Pralsetinib (Blu667)

Pralsetinib (Blu667) is a highly potent and selective RET inhibitor with an IC50 of 0.4 nM for wild type RET kinase.

Pralsetinib (Blu667) is a RET inhibitor extracted from patent US20170121312A1, compound example 129[1]. Pralsetinib (Blu667) demonstrates more than 10-fold increased potency over approved MKIs against oncogenic RET variants and resistance mutants. Pralsetinib (Blu667) demonstrates potent activity (IC50=0.4 nM) against common oncogenic RET alterations, including RET M918T, an activating mutation found in MTC, as well as the CCDC6-RET fusion observed in PTC and NSCLC. Pralsetinib (Blu667) suppresses RET pathway signaling in a panel of RET-driven cell lines: LC2/ad (CCDC6-RET, NSCLC), MZ-CRC-1 (RET M918T, MTC), and TT (RET C634W, MTC)[2].

Pralsetinib (Blu667) potently inhibits growth of NSCLC and thyroid cancer xenografts driven by various RET mutations and fusions without inhibiting vascular endothelial growth factor receptor 2 (VEGFR-2). Pralsetinib (Blu667) showed potent dose dependent activity against both KIF5B-RET Ba/F3 and KIF5B-RET V804L Ba/F3 allograft tumors with doses as low as 10 mg/kg twice-daily[2].

[1]. Brumaker J, et al. Inhibitors of ret. US20170121312A1. [2]. Subbiah V, et al. Precision Targeted Therapy With BLU-667 for RET-Driven Cancers. American Association for Cancer Research. 10.1158/2159-8290.CD-18-0338.