General Information of Drug Combination (ID: DCGJ5EZ)

Drug Combination Name
GSK525762 Lomustine
Indication
Disease Entry Status REF
Mesothelioma Investigative [1]
Component Drugs GSK525762   DMPAWBN Lomustine   DMMWSUL
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL is unavailable 3D MOL
High-throughput Screening Result Testing Cell Line: MSTO
Zero Interaction Potency (ZIP) Score: 21.6
Bliss Independence Score: 20.03
Loewe Additivity Score: 19.38
LHighest Single Agent (HSA) Score: 22.37

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of GSK525762
Disease Entry ICD 11 Status REF
Haematological malignancy 2B33.Y Phase 1 [2]
Solid tumour/cancer 2A00-2F9Z Phase 1 [3]
GSK525762 Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Bromodomain-containing protein 4 (BRD4) TTRA6BO BRD4_HUMAN Modulator [7]
Bromodomain and extraterminal domain protein (BET) TTE4BSY NOUNIPROTAC Inhibitor [2]
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GSK525762 Interacts with 11 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Apolipoprotein A-I (APOA1) OT5THARI APOA1_HUMAN Increases Expression [8]
Estrogen receptor (ESR1) OTKLU61J ESR1_HUMAN Decreases Expression [9]
Trefoil factor 1 (TFF1) OTCYQH4F TFF1_HUMAN Decreases Expression [9]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [9]
Protein-lysine 6-oxidase (LOX) OT1C2HIU LYOX_HUMAN Decreases Expression [6]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Increases Activity [10]
Caspase-7 (CASP7) OTAPJ040 CASP7_HUMAN Increases Activity [10]
Carbonic anhydrase 9 (CA9) OTNA51XT CAH9_HUMAN Decreases Expression [6]
6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) OT25JBA3 F263_HUMAN Increases Expression [6]
Protein GREB1 (GREB1) OTU6ZA26 GREB1_HUMAN Decreases Expression [9]
Endothelial PAS domain-containing protein 1 (EPAS1) OTRE3O8U EPAS1_HUMAN Increases Expression [6]
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⏷ Show the Full List of 11 DOT(s)
Indication(s) of Lomustine
Disease Entry ICD 11 Status REF
Brain cancer 2A00 Approved [4]
Central nervous system neoplasm N.A. Approved [5]
Primitive neuroectodermal tumor N.A. Approved [5]
Classic Hodgkin lymphoma N.A. Investigative [5]
Lomustine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Human Deoxyribonucleic acid (hDNA) TTUTN1I NOUNIPROTAC Inhibitor [11]
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Lomustine Interacts with 8 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Suppressor of cytokine signaling 1 (SOCS1) OTWA9KFU SOCS1_HUMAN Decreases Expression [12]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Expression [13]
DNA damage-inducible transcript 3 protein (DDIT3) OTI8YKKE DDIT3_HUMAN Increases Expression [14]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [15]
Angiotensin-converting enzyme 2 (ACE2) OTTRZGU7 ACE2_HUMAN Decreases Expression [16]
DNA polymerase eta (POLH) OTN07WXU POLH_HUMAN Increases Expression [17]
Methylated-DNA--protein-cysteine methyltransferase (MGMT) OT40A9WH MGMT_HUMAN Decreases Response To Substance [18]
Stathmin (STMN1) OTDJ4RV0 STMN1_HUMAN Affects Response To Substance [19]
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⏷ Show the Full List of 8 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Breast carcinoma DC2TT9H OCUBM Investigative [20]
Adenocarcinoma DC3GETX HCT116 Investigative [1]
Ovarian endometrioid adenocarcinoma DCA7CLG A2780 Investigative [1]
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References

1 Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy.Hum Genet. 2018 Apr;137(4):293-303. doi: 10.1007/s00439-018-1882-3. Epub 2018 Apr 24.
2 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
3 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. (Ligand id: 7033).
4 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. (Ligand id: 7214).
5 Lomustine FDA Label
6 The BET inhibitor JQ1 selectively impairs tumour response to hypoxia and downregulates CA9 and angiogenesis in triple negative breast cancer. Oncogene. 2017 Jan 5;36(1):122-132. doi: 10.1038/onc.2016.184. Epub 2016 Jun 13.
7 Targeting bromodomains: epigenetic readers of lysine acetylation.Nat Rev Drug Discov.2014 May;13(5):337-56.
8 Discovery and characterization of small molecule inhibitors of the BET family bromodomains. J Med Chem. 2011 Jun 9;54(11):3827-38.
9 An epigenomic approach to therapy for tamoxifen-resistant breast cancer. Cell Res. 2014 Jul;24(7):809-19. doi: 10.1038/cr.2014.71. Epub 2014 May 30.
10 MCM5 as a target of BET inhibitors in thyroid cancer cells. Endocr Relat Cancer. 2016 Apr;23(4):335-47. doi: 10.1530/ERC-15-0322. Epub 2016 Feb 24.
11 Synthesis and evaluation of ethylnitrosoureas of substituted naphthalimides as anticancer compounds. Acta Pol Pharm. 2007 Jan-Feb;64(1):27-33.
12 Characterization of DNA reactive and non-DNA reactive anticancer drugs by gene expression profiling. Mutat Res. 2007 Jun 1;619(1-2):16-29. doi: 10.1016/j.mrfmmm.2006.12.007. Epub 2007 Feb 8.
13 Enhanced in vitro invasiveness and drug resistance with altered gene expression patterns in a human lung carcinoma cell line after pulse selection with anticancer drugs. Int J Cancer. 2004 Sep 10;111(4):484-93. doi: 10.1002/ijc.20230.
14 High-content imaging-based BAC-GFP toxicity pathway reporters to assess chemical adversity liabilities. Arch Toxicol. 2017 Mar;91(3):1367-1383. doi: 10.1007/s00204-016-1781-0. Epub 2016 Jun 29.
15 Utilization of CDKN1A/p21 gene for class discrimination of DNA damage-induced clastogenicity. Toxicology. 2014 Jan 6;315:8-16. doi: 10.1016/j.tox.2013.10.009. Epub 2013 Nov 6.
16 Effect of common medications on the expression of SARS-CoV-2 entry receptors in liver tissue. Arch Toxicol. 2020 Dec;94(12):4037-4041. doi: 10.1007/s00204-020-02869-1. Epub 2020 Aug 17.
17 Translesion polymerase is upregulated by cancer therapeutics and confers anticancer drug resistance. Cancer Res. 2014 Oct 1;74(19):5585-96. doi: 10.1158/0008-5472.CAN-14-0953. Epub 2014 Aug 14.
18 Human osteosarcoma xenografts and their sensitivity to chemotherapy. Pathol Oncol Res. 2004;10(3):133-41. doi: 10.1007/BF03033741. Epub 2004 Sep 25.
19 The 1p-encoded protein stathmin and resistance of malignant gliomas to nitrosoureas. J Natl Cancer Inst. 2007 Apr 18;99(8):639-52. doi: 10.1093/jnci/djk135.
20 Biologically active neutrophil chemokine pattern in tonsillitis.Clin Exp Immunol. 2004 Mar;135(3):511-8. doi: 10.1111/j.1365-2249.2003.02390.x.