aleglitazar: a dual peroxisome PPAR-alpha and PPAR-gamma agonist for type 2 diabetes [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]
| ID Source | ID |
|---|---|
| PubMed CID | 10274777 |
| CHEMBL ID | 519504 |
| SCHEMBL ID | 482284 |
| MeSH ID | M0537835 |
| Synonym |
|---|
| (2s)-2-methoxy-3-{4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]-1-benzothiophen-7-yl}propanoic acid |
| ro7 , |
| CHEMBL519504 , |
| aleglitazar |
| ro-0728804 |
| R1439 , |
| r-1439 |
| ro0728804 |
| aleglitazar (usan) |
| 475479-34-6 |
| D08845 |
| bdbm50277897 |
| benzo(b)thiophene-7-propanoic acid, alpha-methoxy-4-(2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy)-, (alphas)- |
| unii-41t4oag59u |
| (s)-2-methoxy-3-(4-(2-(5-methyl-2-phenyloxazol-4-yl-ethoxy)benzo(b)thiophen-7-yl)propionic acid |
| r 1439 |
| (2s)-2-methoxy-3-(4-(2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy)-benzothiophen-7-yl)propionic acid |
| ro 0728804 |
| aleglitazar [usan:inn] |
| 41t4oag59u , |
| rg-1439 |
| ro-0728804-000 |
| ro-728804 |
| HY-14728 |
| CS-1134 |
| aleglitazar [usan] |
| aleglitazar [inn] |
| (2s)-2-methoxy-3-{4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]-benzothiophen-7-yl}propionic acid |
| aleglitazar [who-dd] |
| aleglitazar [mi] |
| benzo(b)thiophene-7-propanoic acid, .alpha.-methoxy-4-(2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy)-, (.alpha.s)- |
| gtpl7405 |
| (2s)-2-methoxy-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]-1-benzothiophen-7-yl]propanoic acid |
| DB08915 |
| AKOS022185537 |
| (s)-2-methoxy-3-{4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-benzo[b]thiophen-7-yl}-propionic acid |
| (5)-2-methoxy-3-{4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-benzo[b]thiophen-7-yl}-propionic acid |
| (s)-2-methoxy-3-[4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-benzo[b]thiophen-7-yl}-propionic acid |
| (s)-2-methoxy-3-{4-[2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-benzo[b]thiophen-7-yl}-prop ionic acid |
| DAYKLWSKQJBGCS-NRFANRHFSA-N |
| SCHEMBL482284 |
| (s)-2-methoxy-3-(4-(2-(5-methyl-2-phenyloxazol-4-yl)ethoxy)benzo[b]thiophen-7-yl)propanoic acid |
| DTXSID70197193 |
| NCGC00378922-01 |
| Q3609417 |
| BCP11370 |
Co-administration of aleglitazar with a statin does not alter the pharmacokinetic profile of either drug. The study was a multicenter, randomized, double-blind, placebo-controlled, ascending-dose study.
| Excerpt | Reference | Relevance |
|---|---|---|
| "This multicenter, randomized, double-blind, placebo-controlled, ascending-dose study investigated the pharmacokinetics, pharmacodynamic effects, safety, and tolerability of aleglitazar, a novel peroxisome proliferator-activated receptor alpha/gamma (PPARalpha/gamma) dual agonist." | ( Pharmacokinetics, pharmacodynamics, and tolerability of aleglitazar in patients with type 2 diabetes: results from a randomized, placebo-controlled clinical study. Banken, L; Jamois, C; Liogier D'ardhuy, X; Sanwald-Ducray, P, 2010) | 0.36 |
| "To investigate the pharmacokinetic effects of co-administration of atorvastatin or rosuvastatin with aleglitazar." | ( Aleglitazar, a balanced PPARα/γ agonist, has no clinically relevant pharmacokinetic interaction with high-dose atorvastatin or rosuvastatin. Foley-Comer, AJ; Jordan, P; Russell-Yarde, F; Young, AM, 2011) | 0.37 |
| " Plasma concentrations of each drug were measured and pharmacokinetic parameters determined on day 7 in each period." | ( Aleglitazar, a balanced PPARα/γ agonist, has no clinically relevant pharmacokinetic interaction with high-dose atorvastatin or rosuvastatin. Foley-Comer, AJ; Jordan, P; Russell-Yarde, F; Young, AM, 2011) | 0.37 |
| "Co-administration of aleglitazar with a statin does not alter the pharmacokinetic profile of either drug." | ( Aleglitazar, a balanced PPARα/γ agonist, has no clinically relevant pharmacokinetic interaction with high-dose atorvastatin or rosuvastatin. Foley-Comer, AJ; Jordan, P; Russell-Yarde, F; Young, AM, 2011) | 0.37 |
| " The primary objective was to investigate the effect of aleglitazar on the pharmacokinetic properties of S-warfarin and on the pharmacodynamics of the racemic mixture; the secondary objectives included the effect of aleglitazar on R-warfarin pharmacokinetics and of racemic warfarin on aleglitazar pharmacokinetics." | ( The effect of aleglitazar on the pharmacokinetics and pharmacodynamics of S- and R-warfarin in healthy male subjects. Banken, L; Jamois, C; Sanwald-Ducray, P, 2014) | 0.4 |
| Excerpt | Reference | Relevance |
|---|---|---|
| "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 |
SESTA R was a 26-week, randomized, double-blind, multicenter study. Compared effects of supratherapeutic dosage of aleglitazar with pioglitazone (45 mg/day) on change in measured GFR (mGFR) in 174 patients.
| Excerpt | Relevance | Reference |
|---|---|---|
| " After a 3-week washout period, 71 patients with type 2 diabetes received either a single oral dose of aleglitazar (20, 50, 100, 300, 600, or 900 microg) or placebo, followed by once-daily dosing for 6 weeks." | ( Pharmacokinetics, pharmacodynamics, and tolerability of aleglitazar in patients with type 2 diabetes: results from a randomized, placebo-controlled clinical study. Banken, L; Jamois, C; Liogier D'ardhuy, X; Sanwald-Ducray, P, 2010) | 0.36 |
| "SESTA R was a 26-week, randomized, double-blind, multicenter study comparing the effects of a supratherapeutic dosage of aleglitazar (600 μg/day) with pioglitazone (45 mg/day) on change in measured GFR (mGFR) in 174 patients with type 2 diabetes and normal to mildly impaired renal function (estimated GFR [eGFR] 60 to 120 ml/min/1." | ( Effects of high dose aleglitazar on renal function in patients with type 2 diabetes. Gaspari, F; Herz, M; Perico, N; Rabbia, M; Urbanowska, T; Viberti, G; Wieczorek Kirk, D, 2011) | 0.37 |
| ", peripheral edema, weight gain, and congestive heart failure) limiting further development of this supratherapeutic dosage of aleglitazar (600 μg/day), these data, together with the data from the dose-ranging SYNCHRONY study, suggest aleglitazar may be a potential new treatment for cardiovascular risk reduction in post-acute coronary syndrome patients at the therapeutic 150 μg daily dose." | ( Effects of high dose aleglitazar on renal function in patients with type 2 diabetes. Gaspari, F; Herz, M; Perico, N; Rabbia, M; Urbanowska, T; Viberti, G; Wieczorek Kirk, D, 2011) | 0.37 |
| " Plasma levels of markers of glycemic and lipid regulation were measured at baseline, at the end of the dosing period, and at the end of the washout period." | ( Effects of aleglitazar, a balanced dual peroxisome proliferator-activated receptor α/γ agonist on glycemic and lipid parameters in a primate model of the metabolic syndrome. Bénardeau, A; Hansen, BC; Meyer, M; Mizrahi, J; Sebokova, E; Tigno, XT, 2011) | 0.37 |
| " A comprehensive, 12-concentration dose-response analysis using a cell-based assay showed aleglitazar to be highly potent, with EC(50) values of 5 nM and 9 nM for PPARα and PPARγ, respectively." | ( Comparative molecular profiling of the PPARα/γ activator aleglitazar: PPAR selectivity, activity and interaction with cofactors. Benz, J; Dietz, M; Grether, U; Hartman, P; Kuhn, B; Maerki, HP; Mohr, P; Ruf, A; Wright, MB, 2012) | 0.38 |
| 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 | 10.6840 | 0.0123 | 7.9835 | 43.2770 | AID1645841 |
| G | Vesicular stomatitis virus | Potency | 26.8370 | 0.0123 | 8.9648 | 39.8107 | AID1645842 |
| Interferon beta | Homo sapiens (human) | Potency | 26.8370 | 0.0033 | 9.1582 | 39.8107 | AID1645842 |
| HLA class I histocompatibility antigen, B alpha chain | Homo sapiens (human) | Potency | 26.8370 | 0.0123 | 8.9648 | 39.8107 | AID1645842 |
| Inositol hexakisphosphate kinase 1 | Homo sapiens (human) | Potency | 26.8370 | 0.0123 | 8.9648 | 39.8107 | AID1645842 |
| cytochrome P450 2C9, partial | Homo sapiens (human) | Potency | 26.8370 | 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) |
|---|---|---|---|---|---|---|---|
| Peroxisome proliferator-activated receptor gamma | Homo sapiens (human) | IC50 (µMol) | 0.0190 | 0.0050 | 1.2051 | 10.0000 | AID354041 |
| Peroxisome proliferator-activated receptor alpha | Homo sapiens (human) | IC50 (µMol) | 0.0380 | 0.0005 | 0.8269 | 6.3100 | AID354040 |
| [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) |
|---|---|---|---|---|---|---|---|
| Peroxisome proliferator-activated receptor alpha | Mus musculus (house mouse) | EC50 (µMol) | 2.3400 | 0.0002 | 1.3971 | 10.0000 | AID354072 |
| Peroxisome proliferator-activated receptor alpha | Rattus norvegicus (Norway rat) | EC50 (µMol) | 2.2600 | 0.1660 | 0.8677 | 2.2600 | AID354071 |
| Peroxisome proliferator-activated receptor gamma | Homo sapiens (human) | EC50 (µMol) | 0.0210 | 0.0000 | 0.9922 | 10.0000 | AID354043 |
| Peroxisome proliferator-activated receptor delta | Homo sapiens (human) | EC50 (µMol) | 0.0530 | 0.0002 | 0.8460 | 9.1000 | AID354052 |
| Peroxisome proliferator-activated receptor alpha | Homo sapiens (human) | EC50 (µMol) | 0.0500 | 0.0006 | 1.6074 | 10.0000 | AID354042 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
| Assay ID | Title | Year | Journal | Article |
|---|---|---|---|---|
| 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. |
| 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. |
| 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. |
| AID354061 | Antidiabetic activity in Zucker fa/fa rat assessed as HOMA-insulin resistance index at 1 mg/kg/day | 2009 | Bioorganic & medicinal chemistry letters, May-01, Volume: 19, Issue:9 | Aleglitazar, a new, potent, and balanced dual PPARalpha/gamma agonist for the treatment of type II diabetes. |
| AID354052 | Agonist activity at PPARdelta by luciferase reporter transactivation assay | 2009 | Bioorganic & medicinal chemistry letters, May-01, Volume: 19, Issue:9 | Aleglitazar, a new, potent, and balanced dual PPARalpha/gamma agonist for the treatment of type II diabetes. |
| AID354068 | Increase in plasma HDLC level in human ApoA1 transgenic mouse model at 3 mg/kg/day after 12 days by FPLC method | 2009 | Bioorganic & medicinal chemistry letters, May-01, Volume: 19, Issue:9 | Aleglitazar, a new, potent, and balanced dual PPARalpha/gamma agonist for the treatment of type II diabetes. |
| AID354048 | Bioavailability in rat | 2009 | Bioorganic & medicinal chemistry letters, May-01, Volume: 19, Issue:9 | Aleglitazar, a new, potent, and balanced dual PPARalpha/gamma agonist for the treatment of type II diabetes. |
| AID354058 | Antidiabetic activity in Zucker fa/fa rat assessed as glucose infusion rate at 1 mg/kg/day after 7 days by hyperinsulinemic-euglycemic clamp study | 2009 | Bioorganic & medicinal chemistry letters, May-01, Volume: 19, Issue:9 | Aleglitazar, a new, potent, and balanced dual PPARalpha/gamma agonist for the treatment of type II diabetes. |
| AID354043 | Agonist activity at human PPARgamma expressed in BHK21 cells assessed as SEAP activity by luciferase reporter transactivation assay | 2009 | Bioorganic & medicinal chemistry letters, May-01, Volume: 19, Issue:9 | Aleglitazar, a new, potent, and balanced dual PPARalpha/gamma agonist for the treatment of type II diabetes. |
| AID354055 | Antidiabetic activity in db/db mouse diabetic model assessed as reduction in post prandial blood glucose level at 0.3 mg/kg/day | 2009 | Bioorganic & medicinal chemistry letters, May-01, Volume: 19, Issue:9 | Aleglitazar, a new, potent, and balanced dual PPARalpha/gamma agonist for the treatment of type II diabetes. |
| AID354056 | Antidiabetic activity in overnight fasted db/db mouse diabetic model assessed as reduction in blood glucose level at 3 mg/kg/day, po chronically for 12 days challenged with glucose 24 hrs post last dose by OGTT | 2009 | Bioorganic & medicinal chemistry letters, May-01, Volume: 19, Issue:9 | Aleglitazar, a new, potent, and balanced dual PPARalpha/gamma agonist for the treatment of type II diabetes. |
| AID354067 | Increase in plasma HDLC level in human ApoA1 transgenic mouse model at 0.3 mg/kg/day after 12 days by FPLC method | 2009 | Bioorganic & medicinal chemistry letters, May-01, Volume: 19, Issue:9 | Aleglitazar, a new, potent, and balanced dual PPARalpha/gamma agonist for the treatment of type II diabetes. |
| AID354042 | Agonist activity at human PPARalpha by luciferase reporter transactivation assay | 2009 | Bioorganic & medicinal chemistry letters, May-01, Volume: 19, Issue:9 | Aleglitazar, a new, potent, and balanced dual PPARalpha/gamma agonist for the treatment of type II diabetes. |
| AID354046 | Total clearance in rat | 2009 | Bioorganic & medicinal chemistry letters, May-01, Volume: 19, Issue:9 | Aleglitazar, a new, potent, and balanced dual PPARalpha/gamma agonist for the treatment of type II diabetes. |
| AID354054 | Antidiabetic activity in overnight fasted db/db mouse diabetic model assessed as reduction in blood glucose level at 0.3 mg/kg/day, po chronically for 12 days challenged with glucose 24 hrs post last dose by OGTT | 2009 | Bioorganic & medicinal chemistry letters, May-01, Volume: 19, Issue:9 | Aleglitazar, a new, potent, and balanced dual PPARalpha/gamma agonist for the treatment of type II diabetes. |
| AID354047 | Total clearance in cynomolgus monkey | 2009 | Bioorganic & medicinal chemistry letters, May-01, Volume: 19, Issue:9 | Aleglitazar, a new, potent, and balanced dual PPARalpha/gamma agonist for the treatment of type II diabetes. |
| AID354044 | Agonist activity at human PPARalpha by luciferase reporter transactivation assay relative to GW-262570 | 2009 | Bioorganic & medicinal chemistry letters, May-01, Volume: 19, Issue:9 | Aleglitazar, a new, potent, and balanced dual PPARalpha/gamma agonist for the treatment of type II diabetes. |
| AID354045 | Agonist activity at human PPARgamma expressed in BHK21 cells assessed as SEAP activity by luciferase reporter transactivation assay relative to edaglitazone | 2009 | Bioorganic & medicinal chemistry letters, May-01, Volume: 19, Issue:9 | Aleglitazar, a new, potent, and balanced dual PPARalpha/gamma agonist for the treatment of type II diabetes. |
| AID354072 | Agonist activity at mouse PPARalpha | 2009 | Bioorganic & medicinal chemistry letters, May-01, Volume: 19, Issue:9 | Aleglitazar, a new, potent, and balanced dual PPARalpha/gamma agonist for the treatment of type II diabetes. |
| AID354050 | Half life in rat | 2009 | Bioorganic & medicinal chemistry letters, May-01, Volume: 19, Issue:9 | Aleglitazar, a new, potent, and balanced dual PPARalpha/gamma agonist for the treatment of type II diabetes. |
| AID354057 | Antidiabetic activity in db/db mouse diabetic model assessed as reduction in post prandial blood glucose level at 3 mg/kg/day | 2009 | Bioorganic & medicinal chemistry letters, May-01, Volume: 19, Issue:9 | Aleglitazar, a new, potent, and balanced dual PPARalpha/gamma agonist for the treatment of type II diabetes. |
| AID354064 | Antidiabetic activity in Zucker fa/fa rat assessed as fasting plasma insulin level at 1 mg/kg/day | 2009 | Bioorganic & medicinal chemistry letters, May-01, Volume: 19, Issue:9 | Aleglitazar, a new, potent, and balanced dual PPARalpha/gamma agonist for the treatment of type II diabetes. |
| AID354040 | Displacement of radio labeled 2(S)-(2-benzoyl-phenylamino)-3-{4-[1,1-ditritio-2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-phenyl}-propionic acid from GST-fused human PPARalpha expressed in Escherichia coli BL21 cells | 2009 | Bioorganic & medicinal chemistry letters, May-01, Volume: 19, Issue:9 | Aleglitazar, a new, potent, and balanced dual PPARalpha/gamma agonist for the treatment of type II diabetes. |
| AID354071 | Agonist activity at rat PPARalpha | 2009 | Bioorganic & medicinal chemistry letters, May-01, Volume: 19, Issue:9 | Aleglitazar, a new, potent, and balanced dual PPARalpha/gamma agonist for the treatment of type II diabetes. |
| AID354051 | Half life in cynomolgus monkey | 2009 | Bioorganic & medicinal chemistry letters, May-01, Volume: 19, Issue:9 | Aleglitazar, a new, potent, and balanced dual PPARalpha/gamma agonist for the treatment of type II diabetes. |
| AID354049 | Bioavailability in cynomolgus monkey | 2009 | Bioorganic & medicinal chemistry letters, May-01, Volume: 19, Issue:9 | Aleglitazar, a new, potent, and balanced dual PPARalpha/gamma agonist for the treatment of type II diabetes. |
| AID354041 | Displacement of radio labeled 2(S)-(2-benzoyl-phenylamino)-3-{4-[1,1-ditritio-2-(5-methyl-2-phenyl-oxazol-4-yl)-ethoxy]-phenyl}-propionic acid from GST-fused human PPARgamma expressed in Escherichia coli BL21 cells by scintillation proximity assay | 2009 | Bioorganic & medicinal chemistry letters, May-01, Volume: 19, Issue:9 | Aleglitazar, a new, potent, and balanced dual PPARalpha/gamma agonist for the treatment of type II diabetes. |
| AID354053 | Agonist activity at PPARdelta by luciferase reporter transactivation assay relative to GW-501516 | 2009 | Bioorganic & medicinal chemistry letters, May-01, Volume: 19, Issue:9 | Aleglitazar, a new, potent, and balanced dual PPARalpha/gamma agonist for the treatment of type II diabetes. |
| [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 | 0 (0.00) | 18.2507 |
| 2000's | 3 (6.98) | 29.6817 |
| 2010's | 34 (79.07) | 24.3611 |
| 2020's | 6 (13.95) | 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 | 19 (44.19%) | 5.53% |
| Reviews | 6 (13.95%) | 6.00% |
| Case Studies | 0 (0.00%) | 4.05% |
| Observational | 0 (0.00%) | 0.25% |
| Other | 18 (41.86%) | 84.16% |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||