Details of the Drug Combination

General Information of Drug Combination (ID: DCUVW85)

• Drug Combination Name: Cabazitaxel + Vincristine
• Indication: Invasive ductal carcinoma; Status: Investigative [1]
• Component Drugs:
  Cabazitaxel (DMPAZHC): Small molecular drug
  Vincristine (DMINOX3): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: BT-549
  Zero Interaction Potency (ZIP) Score: 2.17
  Bliss Independence Score: 2.76
  Loewe Additivity Score: 2.55
  LHighest Single Agent (HSA) Score: 7.19

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Cabazitaxel

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

Cabazitaxel Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Tubulin (TUB)	TTML2WA	NOUNIPROTAC	Inhibitor	[6]

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	[7]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[7]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[7]

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	[8]
Proline-rich AKT1 substrate 1 (AKT1S1)	OT4JHN4Y	AKTS1_HUMAN	Decreases Expression	[8]

Indication(s) of Vincristine

Disease Entry	ICD 11	Status	REF
Acute lymphoblastic leukaemia	2A85	Approved	[4]
Adult kidney Wilms tumor	N.A.	Approved	[5]
Beckwith-Wiedemann syndrome	N.A.	Approved	[5]
Burkitt lymphoma	N.A.	Approved	[5]
Central nervous system neoplasm	N.A.	Approved	[5]
Childhood acute lymphoblastic leukemia	N.A.	Approved	[5]
Childhood kidney Wilms tumor	N.A.	Approved	[5]
Hamartoma	N.A.	Approved	[5]
Kidney neoplasm	N.A.	Approved	[5]
Leukemia	N.A.	Approved	[5]
MALT lymphoma	N.A.	Approved	[5]
Nodal marginal zone lymphoma	2A85.0	Approved	[5]
Plasma cell myeloma	2A83.1	Approved	[5]
Primitive neuroectodermal tumor	N.A.	Approved	[5]
Splenic marginal zone lymphoma	N.A.	Approved	[5]
Testicular lymphoma	N.A.	Approved	[5]
Wilms tumor	N.A.	Approved	[5]
Classic Hodgkin lymphoma	N.A.	Investigative	[5]
Follicular lymphoma	2A80	Investigative	[5]
Neuroblastoma	2D11.2	Investigative	[5]

Vincristine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Tubulin beta (TUBB)	TTYFKSZ	NOUNIPROTAC	Modulator	[9]

Vincristine Interacts with 4 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 1 (ABCC1)	DTSYQGK	MRP1_HUMAN	Substrate	[10]
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[11]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[12]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[13]

Vincristine Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[14]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[14]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[15]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adenocarcinoma	DC0X5FB	DU-145	Investigative	[16]
Adenocarcinoma	DCHR3JP	OVCAR3	Investigative	[16]
Adenocarcinoma	DCWN328	HCT-15	Investigative	[16]
Adenocarcinoma	DCRT3BG	HCC-2998	Investigative	[16]
Adenocarcinoma	DCV5J7A	HCT116	Investigative	[16]
Adenocarcinoma	DCLJSXB	HT29	Investigative	[16]
Adult acute myeloid leukemia	DCT8VKH	HL-60(TB)	Investigative	[16]
Adult T acute lymphoblastic leukemia	DCKJ4NN	MOLT-4	Investigative	[16]
Anaplastic large cell lymphoma	DC35GTA	SR	Investigative	[16]
Childhood T acute lymphoblastic leukemia	DCCZ7OK	CCRF-CEM	Investigative	[16]
Clear cell renal cell carcinoma	DC6FJ7Q	786-0	Investigative	[16]
Glioma	DCM8W84	SF-539	Investigative	[16]
Glioma	DCNP0PM	SF-295	Investigative	[16]
High grade ovarian serous adenocarcinoma	DC9ZEF7	OVCAR-4	Investigative	[16]
Large cell lung carcinoma	DCC7BHU	NCI-H460	Investigative	[16]
Lung adenocarcinoma	DCAT2EX	NCI-H522	Investigative	[16]
Malignant melanoma	DCVX2JS	UACC62	Investigative	[16]
Minimally invasive lung adenocarcinoma	DCFQXR9	NCI-H322M	Investigative	[16]
Ovarian serous cystadenocarcinoma	DCR36OI	SK-OV-3	Investigative	[16]
Plasma cell myeloma	DCREWE5	RPMI-8226	Investigative	[16]
Prostate carcinoma	DCP63RT	PC-3	Investigative	[16]
Renal cell carcinoma	DCPGT88	SN12C	Investigative	[16]
Breast adenocarcinoma	DC414L0	MDA-MB-468	Investigative	[1]
Carcinoma	DC8MV6Z	RXF 393	Investigative	[1]
Carcinoma	DC84J5F	MCF7	Investigative	[1]
Invasive ductal carcinoma	DCF7AH2	HS 578T	Investigative	[1]

References

• [1] 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.
• [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: 6798).
• [3] Cabazitaxel FDA Label
• [4] 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: 6785).
• [5] Vincristine FDA Label
• [6] Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
• [7] DAILYMED.nlm.nih.gov: JEVTANA- cabazitaxel kit.
• [8] 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.
• [9] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [10] Interaction of plant cannabinoids with the multidrug transporter ABCC1 (MRP1). Eur J Pharmacol. 2008 Sep 4;591(1-3):128-31.
• [11] Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
• [12] L-type calcium channel blockers reverse docetaxel and vincristine-induced multidrug resistance independent of ABCB1 expression in human lung cancer cell lines. Toxicol Lett. 2010 Feb 15;192(3):408-18.
• [13] Mutant Gly482 and Thr482 ABCG2 mediate high-level resistance to lipophilic antifolates. Cancer Chemother Pharmacol. 2006 Dec;58(6):826-34.
• [14] Association of CYP3A5 expression and vincristine neurotoxicity in pediatric malignancies in Turkish population. J Pediatr Hematol Oncol. 2017 Aug;39(6):458-462.
• [15] Drug Interactions Flockhart Table
• [16] 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.