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Ref Type Journal Article
PMID (24900443)
Authors 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
Title Discovery of GNF-5837, a Selective TRK Inhibitor with Efficacy in Rodent Cancer Tumor Models.
Journal Vol Issue Date Pages Journal Short Title
ACS medicinal chemistry letters 3 2 2012 Feb 9 140-5 ACS Med Chem Lett
URL
Abstract Text Neurotrophins 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.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
GNF-5837 GNF-5837 1 0
Drug Name Trade Name Synonyms Drug Classes Drug Description
GNF-5837 Trk Receptor Inhibitor (Pan) 33 GNF-5837 is a small molecule inhibitor of tropomyosin receptor kinases NTRK1 (TRKA), NTRK2 (TRKB), and NTRK3 (TRKC), preventing proliferation of cancer cell models (PMID: 24900443, PMID: 31485624).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
NTRK1 positive gastrointestinal system cancer sensitive GNF-5837 Preclinical - Cell line xenograft Actionable In a preclinical study, GNF-5837 prevented proliferation of transformed rat intestinal epithelial cells expressing Ntrk1 in culture and in xenograft mouse models (PMID: 24900443). 24900443