3v5q
Discovery of a selective TRK Inhibitor with efficacy in rodent cancer tumor modelsDiscovery of a selective TRK Inhibitor with efficacy in rodent cancer tumor models
Structural highlights
Function[NTRK3_HUMAN] Receptor for neurotrophin-3 (NT-3). This is a tyrosine-protein kinase receptor. Known substrates for the trk receptors are SHC1, PI-3 kinase, and PLCG1. The different isoforms do not have identical signaling properties. Publication Abstract from PubMedNeurotrophins and their receptors (TRKs) play key roles in the development of the nervous system and the maintenance of the neural network. Accumulating evidence points to their role in malignant transformations, chemotaxis, metastasis, and survival signaling and may contribute to the pathogenesis of a variety of tumors of both neural and non-neural origin. By screening the GNF kinase collection, a series of novel oxindole inhibitors of TRKs were identified. Optimization led to the identification of GNF-5837 (22), a potent, selective, and orally bioavailable pan-TRK inhibitor that inhibited tumor growth in a mouse xenograft model derived from RIE cells expressing both TRKA and NGF. The properties of 22 make it a good tool for the elucidation of TRK biology in cancer and other nononcology indications. Discovery of GNF-5837, a Selective TRK Inhibitor with Efficacy in Rodent Cancer Tumor Models.,Albaugh P, Fan Y, Mi Y, Sun F, Adrian F, Li N, Jia Y, Sarkisova Y, Kreusch A, Hood T, Lu M, Liu G, Huang S, Liu Z, Loren J, Tuntland T, Karanewsky DS, Seidel HM, Molteni V ACS Med Chem Lett. 2012 Jan 1;3(2):140-5. doi: 10.1021/ml200261d. eCollection, 2012 Feb 9. PMID:24900443[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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