Pralsetinib

Pralsetinib (BLU-667) is a highly potent, selective RET inhibitor (IC50s: 0.4, 0.3, 0.4, 0.4, and 0.4 nM for WT RET, RET mutants V804L, V804M, M918T and CCDC6-RET fusion) .Pralsetinib demonstrates more than 10-fold increased potency over approved MKIs against oncogenic RET variants and resistance mutants. Pralsetinib 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 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) .Pralsetinib potently inhibits the growth of NSCLC and thyroid cancer xenografts driven by various RET mutations and fusions without inhibiting VEGFR-2. Pralsetinib shows 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. (In Vitro) :Pralsetinib (BLU-667) demonstrates more than 10-fold increased potency over approved MKIs against oncogenic RET variants and resistance mutants.Pralsetinib (BLU-667) 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 (BLU-667) 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) . (In Vivo) :Pralsetinib (BLU-667) 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 (BLU-667) shows 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.

2097132-94-8

Blu667

Pharmacology & Drug Discovery

>98% (HPLC)

DMSO:95 mg/mL (178.04 mM)

COC1 (CCC (CC1) C1=NC (C) =CC (NC2=NNC (C) =C2) =N1) C (=O) N[C@@H] (C) C1=CN=C (C=C1) N1C=C (F) C=N1

C27H30FN9O2

533.6

Storage temperature: -20°C. Stability: ≥ 2 years