Details of the Drug Combination

General Information of Drug Combination (ID: DCGI67H)

• Drug Combination Name: Valrubicin + FORMESTANE
• Indication: Malignant melanoma; Status: Investigative [1]
• Component Drugs:
  Valrubicin (DMOYJFK): Small molecular drug
  FORMESTANE (DMWIDJK): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: LOX IMVI
  Zero Interaction Potency (ZIP) Score: 5.52
  Bliss Independence Score: 7.15
  Loewe Additivity Score: 4
  LHighest Single Agent (HSA) Score: 4.12

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Valrubicin

Disease Entry	ICD 11	Status	REF
Bladder cancer	2C94	Approved	[2]
In situ carcinoma	N.A.	Approved	[3]
Urinary bladder cancer	N.A.	Approved	[3]
Psoriasis vulgaris	EA90	Phase 2	[4]

Valrubicin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
DNA topoisomerase II (TOP2)	TT0IHXV	TOP2A_HUMAN; TOP2B_HUMAN	Inhibitor	[5]

Valrubicin Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[6]

Indication(s) of FORMESTANE

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Withdrawn from market	[4]

FORMESTANE Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Aromatase (CYP19A1)	TTSZLWK	CP19A_HUMAN	Inhibitor	[7]

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	[8]
Aromatase (CYP19A1)	OTZ6XF74	CP19A_HUMAN	Decreases Activity	[9]
17-beta-hydroxysteroid dehydrogenase type 1 (HSD17B1)	OT6EBDHM	DHB1_HUMAN	Decreases Activity	[10]
Estrogen receptor (ESR1)	OTKLU61J	ESR1_HUMAN	Increases Expression	[11]
Androgen receptor (AR)	OTUBKAZZ	ANDR_HUMAN	Increases Expression	[11]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Astrocytoma	DC8JU71	U251	Investigative	[12]
Astrocytoma	DCBDP2O	SNB-19	Investigative	[12]
Renal cell carcinoma	DCWMNIP	SN12C	Investigative	[12]
Carcinoma	DCQBZDC	RXF 393	Investigative	[13]
Carcinoma	DCPIJEX	MCF7	Investigative	[13]
Adenocarcinoma	DCBI8JR	DU-145	Investigative	[1]
Adenocarcinoma	DCLX43N	A549	Investigative	[1]
Adenocarcinoma	DCEDY43	HCT116	Investigative	[1]
Adenocarcinoma	DCITBN0	HT29	Investigative	[1]
High grade ovarian serous adenocarcinoma	DCSXK71	OVCAR-8	Investigative	[1]
Large cell lung carcinoma	DC0DDIK	NCI-H460	Investigative	[1]
Lung adenocarcinoma	DC0IM15	MDA-MB-231	Investigative	[1]
Melanoma	DCIBCYP	SK-MEL-2	Investigative	[1]
Mixed endometrioid and clear cell carcinoma	DCPIC89	IGROV1	Investigative	[1]
Non-small cell lung carcinoma	DCUZ8D1	HOP-92	Investigative	[1]
Prostate carcinoma	DC3PN0D	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] Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
• [3] Valrubicin FDA Label
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [5] Metabolic activation of N-acylanthracyclines precedes their interaction with DNA topoisomerase II. NCI Monogr. 1987;(4):111-5.
• [6] A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development. Toxicol Sci. 2013 Nov;136(1):216-41.
• [7] The taiwaniaquinoids: a review. J Nat Prod. 2010 Feb 26;73(2):284-98.
• [8] 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.
• [9] Screening of selected pesticides for inhibition of CYP19 aromatase activity in vitro. Toxicol In Vitro. 2000 Jun;14(3):227-34.
• [10] 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.
• [11] 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.
• [12] 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.
• [13] 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.