Pralsetinib CAS# 2097132-94-8 BLU-667(拉西替尼)

Pralsetinib (BLU-667) is a potent, selective, orally bioavailable RET kinase inhibitor. In preclinical biochemical assays, it inhibited wild-type RET with an IC50 of ~0.4 nM and retained strong activity against RET fusions and activating mutations, including RET V804M/L gatekeeper variants. It showed >100-fold selectivity over other kinases. In RET-driven cancer cell lines, pralsetinib suppressed RET phosphorylation and downstream MAPK signaling, leading to growth inhibition and apoptosis (IC50 values <10 nM). In xenograft mouse models of RET fusion–positive or mutant tumors, oral pralsetinib induced marked tumor regression. Pharmacokinetic studies demonstrated good oral exposure and sustained target inhibition, supporting clinical development.