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

General Information of Drug (ID: DMM7ZXR)

Drug Name
GSK2126458 Drug Info
Synonyms
1086062-66-9; Omipalisib; GSK-2126458; GSK 2126458; UNII-1X8F5A3NA0; 2,4-difluoro-N-(2-methoxy-5-(4-(pyridazin-4-yl)quinolin-6-yl)pyridin-3-yl)benzenesulfonamide; 2,4-difluoro-N-[2-methoxy-5-(4-pyridazin-4-ylquinolin-6-yl)pyridin-3-yl]benzenesulfonamide; 2,4-Difluoro-N-[2-methoxy-5-[4-(4-pyridazinyl)-6-quinolinyl]-3-pyridinyl]benzenesulfonamide; 1X8F5A3NA0; Omipalisib (GSK2126458, GSK458); C25H17F2N5O3S; Omipalisib [USAN:INN]
Indication
Disease Entry ICD 11 Status REF
Lymphoma 2A80-2A86 Phase 1 [1]
Cross-matching ID
PubChem CID
25167777
ChEBI ID
CHEMBL1236962
CAS Number
CAS 1086062-66-9
TTD Drug ID
DMM7ZXR

Molecule-Related Drug Atlas

Molecule-Related Drug Atlas
Molecule Type:
DTT
DOT
Drug Status:
Approved Drug(s)
Clinical Trial Drug(s)
Download the Complete Related Drug List
Drug(s) Targeting PI3-kinase gamma (PIK3CG)
Drug Name Drug ID Indication ICD 11 Highest Status REF
BAY 80-6946 DMLOS5R Follicular lymphoma 2A80 Approved [5]
IPI-145 DMWA24P Follicular lymphoma 2A80 Approved [6]
Buparlisib DM1WEHC Breast cancer 2C60-2C65 Phase 3 [7]
Enzastaurin DM5H0R9 Diffuse large B-cell lymphoma 2A81 Phase 3 [8]
Rigosertib DMOSTXF Myelodysplastic syndrome 2A37 Phase 3 [9]
GDC-0032 DMT4QHD Breast cancer 2C60-2C65 Phase 3 [8]
PQR309 DMMCYZ8 Squamous head and neck cell carcinom 2D60.0 Phase 2 [10]
SAR245409 DMQM7IL Solid tumour/cancer 2A00-2F9Z Phase 2 [11]
XL147 DMML7BE Solid tumour/cancer 2A00-2F9Z Phase 2 [11]
SF1126 DML10K3 Head and neck cancer 2D42 Phase 2 [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 Mitogen-activated protein kinase 3 (MAPK3)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Cisplatin DMRHGI9 Adenocarcinoma 2D40 Approved [22]
Progesterone DMUY35B Amenorrhea GA20.0 Approved [23]
Cannabidiol DM0659E Dravet syndrome 8A61.11 Approved [24]
Sertraline DM0FB1J Coronary heart disease BA80.Z Approved [25]
Beta-carotene DM0RXBT Vitamin deficiency 5B55-5B71 Approved [26]
Fulvestrant DM0YZC6 Breast cancer 2C60-2C65 Approved [27]
Secobarbital DM14RF5 Epilepsy 8A60-8A68 Approved [28]
Gefitinib DM15F0X Colon adenocarcinoma Approved [29]
Fexofenadine DM17ONX Allergic rhinitis CA08.0 Approved [30]
Hydrogen peroxide DM1NG5W Infectious disease 1A00-CA43.1 Approved [31]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Affected By Mitogen-activated protein kinase 1 (MAPK1)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Ethanol DMDRQZU Chronic pain MG30 Approved [32]
Progesterone DMUY35B Amenorrhea GA20.0 Approved [23]
Carvedilol DMHTEAO Chronic heart failure BD1Z Approved [33]
Paclitaxel DMLB81S Breast carcinoma Approved [34]
Etoposide DMNH3PG Acute myelogenous leukaemia 2A41 Approved [35]
Cisplatin DMRHGI9 Adenocarcinoma 2D40 Approved [22]
Urokinase DM0GOUD Myocardial infarction BA41-BA43 Approved [36]
Cannabidiol DM0659E Dravet syndrome 8A61.11 Approved [37]
Sertraline DM0FB1J Coronary heart disease BA80.Z Approved [25]
Beta-carotene DM0RXBT Vitamin deficiency 5B55-5B71 Approved [26]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Affected By Small ribosomal subunit protein eS6 (RPS6)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Cannabidiol DM0659E Dravet syndrome 8A61.11 Approved [38]
Methotrexate DM2TEOL Anterior urethra cancer Approved [39]
Crizotinib DM4F29C Non-small-cell lung cancer 2C25.Y Approved [40]
Glucosamine DM4ZLFD Osteoarthritis FA00-FA05 Approved [41]
Arsenic trioxide DM61TA4 Acute lymphoblastic leukaemia 2A85 Approved [42]
Aspirin DM672AH Acute coronary syndrome BA41 Approved [43]
Testosterone DM7HUNW Hot flushes GA30 Approved [44]
Imatinib DM7RJXL Acute lymphoblastic leukaemia 2A85 Approved [45]
Capivasertib DM9SKW8 Breast cancer 2C60-2C65 Approved [46]
Ciclosporin DMAZJFX Graft-versus-host disease 4B24 Approved [47]
⏷ 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
PI3-kinase gamma (PIK3CG) TTHBTOP PK3CG_HUMAN Modulator [2]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Post-Translational Modifications [3]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Post-Translational Modifications [3]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Post-Translational Modifications [4]
Small ribosomal subunit protein eS6 (RPS6) OTT4D1LN RS6_HUMAN Post-Translational Modifications [4]

References

1 Dual PI3K/mTOR inhibitors, GSK2126458 and PKI-587, suppress tumor progression and increase radiosensitivity in nasopharyngeal carcinoma. Mol Cancer Ther. 2015 Feb;14(2):429-39.
2 Company report (GSK)
3 Combination small molecule MEK and PI3K inhibition enhances uveal melanoma cell death in a mutant GNAQ- and GNA11-dependent manner. Clin Cancer Res. 2012 Aug 15;18(16):4345-55. doi: 10.1158/1078-0432.CCR-11-3227. Epub 2012 Jun 25.
4 Comparison of the effects of the PI3K/mTOR inhibitors NVP-BEZ235 and GSK2126458 on tamoxifen-resistant breast cancer cells. Cancer Biol Ther. 2011 Jun 1;11(11):938-46. doi: 10.4161/cbt.11.11.15527. Epub 2011 Jun 1.
5 BAY 80-6946 is a highly selective intravenous PI3K inhibitor with potent p110 and p110 activities in tumor cell lines and xenograft models.Mol Cancer Ther.2013 Nov;12(11):2319-30.
6 PI3K-delta and PI3K-gamma inhibition by IPI-145 abrogates immune responses and suppresses activity in autoimmune and inflammatory disease models. Chem Biol. 2013 Nov 21;20(11):1364-74.
7 Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov. 2009 Aug;8(8):627-44.
8 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
9 Phase I study of oral rigosertib (ON 01910.Na), a dual inhibitor of the PI3K and Plk1 pathways, in adult patients with advanced solid malignancies. Clin Cancer Res. 2014 Mar 15;20(6):1656-65.
10 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2155).
11 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2156).
12 An integrin-targeted, pan-isoform, phosphoinositide-3 kinase inhibitor, SF1126, has activity against multiple myeloma in vivo.Cancer Chemother Pharmacol.2013 Apr;71(4):867-81.
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 Treatment with anticancer agents induces dysregulation of specific Wnt signaling pathways in human ovarian luteinized granulosa cells in vitro. Toxicol Sci. 2013 Nov;136(1):183-92. doi: 10.1093/toxsci/kft175. Epub 2013 Aug 16.
23 Progesterone increases csk homologous kinase in HMC-1560 human mast cells and reduces cell proliferation. J Cell Biochem. 2007 Dec 1;102(5):1271-80. doi: 10.1002/jcb.21357.
24 Cannabidiol upregulates melanogenesis through CB1 dependent pathway by activating p38 MAPK and p42/44 MAPK. Chem Biol Interact. 2017 Aug 1;273:107-114. doi: 10.1016/j.cbi.2017.06.005. Epub 2017 Jun 7.
25 Sertraline, an antidepressant, induces apoptosis in hepatic cells through the mitogen-activated protein kinase pathway. Toxicol Sci. 2014 Feb;137(2):404-15. doi: 10.1093/toxsci/kft254. Epub 2013 Nov 5.
26 Growth stimulation of human pulmonary adenocarcinoma cells and small airway epithelial cells by beta-carotene via activation of cAMP, PKA, CREB and ERK1/2. Int J Cancer. 2006 Mar 15;118(6):1370-80. doi: 10.1002/ijc.21537.
27 Estrogen and pure antiestrogen fulvestrant (ICI 182 780) augment cell-matrigel adhesion of MCF-7 breast cancer cells through a novel G protein coupled estrogen receptor (GPR30)-to-calpain signaling axis. Toxicol Appl Pharmacol. 2014 Mar 1;275(2):176-81. doi: 10.1016/j.taap.2014.01.005. Epub 2014 Jan 17.
28 Inhibition of activator protein 1 by barbiturates is mediated by differential effects on mitogen-activated protein kinases and the small G proteins ras and rac-1. J Pharmacol Exp Ther. 2004 Dec;311(3):1232-40. doi: 10.1124/jpet.104.071332. Epub 2004 Jul 19.
29 Growth of hormone-dependent MCF-7 breast cancer cells is promoted by constitutive caveolin-1 whose expression is lost in an EGF-R-mediated manner during development of tamoxifen resistance. Breast Cancer Res Treat. 2010 Feb;119(3):575-91. doi: 10.1007/s10549-009-0355-8. Epub 2009 Mar 15.
30 Effect of histamine H1 receptor antagonists on TARC/CCL17 and MDC/CCL22 production from CD14+ cells induced by antigenic stimulation in vitro. Int Arch Allergy Immunol. 2011;155(1):38-51. doi: 10.1159/000318720. Epub 2010 Nov 25.
31 SIRT3 Mediates the Antioxidant Effect of Hydrogen Sulfide in Endothelial Cells. Antioxid Redox Signal. 2016 Feb 20;24(6):329-43. doi: 10.1089/ars.2015.6331. Epub 2015 Nov 10.
32 Downregulation of mitogen-activated protein kinases (MAPKs) in chronic ethanol-induced fatty liver. Toxicol Mech Methods. 2020 Jul;30(6):407-416. doi: 10.1080/15376516.2020.1747126. Epub 2020 Apr 1.
33 A unique mechanism of beta-blocker action: carvedilol stimulates beta-arrestin signaling. Proc Natl Acad Sci U S A. 2007 Oct 16;104(42):16657-62. doi: 10.1073/pnas.0707936104. Epub 2007 Oct 9.
34 The stent-eluting drugs sirolimus and paclitaxel suppress healing of the endothelium by induction of autophagy. Am J Pathol. 2009 Nov;175(5):2226-34.
35 Modulation of apoptosis in HaCaT keratinocytes via differential regulation of ERK signaling pathway by flavonoids. J Biol Chem. 2005 Sep 9;280(36):31498-507. doi: 10.1074/jbc.M505537200. Epub 2005 Jul 13.
36 ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
37 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.
38 Cannabidiol Reduces Leukemic Cell Size - But Is It Important?. Front Pharmacol. 2017 Mar 24;8:144. doi: 10.3389/fphar.2017.00144. eCollection 2017.
39 Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
40 Crizotinib-resistant mutants of EML4-ALK identified through an accelerated mutagenesis screen. Chem Biol Drug Des. 2011 Dec;78(6):999-1005. doi: 10.1111/j.1747-0285.2011.01239.x. Epub 2011 Oct 31.
41 D-glucosamine down-regulates HIF-1alpha through inhibition of protein translation in DU145 prostate cancer cells. Biochem Biophys Res Commun. 2009 Apr 24;382(1):96-101. doi: 10.1016/j.bbrc.2009.02.129. Epub 2009 Feb 28.
42 Proteomics-based identification of differentially abundant proteins from human keratinocytes exposed to arsenic trioxide. J Proteomics Bioinform. 2014 Jul;7(7):166-178.
43 Potential anti-aging agents suppress the level of constitutive mTOR- and DNA damage- signaling. Aging (Albany NY). 2012 Dec;4(12):952-65. doi: 10.18632/aging.100521.
44 Androgen receptor-mTOR crosstalk is regulated by testosterone availability: implication for prostate cancer cell survival. Anticancer Res. 2010 Oct;30(10):3895-901.
45 Imatinib disturbs lysosomal function and morphology and impairs the activity of mTORC1 in human hepatocyte cell lines. Food Chem Toxicol. 2022 Apr;162:112869. doi: 10.1016/j.fct.2022.112869. Epub 2022 Feb 16.
46 Inhibition of cholesterol metabolism underlies synergy between mTOR pathway inhibition and chloroquine in bladder cancer cells. Oncogene. 2016 Aug 25;35(34):4518-28. doi: 10.1038/onc.2015.511. Epub 2016 Feb 8.
47 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.