Selitrectinib

Selitrectinib (CAS No.: 2097002-61-2) is a synthetic small-molecule, second-generation ATP-competitive inhibitor of the tropomyosin receptor kinase (TRK) family, also known as LOXO?195 or BAY 2731954, intended for kinase signaling analysis in biomedical research and drug discovery, as well as oncology-related target validation. By inhibiting the catalytic activity of the kinase domains of TrkA, TrkB, and TrkC, it blocks neurotrophin-driven signaling mediated by receptors encoded by NTRK1, NTRK2, and NTRK3, thereby reducing functional readouts of downstream pathways such as MAPK/ERK, PI3K/AKT, and PLCγ; this molecule was designed to maintain inhibitory activity against acquired resistance substitution sites, and it retains potent activity against multiple reported TRK mutants (such as TrkA G595R, G667C and TrkC G623R, G696A). In in vitro biochemical and cellular assays, it exhibits inhibitory activity against TRK isoforms and related resistance variants in the subnanomolar to low-nanomolar range, and selectively inhibits proliferation or signal transduction at nanomolar levels in TRK fusion-positive cell models, while showing limited effects in TRK fusion-negative cell lines up to high micromolar concentrations; it also demonstrates more than thousand-fold selectivity over the vast majority of non-TRK kinases. Typical research applications include in vitro kinase profiling and pathway intervention studies, validation of TRK dependence in engineered or fusion-positive cells, evaluation of acquired resistance mechanisms and structure-activity relationships, and mechanistic assessment in animal models in combination with pharmacodynamic biomarkers; the concentrations or doses used in experiments generally depend on the research objective and system conditions, and optimization is recommended for each cell system or in vivo protocol. This product is for laboratory research use only and is not intended for human or veterinary use.