Hangzhou JINLAN Pharm-Drugs Technology Co., Ltd

1. Core Identifier Common Name: Pazopanib English Abbreviation: PAZ CAS Number: 444731-52-6 Chemical Name: 5-[[4-[(2,3-dimethyl-2H-indazole-6-yl)methylamino]-2-pyrimidinyl]amino]-2-methylbenzenesulfonamide Molecular Formula: C₂₄H₂₄N₈O₂S Molecular Weight: 476.56 g/mol Chemical Structural Characteristics: Belongs to the pyrimidinazole class of TKIs. The molecule contains three key active structures that determine its multi-target inhibitory properties: Pyrimidine ring core: Forms hydrogen bonds with the hinge region of the tyrosine kinase ATP binding site (such as Cys919 of VEGFR2), which is the basis for target binding; 2,3-dimethylindazole side chain: Embedded in the hydrophobic pocket of the kinase, enhancing the selectivity for VEGFR/PDGFR (for VEGFR2). The IC₅₀ for EGFR is 10 nM, which is much lower than the IC₅₀ for EGFR (>1000 nM). The benzenesulfonamide group forms an electrostatic interaction with basic amino acids (such as Lys868) at the kinase active site, further enhancing binding affinity. The molecule contains one chiral center (a methyl carbon adjacent to the indazole ring), but the racemic form is used clinically (the (R)- and (S)- types have similar inhibitory activities, so chiral resolution is not required), and only diastereomeric impurities need to be controlled.