Nobuo Watanabe, Yoshiko Shinozaki, Sanae Ogiwara, Riko Miyagasako, Ayumi Sasaki, Yusuke Suzuki, Junko Kato, Natsuko Fukunishi, Yoshinori Okada, Takeshi Saito, Yumi Iida, Misaki Higashiseto, Haruchika Masuda, Kazuhito Goto, Mari Amino, Tomoatsu Tsuji, Seiji Morita, Eiichiro Nagata, Yoshihide Nakagawa, Noriaki Hirayama, Sadaki Inokuchi
Platelet C-type lectin-like receptor 2 (CLEC-2) induces platelet activation and aggregation after clustering by its ligand podoplanin (PDPN). PDPN, which is not normally expressed in cells in contact with blood flow, is induced in inflammatory immune cells and some malignant tumor cells, thereby increasing the risk of venous thromboembolism (VTE) and tumor metastasis. Therefore, small-molecule compounds that can interfere with the PDPN-CLEC-2 axis have the potential to become selective antiplatelet agents. Using molecular docking analysis of CLEC-2 and a PDPN-CLEC-2 binding-inhibition assay, we identified a group of diphenyl-tetrazol-propanamide derivatives as novel CLEC-2 inhibitors...
November 15, 2023: Thrombosis and Haemostasis