Details of the Drug Combination

General Information of Drug Combination (ID: DCH4M83)

Drug Combination Name

Ospemifene Sunitinib malate

Indication

Disease Entry	Status	REF
Lymphoid neoplasm	Investigative	[1]

Component Drugs

Ospemifene DMC4GEI

Sunitinib malate DMN8E5D

Small molecular drug

2D MOL

3D MOL

High-throughput Screening Result

Testing Cell Line: Mak

Zero Interaction Potency (ZIP) Score: 16.662

Bliss Independence Score: 16.614

Loewe Additivity Score: 10.323

LHighest Single Agent (HSA) Score: 16.305

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

Indication(s) of Ospemifene

Disease Entry	ICD 11	Status	REF
Dyspareunia	GA12	Approved	[2]
Postmenopausal vaginal atrophy	GA30.2	Phase 3	[2]

Ospemifene Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Estrogen receptor (ESR)	TTZAYWL	ESR1_HUMAN	Modulator	[3]
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Ospemifene Interacts with 4 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[4]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[4]
Cytochrome P450 2B6 (CYP2B6)	DEPKLMQ	CP2B6_HUMAN	Metabolism	[4]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[4]
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Ospemifene Interacts with 3 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Estrogen receptor (ESR1)	OTKLU61J	ESR1_HUMAN	Decreases Expression	[5]
Trefoil factor 1 (TFF1)	OTCYQH4F	TFF1_HUMAN	Decreases Expression	[5]
Androgen receptor (AR)	OTUBKAZZ	ANDR_HUMAN	Decreases Expression	[5]
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Sunitinib malate Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[6]
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References

1	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.
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: 7349).
3	Clinical pipeline report, company report or official report of Shionogi (2011).
4	Ospemifene metabolism in humans in vitro and in vivo: metabolite identification, quantitation, and CYP assignment of major hydroxylations. Drug Metabol Drug Interact. 2013;28(3):153-61.
5	Effects of ospemifene, a novel selective estrogen-receptor modulator, on human breast tissue ex vivo. Menopause. 2016 Jul;23(7):719-30. doi: 10.1097/GME.0000000000000624.
6	JNK-AKT-NF-kB controls P-glycoprotein expression to attenuate the cytotoxicity of deoxynivalenol in mammalian cells. Biochem Pharmacol. 2018 Oct;156:120-134.