Identification and characterization of potent and selective inhibitors targeting protein tyrosine phosphatase 1B (PTP1B)
文献类型：期刊论文
| 作者 | Jin, Jia1,2; Ye, Xiaoqing1,3; Boateng, Derrick1; Dai, Kaili1; Ye, Fei1; Du, Pengfei4; Yu, Han5 |
| 刊名 | BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
 |
| 出版日期 | 2019-08-15 |
| 卷号 | 29期号:16页码:2358-2363 |
| 关键词 | PTP1B TCPTP Type 2 diabetes Selective inhibitors Dihydropyridine thione |
| ISSN号 | 0960-894X |
| DOI | 10.1016/j.bmcl.2019.06.011 |
| 文献子类 | Article |
| 英文摘要 | Protein tyrosine phosphatase 1B (PTP1B) plays an important role in the negative regulation of insulin and leptin signaling. The development of small molecular inhibitors targeting PTP1B has been validated as a potential therapeutic strategy for Type 2 diabetes (T2D). In this work, we have identified a series of compounds containing dihydropyridine thione and particular chiral structure as novel PTP1B inhibitors. Among those, compound 4b showed moderate activity with IC50 value of 3.33 mu M and meanwhile with good selectivity ( > 30-fold) against TCPTP. The further MOA study of PTP1B demonstrated that compounds 4b is a substrate-competitive inhibitor. The binding mode analysis suggested that compound 4b simultaneously occupies the active site and the second phosphotyrosine (pTyr) binding site of PTP1B. Furthermore, the cell viability assay of compound 4b showed tolerable cytotoxicity in L02 cells, thus 4b may be prospectively used to further in vivo study. |
| WOS关键词 | OLEANOLIC ACID-DERIVATIVES ; BIOLOGICAL EVALUATION ; NEGATIVE REGULATOR ; STRUCTURAL BASIS ; IN-VIVO ; INSULIN |
| WOS研究方向 | Pharmacology & Pharmacy ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000480235700063 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/309423]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Jin, Jia; Du, Pengfei; Yu, Han |
| 作者单位 | 1.Zhejiang Sci Tech Univ, Coll Life Sci & Med, Hangzhou 310018, Zhejiang, Peoples R China; 2.Zhejiang Prov Key Lab Silkworm Bioreactor & Biome, Hangzhou 310018, Zhejiang, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Materta Med, State Key Lab Drug Res, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China; 4.Jiaxing Univ, Affiliated Hosp 2, Dept Endocrinol, Jiaxing 314000, Peoples R China; 5.Shanghai Inst Technol, Sch Chem & Environm Engn, Shanghai 201418, Peoples R China |
| 推荐引用方式 GB/T 7714 | Jin, Jia,Ye, Xiaoqing,Boateng, Derrick,et al. Identification and characterization of potent and selective inhibitors targeting protein tyrosine phosphatase 1B (PTP1B)[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,2019,29(16):2358-2363. |
| APA | Jin, Jia.,Ye, Xiaoqing.,Boateng, Derrick.,Dai, Kaili.,Ye, Fei.,...&Yu, Han.(2019).Identification and characterization of potent and selective inhibitors targeting protein tyrosine phosphatase 1B (PTP1B).BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,29(16),2358-2363. |
| MLA | Jin, Jia,et al."Identification and characterization of potent and selective inhibitors targeting protein tyrosine phosphatase 1B (PTP1B)".BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 29.16(2019):2358-2363. |
入库方式： OAI收割
来源：上海药物研究所
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