Details of the Drug Combination

General Information of Drug Combination (ID: DCD8BQ5)

• Drug Combination Name: Raloxifene + ABIRATERONE
• Indication: Adenocarcinoma; Status: Investigative [1]
• Component Drugs:
  Raloxifene (DMDKF3M): Small molecular drug
  ABIRATERONE (DM8V75C): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: DU-145
  Zero Interaction Potency (ZIP) Score: 10.51
  Bliss Independence Score: 16.92
  Loewe Additivity Score: 11.7
  LHighest Single Agent (HSA) Score: 12.34

Molecular Interaction Atlas of This Drug Combination

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]

Indication(s) of ABIRATERONE

Disease Entry	ICD 11	Status	REF
Prostate cancer	2C82.0	Approved	[3]

ABIRATERONE Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Steroid 17-alpha-monooxygenase (S17AH)	TTRA5BZ	CP17A_HUMAN	Modulator	[9]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adult T acute lymphoblastic leukemia	DC912R2	MOLT-4	Investigative	[10]
Clear cell renal cell carcinoma	DCOQX8F	TK-10	Investigative	[10]
Glioma	DCGRV3P	SF-268	Investigative	[10]
Invasive ductal carcinoma	DCRGI3J	BT-549	Investigative	[11]
Invasive ductal carcinoma	DCB8E1W	HS 578T	Investigative	[11]
Adenocarcinoma	DCMT2AD	NCIH23	Investigative	[1]
Adenocarcinoma	DCRMYLN	HCT-15	Investigative	[1]
Amelanotic melanoma	DC984Q1	M14	Investigative	[1]
Cutaneous melanoma	DCTLHNA	SK-MEL-28	Investigative	[1]
Cutaneous melanoma	DCUFUBS	SK-MEL-5	Investigative	[1]
High grade ovarian serous adenocarcinoma	DC2XQJD	OVCAR-8	Investigative	[1]
Large cell lung carcinoma	DC9PAV8	NCI-H460	Investigative	[1]
Malignant melanoma	DCPCYMR	UACC62	Investigative	[1]
Melanoma	DC2IW26	SK-MEL-2	Investigative	[1]
Prostate carcinoma	DCM2JTD	PC-3	Investigative	[1]

References

• [1] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125976
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [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: 6745).
• [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] 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
• [10] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
• [11] CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1126165