Details of the Drug Combination

General Information of Drug Combination (ID: DCL7OFC)

• Drug Combination Name: Pazopanib HCl + Aminosalicylic Acid
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Pazopanib HCl (DM6U9CQ): Small molecular drug
  Aminosalicylic Acid (DMENSL5): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 3.56
  Bliss Independence Score: 3.56
  Loewe Additivity Score: 18.45
  LHighest Single Agent (HSA) Score: 18.46

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	[5]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[5]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[6]

Indication(s) of Aminosalicylic Acid

Disease Entry	ICD 11	Status	REF
Crohn disease	DD70	Approved	[3]
Inflammatory bowel disease	DD72	Approved	[4]
Pulmonary and extrapulmonary tuberculosis	1B10.Z	Approved	[4]
Pulmonary tuberculosis	1B10.Z	Approved	[3]
Ulcerative colitis	DD71	Approved	[3]

Aminosalicylic Acid Interacts with 3 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Dihydrofolate reductase (DHFR)	TTYZVDJ	DYR_HUMAN	Modulator	[7]
Prostaglandin G/H synthase 1 (COX-1)	TT8NGED	PGH1_HUMAN	Modulator	[7]
Prostaglandin G/H synthase 2 (COX-2)	TTVKILB	PGH2_HUMAN	Modulator	[7]

Aminosalicylic Acid Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Sodium-coupled neutral amino acid transporter 3 (SLC38A3)	DTKWJH3	S38A3_HUMAN	Substrate	[8]

Aminosalicylic Acid Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
N-acetyltransferase 2 (NAT2)	DER7TA0	ARY2_HUMAN	Metabolism	[9]

Aminosalicylic Acid Interacts with 9 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Proepiregulin (EREG)	OTRM4NQY	EREG_HUMAN	Increases Expression	[10]
Antileukoproteinase (SLPI)	OTUNFUU8	SLPI_HUMAN	Increases Expression	[10]
Hepatocyte growth factor receptor (MET)	OT7K55MU	MET_HUMAN	Increases Expression	[10]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[10]
Bone morphogenetic protein 6 (BMP6)	OT9WN536	BMP6_HUMAN	Increases Expression	[10]
Interleukin-24 (IL24)	OT4VUWH1	IL24_HUMAN	Increases Expression	[10]
PTB-containing, cubilin and LRP1-interacting protein (PID1)	OT5YJ7FI	PCLI1_HUMAN	Increases Expression	[10]
Cystine/glutamate transporter (SLC7A11)	OTKJ6PXW	XCT_HUMAN	Increases Expression	[10]
Arylamine N-acetyltransferase 1 (NAT1)	OTCCNQ3H	ARY1_HUMAN	Increases Acetylation	[11]

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] Aminosalicylic acid FDA Label
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [5] Bioavailability, metabolism and disposition of oral pazopanib in patients with advanced cancer. Xenobiotica. 2013 May;43(5):443-53.
• [6] Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. Pharmacol Rev. 2011 Mar;63(1):157-81.
• [7] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [8] Identification of amino acids imparting acceptor substrate selectivity to human arylamine acetyltransferases NAT1 and NAT2. Biochem J. 2000 May 15;348 Pt 1:159-66.
• [9] Importance of the evaluation of N-acetyltransferase enzyme activity prior to 5-aminosalicylic acid medication for ulcerative colitis. Inflamm Bowel Dis. 2016 Aug;22(8):1793-802.
• [10] An in vitro coculture system of human peripheral blood mononuclear cells with hepatocellular carcinoma-derived cells for predicting drug-induced liver injury. Arch Toxicol. 2021 Jan;95(1):149-168. doi: 10.1007/s00204-020-02882-4. Epub 2020 Aug 20.
• [11] Eukaryotic arylamine N-acetyltransferase. Investigation of substrate specificity by high-throughput screening. Biochem Pharmacol. 2005 Jan 15;69(2):347-59. doi: 10.1016/j.bcp.2004.09.014. Epub 2004 Nov 24.