General Information of Drug Combination (ID: DCLL8FP)

Drug Combination Name
MK-5108 Lomustine
Indication
Disease Entry Status REF
Adenocarcinoma Investigative [1]
Component Drugs MK-5108   DMFGYKS Lomustine   DMMWSUL
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: OVCAR3
Zero Interaction Potency (ZIP) Score: 1.34
Bliss Independence Score: 5.25
Loewe Additivity Score: 7.18
LHighest Single Agent (HSA) Score: 9.41

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of MK-5108
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Phase 1 [2]
MK-5108 Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Aurora kinase B (AURKB) TT5LS6T AURKB_HUMAN Inhibitor [5]
Aurora kinase A (AURKA) TTPS3C0 AURKA_HUMAN Inhibitor [5]
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Indication(s) of Lomustine
Disease Entry ICD 11 Status REF
Brain cancer 2A00 Approved [3]
Central nervous system neoplasm N.A. Approved [4]
Primitive neuroectodermal tumor N.A. Approved [4]
Classic Hodgkin lymphoma N.A. Investigative [4]
Lomustine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Human Deoxyribonucleic acid (hDNA) TTUTN1I NOUNIPROTAC Inhibitor [6]
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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 [7]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Expression [8]
DNA damage-inducible transcript 3 protein (DDIT3) OTI8YKKE DDIT3_HUMAN Increases Expression [9]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [10]
Angiotensin-converting enzyme 2 (ACE2) OTTRZGU7 ACE2_HUMAN Decreases Expression [11]
DNA polymerase eta (POLH) OTN07WXU POLH_HUMAN Increases Expression [12]
Methylated-DNA--protein-cysteine methyltransferase (MGMT) OT40A9WH MGMT_HUMAN Decreases Response To Substance [13]
Stathmin (STMN1) OTDJ4RV0 STMN1_HUMAN Affects Response To Substance [14]
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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 DCD6M7Z OCUBM Investigative [15]
Colon carcinoma DC1J1GH RKO Investigative [15]
Adenocarcinoma DCTQGNK CAOV3 Investigative [1]
Adenocarcinoma DCFA2UY NCIH23 Investigative [1]
Adenocarcinoma DCYIDWC COLO320DM Investigative [1]
Adenocarcinoma DCPJLJD HCT116 Investigative [1]
Adenocarcinoma DC2FWLJ HT29 Investigative [1]
Adenocarcinoma DCTSM72 SW-620 Investigative [1]
Germ cell tumour DCE5G6U PA1 Investigative [1]
Malignant melanoma DC71E68 RPMI7951 Investigative [1]
Malignant melanoma DCXOI1H SKMEL30 Investigative [1]
Mesothelioma DCLNHEK MSTO Investigative [1]
Ovarian endometrioid adenocarcinoma DC1F6QV A2780 Investigative [1]
Ovarian serous cystadenocarcinoma DCGF0MN SK-OV-3 Investigative [1]
Prostate carcinoma DCT3SNE LNCAP Investigative [1]
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⏷ Show the Full List of 15 DrugCom(s)

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 ClinicalTrials.gov (NCT00543387) Treatment of Participants With Advanced and/or Refractory Solid Tumors (MK-5108-001 AM4). U.S. National Institutes of Health.
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: 7214).
4 Lomustine FDA Label
5 A novel c-Met inhibitor, MK8033, synergizes with carboplatin plus paclitaxel to inhibit ovarian cancer cell growth. Oncol Rep. 2013 May;29(5):2011-8.
6 Synthesis and evaluation of ethylnitrosoureas of substituted naphthalimides as anticancer compounds. Acta Pol Pharm. 2007 Jan-Feb;64(1):27-33.
7 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.
8 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.
9 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.
10 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.
11 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.
12 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.
13 Human osteosarcoma xenografts and their sensitivity to chemotherapy. Pathol Oncol Res. 2004;10(3):133-41. doi: 10.1007/BF03033741. Epub 2004 Sep 25.
14 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.
15 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.