Details of the Drug Combination

General Information of Drug Combination (ID: DC72IAJ)

• Drug Combination Name: Vincristine + Pelitinib
• Indication: Hodgkin lymphoma; Status: Investigative [1]
• Component Drugs:
  Vincristine (DMINOX3): Small molecular drug
  Pelitinib (DMIW453): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: U-HO1
  Zero Interaction Potency (ZIP) Score: 7.326
  Bliss Independence Score: 6.067
  Loewe Additivity Score: 5.743
  LHighest Single Agent (HSA) Score: 8.285

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Vincristine

Disease Entry	ICD 11	Status	REF
Acute lymphoblastic leukaemia	2A85	Approved	[2]
Adult kidney Wilms tumor	N.A.	Approved	[3]
Beckwith-Wiedemann syndrome	N.A.	Approved	[3]
Burkitt lymphoma	N.A.	Approved	[3]
Central nervous system neoplasm	N.A.	Approved	[3]
Childhood acute lymphoblastic leukemia	N.A.	Approved	[3]
Childhood kidney Wilms tumor	N.A.	Approved	[3]
Hamartoma	N.A.	Approved	[3]
Kidney neoplasm	N.A.	Approved	[3]
Leukemia	N.A.	Approved	[3]
MALT lymphoma	N.A.	Approved	[3]
Nodal marginal zone lymphoma	2A85.0	Approved	[3]
Plasma cell myeloma	2A83.1	Approved	[3]
Primitive neuroectodermal tumor	N.A.	Approved	[3]
Splenic marginal zone lymphoma	N.A.	Approved	[3]
Testicular lymphoma	N.A.	Approved	[3]
Wilms tumor	N.A.	Approved	[3]
Classic Hodgkin lymphoma	N.A.	Investigative	[3]
Follicular lymphoma	2A80	Investigative	[3]
Neuroblastoma	2D11.2	Investigative	[3]

Vincristine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Tubulin beta (TUBB)	TTYFKSZ	NOUNIPROTAC	Modulator	[5]

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	[6]
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[7]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[8]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[9]

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	[10]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[10]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[11]

Indication(s) of Pelitinib

Disease Entry	ICD 11	Status	REF
Lymphoma	2A80-2A86	Phase 2	[4]

Pelitinib Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Epidermal growth factor receptor (EGFR)	TTGKNB4	EGFR_HUMAN	Modulator	[12]

Pelitinib Interacts with 14 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Inhibitor of nuclear factor kappa-B kinase subunit beta (IKBKB)	OT9RDS3H	IKKB_HUMAN	Decreases Expression	[13]
Baculoviral IAP repeat-containing protein 5 (BIRC5)	OTILXZYL	BIRC5_HUMAN	Decreases Expression	[13]
B-cell lymphoma/leukemia 10 (BCL10)	OT47MCLI	BCL10_HUMAN	Decreases Expression	[13]
Epidermal growth factor receptor (EGFR)	OTAPLO1S	EGFR_HUMAN	Decreases Activity	[14]
Transcription factor Sp1 (SP1)	OTISPT4X	SP1_HUMAN	Decreases Activity	[13]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[13]
Cyclic AMP-dependent transcription factor ATF-1 (ATF1)	OT251CI0	ATF1_HUMAN	Decreases Expression	[13]
B-cell lymphoma 3 protein (BCL3)	OT1M5B95	BCL3_HUMAN	Decreases Expression	[13]
NF-kappa-B inhibitor alpha (NFKBIA)	OTFT924M	IKBA_HUMAN	Increases Expression	[13]
RAC-alpha serine/threonine-protein kinase (AKT1)	OT8H2YY7	AKT1_HUMAN	Decreases Expression	[13]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[13]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Expression	[13]
Baculoviral IAP repeat-containing protein 1 (NAIP)	OTLA925F	BIRC1_HUMAN	Decreases Expression	[13]
Baculoviral IAP repeat-containing protein 2 (BIRC2)	OTFXFREP	BIRC2_HUMAN	Decreases Expression	[13]

References

• [1] 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.
• [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: 6785).
• [3] Vincristine 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: 7644).
• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [6] Interaction of plant cannabinoids with the multidrug transporter ABCC1 (MRP1). Eur J Pharmacol. 2008 Sep 4;591(1-3):128-31.
• [7] 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.
• [8] 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.
• [9] Mutant Gly482 and Thr482 ABCG2 mediate high-level resistance to lipophilic antifolates. Cancer Chemother Pharmacol. 2006 Dec;58(6):826-34.
• [10] Association of CYP3A5 expression and vincristine neurotoxicity in pediatric malignancies in Turkish population. J Pediatr Hematol Oncol. 2017 Aug;39(6):458-462.
• [11] Drug Interactions Flockhart Table
• [12] EGFR tyrosine kinase inhibitor pelitinib regulates radiation-induced p65-dependent telomerase activation in squamous cell carcinoma.Radiat Res.2013 Mar;179(3):304-12.
• [13] Irreversible EGFR inhibitor EKB-569 targets low-LET -radiation-triggered rel orchestration and potentiates cell death in squamous cell carcinoma. PLoS One. 2011;6(12):e29705. doi: 10.1371/journal.pone.0029705. Epub 2011 Dec 29.
• [14] Cysteine mapping in conformationally distinct kinase nucleotide binding sites: application to the design of selective covalent inhibitors. J Med Chem. 2011 Mar 10;54(5):1347-55. doi: 10.1021/jm101396q. Epub 2011 Feb 15.