Pz-1 is a potent, dual pan-RET/VEGFR2 kinase inhibitor with IC50s of <1 nM for all RET, RET V804M and VEGFR2.
Pz-1 displays good global kinase selectivity with only 7 kinases against a 91 kinase panel at 50 nM, strongly inhibites phosphorylation of RET and mutant RET oncoproteins at 1 nM in cell-based assays, inhibits RETC634Y NIH3T3 fibroblast proliferation with IC50 of 0.5 nM.
Pz-1 abrogates the formation of tumors induced by RET-mutant fibroblasts and blocks the phosphorylation of both RET and VEGFR2 in tumor tissue at 1.0 mg/kg without detectable toxicity.
