Details of the Drug Combination

General Information of Drug Combination (ID: DCIFXMF)

• Drug Combination Name: Eptifibatide + VR-776
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Eptifibatide (DMQXTJS): Small molecular drug
  VR-776 (DMFQWNI): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 0.02
  Bliss Independence Score: 0.02
  Loewe Additivity Score: 15.74
  LHighest Single Agent (HSA) Score: 15.74

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Eptifibatide

Disease Entry	ICD 11	Status	REF
Acute cardiac ischemic events	BA40.Z	Approved	[2]
Acute coronary syndrome	BA41	Approved	[3]
Pneumonia	CA40	Approved	[3]

Eptifibatide Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Glycoprotein IIb/IIIa receptor (GPIIb/IIIa)	TT38RM1	ITA2B_HUMAN; ITB3_HUMAN	Modulator	[5]

Eptifibatide Interacts with 6 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Prothrombin (F2)	OTNFSM49	THRB_HUMAN	Increases Expression	[6]
C-reactive protein (CRP)	OT0RFT8F	CRP_HUMAN	Increases Expression	[6]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Increases Expression	[6]
CD40 ligand (CD40LG)	OT75Z6A6	CD40L_HUMAN	Decreases Expression	[6]
Integrin alpha-IIb (ITGA2B)	OT4Y17PY	ITA2B_HUMAN	Increases ADR	[7]
Integrin beta-3 (ITGB3)	OTWCK1K6	ITB3_HUMAN	Increases ADR	[7]

Indication(s) of VR-776

Disease Entry	ICD 11	Status	REF
Premature ejaculation	HA03.0Z	Discontinued in Phase 1	[4]

VR-776 Interacts with 5 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[8]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[9]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[10]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[11]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[12]

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: 6585).
• [3] Eptifibatide FDA Label
• [4] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800022099)
• [5] Barbourin. A GPIIb-IIIa-specific integrin antagonist from the venom of Sistrurus m. barbouri. J Biol Chem. 1991 May 25;266(15):9359-62.
• [6] Eptifibatide in peripheral vascular interventions: results of the Integrilin Reduces Inflammation in Peripheral Vascular Interventions (INFLAME) trial. J Invasive Cardiol. 2006 Jan;18(1):6-12.
• [7] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [8] Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. Br J Pharmacol. 2007 Jul;151(6):737-48.
• [9] Erythromycin interaction with risperidone or clomipramine in an adolescent. J Child Adolesc Psychopharmacol. 1996 Summer;6(2):133-8.
• [10] Role of human UGT2B10 in N-glucuronidation of tricyclic antidepressants, amitriptyline, imipramine, clomipramine, and trimipramine. Drug Metab Dispos. 2010 May;38(5):863-70.
• [11] The biotransformation of clomipramine in vitro, identification of the cytochrome P450s responsible for the separate metabolic pathways. J Pharmacol Exp Ther. 1996 Jun;277(3):1659-64.
• [12] Serum clomipramine and desmethylclomipramine levels in a CYP2C19 and CYP2D6 intermediate metabolizer. Pharmacogenomics. 2017 May;18(7):601-605.