Targeting tropomyosin receptor kinase for cancer therapy

Eur J Med Chem. 2019 Aug 1:175:129-148. doi: 10.1016/j.ejmech.2019.04.053.

Qi Miao ¹, Kun Ma ², Dong Chen ¹, Xiaoxing Wu ³, Sheng Jiang ⁴

Affiliations

1 State Key Laboratory of Natural Medicines and Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, China.
2 Center for Drug Evaluation, China Food and Drug Administration, Beijing, 100038, China.
3 State Key Laboratory of Natural Medicines and Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, China. Electronic address: wu_xiaoxing@hotmail.com.
4 State Key Laboratory of Natural Medicines and Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, China. Electronic address: jiangsh9@gmail.com.

PMID: 31077998 DOI: 10.1016/j.ejmech.2019.04.053

Abstract

NTRKs and their expression product tropomyosin receptor kinases (Trks) are widely distributed in mammals. While neural growth factor (NGF)-induced normal Trk activation plays a key role in nerve growth, NTRK alternations occurring in tumor cells were highly correlated to tumor progression and invasion. Recent clinical data from several pan-Trk inhibitors have demonstrated potential and broad applications in various cancers. This intrigues us to summarize the development of inhibitors targeting Trks with different mechanisms of action and their applications in Cancer therapy. We believe that this perspective would be of great help in investigating novel Anticancer drugs with better therapeutic index.

Keywords

Gene alterations; Neoplasm; Receptor kinase inhibitor; Tropomyosin receptor kinase.

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