Details of the Drug Combination

General Information of Drug Combination (ID: DCJUU05)

• Drug Combination Name: ABIRATERONE + Cabazitaxel
• Indication: Melanoma; Status: Investigative [1]
• Component Drugs:
  ABIRATERONE (DM8V75C): Small molecular drug
  Cabazitaxel (DMPAZHC): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: MALME-3M
  Zero Interaction Potency (ZIP) Score: 15.69
  Bliss Independence Score: 15.71
  Loewe Additivity Score: 14.27
  LHighest Single Agent (HSA) Score: 16.19

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	[5]

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	[6]
Tissue factor (F3)	OT3MSU3B	TF_HUMAN	Increases Expression	[7]
Membrane cofactor protein (CD46)	OTQ8NWJD	MCP_HUMAN	Increases Expression	[8]
Androgen receptor (AR)	OTUBKAZZ	ANDR_HUMAN	Decreases Response To Substance	[9]

Indication(s) of Cabazitaxel

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Approved	[3]
Solid tumour/cancer	2A00-2F9Z	Phase 2	[3]
Metastatic prostate carcinoma	N.A.	Investigative	[4]

Cabazitaxel Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Tubulin (TUB)	TTML2WA	NOUNIPROTAC	Inhibitor	[10]

Cabazitaxel Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[11]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[11]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[11]

Cabazitaxel Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Forkhead box protein O3 (FOXO3)	OTHXQG4P	FOXO3_HUMAN	Affects Expression	[12]
Proline-rich AKT1 substrate 1 (AKT1S1)	OT4JHN4Y	AKTS1_HUMAN	Decreases Expression	[12]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Anaplastic large cell lymphoma	DCJ0WAD	SR	Investigative	[13]
Astrocytoma	DCP4TN0	U251	Investigative	[13]
Astrocytoma	DC159T4	SNB-19	Investigative	[13]
Childhood T acute lymphoblastic leukemia	DCJJ1OH	CCRF-CEM	Investigative	[13]
Chronic myelogenous leukemia	DC2WGZL	K-562	Investigative	[13]
Clear cell renal cell carcinoma	DCNUQHC	TK-10	Investigative	[13]
Glioma	DCY8ZRB	SF-268	Investigative	[13]
Glioma	DCZ8LDN	SF-539	Investigative	[13]
Plasma cell myeloma	DC0RMWZ	RPMI-8226	Investigative	[13]
Carcinoma	DCFKCXX	MCF7	Investigative	[14]
Adenocarcinoma	DCX8C1Z	OVCAR3	Investigative	[1]
Adenocarcinoma	DC51U2B	A549	Investigative	[1]
Adenocarcinoma	DCXP0I1	NCIH23	Investigative	[1]
Adenocarcinoma	DC00OAE	HCT-15	Investigative	[1]
Adenocarcinoma	DCO9NVH	HCC-2998	Investigative	[1]
Adenocarcinoma	DCPUG5X	HCT116	Investigative	[1]
Adenocarcinoma	DC5CI13	HT29	Investigative	[1]
Adenocarcinoma	DCG7RRX	SW-620	Investigative	[1]
Amelanotic melanoma	DCZZYID	MDA-MB-435	Investigative	[1]
Amelanotic melanoma	DCV9CDH	M14	Investigative	[1]
Cutaneous melanoma	DCC2JR4	SK-MEL-28	Investigative	[1]
High grade ovarian serous adenocarcinoma	DC1FWX5	OVCAR-8	Investigative	[1]
High grade ovarian serous adenocarcinoma	DCCGPJR	NCI\\/ADR-RES	Investigative	[1]
Lung adenocarcinoma	DCUWW58	HOP-62	Investigative	[1]
Lung adenocarcinoma	DCC54ZT	MDA-MB-231	Investigative	[1]
Malignant melanoma	DC0QPLD	LOX IMVI	Investigative	[1]
Melanoma	DCP2OCJ	UACC-257	Investigative	[1]
Pleural epithelioid mesothelioma	DC4YO2T	NCI-H226	Investigative	[1]

References

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• [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] 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: 6798).
• [4] Cabazitaxel FDA Label
• [5] 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
• [11] DAILYMED.nlm.nih.gov: JEVTANA- cabazitaxel kit.
• [12] The triphenyltin carboxylate derivative triphenylstannyl 2-(benzylcarbamoyl)benzoate impedes prostate cancer progression via modulation of Akt/FOXO3a signaling. Toxicol Appl Pharmacol. 2020 Aug 15;401:115091. doi: 10.1016/j.taap.2020.115091. Epub 2020 Jun 7.
• [13] 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.
• [14] 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.