Details of the Drug Combination

General Information of Drug Combination (ID: DCSUW6Q)

• Drug Combination Name: BIO-300 + Vincristine
• Indication: Amelanotic melanoma; Status: Investigative [1]
• Component Drugs:
  BIO-300 (DMJ7NVI): N.A.
  Vincristine (DMINOX3): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: M14
  Zero Interaction Potency (ZIP) Score: 4.38
  Bliss Independence Score: 4.51
  Loewe Additivity Score: 0.31
  LHighest Single Agent (HSA) Score: 3.94

Molecular Interaction Atlas of This Drug Combination

Indication(s) of BIO-300

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[2]
Rheumatoid arthritis	FA20	Phase 1	[3]

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	[6]

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	[7]
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[8]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[9]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[10]

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	[11]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[11]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[12]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adult T acute lymphoblastic leukemia	DCFXLB3	MOLT-4	Investigative	[13]
Anaplastic large cell lymphoma	DCREU0P	SR	Investigative	[13]
Astrocytoma	DC52PE0	U251	Investigative	[13]
Childhood T acute lymphoblastic leukemia	DC0EHOB	CCRF-CEM	Investigative	[13]
Chronic myelogenous leukemia	DCKXUPC	K-562	Investigative	[13]
Clear cell renal cell carcinoma	DCSY7LN	A498	Investigative	[13]
Clear cell renal cell carcinoma	DCXYX9X	TK-10	Investigative	[13]
Clear cell renal cell carcinoma	DC5M3DL	CAKI-1	Investigative	[13]
Glioma	DC4U7HV	SF-268	Investigative	[13]
Glioma	DCYOJTX	SF-539	Investigative	[13]
Glioma	DC3DUFW	SF-295	Investigative	[13]
Renal cell carcinoma	DC6LBV9	SN12C	Investigative	[13]
Carcinoma	DCHXL81	RXF 393	Investigative	[14]
Carcinoma	DC2X6UN	MCF7	Investigative	[14]
Colon adenocarcinoma	DCPD3VR	COLO 205	Investigative	[14]
Adenocarcinoma	DCAEIHX	DU-145	Investigative	[1]
Adenocarcinoma	DCT0YWC	OVCAR3	Investigative	[1]
Adenocarcinoma	DCKPBVF	NCIH23	Investigative	[1]
Adenocarcinoma	DC6IXPW	A549	Investigative	[1]
Adenocarcinoma	DCA8125	HCT-15	Investigative	[1]
Adenocarcinoma	DCNF0QM	SW-620	Investigative	[1]
Adenocarcinoma	DC6DSUS	HCT116	Investigative	[1]
High grade ovarian serous adenocarcinoma	DCVFN7D	OVCAR-5	Investigative	[1]
Large cell lung carcinoma	DCWMU5H	NCI-H460	Investigative	[1]
Lung adenocarcinoma	DC0DFK4	HOP-62	Investigative	[1]
Malignant melanoma	DCP5CBG	UACC62	Investigative	[1]
Minimally invasive lung adenocarcinoma	DC3M762	NCI-H322M	Investigative	[1]
Mixed endometrioid and clear cell carcinoma	DCQCZ2Q	IGROV1	Investigative	[1]
Non-small cell lung carcinoma	DC7MK4Y	HOP-92	Investigative	[1]
Ovarian serous cystadenocarcinoma	DCX2L4H	SK-OV-3	Investigative	[1]
Pleural epithelioid mesothelioma	DCGKVQS	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] Clinical pipeline report, company report or official report of Humanetics.
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [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] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [7] Interaction of plant cannabinoids with the multidrug transporter ABCC1 (MRP1). Eur J Pharmacol. 2008 Sep 4;591(1-3):128-31.
• [8] 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.
• [9] 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.
• [10] Mutant Gly482 and Thr482 ABCG2 mediate high-level resistance to lipophilic antifolates. Cancer Chemother Pharmacol. 2006 Dec;58(6):826-34.
• [11] Association of CYP3A5 expression and vincristine neurotoxicity in pediatric malignancies in Turkish population. J Pediatr Hematol Oncol. 2017 Aug;39(6):458-462.
• [12] Drug Interactions Flockhart Table
• [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.