Details of the Drug Combination

General Information of Drug Combination (ID: DC6A03K)

Drug Combination Name

MK-4815 Dydrogesterone

Indication

Disease Entry	Status	REF
DD2	Investigative	[1]

Component Drugs

MK-4815 DMT9K74

Dydrogesterone DMAKIDV

N.A.

Small molecular drug

2D MOL

3D MOL

High-throughput Screening Result

Testing Cell Line: DD2

Zero Interaction Potency (ZIP) Score: 1.774

Bliss Independence Score: 2.792

Loewe Additivity Score: 0.205

LHighest Single Agent (HSA) Score: 3.803

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

Indication(s) of MK-4815

Disease Entry	ICD 11	Status	REF
Malaria	1F40-1F45	Investigative	[2]

Indication(s) of Dydrogesterone

Disease Entry	ICD 11	Status	REF
Menstrual disorder	GA20.3	Approved	[3]

Dydrogesterone Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Progesterone receptor (PGR)	TTUV8G9	PRGR_HUMAN	Agonist	[4]
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Dydrogesterone Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[5]
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Dydrogesterone Interacts with 10 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
3-oxo-5-alpha-steroid 4-dehydrogenase 1 (SRD5A1)	OTQRET2B	S5A1_HUMAN	Decreases Expression	[6]
17-beta-hydroxysteroid dehydrogenase type 2 (HSD17B2)	OT3K7HY5	DHB2_HUMAN	Decreases Expression	[6]
Aldo-keto reductase family 1 member C3 (AKR1C3)	OTU2SXBA	AK1C3_HUMAN	Decreases Expression	[6]
Aldo-keto reductase family 1 member C2 (AKR1C2)	OTQ2XMO3	AK1C2_HUMAN	Decreases Expression	[6]
Aldo-keto reductase family 1 member C1 (AKR1C1)	OTQKR4CM	AK1C1_HUMAN	Decreases Expression	[6]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Decreases Expression	[7]
Interferon gamma (IFNG)	OTXG9JM7	IFNG_HUMAN	Decreases Expression	[7]
Interleukin-4 (IL4)	OTOXBWAU	IL4_HUMAN	Increases Expression	[7]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Increases Expression	[7]
Progesterone-induced-blocking factor 1 (PIBF1)	OTCBT1A1	PIBF1_HUMAN	Increases Expression	[7]
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⏷ Show the Full List of 10 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Hepatoblastoma	DCEQGMU	HB3	Investigative	[8]
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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	The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
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: 2878).
4	Dienogest is a selective progesterone receptor agonist in transactivation analysis with potent oral endometrial activity due to its efficient pharm... Steroids. 2008 Feb;73(2):222-31.
5	Dydrogesterone metabolism in human liver by aldo-keto reductases and cytochrome P450 enzymes. Xenobiotica. 2016 Oct;46(10):868-74.
6	Progestin effects on expression of AKR1C1-AKR1C3, SRD5A1 and PGR in the Z-12 endometriotic epithelial cell line. Chem Biol Interact. 2013 Feb 25;202(1-3):218-25.
7	Modulation of cytokine production by dydrogesterone in lymphocytes from women with recurrent miscarriage. BJOG. 2005 Aug;112(8):1096-101. doi: 10.1111/j.1471-0528.2005.00633.x.
8	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.