Details of the Drug Combination

General Information of Drug Combination (ID: DCAOS0W)

• Drug Combination Name: ABIRATERONE + Indazole derivative 5
• Indication: Amelanotic melanoma; Status: Investigative [1]
• Component Drugs:
  ABIRATERONE (DM8V75C): Small molecular drug
  Indazole derivative 5 (DMM1I8R): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: M14
  Zero Interaction Potency (ZIP) Score: 2.38
  Bliss Independence Score: 6.16
  Loewe Additivity Score: 1.56
  LHighest Single Agent (HSA) Score: 2.05

Molecular Interaction Atlas of This Drug Combination

Indication(s) of ABIRATERONE

Disease Entry	ICD 11	Status	REF
Prostate cancer	2C82.0	Approved	[2]

ABIRATERONE Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Steroid 17-alpha-monooxygenase (S17AH)	TTRA5BZ	CP17A_HUMAN	Modulator	[3]

ABIRATERONE Interacts with 4 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Steroid 17-alpha-hydroxylase/17,20 lyase (CYP17A1)	OTZKVLVJ	CP17A_HUMAN	Decreases Activity	[4]
Tissue factor (F3)	OT3MSU3B	TF_HUMAN	Increases Expression	[5]
Membrane cofactor protein (CD46)	OTQ8NWJD	MCP_HUMAN	Increases Expression	[6]
Androgen receptor (AR)	OTUBKAZZ	ANDR_HUMAN	Decreases Response To Substance	[7]

Indazole derivative 5 Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
ABL T315I mutant (ABL T315I)	TTZJTWA	ABL1_HUMAN	Inhibitor	[8]
Fusion protein Bcr-Abl T315I mutant (Bcr-Abl T315I)	TTIV39N	BCR_HUMAN-ABL1_HUMAN	Inhibitor	[8]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Astrocytoma	DC9XTHR	U251	Investigative	[9]
Chronic myelogenous leukemia	DCDKTRM	K-562	Investigative	[9]
Clear cell renal cell carcinoma	DCVHE9C	CAKI-1	Investigative	[9]
Papillary renal cell carcinoma	DCND3JP	ACHN	Investigative	[9]
Breast adenocarcinoma	DC98QNJ	MDA-MB-468	Investigative	[10]
Colon adenocarcinoma	DC2D5HA	COLO 205	Investigative	[10]
Invasive ductal carcinoma	DCDHIOL	BT-549	Investigative	[10]
Invasive ductal carcinoma	DCLYH34	T-47D	Investigative	[10]
Adenocarcinoma	DC7QNJW	DU-145	Investigative	[1]
Adenocarcinoma	DCNNQHL	NCIH23	Investigative	[1]
Adenocarcinoma	DCWLZZW	HCT116	Investigative	[1]
Cutaneous melanoma	DC9F1R4	SK-MEL-28	Investigative	[1]
High grade ovarian serous adenocarcinoma	DCHFFFZ	NCI\\/ADR-RES	Investigative	[1]
Large cell lung carcinoma	DCCJLTZ	NCI-H460	Investigative	[1]
Lung adenocarcinoma	DCEWESD	HOP-62	Investigative	[1]
Melanoma	DC1W04T	SK-MEL-2	Investigative	[1]
Melanoma	DCI54IX	UACC-257	Investigative	[1]
Minimally invasive lung adenocarcinoma	DCONUQQ	NCI-H322M	Investigative	[1]
Ovarian serous cystadenocarcinoma	DCRUCY9	SK-OV-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] 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: 6745).
• [3] 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
• [4] A fission yeast-based test system for the determination of IC50 values of anti-prostate tumor drugs acting on CYP21. J Enzyme Inhib Med Chem. 2006 Oct;21(5):547-56.
• [5] Elucidating mechanisms of toxicity using phenotypic data from primary human cell systems--a chemical biology approach for thrombosis-related side effects. Int J Mol Sci. 2015 Jan 5;16(1):1008-29. doi: 10.3390/ijms16011008.
• [6] Targeting CD46 for both adenocarcinoma and neuroendocrine prostate cancer. JCI Insight. 2018 Sep 6;3(17):e121497. doi: 10.1172/jci.insight.121497. eCollection 2018 Sep 6.
• [7] Targeting chromatin binding regulation of constitutively active AR variants to overcome prostate cancer resistance to endocrine-based therapies. Nucleic Acids Res. 2015 Jul 13;43(12):5880-97. doi: 10.1093/nar/gkv262. Epub 2015 Apr 23.
• [8] Bcr-Abl tyrosine kinase inhibitors: a patent review.Expert Opin Ther Pat. 2015 Apr;25(4):397-412.
• [9] 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.
• [10] 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.