503146-00-7Relevant articles and documents
Structure-Based Discovery of a Subtype-Selective Inhibitor Targeting a Transient Receptor Potential Vanilloid Channel
Chai, Hao,Cheng, Xi,Zhou, Bin,Zhao, Lifen,Lin, Xianhua,Huang, Dongping,Lu, Weiqiang,Lv, Hao,Tang, Feng,Zhang, Qiansen,Huang, Wei,Li, Yang,Yang, Huaiyu
, p. 1373 - 1384 (2019)
Discovery of potent selective inhibitors targeting a protein from a highly conserved family is challenging. Using a strategy combining structural and evolutionary information, we discovered transient receptor potential (TRP) subtype-selective inhibitors (transient receptor potential vanilloid type 2 (TRPV2) inhibitors). We unveiled three ligand-binding sites of TRPV2 and compounds that bind to these sites. Structural optimization of the best-hit compound provided a potent selective TRPV2 inhibitor, SET2. The molecular basis and subtype-selective inhibition mechanism were quantitatively characterized and experimentally verified. Then, as an effective chemical probe, SET2 was used to investigate the function role of TRPV2. SET2-induced inhibition of TRPV2 reduced prostate cancer migration, which indicated TRPV2 as an antimetastasis therapeutic target. In addition, functional assays suggested that TRPV2 was coupled to a validated metastasis mediator, LPAR1. The discovery of the potent selective inhibitor potentially leads to novel avenues for pharmacological applications and therapeutic development targeting the TRPV2 channel.
THIAZOLIDINE DERIVATIVE AND MEDICINAL USE THEREOF
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Page 29-30, (2010/02/07)
A thiazolidine derivative represented by the formula (I) wherein each symbol is as defined in the specification, and a pharmaceutically acceptable salt thereof exhibit a potent DPP-IV inhibitory activity, and can be provided as an agent for the prophylaxis or treatment of diabetes, an agent for the prophylaxis or treatment of obesity and the like.
