Details of the Drug Combination

General Information of Drug Combination (ID: DC3YOTX)

• Drug Combination Name: Lomustine + SCH-900776
• Indication: Breast and ovarian cancer syndrome; Status: Investigative [1]
• Component Drugs:
  Lomustine (DMMWSUL): Small molecular drug
  SCH-900776 (DM67EMK): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: UWB1289+BRCA1
  Zero Interaction Potency (ZIP) Score: 2.08
  Bliss Independence Score: 0.3
  Loewe Additivity Score: 5.46
  LHighest Single Agent (HSA) Score: 2.38

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Lomustine

Disease Entry	ICD 11	Status	REF
Brain cancer	2A00	Approved	[2]
Central nervous system neoplasm	N.A.	Approved	[3]
Primitive neuroectodermal tumor	N.A.	Approved	[3]
Classic Hodgkin lymphoma	N.A.	Investigative	[3]

Lomustine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human Deoxyribonucleic acid (hDNA)	TTUTN1I	NOUNIPROTAC	Inhibitor	[5]

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	[6]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Expression	[7]
DNA damage-inducible transcript 3 protein (DDIT3)	OTI8YKKE	DDIT3_HUMAN	Increases Expression	[8]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Increases Expression	[9]
Angiotensin-converting enzyme 2 (ACE2)	OTTRZGU7	ACE2_HUMAN	Decreases Expression	[10]
DNA polymerase eta (POLH)	OTN07WXU	POLH_HUMAN	Increases Expression	[11]
Methylated-DNA--protein-cysteine methyltransferase (MGMT)	OT40A9WH	MGMT_HUMAN	Decreases Response To Substance	[12]
Stathmin (STMN1)	OTDJ4RV0	STMN1_HUMAN	Affects Response To Substance	[13]

Indication(s) of SCH-900776

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Phase 2	[4]

SCH-900776 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Checkpoint kinase-1 (CHK1)	TTTU902	CHK1_HUMAN	Inhibitor	[14]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Breast carcinoma	DCGKLP4	KPL1	Investigative	[1]
Breast carcinoma	DCK0390	OCUBM	Investigative	[1]
Colon carcinoma	DCMFRHQ	RKO	Investigative	[1]
Adenocarcinoma	DC3BV33	CAOV3	Investigative	[15]
Adenocarcinoma	DC2EPM7	A427	Investigative	[15]
Adenocarcinoma	DC1BEJC	NCIH1650	Investigative	[15]
Adenocarcinoma	DCN2YBN	NCIH2122	Investigative	[15]
Adenocarcinoma	DC45KXH	NCIH23	Investigative	[15]
Adenocarcinoma	DCX4JWN	COLO320DM	Investigative	[15]
Adenocarcinoma	DCEUH1X	HCT116	Investigative	[15]
Adenocarcinoma	DC64ASW	HT29	Investigative	[15]
Amelanotic melanoma	DCUFNLS	A2058	Investigative	[15]
Malignant melanoma	DCPQB8U	A375	Investigative	[15]
Malignant melanoma	DCMPILU	RPMI7951	Investigative	[15]
Malignant melanoma	DCE774H	SKMEL30	Investigative	[15]
Mesothelioma	DCVOQCN	MSTO	Investigative	[15]
Non small cell carcinoma	DCYWW4F	SKMES1	Investigative	[15]
Ovarian endometrioid adenocarcinoma	DCX0734	A2780	Investigative	[15]
Ovarian serous cystadenocarcinoma	DC2VN67	SK-OV-3	Investigative	[15]
Prostate carcinoma	DCZGVUP	LNCAP	Investigative	[15]

References

• [1] 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.
• [2] 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).
• [3] Lomustine FDA Label
• [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: 7943).
• [5] Synthesis and evaluation of ethylnitrosoureas of substituted naphthalimides as anticancer compounds. Acta Pol Pharm. 2007 Jan-Feb;64(1):27-33.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] 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.
• [12] Human osteosarcoma xenografts and their sensitivity to chemotherapy. Pathol Oncol Res. 2004;10(3):133-41. doi: 10.1007/BF03033741. Epub 2004 Sep 25.
• [13] 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.
• [14] Targeting the replication checkpoint using SCH 900776, a potent and functionally selective CHK1 inhibitor identified via high content screening. Mol Cancer Ther. 2011 Apr;10(4):591-602.
• [15] 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.