glasdegib profile

glasdegib: a smoothened inhibitor [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

glasdegib : A member of the class of benzimidazoles that is 1H-benzimidazole which is substituted by a (2R,4S)-4-{[(4-cyanophenyl)carbamoyl]amino}-1-methylpiperidin-2-yl group at position 2. It is a hedgehog signalling pathway inhibitor that acts by binding to Smoothened (SMO) receptors and blocking signal transduction (IC50 = 5 nM). It is used in combination with low-dose cytarabine, for the treatment of newly-diagnosed acute myeloid leukemia (AML) in adult patients (aged >= 75 years), or who have medical conditions that prevent the use of standard chemotherapy. [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]

ID Source	ID
PubMed CID	25166913
CHEMBL ID	2043437
CHEBI ID	145428
SCHEMBL ID	2068480
MeSH ID	M000599270

Synonym
glasdegib
glasdegibum
pf-913
n-[(2r,4r)-2-(1h-benzimidazol-2-yl)-1-methylpiperidin-4-yl]-n'-(4-cyanophenyl)urea
pf-04449913
1-[(2r,4r)-2-(1h-benzimidazol-2-yl)-1-methylpiperidin-4-yl]-3-(4-cyanophenyl)urea
1095173-27-5
CHEBI:145428 ,
pf-4449913
bdbm50385635
glasdegib [usan]
urea, n-((2r,4r)-2-(1h-benzimidazol-2-yl)-1-methyl-4-piperidinyl)-n'-(4-cyanophenyl)-
glasdegib [mi]
glasdegib [who-dd]
n-((2r,4r)-2-(1h-benzimidazol-2-yl)-1-methylpiperidin-4-yl)-n'-(4-cyanophenyl)urea
glasdegib [inn]
CHEMBL2043437 ,
gtpl8201
HY-16391
SFNSLLSYNZWZQG-VQIMIIECSA-N
k673dmo5h9 ,
unii-k673dmo5h9
pf 04449913
glasdegib [usan:inn]
SCHEMBL2068480
c21h22n6o
1-((2r,4r)-2-(1h-benzo[d]imidazol-2-yl)-1-methylpiperidin-4-yl)-3-(4-cyanophenyl)urea
glasdegib (usan/inn)
D10636
4-[(2r)-2-[(1r)-2,2,2-trifluoro-1-hydroxyethyl]-1-pyrrolidinyl]-2-(trifluoromethyl)-benzonitrile
J-690029
EX-A858
pf-04449913;glasdegib
AC-35176
AKOS027324121
glasdegib (pf-04449913)
NCGC00378600-02
glasdegib(pf-04449913)
urea, n-[(2r,4r)-2-(1h-benzimidazol-2-yl)-1-methyl-4-piperidinyl]-n'-(4-cyanophenyl)-
DB11978
n-[(2r,4r)-2-(1h-benzimidazol-2-yl)-1-methyl-4-piperidinyl]-n'-(4-cyanophenyl)urea
mfcd25976839
BS-14357
Q27077810
AMY38164
CCG-268350
S7160
nsc-775772
nsc775772
VTB17327
DTXSID201025881
EN300-18161184
3-[(2r,4r)-2-(1h-1,3-benzodiazol-2-yl)-1-methylpiperidin-4-yl]-1-(4-cyanophenyl)urea
1-((2r,4r)-2-(1h-benzimidazol-2-yl)-1-methylpiperidin-4-yl)-3-(4-cyanophenyl)urea
pf04449913
l01xx63

Excerpt	Reference	Relevance
"Glasdegib is a small-molecule inhibitor of a component of the hedgehog (HH) pathway, an upregulated pathway in leukemia and leukemia stem cells that is associated with relapse, drug resistance and poor survival."	( Glasdegib for the treatment of adult patients with newly diagnosed acute myeloid leukemia or high-grade myelodysplastic syndrome who are elderly or otherwise unfit for standard induction chemotherapy. Goldsmith, SR; Lovell, AR; Schroeder, MA, 2019)	2.68
"Glasdegib is a potent, selective oral inhibitor of the Hedgehog signaling pathway. "	( Clinical and Model-Based Evaluation of the Effect of Glasdegib on Cardiac Repolarization From a Randomized Thorough QT Study. Hee, B; LaBadie, RR; Masters, JC; Mendes da Costa, L; Shaik, N, 2021)	2.31
"Glasdegib + LDAraC is a fairly safe, non-intensive, outpatient regimen inducing complete remission and resulting in prolonged survival in some R/R AML patients."	( Glasdegib in combination with low-dose Cytarabine for the outpatient treatment of relapsed or refractory acute myeloid leukemia in unfit patients. Burzdikaite, P; Dapkeviciute, A; Daukelaite, G; Davainis, L; Griskevicius, L; Maneikis, K; Pugaciute, B; Ringeleviciute, U; Staras, V; Zucenka, A, 2021)	2.79
"Glasdegib is a Hedgehog pathway inhibitor. "	( Randomized comparison of low dose cytarabine with or without glasdegib in patients with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome. Chan, G; Cortes, JE; DesJardins, P; Fiedler, W; Heidel, FH; Hellmann, A; Heuser, M; Laird, AD; Ma, WW; Montesinos, P; O'Connell, A; Ottmann, O; Pollyea, DA; Robak, T; Shaik, MN; Smith, BD; Zeremski, M, 2019)	2.2
"Glasdegib (DAURISMO™) is an oral inhibitor of the Hedgehog signalling pathway, the activation of which is associated with a number of malignancies. "	( Glasdegib: First Global Approval. Hoy, SM, 2019)	3.4
"Glasdegib is a potent and selective oral inhibitor of the Hedgehog pathway. "	( Phase 1/2 trial of glasdegib in patients with primary or secondary myelofibrosis previously treated with ruxolitinib. Chan, G; Deininger, M; DiRienzo, C; Gerds, AT; Heaney, M; Jamieson, C; Komatsu, N; Mesa, R; Minami, H; Ritchie, E; Shaik, N; Su, Y; Talpaz, M; Tauchi, T; Zeremski, M; Zhang, X, 2019)	2.29
"Glasdegib (PF-04449913) is an oral small-molecule inhibitor of the Hedgehog signaling pathway under development for treating myeloid malignancies. "	( Absolute Oral Bioavailability of Glasdegib (PF-04449913), a Smoothened Inhibitor, in Randomized Healthy Volunteers. Hee, B; LaBadie, RR; Liang, Y; Shaik, N, 2019)	2.24

Excerpt	Reference	Relevance
"Glasdegib plus LDAC has a favorable benefit-risk profile and may be a promising option for AML patients unsuitable for intensive chemotherapy."	( Randomized comparison of low dose cytarabine with or without glasdegib in patients with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome. Chan, G; Cortes, JE; DesJardins, P; Fiedler, W; Heidel, FH; Hellmann, A; Heuser, M; Laird, AD; Ma, WW; Montesinos, P; O'Connell, A; Ottmann, O; Pollyea, DA; Robak, T; Shaik, MN; Smith, BD; Zeremski, M, 2019)	1.48

Excerpt	Reference	Relevance
" Patients received PF-04449913 once daily continuously until disease progression, unacceptable toxic effects, or patient withdrawal for up to 12 28-day cycles."	( Treatment with PF-04449913, an oral smoothened antagonist, in patients with myeloid malignancies: a phase 1 safety and pharmacokinetics study. Baccarani, M; Cortes, JE; Courtney, R; Jamieson, C; Kantarjian, HM; Levin, WJ; Martinelli, G; McLachlan, KR; O'Connell, A; Oehler, VG; Papayannidis, C; Radich, J; Shaik, MN; Zhang, X; Zheng, X, 2015)	0.42
" Of the 47 patients enrolled, 28 (60%) experienced treatment-related adverse events, three of which were grade 4 in severity."	( Treatment with PF-04449913, an oral smoothened antagonist, in patients with myeloid malignancies: a phase 1 safety and pharmacokinetics study. Baccarani, M; Cortes, JE; Courtney, R; Jamieson, C; Kantarjian, HM; Levin, WJ; Martinelli, G; McLachlan, KR; O'Connell, A; Oehler, VG; Papayannidis, C; Radich, J; Shaik, MN; Zhang, X; Zheng, X, 2015)	0.42
" The relationship between glasdegib exposure and adverse event (AE) cluster terms of clinical concern was explored in this analysis."	( Evaluation of the Relationship of Glasdegib Exposure and Safety End Points in Patients With Refractory Solid Tumors and Hematologic Malignancies. Chan, G; Heuser, M; Jamieson, C; Lin, S; Ruiz-Garcia, A; Shaik, N, 2021)	1.2

Excerpt	Reference	Relevance
" The mean half-life was 23·9 h (SD 14·0) in the MTD group."	( Treatment with PF-04449913, an oral smoothened antagonist, in patients with myeloid malignancies: a phase 1 safety and pharmacokinetics study. Baccarani, M; Cortes, JE; Courtney, R; Jamieson, C; Kantarjian, HM; Levin, WJ; Martinelli, G; McLachlan, KR; O'Connell, A; Oehler, VG; Papayannidis, C; Radich, J; Shaik, MN; Zhang, X; Zheng, X, 2015)	0.42

Excerpt	Reference	Relevance
" These targeted therapies could be more tolerable than classical antineoplastics, but potential drug-drug interactions (DDI) are relatively frequent."	( Drug-drug interactions of newly approved small molecule inhibitors for acute myeloid leukemia. Ballesta-López, O; Martínez-Cuadrón, D; Megías-Vericat, JE; Montesinos, P; Solana-Altabella, A, 2020)	0.56
"The clinical efficacy and safety of DAURISMO (glasdegib) combined with low-dose cytarabine (LDAC) were demonstrated in the BRIGHT AML 1003 study among newly diagnosed acute myeloid leukemia patients who are not eligible to receive intensive chemotherapy."	( The cost-effectiveness of glasdegib in combination with low-dose cytarabine, for the treatment of newly diagnosed acute myeloid leukemia in adult patients who are not eligible to receive intensive induction chemotherapy in Canada. Bell, T; Charaan, M; Heeg, B; Hu, Y; van Oostrum, I, )	0.69

Excerpt	Reference	Relevance
"This phase I open-label study investigated the oral bioavailability of two novel maleate salt-based glasdegib (PF-04449913) tablet formulations (small- and large-particle size) relative to the current clinical formulation (diHCl salt-based)."	( Evaluation of the effect of new formulation, food, or a proton pump inhibitor on the relative bioavailability of the smoothened inhibitor glasdegib (PF-04449913) in healthy volunteers. Giri, N; Hee, B; Jiang, H; Krzyzaniak, JF; LaBadie, RR; Lam, LH; Liang, Y; Shaik, MN, 2017)	0.87
" This was an open-label phase 1, randomized, 2-sequence, 2-treatment, 2-period, crossover study evaluating the absolute bioavailability of glasdegib in healthy volunteers under fasting condition (NCT03270878)."	( Absolute Oral Bioavailability of Glasdegib (PF-04449913), a Smoothened Inhibitor, in Randomized Healthy Volunteers. Hee, B; LaBadie, RR; Liang, Y; Shaik, N, 2019)	1
"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

Role	Description
SMO receptor antagonist	An antagonist that interferes with the action of smoothened (SMO) receptor.
Hedgehog signaling pathway inhibitor	Any pathway inhibitor that inhibits the Hedgehog signalling pathway.
antineoplastic agent	A substance that inhibits or prevents the proliferation of neoplasms.
[role 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]

Class	Description
benzimidazoles	An organic heterocyclic compound containing a benzene ring fused to an imidazole ring.
piperidines
phenylureas	Any member of the class of ureas in which at least one of the nitrogens of the urea moiety is substituted by a phenyl or substituted phenyl group.
nitrile	A compound having the structure RC#N; thus a C-substituted derivative of hydrocyanic acid, HC#N. In systematic nomenclature, the suffix nitrile denotes the triply bound #N atom, not the carbon atom attached to it.
[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	Min (ref.)	Avg (ref.)	Max (ref.)	Bioassay(s)
Cytochrome P450 1A2	Homo sapiens (human)	IC50 (µMol)	30.0000	0.0001	1.7740	10.0000	AID668867
Cytochrome P450 3A4	Homo sapiens (human)	IC50 (µMol)	30.0000	0.0001	1.7536	10.0000	AID668872
Cytochrome P450 2C8	Homo sapiens (human)	IC50 (µMol)	30.0000	0.0008	1.8848	7.9000	AID668868
Cytochrome P450 2D6	Homo sapiens (human)	IC50 (µMol)	30.0000	0.0000	2.0151	10.0000	AID668871
Cytochrome P450 2C9	Homo sapiens (human)	IC50 (µMol)	30.0000	0.0000	2.8005	10.0000	AID668869
Cytochrome P450 2C19	Homo sapiens (human)	IC50 (µMol)	30.0000	0.0000	2.3983	10.0000	AID668870
Smoothened homolog	Mus musculus (house mouse)	IC50 (µMol)	0.0050	0.0012	0.3768	1.9000	AID668854
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Process	via Protein(s)	Taxonomy
steroid catabolic process	Cytochrome P450 1A2	Homo sapiens (human)
porphyrin-containing compound metabolic process	Cytochrome P450 1A2	Homo sapiens (human)
xenobiotic metabolic process	Cytochrome P450 1A2	Homo sapiens (human)
cholesterol metabolic process	Cytochrome P450 1A2	Homo sapiens (human)
estrogen metabolic process	Cytochrome P450 1A2	Homo sapiens (human)
toxin biosynthetic process	Cytochrome P450 1A2	Homo sapiens (human)
post-embryonic development	Cytochrome P450 1A2	Homo sapiens (human)
alkaloid metabolic process	Cytochrome P450 1A2	Homo sapiens (human)
regulation of gene expression	Cytochrome P450 1A2	Homo sapiens (human)
monoterpenoid metabolic process	Cytochrome P450 1A2	Homo sapiens (human)
dibenzo-p-dioxin metabolic process	Cytochrome P450 1A2	Homo sapiens (human)
epoxygenase P450 pathway	Cytochrome P450 1A2	Homo sapiens (human)
lung development	Cytochrome P450 1A2	Homo sapiens (human)
methylation	Cytochrome P450 1A2	Homo sapiens (human)
monocarboxylic acid metabolic process	Cytochrome P450 1A2	Homo sapiens (human)
xenobiotic catabolic process	Cytochrome P450 1A2	Homo sapiens (human)
retinol metabolic process	Cytochrome P450 1A2	Homo sapiens (human)
long-chain fatty acid biosynthetic process	Cytochrome P450 1A2	Homo sapiens (human)
cellular respiration	Cytochrome P450 1A2	Homo sapiens (human)
aflatoxin metabolic process	Cytochrome P450 1A2	Homo sapiens (human)
hydrogen peroxide biosynthetic process	Cytochrome P450 1A2	Homo sapiens (human)
oxidative demethylation	Cytochrome P450 1A2	Homo sapiens (human)
cellular response to cadmium ion	Cytochrome P450 1A2	Homo sapiens (human)
omega-hydroxylase P450 pathway	Cytochrome P450 1A2	Homo sapiens (human)
lipid hydroxylation	Cytochrome P450 3A4	Homo sapiens (human)
lipid metabolic process	Cytochrome P450 3A4	Homo sapiens (human)
steroid catabolic process	Cytochrome P450 3A4	Homo sapiens (human)
xenobiotic metabolic process	Cytochrome P450 3A4	Homo sapiens (human)
steroid metabolic process	Cytochrome P450 3A4	Homo sapiens (human)
cholesterol metabolic process	Cytochrome P450 3A4	Homo sapiens (human)
androgen metabolic process	Cytochrome P450 3A4	Homo sapiens (human)
estrogen metabolic process	Cytochrome P450 3A4	Homo sapiens (human)
alkaloid catabolic process	Cytochrome P450 3A4	Homo sapiens (human)
monoterpenoid metabolic process	Cytochrome P450 3A4	Homo sapiens (human)
calcitriol biosynthetic process from calciol	Cytochrome P450 3A4	Homo sapiens (human)
xenobiotic catabolic process	Cytochrome P450 3A4	Homo sapiens (human)
vitamin D metabolic process	Cytochrome P450 3A4	Homo sapiens (human)
vitamin D catabolic process	Cytochrome P450 3A4	Homo sapiens (human)
retinol metabolic process	Cytochrome P450 3A4	Homo sapiens (human)
retinoic acid metabolic process	Cytochrome P450 3A4	Homo sapiens (human)
long-chain fatty acid biosynthetic process	Cytochrome P450 3A4	Homo sapiens (human)
aflatoxin metabolic process	Cytochrome P450 3A4	Homo sapiens (human)
oxidative demethylation	Cytochrome P450 3A4	Homo sapiens (human)
lipid hydroxylation	Cytochrome P450 2C8	Homo sapiens (human)
organic acid metabolic process	Cytochrome P450 2C8	Homo sapiens (human)
xenobiotic metabolic process	Cytochrome P450 2C8	Homo sapiens (human)
steroid metabolic process	Cytochrome P450 2C8	Homo sapiens (human)
estrogen metabolic process	Cytochrome P450 2C8	Homo sapiens (human)
epoxygenase P450 pathway	Cytochrome P450 2C8	Homo sapiens (human)
xenobiotic catabolic process	Cytochrome P450 2C8	Homo sapiens (human)
retinol metabolic process	Cytochrome P450 2C8	Homo sapiens (human)
retinoic acid metabolic process	Cytochrome P450 2C8	Homo sapiens (human)
long-chain fatty acid biosynthetic process	Cytochrome P450 2C8	Homo sapiens (human)
icosanoid biosynthetic process	Cytochrome P450 2C8	Homo sapiens (human)
oxidative demethylation	Cytochrome P450 2C8	Homo sapiens (human)
omega-hydroxylase P450 pathway	Cytochrome P450 2C8	Homo sapiens (human)
xenobiotic metabolic process	Cytochrome P450 2D6	Homo sapiens (human)
steroid metabolic process	Cytochrome P450 2D6	Homo sapiens (human)
cholesterol metabolic process	Cytochrome P450 2D6	Homo sapiens (human)
estrogen metabolic process	Cytochrome P450 2D6	Homo sapiens (human)
coumarin metabolic process	Cytochrome P450 2D6	Homo sapiens (human)
alkaloid metabolic process	Cytochrome P450 2D6	Homo sapiens (human)
alkaloid catabolic process	Cytochrome P450 2D6	Homo sapiens (human)
monoterpenoid metabolic process	Cytochrome P450 2D6	Homo sapiens (human)
isoquinoline alkaloid metabolic process	Cytochrome P450 2D6	Homo sapiens (human)
xenobiotic catabolic process	Cytochrome P450 2D6	Homo sapiens (human)
retinol metabolic process	Cytochrome P450 2D6	Homo sapiens (human)
long-chain fatty acid biosynthetic process	Cytochrome P450 2D6	Homo sapiens (human)
negative regulation of binding	Cytochrome P450 2D6	Homo sapiens (human)
oxidative demethylation	Cytochrome P450 2D6	Homo sapiens (human)
negative regulation of cellular organofluorine metabolic process	Cytochrome P450 2D6	Homo sapiens (human)
arachidonic acid metabolic process	Cytochrome P450 2D6	Homo sapiens (human)
xenobiotic metabolic process	Cytochrome P450 2C9	Homo sapiens (human)
steroid metabolic process	Cytochrome P450 2C9	Homo sapiens (human)
cholesterol metabolic process	Cytochrome P450 2C9	Homo sapiens (human)
estrogen metabolic process	Cytochrome P450 2C9	Homo sapiens (human)
monoterpenoid metabolic process	Cytochrome P450 2C9	Homo sapiens (human)
epoxygenase P450 pathway	Cytochrome P450 2C9	Homo sapiens (human)
urea metabolic process	Cytochrome P450 2C9	Homo sapiens (human)
monocarboxylic acid metabolic process	Cytochrome P450 2C9	Homo sapiens (human)
xenobiotic catabolic process	Cytochrome P450 2C9	Homo sapiens (human)
long-chain fatty acid biosynthetic process	Cytochrome P450 2C9	Homo sapiens (human)
amide metabolic process	Cytochrome P450 2C9	Homo sapiens (human)
icosanoid biosynthetic process	Cytochrome P450 2C9	Homo sapiens (human)
oxidative demethylation	Cytochrome P450 2C9	Homo sapiens (human)
omega-hydroxylase P450 pathway	Cytochrome P450 2C9	Homo sapiens (human)
long-chain fatty acid metabolic process	Cytochrome P450 2C19	Homo sapiens (human)
xenobiotic metabolic process	Cytochrome P450 2C19	Homo sapiens (human)
steroid metabolic process	Cytochrome P450 2C19	Homo sapiens (human)
monoterpenoid metabolic process	Cytochrome P450 2C19	Homo sapiens (human)
epoxygenase P450 pathway	Cytochrome P450 2C19	Homo sapiens (human)
xenobiotic catabolic process	Cytochrome P450 2C19	Homo sapiens (human)
omega-hydroxylase P450 pathway	Cytochrome P450 2C19	Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Process	via Protein(s)	Taxonomy
monooxygenase activity	Cytochrome P450 1A2	Homo sapiens (human)
iron ion binding	Cytochrome P450 1A2	Homo sapiens (human)
protein binding	Cytochrome P450 1A2	Homo sapiens (human)
electron transfer activity	Cytochrome P450 1A2	Homo sapiens (human)
oxidoreductase activity	Cytochrome P450 1A2	Homo sapiens (human)
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen	Cytochrome P450 1A2	Homo sapiens (human)
enzyme binding	Cytochrome P450 1A2	Homo sapiens (human)
heme binding	Cytochrome P450 1A2	Homo sapiens (human)
demethylase activity	Cytochrome P450 1A2	Homo sapiens (human)
caffeine oxidase activity	Cytochrome P450 1A2	Homo sapiens (human)
aromatase activity	Cytochrome P450 1A2	Homo sapiens (human)
estrogen 16-alpha-hydroxylase activity	Cytochrome P450 1A2	Homo sapiens (human)
estrogen 2-hydroxylase activity	Cytochrome P450 1A2	Homo sapiens (human)
hydroperoxy icosatetraenoate dehydratase activity	Cytochrome P450 1A2	Homo sapiens (human)
monooxygenase activity	Cytochrome P450 3A4	Homo sapiens (human)
steroid binding	Cytochrome P450 3A4	Homo sapiens (human)
iron ion binding	Cytochrome P450 3A4	Homo sapiens (human)
protein binding	Cytochrome P450 3A4	Homo sapiens (human)
steroid hydroxylase activity	Cytochrome P450 3A4	Homo sapiens (human)
retinoic acid 4-hydroxylase activity	Cytochrome P450 3A4	Homo sapiens (human)
oxidoreductase activity	Cytochrome P450 3A4	Homo sapiens (human)
oxygen binding	Cytochrome P450 3A4	Homo sapiens (human)
enzyme binding	Cytochrome P450 3A4	Homo sapiens (human)
heme binding	Cytochrome P450 3A4	Homo sapiens (human)
vitamin D3 25-hydroxylase activity	Cytochrome P450 3A4	Homo sapiens (human)
caffeine oxidase activity	Cytochrome P450 3A4	Homo sapiens (human)
quinine 3-monooxygenase activity	Cytochrome P450 3A4	Homo sapiens (human)
testosterone 6-beta-hydroxylase activity	Cytochrome P450 3A4	Homo sapiens (human)
1-alpha,25-dihydroxyvitamin D3 23-hydroxylase activity	Cytochrome P450 3A4	Homo sapiens (human)
anandamide 8,9 epoxidase activity	Cytochrome P450 3A4	Homo sapiens (human)
anandamide 11,12 epoxidase activity	Cytochrome P450 3A4	Homo sapiens (human)
anandamide 14,15 epoxidase activity	Cytochrome P450 3A4	Homo sapiens (human)
aromatase activity	Cytochrome P450 3A4	Homo sapiens (human)
vitamin D 24-hydroxylase activity	Cytochrome P450 3A4	Homo sapiens (human)
estrogen 16-alpha-hydroxylase activity	Cytochrome P450 3A4	Homo sapiens (human)
estrogen 2-hydroxylase activity	Cytochrome P450 3A4	Homo sapiens (human)
1,8-cineole 2-exo-monooxygenase activity	Cytochrome P450 3A4	Homo sapiens (human)
monooxygenase activity	Cytochrome P450 2C8	Homo sapiens (human)
iron ion binding	Cytochrome P450 2C8	Homo sapiens (human)
protein binding	Cytochrome P450 2C8	Homo sapiens (human)
arachidonic acid epoxygenase activity	Cytochrome P450 2C8	Homo sapiens (human)
retinoic acid 4-hydroxylase activity	Cytochrome P450 2C8	Homo sapiens (human)
caffeine oxidase activity	Cytochrome P450 2C8	Homo sapiens (human)
aromatase activity	Cytochrome P450 2C8	Homo sapiens (human)
estrogen 16-alpha-hydroxylase activity	Cytochrome P450 2C8	Homo sapiens (human)
heme binding	Cytochrome P450 2C8	Homo sapiens (human)
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen	Cytochrome P450 2C8	Homo sapiens (human)
monooxygenase activity	Cytochrome P450 2D6	Homo sapiens (human)
iron ion binding	Cytochrome P450 2D6	Homo sapiens (human)
oxidoreductase activity	Cytochrome P450 2D6	Homo sapiens (human)
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen	Cytochrome P450 2D6	Homo sapiens (human)
heme binding	Cytochrome P450 2D6	Homo sapiens (human)
anandamide 8,9 epoxidase activity	Cytochrome P450 2D6	Homo sapiens (human)
anandamide 11,12 epoxidase activity	Cytochrome P450 2D6	Homo sapiens (human)
anandamide 14,15 epoxidase activity	Cytochrome P450 2D6	Homo sapiens (human)
monooxygenase activity	Cytochrome P450 2C9	Homo sapiens (human)
iron ion binding	Cytochrome P450 2C9	Homo sapiens (human)
arachidonic acid epoxygenase activity	Cytochrome P450 2C9	Homo sapiens (human)
steroid hydroxylase activity	Cytochrome P450 2C9	Homo sapiens (human)
arachidonic acid 14,15-epoxygenase activity	Cytochrome P450 2C9	Homo sapiens (human)
arachidonic acid 11,12-epoxygenase activity	Cytochrome P450 2C9	Homo sapiens (human)
oxidoreductase activity	Cytochrome P450 2C9	Homo sapiens (human)
(S)-limonene 6-monooxygenase activity	Cytochrome P450 2C9	Homo sapiens (human)
(S)-limonene 7-monooxygenase activity	Cytochrome P450 2C9	Homo sapiens (human)
caffeine oxidase activity	Cytochrome P450 2C9	Homo sapiens (human)
(R)-limonene 6-monooxygenase activity	Cytochrome P450 2C9	Homo sapiens (human)
aromatase activity	Cytochrome P450 2C9	Homo sapiens (human)
heme binding	Cytochrome P450 2C9	Homo sapiens (human)
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen	Cytochrome P450 2C9	Homo sapiens (human)
monooxygenase activity	Cytochrome P450 2C19	Homo sapiens (human)
iron ion binding	Cytochrome P450 2C19	Homo sapiens (human)
steroid hydroxylase activity	Cytochrome P450 2C19	Homo sapiens (human)
oxidoreductase activity	Cytochrome P450 2C19	Homo sapiens (human)
(S)-limonene 6-monooxygenase activity	Cytochrome P450 2C19	Homo sapiens (human)
(S)-limonene 7-monooxygenase activity	Cytochrome P450 2C19	Homo sapiens (human)
oxygen binding	Cytochrome P450 2C19	Homo sapiens (human)
enzyme binding	Cytochrome P450 2C19	Homo sapiens (human)
heme binding	Cytochrome P450 2C19	Homo sapiens (human)
(R)-limonene 6-monooxygenase activity	Cytochrome P450 2C19	Homo sapiens (human)
aromatase activity	Cytochrome P450 2C19	Homo sapiens (human)
long-chain fatty acid omega-1 hydroxylase activity	Cytochrome P450 2C19	Homo sapiens (human)
arachidonic acid epoxygenase activity	Cytochrome P450 2C19	Homo sapiens (human)
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen	Cytochrome P450 2C19	Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Process	via Protein(s)	Taxonomy
endoplasmic reticulum membrane	Cytochrome P450 1A2	Homo sapiens (human)
intracellular membrane-bounded organelle	Cytochrome P450 1A2	Homo sapiens (human)
intracellular membrane-bounded organelle	Cytochrome P450 1A2	Homo sapiens (human)
cytoplasm	Cytochrome P450 3A4	Homo sapiens (human)
endoplasmic reticulum membrane	Cytochrome P450 3A4	Homo sapiens (human)
intracellular membrane-bounded organelle	Cytochrome P450 3A4	Homo sapiens (human)
endoplasmic reticulum membrane	Cytochrome P450 2C8	Homo sapiens (human)
plasma membrane	Cytochrome P450 2C8	Homo sapiens (human)
intracellular membrane-bounded organelle	Cytochrome P450 2C8	Homo sapiens (human)
cytoplasm	Cytochrome P450 2C8	Homo sapiens (human)
intracellular membrane-bounded organelle	Cytochrome P450 2C8	Homo sapiens (human)
mitochondrion	Cytochrome P450 2D6	Homo sapiens (human)
endoplasmic reticulum	Cytochrome P450 2D6	Homo sapiens (human)
endoplasmic reticulum membrane	Cytochrome P450 2D6	Homo sapiens (human)
cytoplasm	Cytochrome P450 2D6	Homo sapiens (human)
intracellular membrane-bounded organelle	Cytochrome P450 2D6	Homo sapiens (human)
endoplasmic reticulum membrane	Cytochrome P450 2C9	Homo sapiens (human)
plasma membrane	Cytochrome P450 2C9	Homo sapiens (human)
intracellular membrane-bounded organelle	Cytochrome P450 2C9	Homo sapiens (human)
cytoplasm	Cytochrome P450 2C9	Homo sapiens (human)
intracellular membrane-bounded organelle	Cytochrome P450 2C9	Homo sapiens (human)
endoplasmic reticulum membrane	Cytochrome P450 2C19	Homo sapiens (human)
plasma membrane	Cytochrome P450 2C19	Homo sapiens (human)
intracellular membrane-bounded organelle	Cytochrome P450 2C19	Homo sapiens (human)
intracellular membrane-bounded organelle	Cytochrome P450 2C19	Homo sapiens (human)
cytoplasm	Cytochrome P450 2C19	Homo sapiens (human)
endocytic vesicle membrane	Smoothened homolog	Mus musculus (house mouse)
ciliary membrane	Smoothened homolog	Mus musculus (house mouse)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (40)

Assay ID	Title	Year	Journal	Article
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.
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.
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.
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.
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.
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.
AID668890	Oral bioavailability in rat at 1 mg/kg	2012	ACS medicinal chemistry letters, Feb-09, Volume: 3, Issue:2	Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened.
AID668889	Clearance in rat at 1 mg/kg, iv and 1 mg/kg, po	2012	ACS medicinal chemistry letters, Feb-09, Volume: 3, Issue:2	Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened.
AID668880	Apparent permeability of the compound across basolateral to apical side in human Caco2 cells	2012	ACS medicinal chemistry letters, Feb-09, Volume: 3, Issue:2	Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened.
AID668865	Fraction unbound in dog liver microsomes	2012	ACS medicinal chemistry letters, Feb-09, Volume: 3, Issue:2	Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened.
AID668871	Inhibition of CYP2D6	2012	ACS medicinal chemistry letters, Feb-09, Volume: 3, Issue:2	Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened.
AID668869	Inhibition of CYP2C9	2012	ACS medicinal chemistry letters, Feb-09, Volume: 3, Issue:2	Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened.
AID668897	Intrinsic clearance in human microsomes	2012	ACS medicinal chemistry letters, Feb-09, Volume: 3, Issue:2	Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened.
AID668882	Induction of genotoxicity in micronucleus by micronucleus test	2012	ACS medicinal chemistry letters, Feb-09, Volume: 3, Issue:2	Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened.
AID668895	Intrinsic clearance in rat microsomes	2012	ACS medicinal chemistry letters, Feb-09, Volume: 3, Issue:2	Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened.
AID668867	Inhibition of CYP1A2	2012	ACS medicinal chemistry letters, Feb-09, Volume: 3, Issue:2	Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened.
AID668873	Dissociation constant, pKa of the compound	2012	ACS medicinal chemistry letters, Feb-09, Volume: 3, Issue:2	Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened.
AID668878	Percentage unbound in human plasma	2012	ACS medicinal chemistry letters, Feb-09, Volume: 3, Issue:2	Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened.
AID668870	Inhibition of CYP2C19	2012	ACS medicinal chemistry letters, Feb-09, Volume: 3, Issue:2	Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened.
AID668877	Percentage unbound in dog plasma	2012	ACS medicinal chemistry letters, Feb-09, Volume: 3, Issue:2	Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened.
AID668876	Percentage unbound in rat plasma	2012	ACS medicinal chemistry letters, Feb-09, Volume: 3, Issue:2	Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened.
AID668872	Inhibition of CYP3A4	2012	ACS medicinal chemistry letters, Feb-09, Volume: 3, Issue:2	Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened.
AID668894	Potency ratio, ratio of IC50 for compound to IC50 for compound 1 in mouse C3H10T1/2 cells by SMO/SHH transient transcriptional activation based Gli-luciferase reporter assay	2012	ACS medicinal chemistry letters, Feb-09, Volume: 3, Issue:2	Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened.
AID668888	Oral bioavailability in dog at 3 mg/kg	2012	ACS medicinal chemistry letters, Feb-09, Volume: 3, Issue:2	Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened.
AID668886	Half life in dog at 0.5 mg/kg, iv and 3 mg/kg, po	2012	ACS medicinal chemistry letters, Feb-09, Volume: 3, Issue:2	Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened.
AID668868	Inhibition of CYP2C8	2012	ACS medicinal chemistry letters, Feb-09, Volume: 3, Issue:2	Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened.
AID668864	Fraction unbound in rat liver microsomes	2012	ACS medicinal chemistry letters, Feb-09, Volume: 3, Issue:2	Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened.
AID668854	Inhibition of Smo in mouse C3H10T1/2 cells using human recombinant SHH assessed as effect on SMO/SHH transient transcriptional activation after 20 hrs by Gli-luciferase reporter assay	2012	ACS medicinal chemistry letters, Feb-09, Volume: 3, Issue:2	Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened.
AID668887	Clearance in dog at 0.5 mg/kg, iv and 3 mg/kg, po	2012	ACS medicinal chemistry letters, Feb-09, Volume: 3, Issue:2	Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened.
AID668885	Volume of distribution at steady state in dog at 0.5 mg/kg, iv and 3 mg/kg, po	2012	ACS medicinal chemistry letters, Feb-09, Volume: 3, Issue:2	Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened.
AID668893	Intrinsic clearance in human liver microsomes	2012	ACS medicinal chemistry letters, Feb-09, Volume: 3, Issue:2	Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened.
AID668881	Induction of genotoxicity in Salmonella typhimurium by Ames test	2012	ACS medicinal chemistry letters, Feb-09, Volume: 3, Issue:2	Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened.
AID668884	Half life in rat at 1 mg/kg, iv and 1 mg/kg, po	2012	ACS medicinal chemistry letters, Feb-09, Volume: 3, Issue:2	Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened.
AID668866	Fraction unbound in human liver microsomes	2012	ACS medicinal chemistry letters, Feb-09, Volume: 3, Issue:2	Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened.
AID668896	Intrinsic clearance in dog microsomes	2012	ACS medicinal chemistry letters, Feb-09, Volume: 3, Issue:2	Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened.
AID668859	Free intrinsic clearance in human liver microsomes	2012	ACS medicinal chemistry letters, Feb-09, Volume: 3, Issue:2	Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened.
AID668883	Volume of distribution at steady state in rat at 1 mg/kg, iv and 1 mg/kg, po	2012	ACS medicinal chemistry letters, Feb-09, Volume: 3, Issue:2	Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened.
AID668879	Apparent permeability of the compound across apical to basolateral side in human Caco2 cells	2012	ACS medicinal chemistry letters, Feb-09, Volume: 3, Issue:2	Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened.
AID668863	Lipophilicity, log D of the compound	2012	ACS medicinal chemistry letters, Feb-09, Volume: 3, Issue:2	Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened.
AID1345944	Human SMO (Class Frizzled GPCRs)	2012	ACS medicinal chemistry letters, Feb-09, Volume: 3, Issue:2	Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened.
[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	0 (0.00)	29.6817
2010's	27 (46.55)	24.3611
2020's	31 (53.45)	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	22 (36.67%)	5.53%
Reviews	17 (28.33%)	6.00%
Case Studies	2 (3.33%)	4.05%
Observational	0 (0.00%)	0.25%
Other	19 (31.67%)	84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Substance	Relationship Strength	Studies	Trials	Classes	Roles
glycine [no description available]	6.64	5	0	alpha-amino acid; amino acid zwitterion; proteinogenic amino acid; serine family amino acid	EC 2.1.2.1 (glycine hydroxymethyltransferase) inhibitor; fundamental metabolite; hepatoprotective agent; micronutrient; neurotransmitter; NMDA receptor agonist; nutraceutical
ketoconazole 1-acetyl-4-(4-{[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazine : A dioxolane that is 1,3-dioxolane which is substituted at positions 2, 2, and 4 by imidazol-1-ylmethyl, 2,4-dichlorophenyl, and [para-(4-acetylpiperazin-1-yl)phenoxy]methyl groups, respectively.	3.48	1	1	dichlorobenzene; dioxolane; ether; imidazoles; N-acylpiperazine; N-arylpiperazine
cytarabine [no description available]	13.64	25	9	beta-D-arabinoside; monosaccharide derivative; pyrimidine nucleoside	antimetabolite; antineoplastic agent; antiviral agent; immunosuppressive agent
quinuclidines Quinuclidines: A class of organic compounds which contain two rings that share a pair of bridgehead carbon atoms and contains an amine group.	3.35	1	0	quinuclidines; saturated organic heterobicyclic parent
cyclopentane Cyclopentanes: A group of alicyclic hydrocarbons with the general formula R-C5H9.. cyclopentanes : Cyclopentane and its derivatives formed by substitution.	3.31	1	0	cycloalkane; cyclopentanes; volatile organic compound	non-polar solvent
pyrazines Pyrazines: A heterocyclic aromatic organic compound with the chemical formula C4H4N2.. pyrazine : A diazine that is benzene in which the carbon atoms at positions 1 and 4 have been replaced by nitrogen atoms.	4.87	3	0	diazine; pyrazines	Daphnia magna metabolite
azacitidine Azacitidine: A pyrimidine analogue that inhibits DNA methyltransferase, impairing DNA methylation. It is also an antimetabolite of cytidine, incorporated primarily into RNA. Azacytidine has been used as an antineoplastic agent.. 5-azacytidine : An N-glycosyl-1,3,5-triazine that is 4-amino-1,3,5-triazin-2(1H)-one substituted by a beta-D-ribofuranosyl residue via an N-glycosidic linkage. An antineoplastic agent, it is used in the treatment of myeloid leukaemia.	14.23	7	2	N-glycosyl-1,3,5-triazine; nucleoside analogue	antineoplastic agent
alpha-aminopyridine alpha-aminopyridine: RN given refers to parent cpd; structure in Merck Index, 9th ed, #485. aminopyridine : Compounds containing a pyridine skeleton substituted by one or more amine groups.	5.16	2	0
arsenic trioxide Arsenic Trioxide: An inorganic compound with the chemical formula As2O3 that is used for the treatment of ACUTE PROMYELOCYTIC LEUKEMIA in patients who have relapsed from, or are resistant to, conventional drug therapy.	3.35	1	0
daunorubicin Daunorubicin: A very toxic anthracycline aminoglycoside antineoplastic isolated from Streptomyces peucetius and others, used in treatment of LEUKEMIA and other NEOPLASMS.. anthracycline : Anthracyclines are polyketides that have a tetrahydronaphthacenedione ring structure attached by a glycosidic linkage to the amino sugar daunosamine.. daunorubicin : A natural product found in Actinomadura roseola.	8.35	5	1	aminoglycoside antibiotic; anthracycline; p-quinones; tetracenequinones	antineoplastic agent; bacterial metabolite
moxifloxacin Moxifloxacin: A fluoroquinolone that acts as an inhibitor of DNA TOPOISOMERASE II and is used as a broad-spectrum antibacterial agent.. moxifloxacin : A quinolone that consists of 4-oxo-1,4-dihydroquinoline-3-carboxylic acid bearing a cyclopropyl substituent at position 1, a fluoro substitiuent at position 6, a (4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl group at position 7 and a methoxy substituent at position 8. A member of the fluoroquinolone class of antibacterial agents.	4.62	1	1	aromatic ether; cyclopropanes; fluoroquinolone antibiotic; pyrrolidinopiperidine; quinolinemonocarboxylic acid; quinolone antibiotic; quinolone	antibacterial drug
tretinoin Tretinoin: An important regulator of GENE EXPRESSION during growth and development, and in NEOPLASMS. Tretinoin, also known as retinoic acid and derived from maternal VITAMIN A, is essential for normal GROWTH; and EMBRYONIC DEVELOPMENT. An excess of tretinoin can be teratogenic. It is used in the treatment of PSORIASIS; ACNE VULGARIS; and several other SKIN DISEASES. It has also been approved for use in promyelocytic leukemia (LEUKEMIA, PROMYELOCYTIC, ACUTE).. retinoic acid : A retinoid consisting of 3,7-dimethylnona-2,4,6,8-tetraenoic acid substituted at position 9 by a 2,6,6-trimethylcyclohex-1-en-1-yl group (geometry of the four exocyclic double bonds is not specified).. all-trans-retinoic acid : A retinoic acid in which all four exocyclic double bonds have E- (trans-) geometry.	3.35	1	0	retinoic acid; vitamin A	anti-inflammatory agent; antineoplastic agent; antioxidant; AP-1 antagonist; human metabolite; keratolytic drug; retinoic acid receptor agonist; retinoid X receptor agonist; signalling molecule
decitabine [no description available]	4.27	2	0	2'-deoxyribonucleoside
alvocidib alvocidib: structure given in first source. alvocidib : A synthetic dihydroxyflavone that is 5,7-dihydroxyflavone which is substituted by a 3-hydroxy-1-methylpiperidin-4-yl group at position 8 and by a chlorine at the 2' position (the (-)-3S,4R stereoisomer). A cyclin-dependent kinase 9 (CDK9) inhibitor, it has been studied for the treatment of acute myeloid leukaemia, arthritis and atherosclerotic plaque formation.	3.31	1	0	dihydroxyflavone; hydroxypiperidine; monochlorobenzenes; tertiary amino compound	antineoplastic agent; antirheumatic drug; apoptosis inducer; EC 2.7.11.22 (cyclin-dependent kinase) inhibitor
staurosporine staurosporinium : Conjugate acid of staurosporine.	5.36	4	0	ammonium ion derivative
midostaurin midostaurin : An organic heterooctacyclic compound that is the N-benzoyl derivative of staurosporine.	5.36	4	0	benzamides; gamma-lactam; indolocarbazole; organic heterooctacyclic compound	antineoplastic agent; EC 2.7.11.13 (protein kinase C) inhibitor
pevonedistat pevonedistat: a potent and selective inhibitor of NAE (NEDD8-activating enzyme). pevonedistat : A pyrrolopyrimidine that is 7H-pyrrolo[2,3-d]pyrimidine which is substituted by a (1S)-2,3-dihydro-1H-inden-1-ylnitrilo group at position 4 and by a (1S,3S,4S)-3-hydroxy-4-[(sulfamoyloxy)methyl]cyclopentyl group at position 7. It is a potent and selective NEDD8-activating enzyme inhibitor with an IC50 of 4.7 nM, and currently under clinical investigation for the treatment of acute myeloid leukemia (AML) and myelodysplastic syndromes.	3.31	1	0	cyclopentanols; indanes; pyrrolopyrimidine; secondary amino compound; sulfamidate	antineoplastic agent; apoptosis inducer
gdc 0449 HhAntag691: inhibits the hedgehog pathway and ABC transporters; has antineoplastic activity	2.07	1	0	benzamides; monochlorobenzenes; pyridines; sulfone	antineoplastic agent; Hedgehog signaling pathway inhibitor; SMO receptor antagonist; teratogenic agent
incb-018424 [no description available]	3.59	1	1	nitrile; pyrazoles; pyrrolopyrimidine	antineoplastic agent; EC 2.7.10.2 (non-specific protein-tyrosine kinase) inhibitor
piperidines Piperidines: A family of hexahydropyridines.	3.31	1	0
gilteritinib gilteritinib: an FLT3/AXL protein tyrosine kinase inhibitor. gilteritinib : A member of the class of pyrazines that is pyrazine-2-carboxamide which is substituted by {3-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}nitrilo, (oxan-4-yl)nitrilo and ethyl groups at positions 3,5 and 6, respectively. It is a potent inhibitor of FLT3 and AXL tyrosine kinase receptors (IC50 = 0.29 nM and 0.73 nM, respectively). Approved by the FDA for the treatment of acute myeloid leukemia in patients who have a FLT3 gene mutation.	4.87	3	0	aromatic amine; monomethoxybenzene; N-methylpiperazine; oxanes; piperidines; primary carboxamide; pyrazines; secondary amino compound	antineoplastic agent; apoptosis inducer; EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor
abt-199 venetoclax: A BCL-2 inhibitor with antineoplastic activity that is used in the treatment of CHRONIC LYMPHOCYTIC LEUKEMIA associated with chromosome 17p deletion; structure in first source.. venetoclax : A member of the class of pyrrolopyridines that is a potent inhibitor of the antiapoptotic protein B-cell lymphoma 2. It is used for treamtment of chronic lymphocytic leukemia with 17p deletion.	8.55	12	0	aromatic ether; C-nitro compound; monochlorobenzenes; N-alkylpiperazine; N-arylpiperazine; N-sulfonylcarboxamide; oxanes; pyrrolopyridine	antineoplastic agent; apoptosis inducer; B-cell lymphoma 2 inhibitor
apr-246 eprenetapopt: works in tandem with cisplatin to cause apoptosis of tumor cells; structure in first source	3.35	1	0
ivosidenib ivosidenib: an inhibitor of isocitrate dehydrogenase 1 (IDH1) for treatment of acute myeloid leukemia (AML). ivosidenib : A tertiary carboxamide resulting from the formal condensation of the carboxy group of (2S)-1-(4-cyanopyridin-2-yl)-5-oxopyrrolidine-2-carboxylic acid with the secondary amino group of (2S)-2-(2-chlorophenyl)-N-(3,3-difluorocyclobutyl)-2-[(5-fluoropyridin-3-yl)amino]acetamide. It is approved by the FDA for the treatment of acute myeloid leukemia (AML) in patients with an isocitrate dehydrogenase-1 (IDH1) mutation.	6.64	5	0	cyanopyridine; monochlorobenzenes; organofluorine compound; pyrrolidin-2-ones; secondary carboxamide; tertiary carboxamide	antineoplastic agent; EC 1.1.1.42 (isocitrate dehydrogenase) inhibitor
enasidenib [no description available]	5.16	2	0	1,3,5-triazines; aminopyridine; aromatic amine; organofluorine compound; secondary amino compound; tertiary alcohol	antineoplastic agent; EC 1.1.1.42 (isocitrate dehydrogenase) inhibitor
rifampin Rifampin: A semisynthetic antibiotic produced from Streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits DNA-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1160)	9.48	1	1	cyclic ketal; hydrazone; N-iminopiperazine; N-methylpiperazine; rifamycins; semisynthetic derivative; zwitterion	angiogenesis inhibitor; antiamoebic agent; antineoplastic agent; antitubercular agent; DNA synthesis inhibitor; EC 2.7.7.6 (RNA polymerase) inhibitor; Escherichia coli metabolite; geroprotector; leprostatic drug; neuroprotective agent; pregnane X receptor agonist; protein synthesis inhibitor

Condition	Indicated	Relationship Strength	Studies	Trials
Congenital Zika Syndrome [description not available]	0	2.25	1	0
Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.	0	2.69	2	0
Zika Virus Infection A viral disease transmitted by the bite of AEDES mosquitoes infected with ZIKA VIRUS. Its mild DENGUE-like symptoms include fever, rash, headaches and ARTHRALGIA. The viral infection during pregnancy, in rare cases, is associated with congenital brain and ocular abnormalities, called Congenital Zika Syndrome, including MICROCEPHALY and may also lead to GUILLAIN-BARRE SYNDROME.	0	2.25	1	0
Asthma, Bronchial [description not available]	0	2.31	1	0
Experimental Lung Inflammation Inflammation of any part, segment or lobe, of the lung parenchyma.	0	2.31	1	0
Asthma A form of bronchial disorder with three distinct components: airway hyper-responsiveness (RESPIRATORY HYPERSENSITIVITY), airway INFLAMMATION, and intermittent AIRWAY OBSTRUCTION. It is characterized by spasmodic contraction of airway smooth muscle, WHEEZING, and dyspnea (DYSPNEA, PAROXYSMAL).	0	2.31	1	0
Pneumonia Infection of the lung often accompanied by inflammation.	0	2.31	1	0
Dysmyelopoietic Syndromes [description not available]	0	10.23	10	7
Acute Myelogenous Leukemia [description not available]	0	15.22	39	14
Myelodysplastic Syndromes Clonal hematopoietic stem cell disorders characterized by dysplasia in one or more hematopoietic cell lineages. They predominantly affect patients over 60, are considered preleukemic conditions, and have high probability of transformation into ACUTE MYELOID LEUKEMIA.	1	12.23	10	7
Leukemia, Myeloid, Acute Clonal expansion of myeloid blasts in bone marrow, blood, and other tissue. Myeloid leukemias develop from changes in cells that normally produce NEUTROPHILS; BASOPHILS; EOSINOPHILS; and MONOCYTES.	1	17.22	39	14
Anemia A reduction in the number of circulating ERYTHROCYTES or in the quantity of HEMOGLOBIN.	0	3.99	1	1
Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses.	0	3.99	1	1
Recrudescence [description not available]	0	3.17	1	0
Local Neoplasm Recurrence [description not available]	0	4.02	2	1
Electrocardiogram QT Prolonged [description not available]	0	3.17	1	0
Long QT Syndrome A condition that is characterized by episodes of fainting (SYNCOPE) and varying degree of ventricular arrhythmia as indicated by the prolonged QT interval. The inherited forms are caused by mutation of genes encoding cardiac ion channel proteins. The two major forms are ROMANO-WARD SYNDROME and JERVELL-LANGE NIELSEN SYNDROME.	0	3.17	1	0
Hematologic Malignancies [description not available]	0	4	2	1
Benign Neoplasms [description not available]	0	7.03	6	1
Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.	1	10.84	12	2
Hematologic Neoplasms Neoplasms located in the blood and blood-forming tissue (the bone marrow and lymphatic tissue). The commonest forms are the various types of LEUKEMIA, of LYMPHOMA, and of the progressive, life-threatening forms of the MYELODYSPLASTIC SYNDROMES.	0	4	2	1
Cholera Infantum [description not available]	0	3.7	1	1
Blood Diseases [description not available]	0	3.7	1	1
Hematologic Diseases Disorders of the blood and blood forming tissues.	0	3.7	1	1
Kidney Failure A severe irreversible decline in the ability of kidneys to remove wastes, concentrate URINE, and maintain ELECTROLYTE BALANCE; BLOOD PRESSURE; and CALCIUM metabolism.	0	4.62	1	1
Renal Insufficiency Conditions in which the KIDNEYS perform below the normal level in the ability to remove wastes, concentrate URINE, and maintain ELECTROLYTE BALANCE; BLOOD PRESSURE; and CALCIUM metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of PROTEINURIA) and reduction in GLOMERULAR FILTRATION RATE.	0	4.62	1	1
Cancer, Second Primary [description not available]	0	4.62	1	1
Agnogenic Myeloid Metaplasia [description not available]	0	5.42	2	2
Primary Myelofibrosis A de novo myeloproliferation arising from an abnormal stem cell. It is characterized by the replacement of bone marrow by fibrous tissue, a process that is mediated by CYTOKINES arising from the abnormal clone.	0	5.42	2	2
Myelomonocytic Leukemia, Chronic [description not available]	0	3.59	1	1
Leukemia, Myelomonocytic, Chronic A myelodysplastic-myeloproliferative disease characterized by monocytosis, increased monocytes in the bone marrow, variable degrees of dysplasia, but an absence of immature granulocytes in the blood.	0	3.59	1	1
Granulocytic Leukemia, Chronic [description not available]	0	4.41	1	1
Leukemia, Myelogenous, Chronic, BCR-ABL Positive Clonal hematopoetic disorder caused by an acquired genetic defect in PLURIPOTENT STEM CELLS. It starts in MYELOID CELLS of the bone marrow, invades the blood and then other organs. The condition progresses from a stable, more indolent, chronic phase (LEUKEMIA, MYELOID, CHRONIC PHASE) lasting up to 7 years, to an advanced phase composed of an accelerated phase (LEUKEMIA, MYELOID, ACCELERATED PHASE) and BLAST CRISIS.	0	4.41	1	1

glasdegib

Description

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Overview

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Research Demand Index: 46.12

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glasdegib

Description

Cross-References

Synonyms (56)

Research Excerpts

Overview

Effects

Toxicity

Pharmacokinetics

Compound-Compound Interactions

Bioavailability

Roles (3)

Drug Classes (4)

Protein Targets (7)

Inhibition Measurements

Biological Processes (43)

Molecular Functions (34)

Ceullar Components (8)

Bioassays (40)

Research

Studies (58)

Market Indicators

Research Demand Index: 46.12

Study Types

Related Drugs (26)

Related Conditions (33)