Details of the Drug Combination

General Information of Drug Combination (ID: DCI9681)

• Drug Combination Name: Taxol + FORMESTANE
• Indication: Plasma cell myeloma; Status: Investigative [1]
• Component Drugs:
  Taxol (DMUOT9V): Small molecular drug
  FORMESTANE (DMWIDJK): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: RPMI-8226
  Zero Interaction Potency (ZIP) Score: 2.84
  Bliss Independence Score: 4.29
  Loewe Additivity Score: 3.87
  LHighest Single Agent (HSA) Score: 0.75

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Taxol

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Approved	[2]
Solid tumour/cancer	2A00-2F9Z	Approved	[3]
Pancreatic cancer	2C10	Phase 3	[4]
Gastric adenocarcinoma	2B72	Phase 2	[5]
Ovarian cancer	2C73	Phase 2	[5]

Taxol Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Apoptosis regulator Bcl-2 (BCL-2)	TTJGNVC	BCL2_HUMAN	Modulator	[2]
Tubulin beta (TUBB)	TTYFKSZ	NOUNIPROTAC	Modulator	[2]

Indication(s) of FORMESTANE

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Withdrawn from market	[3]

FORMESTANE Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Aromatase (CYP19A1)	TTSZLWK	CP19A_HUMAN	Inhibitor	[6]

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	[7]
Aromatase (CYP19A1)	OTZ6XF74	CP19A_HUMAN	Decreases Activity	[8]
17-beta-hydroxysteroid dehydrogenase type 1 (HSD17B1)	OT6EBDHM	DHB1_HUMAN	Decreases Activity	[9]
Estrogen receptor (ESR1)	OTKLU61J	ESR1_HUMAN	Increases Expression	[10]
Androgen receptor (AR)	OTUBKAZZ	ANDR_HUMAN	Increases Expression	[10]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adenocarcinoma	DCAW6FH	DU-145	Investigative	[11]
Adenocarcinoma	DCSZ8W8	OVCAR3	Investigative	[11]
Adenocarcinoma	DC53G4J	SW-620	Investigative	[11]
Melanoma	DCWPGAQ	MALME-3M	Investigative	[11]
Mixed endometrioid and clear cell carcinoma	DCPTPIC	IGROV1	Investigative	[11]

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] Paclitaxel directly binds to Bcl-2 and functionally mimics activity of Nur77. Cancer Res. 2009 Sep 1;69(17):6906-14.
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [4] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [5] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [6] The taiwaniaquinoids: a review. J Nat Prod. 2010 Feb 26;73(2):284-98.
• [7] 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.
• [8] Screening of selected pesticides for inhibition of CYP19 aromatase activity in vitro. Toxicol In Vitro. 2000 Jun;14(3):227-34.
• [9] 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.
• [10] 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.
• [11] 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.