Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DM94NBE)

Drug Name
PF-04991532 Drug Info
Indication
Disease Entry ICD 11 Status REF
Diabetic complication 5A2Y Phase 2 [1]
Cross-matching ID
PubChem CID
46181428
ChEBI ID
CHEMBL2165620
CAS Number
CAS 1215197-37-7
TTD Drug ID
DM94NBE

Molecule-Related Drug Atlas

Molecule-Related Drug Atlas
Molecule Type:
DTT
DOT
Drug Status:
Clinical Trial Drug(s)
Approved Drug(s)
Download the Complete Related Drug List
Drug(s) Targeting Glucokinase (GCK)
Drug Name Drug ID Indication ICD 11 Highest Status REF
LY-2599506 DMMI0RH Diabetic complication 5A2Y Phase 2 [4]
AMG 151 DMGOFL3 Type-2 diabetes 5A11 Phase 2 [4]
GK1-399 DMLFSMX Diabetic complication 5A2Y Phase 2 [5]
LY-2608204 DM4EF9Y Type-2 diabetes 5A11 Phase 2 [6]
PF-04937319 DMQMF4O Type-2 diabetes 5A11 Phase 2 [7]
AZD1656 DMUE90I Diabetic complication 5A2Y Phase 2 [8]
TTP399 DMBKQSZ Type 2 diabetes 5A11 Phase 2 [9]
HMS5552 DMRYM03 Type-2 diabetes 5A11 Phase 1 [10]
BMS-820132 DMCX0H7 Type-2 diabetes 5A11 Phase 1 [11]
DS-7309 DM7C4U9 Diabetic complication 5A2Y Phase 1 [12]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Affected By Poly polymerase 1 (PARP1)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Cannabidiol DM0659E Dravet syndrome 8A61.11 Approved [13]
Gefitinib DM15F0X Colon adenocarcinoma Approved [14]
Hydrogen peroxide DM1NG5W Infectious disease 1A00-CA43.1 Approved [15]
Nitric Oxide DM1RBYG Hypertension BA00-BA04 Approved [16]
Citalopram DM2G9AE Acute coronary syndrome BA41 Approved [17]
Ciprofloxacin XR DM2NLS9 Acute gonococcal cervicitis Approved [18]
Imipramine DM2NUH3 Depression 6A70-6A7Z Approved [17]
Colchicine DM2POTE Acute gout flare FA25.0 Approved [19]
Sulindac DM2QHZU Acute myelogenous leukaemia 2A41 Approved [20]
Methotrexate DM2TEOL Anterior urethra cancer Approved [21]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Affected By Histone H2AX (H2AX)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Cannabidiol DM0659E Dravet syndrome 8A61.11 Approved [22]
Hydrogen peroxide DM1NG5W Infectious disease 1A00-CA43.1 Approved [23]
Selenium DM25CGV N. A. N. A. Approved [24]
Ribavirin DMEYLH9 Hepatitis C virus infection 1E51.1 Approved [25]
Etretinate DM2CZFA Keratosis ED56 Approved [26]
Methotrexate DM2TEOL Anterior urethra cancer Approved [27]
Dactinomycin DM2YGNW Adult kidney Wilms tumor Approved [28]
Simvastatin DM30SGU Arteriosclerosis BD40 Approved [29]
Lapatinib DM3BH1Y Breast cancer 2C60-2C65 Approved [30]
Quercetin DM3NC4M Obesity 5B81 Approved [31]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Affected By M-phase inducer phosphatase 3 (CDC25C)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Cannabidiol DM0659E Dravet syndrome 8A61.11 Approved [32]
Hydrogen peroxide DM1NG5W Infectious disease 1A00-CA43.1 Approved [33]
Methotrexate DM2TEOL Anterior urethra cancer Approved [34]
Quercetin DM3NC4M Obesity 5B81 Approved [35]
Troglitazone DM3VFPD Diabetic complication 5A2Y Approved [36]
Tretinoin DM49DUI Acne vulgaris ED80 Approved [37]
Acetic Acid, Glacial DM4SJ5Y infection in the ear canal AA0Y Approved [38]
Arsenic trioxide DM61TA4 Acute lymphoblastic leukaemia 2A85 Approved [39]
Marinol DM70IK5 Anorexia nervosa cachexia 6B80 Approved [40]
Testosterone DM7HUNW Hot flushes GA30 Approved [41]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Affected By BH3-interacting domain death agonist (BID)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Cannabidiol DM0659E Dravet syndrome 8A61.11 Approved [42]
Nitric Oxide DM1RBYG Hypertension BA00-BA04 Approved [16]
Selenium DM25CGV N. A. N. A. Approved [43]
Quercetin DM3NC4M Obesity 5B81 Approved [44]
obeticholic acid DM3Q1SM Primary biliary cholangitis DB96.1 Approved [45]
Tretinoin DM49DUI Acne vulgaris ED80 Approved [46]
Arsenic trioxide DM61TA4 Acute lymphoblastic leukaemia 2A85 Approved [47]
Aspirin DM672AH Acute coronary syndrome BA41 Approved [48]
Hydroquinone DM6AVR4 Melasma ED60.1 Approved [49]
Ciclosporin DMAZJFX Graft-versus-host disease 4B24 Approved [50]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Affected By Bcl-2-like protein 1 (BCL2L1)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Cannabidiol DM0659E Dravet syndrome 8A61.11 Approved [51]
Hydrogen peroxide DM1NG5W Infectious disease 1A00-CA43.1 Approved [52]
Nitric Oxide DM1RBYG Hypertension BA00-BA04 Approved [16]
Selenium DM25CGV N. A. N. A. Approved [24]
Sulindac DM2QHZU Acute myelogenous leukaemia 2A41 Approved [53]
Methotrexate DM2TEOL Anterior urethra cancer Approved [34]
Dactinomycin DM2YGNW Adult kidney Wilms tumor Approved [54]
Simvastatin DM30SGU Arteriosclerosis BD40 Approved [55]
Quercetin DM3NC4M Obesity 5B81 Approved [44]
Troglitazone DM3VFPD Diabetic complication 5A2Y Approved [56]
⏷ Show the Full List of 10 Drug(s)

Molecular Interaction Atlas of This Drug

Molecular Interaction Atlas
Download the Complete Interaction Atlas for Visualization in Cytoscape

Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Glucokinase (GCK) TTDLNGZ HXK4_HUMAN Activator [2]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Gene/Protein Processing [3]
BH3-interacting domain death agonist (BID) OTOSHSHU BID_HUMAN Gene/Protein Processing [3]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Gene/Protein Processing [3]
M-phase inducer phosphatase 3 (CDC25C) OTPQI71S MPIP3_HUMAN Post-Translational Modifications [3]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Protein Interaction/Cellular Processes [3]

References

1 ClinicalTrials.gov (NCT01338870) Study of Safety and Efficacy of PF-04991532 in Subjects With Type 2 Diabetes. U.S. National Institutes of Health.
2 The hepatoselective glucokinase activator PF-04991532 ameliorates hyperglycemia without causing hepatic steatosis in diabetic rats. PLoS One. 2014 May 23;9(5):e97139.
3 In vitro antitumor mechanism of (E)-N-(2-methoxy-5-(((2,4,6-trimethoxystyryl)sulfonyl)methyl)pyridin-3-yl)methanesulfonamide. Mol Pharmacol. 2015 Jan;87(1):18-30. doi: 10.1124/mol.114.093245. Epub 2014 Oct 14.
4 This week in therapeutics Endocrine disease. SciBX 2(37); doi:10.1038/scibx.2009.1408. Sept. 24, 2009
5 Clinical pipeline report, company report or official report of vTv Therapeutics, NCT02405260.
6 Clinical pipeline report, company report or official report of Eli Lilly.
7 Two dose-ranging studies with PF-04937319, a systemic partial activator of glucokinase, as add-on therapy to metformin in adults with type 2 diabetes. Diabetes Obes Metab. 2015 Aug;17(8):751-9.
8 Clinical pipeline report, company report or official report of AstraZeneca (2009).
9 Clinical pipeline report, company report or official report of vTv Therapeutics.
10 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
11 Utilization of the Zucker Diabetic Fatty (ZDF) Rat Model for Investigating Hypoglycemia-related Toxicities. Toxicol Pathol. 2015 Aug;43(6):825-37.
12 Glucokinase alternative. SciBX 6(45); doi:10.1038/scibx.2013.1279. Nov. 21 2013
13 Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma. Sci Rep. 2020 Nov 26;10(1):20622. doi: 10.1038/s41598-020-77674-y.
14 Evidence of securin-mediated resistance to gefitinib-induced apoptosis in human cancer cells. Chem Biol Interact. 2013 Apr 25;203(2):412-22. doi: 10.1016/j.cbi.2013.03.011. Epub 2013 Mar 22.
15 Cigarette smoke and asbestos activate poly-ADP-ribose polymerase in alveolar epithelial cells. J Investig Med. 2001 Jan;49(1):68-76. doi: 10.2310/6650.2001.34092.
16 Apoptotic signaling pathways induced by nitric oxide in human lymphoblastoid cells expressing wild-type or mutant p53. Cancer Res. 2004 May 1;64(9):3022-9. doi: 10.1158/0008-5472.can-03-1880.
17 The antidepressants imipramine, clomipramine, and citalopram induce apoptosis in human acute myeloid leukemia HL-60 cells via caspase-3 activation. J Biochem Mol Toxicol. 1999;13(6):338-47. doi: 10.1002/(sici)1099-0461(1999)13:6<338::aid-jbt8>3.0.co;2-7.
18 Ciprofloxacin mediated cell growth inhibition, S/G2-M cell cycle arrest, and apoptosis in a human transitional cell carcinoma of the bladder cell line. Clin Cancer Res. 2000 Mar;6(3):891-900.
19 Investigation of molecular mechanisms underlying the antiproliferative effects of colchicine against PC3 prostate cancer cells. Toxicol In Vitro. 2021 Jun;73:105138. doi: 10.1016/j.tiv.2021.105138. Epub 2021 Mar 6.
20 Sulindac enhances adenoviral vector expressing mda-7/IL-24-mediated apoptosis in human lung cancer. Mol Cancer Ther. 2005 Feb;4(2):291-304.
21 Methotrexate induces poly(ADP-ribose) polymerase-dependent, caspase 3-independent apoptosis in subsets of proliferating CD4+ T cells. Clin Exp Immunol. 2007 May;148(2):288-95. doi: 10.1111/j.1365-2249.2007.03335.x. Epub 2007 Feb 7.
22 Cannabinoids synergize with carfilzomib, reducing multiple myeloma cells viability and migration. Oncotarget. 2016 Nov 22;7(47):77543-77557. doi: 10.18632/oncotarget.12721.
23 Hsa-let-7g miRNA regulates the anti-tumor effects of gastric cancer cells under oxidative stress through the expression of DDR genes. J Toxicol Sci. 2015 Jun;40(3):329-38. doi: 10.2131/jts.40.329.
24 Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
25 Inhibition of cardiomyocyte differentiation of human induced pluripotent stem cells by Ribavirin: Implication for its cardiac developmental toxicity. Toxicology. 2020 Apr 15;435:152422. doi: 10.1016/j.tox.2020.152422. Epub 2020 Feb 26.
26 Synthesis and structure-activity relationships of new antiproliferative and proapoptotic retinoid-related biphenyl-4-yl-acrylic acids. Bioorg Med Chem. 2007 Jul 15;15(14):4863-75. doi: 10.1016/j.bmc.2007.04.057. Epub 2007 May 3.
27 Methotrexate induces apoptosis through p53/p21-dependent pathway and increases E-cadherin expression through downregulation of HDAC/EZH2. Biochem Pharmacol. 2011 Feb 15;81(4):510-7. doi: 10.1016/j.bcp.2010.11.014. Epub 2010 Nov 27.
28 Actinomycin D inhibits the expression of the cystine/glutamate transporter xCT via attenuation of CD133 synthesis in CD133(+) HCC. Chem Biol Interact. 2019 Aug 25;309:108713. doi: 10.1016/j.cbi.2019.06.026. Epub 2019 Jun 19.
29 Simvastatin and purine analogs have a synergic effect on apoptosis of chronic lymphocytic leukemia cells. Ann Hematol. 2010 Nov;89(11):1115-24. doi: 10.1007/s00277-010-0988-z. Epub 2010 May 25.
30 The involvement of hepatic cytochrome P450s in the cytotoxicity of lapatinib. Toxicol Sci. 2023 Dec 21;197(1):69-78. doi: 10.1093/toxsci/kfad099.
31 The isoflavonoids genistein and quercetin activate different stress signaling pathways as shown by analysis of site-specific phosphorylation of ATM, p53 and histone H2AX. DNA Repair (Amst). 2004 Mar 4;3(3):235-44. doi: 10.1016/j.dnarep.2003.10.014.
32 Cannabidiol-induced transcriptomic changes and cellular senescence in human Sertoli cells. Toxicol Sci. 2023 Feb 17;191(2):227-238. doi: 10.1093/toxsci/kfac131.
33 Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.
34 Functional gene expression profile underlying methotrexate-induced senescence in human colon cancer cells. Tumour Biol. 2011 Oct;32(5):965-76.
35 Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
36 Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
37 Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
38 Motexafin gadolinium and zinc induce oxidative stress responses and apoptosis in B-cell lymphoma lines. Cancer Res. 2005 Dec 15;65(24):11676-88.
39 Arsenic trioxide-mediated growth inhibition in MC/CAR myeloma cells via cell cycle arrest in association with induction of cyclin-dependent kinase inhibitor, p21, and apoptosis. Cancer Res. 2000 Jun 1;60(11):3065-71.
40 Delta9-tetrahydrocannabinol inhibits cell cycle progression in human breast cancer cells through Cdc2 regulation. Cancer Res. 2006 Jul 1;66(13):6615-21. doi: 10.1158/0008-5472.CAN-05-4566.
41 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
42 Cannabidiol Modulates the Immunophenotype and Inhibits the Activation of the Inflammasome in Human Gingival Mesenchymal Stem Cells. Front Physiol. 2016 Nov 24;7:559. doi: 10.3389/fphys.2016.00559. eCollection 2016.
43 Death receptor 5 regulation during selenium-mediated apoptosis in human prostate cancer cells. Cancer Biol Ther. 2002 May-Jun;1(3):287-90. doi: 10.4161/cbt.83.
44 Quercetin potentiates apoptosis by inhibiting nuclear factor-kappaB signaling in H460 lung cancer cells. Biol Pharm Bull. 2013;36(6):944-51. doi: 10.1248/bpb.b12-01004.
45 Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
46 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
47 Combination of Poly I:C and arsenic trioxide triggers apoptosis synergistically via activation of TLR3 and mitochondrial pathways in hepatocellular carcinoma cells. Cell Biol Int. 2011 Aug;35(8):803-10. doi: 10.1042/CBI20100739.
48 Role of mitochondria in aspirin-induced apoptosis in human gastric epithelial cells. Am J Physiol Gastrointest Liver Physiol. 2005 Oct;289(4):G731-8. doi: 10.1152/ajpgi.00150.2005. Epub 2005 Jun 23.
49 p38 MAPK/PP2Ac/TTP pathway on the connection of TNF- and caspases activation on hydroquinone-induced apoptosis. Carcinogenesis. 2013 Apr;34(4):818-27. doi: 10.1093/carcin/bgs409. Epub 2013 Jan 3.
50 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
51 Role of miRNA in the regulation of cannabidiol-mediated apoptosis in neuroblastoma cells. Oncotarget. 2019 Jan 1;10(1):45-59. doi: 10.18632/oncotarget.26534. eCollection 2019 Jan 1.
52 Expression of the retinoic acid-metabolizing enzyme CYP26A1 limits programmed cell death. Mol Pharmacol. 2005 May;67(5):1808-17. doi: 10.1124/mol.104.005769. Epub 2005 Feb 9.
53 Role of BAX in the apoptotic response to anticancer agents. Science. 2000 Nov 3;290(5493):989-92. doi: 10.1126/science.290.5493.989.
54 Mechanisms of thymidine kinase/ganciclovir and cytosine deaminase/ 5-fluorocytosine suicide gene therapy-induced cell death in glioma cells. Oncogene. 2005 Feb 10;24(7):1231-43. doi: 10.1038/sj.onc.1208290.
55 Simvastatin induces apoptosis in human colon cancer cells and in tumor xenografts, and attenuates colitis-associated colon cancer in mice. Int J Cancer. 2008 Aug 15;123(4):951-7. doi: 10.1002/ijc.23593.
56 Increased sensitivity for troglitazone-induced cytotoxicity using a human in vitro co-culture model. Toxicol In Vitro. 2009 Oct;23(7):1387-95.