Details of the Drug Combination

General Information of Drug Combination (ID: DCQ3WYL)

• Drug Combination Name: FORMESTANE + Dantrolene
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  FORMESTANE (DMWIDJK): Small molecular drug
  Dantrolene (DM1D8XY): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 8.7
  Bliss Independence Score: 8.7
  Loewe Additivity Score: 12.86
  LHighest Single Agent (HSA) Score: 12.86

Molecular Interaction Atlas of This Drug Combination

Indication(s) of FORMESTANE

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Withdrawn from market	[2]

FORMESTANE Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Aromatase (CYP19A1)	TTSZLWK	CP19A_HUMAN	Inhibitor	[4]

FORMESTANE Interacts with 5 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Adenylate kinase isoenzyme 1 (AK1)	OT614AR3	KAD1_HUMAN	Increases ADR	[5]
Aromatase (CYP19A1)	OTZ6XF74	CP19A_HUMAN	Decreases Activity	[6]
17-beta-hydroxysteroid dehydrogenase type 1 (HSD17B1)	OT6EBDHM	DHB1_HUMAN	Decreases Activity	[7]
Estrogen receptor (ESR1)	OTKLU61J	ESR1_HUMAN	Increases Expression	[8]
Androgen receptor (AR)	OTUBKAZZ	ANDR_HUMAN	Increases Expression	[8]

Indication(s) of Dantrolene

Disease Entry	ICD 11	Status	REF
Hyperthermia	MG26	Approved	[3]

Dantrolene Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Ryanodine receptor (RYR)	TT9YXM1	NOUNIPROTAC	Modulator	[9]

Dantrolene Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[10]

Dantrolene Interacts with 4 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Insulin-like growth factor II (IGF2)	OTJ4O6MW	IGF2_HUMAN	Decreases Response To Substance	[11]
Insulin-like growth factor I (IGF1)	OTIIZR61	IGF1_HUMAN	Decreases Response To Substance	[11]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Decreases Activity	[12]
Angiotensin-converting enzyme 2 (ACE2)	OTTRZGU7	ACE2_HUMAN	Increases Expression	[13]

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] 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: 4172).
• [4] The taiwaniaquinoids: a review. J Nat Prod. 2010 Feb 26;73(2):284-98.
• [5] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [6] Screening of selected pesticides for inhibition of CYP19 aromatase activity in vitro. Toxicol In Vitro. 2000 Jun;14(3):227-34.
• [7] Mammalian lignans and genistein decrease the activities of aromatase and 17beta-hydroxysteroid dehydrogenase in MCF-7 cells. J Steroid Biochem Mol Biol. 2005 Apr;94(5):461-7.
• [8] Androgen- and estrogen-receptor mediated activities of 4-hydroxytestosterone, 4-hydroxyandrostenedione and their human metabolites in yeast based assays. Toxicol Lett. 2018 Aug;292:39-45. doi: 10.1016/j.toxlet.2018.04.026. Epub 2018 Apr 24.
• [9] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [10] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [11] Insulin-like growth factors (IGF) I and II utilize different calcium signaling pathways in a primary human parathyroid cell culture model. World J Surg. 2006 Mar;30(3):333-45. doi: 10.1007/s00268-005-0339-8.
• [12] Refining the human iPSC-cardiomyocyte arrhythmic risk assessment model. Toxicol Sci. 2013 Dec;136(2):581-94. doi: 10.1093/toxsci/kft205. Epub 2013 Sep 19.
• [13] Effect of common medications on the expression of SARS-CoV-2 entry receptors in liver tissue. Arch Toxicol. 2020 Dec;94(12):4037-4041. doi: 10.1007/s00204-020-02869-1. Epub 2020 Aug 17.