Details of the Drug Combination

General Information of Drug Combination (ID: DC5X0S0)

• Drug Combination Name: Raloxifene + ER819762
• Indication: Lung adenocarcinoma; Status: Investigative [1]
• Component Drugs:
  Raloxifene (DMDKF3M): Small molecular drug
  ER819762 (DMSG91J): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: HOP-62
  Zero Interaction Potency (ZIP) Score: 0.26
  Bliss Independence Score: 4.34
  Loewe Additivity Score: 1.53
  LHighest Single Agent (HSA) Score: 1.34

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 ER819762

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[3]

ER819762 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Prostaglandin E2 receptor EP4 (PTGER4)	TT79WV3	PE2R4_HUMAN	Antagonist	[9]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adult T acute lymphoblastic leukemia	DC2VLTK	MOLT-4	Investigative	[10]
Clear cell renal cell carcinoma	DCPN695	786-0	Investigative	[10]
Glioma	DC8I3LY	SF-295	Investigative	[10]
Papillary renal cell carcinoma	DCSWECQ	ACHN	Investigative	[10]
Plasma cell myeloma	DCAUHFQ	RPMI-8226	Investigative	[10]
Invasive ductal carcinoma	DCPQLY8	HS 578T	Investigative	[11]
Adenocarcinoma	DC8B5WN	DU-145	Investigative	[1]
Adenocarcinoma	DCDPQZ9	A549	Investigative	[1]
Adenocarcinoma	DCEIQ1U	HCC-2998	Investigative	[1]
Adenocarcinoma	DCDM6KU	SW-620	Investigative	[1]
Amelanotic melanoma	DC6PWO1	MDA-MB-435	Investigative	[1]
Cutaneous melanoma	DCW8OF9	SK-MEL-5	Investigative	[1]
Cutaneous melanoma	DCPX0Q8	SK-MEL-28	Investigative	[1]
Large cell lung carcinoma	DCBVQCK	NCI-H460	Investigative	[1]
Mixed endometrioid and clear cell carcinoma	DCC30EM	IGROV1	Investigative	[1]
Prostate carcinoma	DCZ9LEM	PC-3	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] 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: 4040).
• [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] A novel antagonist of the prostaglandin E(2) EP(4) receptor inhibits Th1 differentiation and Th17 expansion and is orally active in arthritis models. Br J Pharmacol. 2010 May;160(2):292-310.
• [10] 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.
• [11] 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.