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

General Information of Drug (ID: DM0P729)

Drug Name
GSK461364 Drug Info
Synonyms
GSK461364; 929095-18-1; GSK-461364; 5-[6-[(4-Methyl-1-piperazinyl)methyl]-1h-benzimidazol-1-yl]-3-[(1r)-1-[2-(trifluoromethyl)phenyl]ethoxy]-2-thiophenecarboxamide; GSK 461364; UNII-8QO27TK6Q4; GSK-461364A; (R)-5-(6-((4-methylpiperazin-1-yl)methyl)-1H-benzo[d]imidazol-1-yl)-3-(1-(2-(trifluoromethyl)phenyl)ethoxy)thiophene-2-carboxamide; 8QO27TK6Q4; CHEMBL1908394; GSK461364A; ZHJGWYRLJUCMRT-QGZVFWFLSA-N; SCHEMBL310080; GTPL5684; C27H28F3N5O2S; CTK8B7590; CHEBI:91333; DTXSID60239197; MolPort-016-633-304; BCP01720; GSK 461364A
Indication
Disease Entry ICD 11 Status REF
Non-hodgkin lymphoma 2B33.5 Phase 1 [1]
Solid tumour/cancer 2A00-2F9Z Phase 1 [1]
Therapeutic Class
Anticancer Agents
Cross-matching ID
PubChem CID
15983966
ChEBI ID
CHEBI:91333
CAS Number
CAS 929095-18-1
TTD Drug ID
DM0P729

Molecule-Related Drug Atlas

Molecule-Related Drug Atlas
Molecule Type:
DTT
DOT
Drug Status:
Clinical Trial Drug(s)
Patented Agent(s)
Discontinued Drug(s)
Approved Drug(s)
Download the Complete Related Drug List
Drug(s) Targeting Polo-like kinase 1 (PLK1)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Rigosertib DMOSTXF Myelodysplastic syndrome 2A37 Phase 3 [4]
Volasertib DMOFH1M Acute myeloid leukaemia 2A60 Phase 3 [5]
PCM-075 DMYFRTB Acute myeloid leukaemia 2A60 Phase 2 [6]
BI 2536 DMJSADP Acute myeloid leukaemia 2A60 Phase 2 [2]
MK-1496 DME1ZAH Solid tumour/cancer 2A00-2F9Z Phase 1 [7]
TAK-960 DMN4OGH Solid tumour/cancer 2A00-2F9Z Phase 1 [8]
CYC140 DMC6PKJ Acute myeloid leukaemia 2A60 Phase 1 [9]
Dihydropyrido pyrazinone compound 3 DM3PEUN N. A. N. A. Patented [10]
Dihydropyrido pyrazinone compound 2 DMOTG2Y N. A. N. A. Patented [10]
HMN-214 DMH4ANG Pancreatic cancer 2C10 Discontinued in Phase 1 [2]
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Drug(s) Affected By Apoptosis regulator Bcl-2 (BCL2)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Sevoflurane DMC9O43 Anaesthesia 9A78.6 Approved [11]
Docetaxel DMDI269 Advanced cancer 2A00-2F9Z Approved [12]
Cisplatin DMRHGI9 Adenocarcinoma 2D40 Approved [13]
Gemcitabine DMSE3I7 Anterior urethra cancer Approved [14]
Etoposide DMNH3PG Acute myelogenous leukaemia 2A41 Approved [15]
Cannabidiol DM0659E Dravet syndrome 8A61.11 Approved [16]
Verapamil DMA7PEW Angina pectoris BA40 Approved [17]
Mechlorethamine DM0CVXA Chronic myelogenous leukaemia 2A20.0 Approved [18]
Sertraline DM0FB1J Coronary heart disease BA80.Z Approved [19]
Beta-carotene DM0RXBT Vitamin deficiency 5B55-5B71 Approved [20]
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Drug(s) Affected By Histone H2AX (H2AX)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Cannabidiol DM0659E Dravet syndrome 8A61.11 Approved [21]
Hydrogen peroxide DM1NG5W Infectious disease 1A00-CA43.1 Approved [22]
Selenium DM25CGV N. A. N. A. Approved [23]
Ribavirin DMEYLH9 Hepatitis C virus infection 1E51.1 Approved [24]
Etretinate DM2CZFA Keratosis ED56 Approved [25]
Methotrexate DM2TEOL Anterior urethra cancer Approved [26]
Dactinomycin DM2YGNW Adult kidney Wilms tumor Approved [27]
Simvastatin DM30SGU Arteriosclerosis BD40 Approved [28]
Lapatinib DM3BH1Y Breast cancer 2C60-2C65 Approved [29]
Quercetin DM3NC4M Obesity 5B81 Approved [30]
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Drug(s) Affected By Caspase-3 (CASP3)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Sevoflurane DMC9O43 Anaesthesia 9A78.6 Approved [31]
Arsenic trioxide DM61TA4 Acute lymphoblastic leukaemia 2A85 Approved [32]
Lovastatin DM9OZWQ Arteriosclerosis BD40 Approved [33]
Cidofovir DMA13GD Cytomegalovirus infection 1D82 Approved [34]
Docetaxel DMDI269 Advanced cancer 2A00-2F9Z Approved [35]
Etoposide DMNH3PG Acute myelogenous leukaemia 2A41 Approved [36]
Cisplatin DMRHGI9 Adenocarcinoma 2D40 Approved [37]
Mannitol DMSCDY9 Bronchiectasis CA24 Approved [38]
Doxorubicin DMVP5YE Acute myelogenous leukaemia 2A41 Approved [39]
Aprepitant DM053KT Depression 6A70-6A7Z Approved [40]
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Drug(s) Affected By Apoptosis regulator BAX (BAX)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Sevoflurane DMC9O43 Anaesthesia 9A78.6 Approved [11]
Aprepitant DM053KT Depression 6A70-6A7Z Approved [40]
Cannabidiol DM0659E Dravet syndrome 8A61.11 Approved [16]
Verapamil DMA7PEW Angina pectoris BA40 Approved [17]
Beta-carotene DM0RXBT Vitamin deficiency 5B55-5B71 Approved [41]
Leuprorelin acetate DM15HAT Prostate cancer 2C82.0 Approved [42]
Talazoparib DM1KS78 Breast cancer 2C60-2C65 Approved [43]
Hydrogen peroxide DM1NG5W Infectious disease 1A00-CA43.1 Approved [44]
Meloxicam DM2AR7L Arthritis FA20 Approved [45]
Ciprofloxacin XR DM2NLS9 Acute gonococcal cervicitis Approved [46]
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Drug(s) Affected By Serine-protein kinase ATM (ATM)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Cannabidiol DM0659E Dravet syndrome 8A61.11 Approved [47]
Paromomycin DM1AGXN Amoebiasis 1A36 Approved [48]
Hydrogen peroxide DM1NG5W Infectious disease 1A00-CA43.1 Approved [49]
Etretinate DM2CZFA Keratosis ED56 Approved [50]
Quercetin DM3NC4M Obesity 5B81 Approved [51]
Tretinoin DM49DUI Acne vulgaris ED80 Approved [52]
Remdesivir DMBFZ6L Coronavirus Disease 2019 (COVID-19) 1D6Y Approved [53]
Acetic Acid, Glacial DM4SJ5Y infection in the ear canal AA0Y Approved [54]
Rifampicin DM5DSFZ Non-insulin dependent diabetes 5A11 Approved [55]
Arsenic trioxide DM61TA4 Acute lymphoblastic leukaemia 2A85 Approved [56]
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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
Polo-like kinase 1 (PLK1) TTIYVQP PLK1_HUMAN Inhibitor [2]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Gene/Protein Processing [3]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Gene/Protein Processing [3]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Protein Interaction/Cellular Processes [3]
Histone H2AX (H2AX) OT18UX57 H2AX_HUMAN Gene/Protein Processing [3]
Serine-protein kinase ATM (ATM) OTQVOHLT ATM_HUMAN Post-Translational Modifications [3]

References

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2 Polo-like kinase (PLK) inhibitors in preclinical and early clinical development in oncology. Oncologist. 2009 Jun;14(6):559-70.
3 A specific inhibitor of polo-like kinase 1, GSK461364A, suppresses proliferation of Raji Burkitt's lymphoma cells through mediating cell cycle arrest, DNA damage, and apoptosis. Chem Biol Interact. 2020 Dec 1;332:109288. doi: 10.1016/j.cbi.2020.109288. Epub 2020 Oct 17.
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6 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
7 J Clin Oncol 29: 2011 (suppl; abstr 3012).
8 TAK-960, a novel, orally available, selective inhibitor of polo-like kinase 1, shows broad-spectrum preclinical antitumor activity in multiple dosing regimens. Mol Cancer Ther. 2012 Mar;11(3):700-9.
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11 4.8% sevoflurane induces activation of autophagy in human neuroblastoma SH-SY5Y cells by the AMPK/mTOR signaling pathway. Neurotoxicology. 2022 May;90:256-264. doi: 10.1016/j.neuro.2022.04.008. Epub 2022 Apr 23.
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13 Breast cancer cells response to the antineoplastic agents cisplatin, carboplatin, and doxorubicin at the mRNA expression levels of distinct apoptosis-related genes, including the new member, BCL2L12. Ann N Y Acad Sci. 2007 Jan;1095:35-44. doi: 10.1196/annals.1397.005.
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16 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.
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18 Inhibition of caspase-dependent mitochondrial permeability transition protects airway epithelial cells against mustard-induced apoptosis. Apoptosis. 2006 Sep;11(9):1545-59. doi: 10.1007/s10495-006-8764-1.
19 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.
20 -Carotene Induces Apoptosis in Human Esophageal Squamous Cell Carcinoma Cell Lines via the Cav-1/AKT/NF-B Signaling Pathway. J Biochem Mol Toxicol. 2016 Mar;30(3):148-57. doi: 10.1002/jbt.21773. Epub 2016 Jan 6.
21 Cannabinoids synergize with carfilzomib, reducing multiple myeloma cells viability and migration. Oncotarget. 2016 Nov 22;7(47):77543-77557. doi: 10.18632/oncotarget.12721.
22 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.
23 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.
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25 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.
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27 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.
28 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.
29 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.
30 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.
31 Different apoptosis ratios and gene expressions in two human cell lines after sevoflurane anaesthesia. Acta Anaesthesiol Scand. 2009 Oct;53(9):1192-9. doi: 10.1111/j.1399-6576.2009.02036.x. Epub 2009 Jun 30.
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33 Lovastatin lactone elicits human lung cancer cell apoptosis via a COX-2/PPAR-dependent pathway. Oncotarget. 2016 Mar 1;7(9):10345-62. doi: 10.18632/oncotarget.7213.
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35 Comparison of burst of reactive oxygen species and activation of caspase-3 in apoptosis of K562 and HL-60 cells induced by docetaxel. Cancer Lett. 2004 Oct 8;214(1):103-13. doi: 10.1016/j.canlet.2004.03.047.
36 Induction of mitochondrial manganese superoxide dismutase confers resistance to apoptosis in acute myeloblastic leukaemia cells exposed to etoposide. Br J Haematol. 2000 Mar;108(3):574-81. doi: 10.1046/j.1365-2141.2000.01852.x.
37 Cisplatin-enhanced sensitivity of glioblastoma multiforme U251 cells to adenovirus-delivered TRAIL in vitro. Tumour Biol. 2010 Dec;31(6):613-22. doi: 10.1007/s13277-010-0077-x. Epub 2010 Jul 11.
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40 Neurokinin-1 receptor (NK1R) inhibition sensitizes APL cells to anti-tumor effect of arsenic trioxide via restriction of NF-B axis: Shedding new light on resistance to Aprepitant. Int J Biochem Cell Biol. 2018 Oct;103:105-114. doi: 10.1016/j.biocel.2018.08.010. Epub 2018 Aug 23.
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42 Effects of gonadotrophin-releasing hormone agonists on apoptosis of granulosa cells. Ann N Y Acad Sci. 2005 May;1042:531-7. doi: 10.1196/annals.1338.065.
43 BMN 673 (talazoparib): A potent PARP inhibitor for triple negative breast cancer with different genetic profile. J Biochem Mol Toxicol. 2019 May;33(5):e22286. doi: 10.1002/jbt.22286. Epub 2019 Jan 23.
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47 Cannabidiol Induces Cell Cycle Arrest and Cell Apoptosis in Human Gastric Cancer SGC-7901 Cells. Biomolecules. 2019 Jul 25;9(8):302. doi: 10.3390/biom9080302.
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49 Pro-oxidant induced DNA damage in human lymphoblastoid cells: homeostatic mechanisms of genotoxic tolerance. Toxicol Sci. 2012 Aug;128(2):387-97. doi: 10.1093/toxsci/kfs152. Epub 2012 Apr 26.
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52 Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
53 An in vitro study on anti-carcinogenic effect of remdesivir in human ovarian cancer cells via generation of reactive oxygen species. Hum Exp Toxicol. 2022 Jan-Dec;41:9603271221089257. doi: 10.1177/09603271221089257.
54 Motexafin gadolinium and zinc induce oxidative stress responses and apoptosis in B-cell lymphoma lines. Cancer Res. 2005 Dec 15;65(24):11676-88.
55 Integrated analysis of rifampicin-induced microRNA and gene expression changes in human hepatocytes. Drug Metab Pharmacokinet. 2014;29(4):333-40.
56 Arsenic trioxide induces apoptosis in NB-4, an acute promyelocytic leukemia cell line, through up-regulation of p73 via suppression of nuclear factor kappa B-mediated inhibition of p73 transcription and prevention of NF-kappaB-mediated induction of XIAP, cIAP2, BCL-XL and survivin. Med Oncol. 2010 Sep;27(3):833-42. doi: 10.1007/s12032-009-9294-9. Epub 2009 Sep 10.