دورية أكاديمية
Identification of BR102910 as a selective fibroblast activation protein (FAP) inhibitor.
| العنوان: | Identification of BR102910 as a selective fibroblast activation protein (FAP) inhibitor. |
|---|---|
| المؤلفون: | Jung HJ; Research Center, Boryung Pharmaceuticals Co. Ltd., Ansan 15425, Republic of Korea; School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea. Electronic address: yesjin00@naver.com., Nam EH; Research Center, Boryung Pharmaceuticals Co. Ltd., Ansan 15425, Republic of Korea., Park JY; Research Center, Boryung Pharmaceuticals Co. Ltd., Ansan 15425, Republic of Korea., Ghosh P; School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea., Kim IS; School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea. Electronic address: insukim@skku.edu. |
| المصدر: | Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2021 Apr 01; Vol. 37, pp. 127846. Date of Electronic Publication: 2021 Feb 09. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Ltd Country of Publication: England NLM ID: 9107377 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1464-3405 (Electronic) Linking ISSN: 0960894X NLM ISO Abbreviation: Bioorg Med Chem Lett Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Oxford : Elsevier Science Ltd Original Publication: Oxford ; New York : Pergamon Press, c1991- |
| مواضيع طبية MeSH: | Membrane Proteins/*antagonists & inhibitors, Animals ; Dose-Response Relationship, Drug ; Endopeptidases/metabolism ; Membrane Proteins/metabolism ; Mice ; Mice, Inbred C57BL ; Molecular Structure ; Structure-Activity Relationship |
| مستخلص: | Fibroblast activation protein (FAP) belongs to the family of prolyl-specific serine proteases and displays both exopeptidase and endopeptidase activities. FAP expression is undetectable in most normal adult tissues, but is greatly upregulated in sites of tissue remodeling, which include fibrosis, inflammation and cancer. Due to its restricted expression pattern and dual enzymatic activities, FAP inhibition is investigated as a therapeutic option for several diseases. In the present study, we described the structure-activity relationship of several synthesized compounds against DPPIV and prolyl oligopeptidase (PREP). In particular, BR102910 (compound 24) showed nanomolar potency and high selectivity. Moreover, the in vivo FAP inhibition study of BR102910 (compound 24) using C57BL/6J mice demonstrated exceptional profiles and satisfactory FAP inhibition efficacy. Based on excellent in vitro and in vivo profiles, the potential of BR102910 (compound 24) as a lead candidate for the treatment of type 2 diabetes is considered. (Copyright © 2021 Elsevier Ltd. All rights reserved.) |
| فهرسة مساهمة: | Keywords: DPPIV; FAP inhibitor; Fibroblast activation protein; Fibroblast growth factor 21; PREP |
| المشرفين على المادة: | 0 (Membrane Proteins) EC 3.4.- (Endopeptidases) EC 3.4.21.- (fibroblast activation protein alpha) |
| تواريخ الأحداث: | Date Created: 20210211 Date Completed: 20210825 Latest Revision: 20210825 |
| رمز التحديث: | 20240829 |
| DOI: | 10.1016/j.bmcl.2021.127846 |
| PMID: | 33571650 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1464-3405 |
|---|---|
| DOI: | 10.1016/j.bmcl.2021.127846 |