Details of the Drug Combination

General Information of Drug Combination (ID: DCETI1X)

• Drug Combination Name: Carboplatin + Vincristine
• Indication: Brain Tumor; Status: Phase 1 [1]
• Component Drugs:
  Carboplatin (DMG281S): Small molecular drug
  Vincristine (DMINOX3): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Carboplatin

Disease Entry	ICD 11	Status	REF
Adenocarcinoma	2D40	Approved	[2]
Carcinoma	2A00-2F9Z	Approved	[2]
Cholangiocarcinoma	2C12.10	Approved	[2]
Cutaneous melanoma	2C30	Approved	[2]
Epithelial ovarian cancer	2B5D	Approved	[2]
Fallopian tube neoplasm	N.A.	Approved	[2]
Gastroesophageal junction adenocarcinoma	2B71	Approved	[2]
Lung adenocarcinoma	N.A.	Approved	[2]
Lung cancer	2C25.0	Approved	[2]
Non-small-cell lung cancer	2C25.Y	Approved	[2]
Ovarian cancer	2C73	Approved	[3]
Ovarian disorder	N.A.	Approved	[2]
Ovarian neoplasm	N.A.	Approved	[2]
Ovarian serous cystadenocarcinoma	N.A.	Approved	[2]
Small-cell lung cancer	2C25.Y	Approved	[2]
Lung large cell carcinoma	N.A.	Investigative	[2]
Neuroblastoma	2D11.2	Investigative	[2]

Carboplatin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human Deoxyribonucleic acid (hDNA)	TTUTN1I	NOUNIPROTAC	Modulator	[6]

Carboplatin Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
High affinity copper uptake protein 1 (SLC31A1)	DTP8L4F	COPT1_HUMAN	Substrate	[7]

Carboplatin Interacts with 7 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Glutathione S-transferase pi (GSTP1)	DEK6079	GSTP1_HUMAN	Metabolism	[8]
Glutathione S-transferase theta-1 (GSTT1)	DE3PKUG	GSTT1_HUMAN	Metabolism	[8]
Metallothionein-1A (MT1A)	DE5ME8A	MT1A_HUMAN	Metabolism	[8]
Metallothionein-2A (MT2A)	DEFKGT7	MT2_HUMAN	Metabolism	[8]
Myeloperoxidase (MPO)	DEA3U9Y	PERM_HUMAN	Metabolism	[8]
Quinone reductase 1 (NQO1)	DENP5RY	NQO1_HUMAN	Metabolism	[8]
Glutathione S-transferase mu-1 (GSTM1)	DEYZEJA	GSTM1_HUMAN	Metabolism	[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
Brain Tumors	DC140UW	N. A.	Phase 1	[16]
Pilomyxoid Astrocytoma	DCYNRYE	N. A.	Phase 1	[17]

References

• [1] ClinicalTrials.gov (NCT00077207) Carboplatin, Vincristine, and Temozolomide in Treating Children With Progressive and/or Symptomatic Low-Grade Glioma
• [2] Carboplatin FDA Label
• [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: 7624).
• [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] Inhibition of carboplatin-induced DNA interstrand cross-link repair by gemcitabine in patients receiving these drugs for platinum-resistant ovarian cancer.Clin Cancer Res.2010 Oct 1;16(19):4899-905.
• [7] Overcoming platinum drug resistance with copper-lowering agents. Anticancer Res. 2013 Oct;33(10):4157-61.
• [8] PharmGKB: A worldwide resource for pharmacogenomic information. Wiley Interdiscip Rev Syst Biol Med. 2018 Jul;10(4):e1417. (ID: PA150642262)
• [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] ClinicalTrials.gov (NCT00002944) Combination Chemotherapy in Treating Children With Progressive Brain Tumors
• [17] ClinicalTrials.gov (NCT01837862) A Phase I Study of Mebendazole for the Treatment of Pediatric Gliomas