1243255-28-8Relevant articles and documents
Substituted 4-carboxymethylpyroglutamic acid diamides as potent and selective inhibitors of fibroblast activation protein
Tsai, Ting-Yueh,Yeh, Teng-Kuang,Chen, Xin,Hsu, Tsu,Jao, Yu-Chen,Huang, Chih-Hsiang,Song, Jen-Shin,Huang, Yu-Chen,Chien, Chia-Hui,Chiu, Jing-Huai,Yen, Shih-Chieh,Tang, Hung-Kuan,Chao, Yu-Sheng,Jiaang, Weir-Torn
supporting information; experimental part, p. 6572 - 6583 (2010/11/17)
Fibroblast activation protein (FAP) belongs to the prolyl peptidase family. FAP inhibition is expected to become a new antitumor target. Most known FAP inhibitors often resemble the dipeptide cleavage products, with a boroproline at the P1 site; however, these inhibitors also inhibit DPP-IV, DPP-II, DPP8, and DPP9. Potent and selective FAP inhibitor is needed in evaluating that FAP as a therapeutic target. Therefore, it is important to develop selective FAP inhibitors for the use of target validation. To achieve this, optimization of the nonselective DPP-IV inhibitor 8 led to the discovery of a new class of substituted 4-carboxymethylpyroglutamic acid diamides as FAP inhibitors. SAR studies resulted in a number of FAP inhibitors having IC50 of 50 > 100 μM). Compounds 18a, 18b, and 19 are the only known potent and selective FAP inhibitors, which prompts us to further study the physiological role of FAP.
