Pz-1 is a potent RET and VEGFR2 inhibitor with IC 50 s of less than 1 nM for both wild type kinases.
In Vitro
Pz-1 is a Type-II tyrosine kinase inhibitor, able to bind the DFG-out conformation of the kinase. In cell-based assays, 1.0 nM of Pz-1 strongly inhibits tyrosine phosphorylation of VEGFR2 and clinically relevant RET mutants, including those refractory to vandetanib and cabozantinib (RET V804M and RET V804L ). MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
Pz-1 is shown active on VEGFR2, which can block blood supply required for RET-stimulated growth. At 1.0 mg/kg/day per os, Pz-1 abrogates formation of tumors induced by RET-mutant fibroblasts and blocks phosphorylation of both RET and VEGFR2 in tumor tissue. Pz-1 features no detectable toxicity up to 100.0 mg/kg, which indicates a large therapeutic window . MCE has not independently confirmed the accuracy of these methods. They are for reference only.
