9LNH9LNH の概要
| エントリーDOI | 10.2210/pdb9lnh/pdb |
| 分子名称 | Peroxiredoxin-1, (2~{S})-2-[[(2~{R},4~{a}~{S},6~{a}~{R},6~{a}~{S},14~{a}~{S},14~{b}~{R})-2,4~{a},6~{a},6~{a},9,14~{a}-hexamethyl-10-oxidanyl-11-oxidanylidene-1,3,4,5,6,13,14,14~{b}-octahydropicen-2-yl]carbamoylamino]butanoic acid (3 entities in total) |
| 機能のキーワード | celastrol derivative, prdx1 inhibitor, oxidoreductase |
| 由来する生物種 | Homo sapiens (human) |
| タンパク質・核酸の鎖数 | 2 |
| 化学式量合計 | 39224.86 |
| 構造登録者 | |
| 主引用文献 | Chen, S.,Wang, Z.,Gao, J.,Wang, Y.,Liang, J.,Zhu, Y.,Xu, H.,Chen, K.,Jin, L.,Zhang, H.,Xiong, H.,Luo, C. Rapid Discovery of Celastrol Derivatives as Potent and Selective PRDX1 Inhibitors via Microplate-Based Parallel Compound Library and In Situ Screening. J.Med.Chem., 68:13609-13627, 2025 Cited by PubMed Abstract: Celastrol has been identified as a reactive oxygen species (ROS) elevator that reduces cancer cell proliferation by inhibiting peroxiredoxin (PRDX) activity, albeit with poor selectivity. We describe a semiautomated and microplate-based parallel compound library approach leading to the rapid discovery of celastrol derivatives that are potent and selective PRDX1 inhibitors. Amide coupling and the urea bond forming reactions were used to construct a 2720-member celastrol derivative library, followed by PRDX1 enzyme inhibition assay screening, leading to the rapid identification of a series of celastrol derivatives demonstrating promising PRDX1 inhibition activity. Compound displayed the best anti-PRDX1 activity (IC = 0.042 μM) with selectivity toward the PRDX family, as well as good antiproliferative activity against colorectal cancer cells. A cocrystal structure of PRDX1 with and molecular docking studies provided insight into the binding mode of the inhibitors with PRDX1, aiding in the structure-based design of future PRDX1 inhibitors. PubMed: 40546088DOI: 10.1021/acs.jmedchem.5c00433 主引用文献が同じPDBエントリー |
| 実験手法 | X-RAY DIFFRACTION (1.63 Å) |
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