1	0	1	0	2	0	2	7	2	1	2	1	2	1	1	3	1	4	9	10	3	1	1	38	0	16	1	2	0	60	8	1	1	20	1	1	47	1	0	1	1	0	0	2	0	2	2	9	10	3	1	1	2	0	0	11	1	1	1	4	0	2	1	1	1	1	0	1	1	1	1	0	0	0	0	0	3	0	1	4	1	1	3	101	0	30	1	0	1	1	2	1	1	0	3	0	0	2	11	1	0	2	11	7	10	140	1	1	4	1	5	0	1	1	2	8	1	0	0	3	7	7	1	2	11	0	1	4	1	0	3	1	0	8	1	0	2	3	0	9	0	8	0	0
Arm II: Atrasentan	2	4	0	0	6	6	1	1	5	0	1	0	1	2	1	0	1	0	1	1	0	1	0	0	4	2	1	8	7	1	0	1	17	1	2	0	0	1	40	20	2	0	24	0	1	22	0	1	0	0	1	1	1	2	1	2	3	3	1	0	2	0	1	1	6	0	2	0	3	2	1	1	0	5	0	1	0	2	0	0	1	1	1	1	1	0	1	1	3	1	0	2	98	1	32	0	2	0	0	2	0	0	1	3	1	1	1	8	0	1	0	5	6	11	154	1	0	0	2	8	1	0	1	2	3	1	1	1	0	4	0	0	1	2	1	0	2	0	1	2	1	1	3	0	1	0	1	1	11	2	7	1	1

Intervention	participants (Number)
	Complete Response	Partial Response	Stable Disease	Progressive Disease
Altrasentan + Doxil	0	0	3	11

Intervention	participants (Number)
	Number of participants with worst grade toxicity 1	Number of participants with worst grade toxicity 2	Number of participants with worst grade toxicity 3	Number of participants with worst grade toxicity 4	Number of participants with worst grade toxicity 5
Altrasentan + Doxil	5	3	3	0	0

Intervention	Participants (Count of Participants)
Intent-to-Treat (ITT) Responder Atrasentan	78
Intent-to-Treat (ITT) Responder Placebo	88

Intervention	Participants (Count of Participants)
Intent-to-Treat (ITT) Atrasentan	152
Intent-to-Treat Placebo	192

Intervention	Picomoles Per Litre (pmol/L) (Mean)
	Treatment Period Week 13	Treatment Period Week 26	Observation Period Week 13	Observation Period Week 26	Observation Period Week 39	Observation Period Week 52
Atrasentan	-11.7	-18.6	-17.8	-47.3	20.3	10.5

atrasentan

Description

Cross-References

Synonyms (46)

Research Excerpts

Overview

Effects

Actions

Treatment

Toxicity

Pharmacokinetics

Compound-Compound Interactions

Bioavailability

Dosage Studied

Drug Classes (1)

Protein Targets (12)

Potency Measurements

Inhibition Measurements

Biological Processes (153)

Molecular Functions (22)

Ceullar Components (23)

Bioassays (48)

Research

Studies (354)

Market Indicators

Research Demand Index: 48.74

Study Types

Clinical Trials (20)

Trial Overview

Trial Outcomes

Compare Elements of Quality of Life Between Treatment Arms: Pain Palliation Response, as Measured by the Brief Pain Inventory (BPI)

Compare Pain Progression Between the Two Study Arms.

Compare Progression-free Survival Between a Control or Standard Therapy Arm of Docetaxel + Placebo + Prednisone With Docetaxel + Atrasentan + Prednisone in Patients With Hormone Refractory Prostate Cancer.

Compare Prostate Specific Antigen (PSA) Response Rates Between the Experimental Arm and the Standard Arm.

Compare Survival Between a Control or Standard Therapy Arm of Docetaxel + Placebo + Prednisone With Docetaxel + Atrasentan + Prednisone in Patients With Hormone Refractory Prostate Cancer.

Number of Patients With a Change in Functional Status

Compare Qualitative and Quantitative Toxicity Between the Two Study Arms

Median Time to Tumor Progression

Overall Survival

Number of Patients With Objective Response

Number of Patients With Worst Grade Toxicities

Time to a 50% Estimated Glomerular Filtration Rate Reduction in the Intent-to-Treat (ITT) Responder Set (as Randomized)

Time to Cardio-renal Composite Endpoint in the Intent-to-Treat (ITT) Responder Set (as Randomized)

Time to First Occurrence of a Component of Composite Renal Endpoint for All Randomized Participants (Pooled)

Time to the Cardiovascular Composite Endpoint in the Intent-to-Treat (ITT) Responder Set (as Randomized)

Time to the First Occurrence of a Component of the Composite Renal Endpoint in the Intent-to-Treat (ITT) Responder Set (as Randomized)

Percentage of Participants Who Entered the Observation Period and Did Not Return to Within 15% of Baseline Sperm Concentration or Above During the 52-Week Observational Period

Percentage of Subjects With a Sperm Concentration < 15 Million Per mL by Treatment Week 26

Change From Baseline up to Treatment Period Week 26 and Observation Period Week 52 in Estradiol

Change From Baseline up to Treatment Period Week 26 and Observation Period Week 52 in in Follicle Stimulating Hormone (FSH)

Change From Baseline up to Treatment Period Week 26 and Observation Period Week 52 in Inhibin B

Change From Baseline up to Treatment Period Week 26 and Observation Period Week 52 in Lutenizing Hormone (LH)

Change From Baseline up to Treatment Period Week 26 and Observation Period Week 52 in Semen Volume

Change From Baseline up to Treatment Period Week 26 and Observation Period Week 52 in Serum Testosterone

Change From Baseline up to Treatment Period Week 26 and Observation Period Week 52 in Sperm Concentration

Change From Baseline up to Treatment Period Week 26 and Observation Period Week 52 in Sperm Morphology

Change From Baseline up to Treatment Period Week 26 and Observation Period Week 52 in Sperm Motility

Related Drugs (181)

Related Conditions (268)