RET-IN-33

RET-IN-33 is a moderately selective inhibitor of RET mutants. RET-IN-33 potently inhibits G810 mutants, with IC₅₀ values of 4.43 nM (G810R), 3.28 nM (G810C) and 0.51 nM (G810S), respectively. RET-IN-33 also inhibits other RET mutants: V804M (IC₅₀ 0.73 nM), V804L (IC₅₀ 0.36 nM), Y806H (IC₅₀ 0.74 nM) and M918T (IC₅₀ 0.55 nM). RET-IN-33 also inhibits other kinases, with an IC₅₀ of 1.50 nM against VEGFR2 and 1.60 nM against PDGFRα. RET-IN-33 blocks the autophosphorylation of RET mutants and the downstream SHC/AKT/ERK signaling pathway. RET-IN-33 selectively inhibits the proliferation of RET-driven cell models without affecting non-RET-dependent or normal cells. RET-IN-33 exhibits dose-dependent antitumor efficacy in RET-driven xenograft models. RET-IN-33 can be used for the research of medullary thyroid carcinoma, papillary thyroid carcinoma and non-small cell lung cancer^[1].