Details of the Drug Combination

General Information of Drug Combination (ID: DC6X86K)

• Drug Combination Name: ABIRATERONE + Taxol
• Indication: Adenocarcinoma; Status: Investigative [1]
• Component Drugs:
  ABIRATERONE (DM8V75C): Small molecular drug
  Taxol (DMUOT9V): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: HCT-15
  Zero Interaction Potency (ZIP) Score: 12.81
  Bliss Independence Score: 20.14
  Loewe Additivity Score: 9.87
  LHighest Single Agent (HSA) Score: 19.22

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	[7]

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	[8]
Tissue factor (F3)	OT3MSU3B	TF_HUMAN	Increases Expression	[9]
Membrane cofactor protein (CD46)	OTQ8NWJD	MCP_HUMAN	Increases Expression	[10]
Androgen receptor (AR)	OTUBKAZZ	ANDR_HUMAN	Decreases Response To Substance	[11]

Indication(s) of Taxol

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Approved	[3]
Solid tumour/cancer	2A00-2F9Z	Approved	[4]
Pancreatic cancer	2C10	Phase 3	[5]
Gastric adenocarcinoma	2B72	Phase 2	[6]
Ovarian cancer	2C73	Phase 2	[6]

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	[3]
Tubulin beta (TUBB)	TTYFKSZ	NOUNIPROTAC	Modulator	[3]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adult T acute lymphoblastic leukemia	DCAQ75W	MOLT-4	Investigative	[12]
Anaplastic large cell lymphoma	DC8SVDT	SR	Investigative	[12]
Astrocytoma	DCCC1G3	U251	Investigative	[12]
Childhood T acute lymphoblastic leukemia	DCM6LCX	CCRF-CEM	Investigative	[12]
Clear cell renal cell carcinoma	DCKDSR0	786-0	Investigative	[12]
Clear cell renal cell carcinoma	DC0P0EW	CAKI-1	Investigative	[12]
Glioma	DCUH30M	SF-295	Investigative	[12]
Plasma cell myeloma	DCMIERP	RPMI-8226	Investigative	[12]
Renal cell carcinoma	DCMMSI0	UO-31	Investigative	[12]
Breast adenocarcinoma	DCI97DE	MDA-MB-468	Investigative	[13]
Carcinoma	DCE9HYZ	RXF 393	Investigative	[13]
Carcinoma	DCSCRU4	MCF7	Investigative	[13]
Colon carcinoma	DCADALD	KM12	Investigative	[13]
Adenocarcinoma	DCBXX2Y	OVCAR3	Investigative	[1]
Adenocarcinoma	DC9AXO9	A549	Investigative	[1]
Adenocarcinoma	DC8FO7S	SW-620	Investigative	[1]
Adenocarcinoma	DCTZV6G	HCT116	Investigative	[1]
Adenocarcinoma	DCGX9OK	HCC-2998	Investigative	[1]
Adenocarcinoma	DCCLVLM	HT29	Investigative	[1]
Amelanotic melanoma	DCXBDK2	MDA-MB-435	Investigative	[1]
Amelanotic melanoma	DCSLWNE	M14	Investigative	[1]
Cutaneous melanoma	DCFKLXA	SK-MEL-28	Investigative	[1]
High grade ovarian serous adenocarcinoma	DCVPQMO	NCI\\/ADR-RES	Investigative	[1]
Lung adenocarcinoma	DCUM32Y	MDA-MB-231	Investigative	[1]
Lung adenocarcinoma	DCQXIZ0	NCI-H522	Investigative	[1]
Malignant melanoma	DCK0Q71	LOX IMVI	Investigative	[1]
Melanoma	DC0GFIV	MALME-3M	Investigative	[1]
Mixed endometrioid and clear cell carcinoma	DCLZ8J5	IGROV1	Investigative	[1]
Pleural epithelioid mesothelioma	DCJ5QOS	NCI-H226	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] Paclitaxel directly binds to Bcl-2 and functionally mimics activity of Nur77. Cancer Res. 2009 Sep 1;69(17):6906-14.
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [5] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [6] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [7] 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
• [8] 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.
• [9] 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.
• [10] 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.
• [11] 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.
• [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.