Details of the Drug Combination

General Information of Drug Combination (ID: DC24OPM)

• Drug Combination Name: Pazopanib HCl + Raltegravir
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Pazopanib HCl (DM6U9CQ): Small molecular drug
  Raltegravir (DMYURI6): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 6.2
  Bliss Independence Score: 6.2
  Loewe Additivity Score: 20.2
  LHighest Single Agent (HSA) Score: 20.2

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Pazopanib HCl

Disease Entry	ICD 11	Status	REF
Renal cell carcinoma	2C90	Approved	[2]

Pazopanib HCl Interacts with 3 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Platelet-derived growth factor receptor (PDGFR)	TTI2WET	NOUNIPROTAC	Inhibitor	[2]
Tyrosine-protein kinase Kit (KIT)	TTX41N9	KIT_HUMAN	Inhibitor	[2]
Vascular endothelial growth factor receptor 2 (KDR)	TTUTJGQ	VGFR2_HUMAN	Inhibitor	[2]

Pazopanib HCl Interacts with 3 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[4]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[4]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[5]

Indication(s) of Raltegravir

Disease Entry	ICD 11	Status	REF
Human immunodeficiency virus infection	1C62	Approved	[3]

Raltegravir Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human immunodeficiency virus Integrase (HIV IN)	TT5FH9Y	POL_HV1B1	Modulator	[3]

Raltegravir Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[7]
Cytochrome P450 1A1 (CYP1A1)	DE6OQ3W	CP1A1_HUMAN	Metabolism	[8]

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] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [3] 2007 FDA drug approvals: a year of flux. Nat Rev Drug Discov. 2008 Feb;7(2):107-9.
• [4] Bioavailability, metabolism and disposition of oral pazopanib in patients with advanced cancer. Xenobiotica. 2013 May;43(5):443-53.
• [5] Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. Pharmacol Rev. 2011 Mar;63(1):157-81.
• [6] Population pharmacokinetic analysis and pharmacogenetics of raltegravir in HIV-positive and healthy individuals. Antimicrob Agents Chemother. 2012 Jun;56(6):2959-66. doi: 10.1128/AAC.05424-11. Epub 2012 Feb 27.
• [7] Successful tacrolimus treatment following renal transplant in a HIV-infected patient with raltegravir previously treated with a protease inhibitor based regimen. Drug Metabol Drug Interact. 2011;26(3):139-41.
• [8] Exposure-related effects of atazanavir on the pharmacokinetics of raltegravir in HIV-1-infected patients. Ther Drug Monit. 2010 Dec;32(6):782-6.