3V5Q: Discovery of a selective TRK Inhibitor with efficacy in rodent cancer tumor models

Citation:
Abstract
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.
PDB ID: 3V5QDownload
MMDB ID: 97120
PDB Deposition Date: 2011/12/16
Updated in MMDB: 2018/02
Experimental Method:
x-ray diffraction
Resolution: 2.2001  Å
Source Organism:
Similar Structures:
Biological Unit for 3V5Q: monomeric; determined by author and by software (PISA)
Molecular Components in 3V5Q
Label Count Molecule
Protein (1 molecule)
1
Nt-3 Growth Factor Receptor(Gene symbol: NTRK3)
Molecule annotation
Chemicals (2 molecules)
1
1
2
1
* Click molecule labels to explore molecular sequence information.

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