2. Academic Validation
  3. Discovery of GNF-5837, a Selective TRK Inhibitor with Efficacy in Rodent Cancer Tumor Models

Discovery of GNF-5837, a Selective TRK Inhibitor with Efficacy in Rodent Cancer Tumor Models

  • ACS Med Chem Lett. 2012 Jan 1;3(2):140-5. doi: 10.1021/ml200261d.
Pam Albaugh 1,  Yi Fan 1,  Yuan Mi 1,  Fangxian Sun 1,  Francisco Adrian 1,  Nanxin Li 1,  Yong Jia 1,  Yelena Sarkisova 1,  Andreas Kreusch 1,  Tami Hood 1,  Min Lu 1,  Guoxun Liu 1,  Shenlin Huang 1,  Zuosheng Liu 1,  Jon Loren 1,  Tove Tuntland 1,  Donald S Karanewsky 1,  H Martin Seidel 1,  Valentina Molteni 1
Affiliations

Affiliation

  • 1 Genomics Institute of the Novartis Research Foundation (GNF), 10675 John Jay Hopkins Drive, San Diego, California 92121, United States.
PMID: 24900443 DOI: 10.1021/ml200261d
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.

Keywords

GNF-5837; NGF; TRK; neurotrophins; oxindole; tropomyosin receptor kinase.

Figures
Products