Details of the Drug Combination

General Information of Drug Combination (ID: DC8E7KZ)

• Drug Combination Name: Indazole derivative 5 + Raloxifene
• Indication: Ovarian serous cystadenocarcinoma; Status: Investigative [1]
• Component Drugs:
  Indazole derivative 5 (DMM1I8R): Small molecular drug
  Raloxifene (DMDKF3M): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: SK-OV-3
  Zero Interaction Potency (ZIP) Score: 2.82
  Bliss Independence Score: 3.57
  Loewe Additivity Score: 1.04
  LHighest Single Agent (HSA) Score: 0.81

Molecular Interaction Atlas of This Drug Combination

Indazole derivative 5 Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
ABL T315I mutant (ABL T315I)	TTZJTWA	ABL1_HUMAN	Inhibitor	[3]
Fusion protein Bcr-Abl T315I mutant (Bcr-Abl T315I)	TTIV39N	BCR_HUMAN-ABL1_HUMAN	Inhibitor	[3]

Indication(s) of Raloxifene

Disease Entry	ICD 11	Status	REF
Osteoporosis	FB83.0	Approved	[2]

Raloxifene Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Estrogen receptor (ESR)	TTZAYWL	ESR1_HUMAN	Modulator	[4]

Raloxifene Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[5]

Raloxifene Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[6]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[7]
UDP-glucuronosyltransferase 1A10 (UGT1A10)	DEL5N6Y	UD110_HUMAN	Metabolism	[8]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adenocarcinoma	DCFF142	HT29	Investigative	[9]
Adult T acute lymphoblastic leukemia	DCFT565	MOLT-4	Investigative	[9]
Astrocytoma	DCRORZ5	SNB-19	Investigative	[9]
Clear cell renal cell carcinoma	DCOYVYF	786-0	Investigative	[9]
Glioma	DCZZLNA	SF-539	Investigative	[9]
Plasma cell myeloma	DCTXNZJ	RPMI-8226	Investigative	[9]
Renal cell carcinoma	DCX1KYU	SN12C	Investigative	[9]
Breast adenocarcinoma	DCRFG0B	MDA-MB-468	Investigative	[10]
Carcinoma	DCNYUWF	MCF7	Investigative	[10]
Colon adenocarcinoma	DCEJUMO	COLO 205	Investigative	[10]
Invasive ductal carcinoma	DC165T1	HS 578T	Investigative	[10]
Invasive ductal carcinoma	DC49MQF	BT-549	Investigative	[10]
Invasive ductal carcinoma	DC5FTAJ	T-47D	Investigative	[10]
Adenocarcinoma	DCDXGEG	DU-145	Investigative	[1]
Adenocarcinoma	DCVDV3K	NCIH23	Investigative	[1]
Amelanotic melanoma	DCG0SN2	M14	Investigative	[1]
Amelanotic melanoma	DC7WU5Z	MDA-MB-435	Investigative	[1]
Cutaneous melanoma	DCBOEH0	SK-MEL-28	Investigative	[1]
High grade ovarian serous adenocarcinoma	DCWYMLD	OVCAR-5	Investigative	[1]
High grade ovarian serous adenocarcinoma	DCLNSSQ	OVCAR-8	Investigative	[1]
High grade ovarian serous adenocarcinoma	DCYKGJ7	NCI\\/ADR-RES	Investigative	[1]
Lung adenocarcinoma	DC0SEVB	HOP-62	Investigative	[1]
Lung adenocarcinoma	DC4GZS6	MDA-MB-231	Investigative	[1]
Melanoma	DCYY8VP	MALME-3M	Investigative	[1]
Melanoma	DCVAC2X	SK-MEL-2	Investigative	[1]
Melanoma	DCUQYGQ	UACC-257	Investigative	[1]
Non-small cell lung carcinoma	DC6R3W0	HOP-92	Investigative	[1]
Pleural epithelioid mesothelioma	DC1ONYO	NCI-H226	Investigative	[1]

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] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [3] Bcr-Abl tyrosine kinase inhibitors: a patent review.Expert Opin Ther Pat. 2015 Apr;25(4):397-412.
• [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. (Target id: 620).
• [5] Influence of hepatic and intestinal efflux transporters and their genetic variants on the pharmacokinetics and pharmacodynamics of raloxifene in osteoporosis treatment. Transl Res. 2012 Oct;160(4):298-308.
• [6] The role of P-glycoprotein in the bioactivation of raloxifene. Drug Metab Dispos. 2006 Dec;34(12):2073-8.
• [7] Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos. 2004 Nov;32(11):1201-8.
• [8] Characterization of raloxifene glucuronidation: potential role of UGT1A8 genotype on raloxifene metabolism in vivo. Cancer Prev Res (Phila). 2013 Jul;6(7):719-30.
• [9] Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
• [10] 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.