Details of the Drug

General Information of Drug (ID: DMF57DM)

Drug Name
Pazopanib
Synonyms
Pazopanib; Pazopanib (GW-786034); 444731-52-6; 5-((4-((2,3-dimethyl-2H-indazol-6-yl)(methyl)amino)pyrimidin-2-yl)amino)-2-methylbenzenesulfonamide; 5-(4-((2,3-dimethyl-2H-indazol-6-yl)(methyl)amino)pyrimidin-2-ylamino)-2-methylbenzenesulfonamide; 5-[[4-[(2,3-dimethylindazol-6-yl)-methyl-amino]pyrimidin-2-yl]amino]-2-methyl-benzenesulfonamide; 790713-33-6; 7RN5DR86CK; CHEBI:71219; DSSTox_CID_28659; DSSTox_GSID_48733; DSSTox_RID_82929; GW 78603; GW 786034; GW-786034; GW786034; MFCD11616589; NCGC00188865-01; UNII-7RN5DR86CK
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 437.5
Logarithm of the Partition Coefficient (xlogp) 3.1
Rotatable Bond Count (rotbonds) 5
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 8
ADMET Property
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [1]
Clearance
The drug present in the plasma can be removed from the body at the rate of 0.06 mL/min/kg [2]
Half-life
The concentration or amount of drug in body reduced by one-half in 35 hours [2]
Metabolism
The drug is metabolized via the CYP3A4 and to a lesser extent by CYP1A2 and CYP2C8 []
Unbound Fraction
The unbound fraction of drug in plasma is 0.01% [2]
Vd
The volume of distribution (Vd) of drug is 11.1 L []
Adverse Drug Reaction (ADR)
ADR Term Variation Related DOT DOT ID REF
Hemorrhage rs3064744 UGT1A1 OTH1C8OJ [3]
Hepatotoxicty rs2395029 HCP5 OTV0YRI8 [4]
Chemical Identifiers
Formula
C21H23N7O2S
IUPAC Name
5-[[4-[(2,3-dimethylindazol-6-yl)-methylamino]pyrimidin-2-yl]amino]-2-methylbenzenesulfonamide
Canonical SMILES
CC1=C(C=C(C=C1)NC2=NC=CC(=N2)N(C)C3=CC4=NN(C(=C4C=C3)C)C)S(=O)(=O)N
InChI
CUIHSIWYWATEQL-UHFFFAOYSA-N
InChIKey
1S/C21H23N7O2S/c1-13-5-6-15(11-19(13)31(22,29)30)24-21-23-10-9-20(25-21)27(3)16-7-8-17-14(2)28(4)26-18(17)12-16/h5-12H,1-4H3,(H2,22,29,30)(H,23,24,25)
Cross-matching ID
PubChem CID
10113978
ChEBI ID
CHEBI:71219
CAS Number
444731-52-6
DrugBank ID
DB06589
INTEDE ID
DR1248
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4)
Main DME 		DE4LYSA CP3A4_HUMAN Substrate [5]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Substrate [6]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Substrate [5]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Substrate [5]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Gene/Protein Processing [7]
Cytochrome P450 1A1 (CYP1A1) OTE4EFH8 CP1A1_HUMAN Gene/Protein Processing [8]
Cytochrome P450 1B1 (CYP1B1) OTYXFLSD CP1B1_HUMAN Gene/Protein Processing [8]
Cytochrome P450 2B6 (CYP2B6) OTOYO4S7 CP2B6_HUMAN Gene/Protein Processing [9]
Cytochrome P450 2C8 (CYP2C8) OTHCWT42 CP2C8_HUMAN Gene/Protein Processing [9]
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Gene/Protein Processing [9]
HLA class I histocompatibility antigen protein P5 (HCP5) OTV0YRI8 HCP5_HUMAN Drug Response [4]
Interleukin-1 beta (IL1B) OT0DWXXB IL1B_HUMAN Protein Interaction/Cellular Processes [10]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Post-Translational Modifications [11]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Post-Translational Modifications [11]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

References

1 BDDCS predictions, self-correcting aspects of BDDCS assignments, BDDCS assignment corrections, and classification for more than 175 additional drugs
2 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
3 Pazopanib-induced hyperbilirubinemia is associated with Gilbert's syndrome UGT1A1 polymorphism. Br J Cancer. 2010 Apr 27;102(9):1371-7. doi: 10.1038/sj.bjc.6605653. Epub 2010 Apr 13.
4 HLA-B*57:01 Confers Susceptibility to Pazopanib-Associated Liver Injury in Patients with Cancer. Clin Cancer Res. 2016 Mar 15;22(6):1371-7. doi: 10.1158/1078-0432.CCR-15-2044. Epub 2015 Nov 6.
5 Pazopanib, a new therapy for metastatic soft tissue sarcoma. Expert Opin Pharmacother. 2013 May;14(7):929-35.
6 Pazopanib: the newest tyrosine kinase inhibitor for the treatment of advanced or metastatic renal cell carcinoma. Drugs. 2011 Mar 5;71(4):443-54.
7 Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development. Toxicol Sci. 2010 Dec; 118(2):485-500.
8 Association of CYP1A1 and CYP1B1 inhibition in in vitro assays with drug-induced liver injury. J Toxicol Sci. 2021;46(4):167-176. doi: 10.2131/jts.46.167.
9 Identification of approved drugs as potent inhibitors of pregnane X receptor activation with differential receptor interaction profiles. Arch Toxicol. 2018 Apr;92(4):1435-1451.
10 Activation of inflammasomes by tyrosine kinase inhibitors of vascular endothelial growth factor receptor: Implications for VEGFR TKIs-induced immune related adverse events. Toxicol In Vitro. 2021 Mar;71:105063. doi: 10.1016/j.tiv.2020.105063. Epub 2020 Dec 1.
11 MEK inhibition abrogates sunitinib resistance in a renal cell carcinoma patient-derived xenograft model. Br J Cancer. 2016 Oct 11;115(8):920-928. doi: 10.1038/bjc.2016.263. Epub 2016 Aug 25.