9UHC の概要
| エントリーDOI | 10.2210/pdb9uhc/pdb |
| 分子名称 | Fibroblast growth factor receptor 1, ~{N}-[1-methyl-3-[2-[1-(2-morpholin-4-ylethyl)pyrazol-4-yl]-5~{H}-pyrrolo[2,3-b]pyrazin-7-yl]indol-6-yl]propanamide, SULFATE ION, ... (4 entities in total) |
| 機能のキーワード | fibroblast growth factor receptor 1, transferase inhibitor, transferase |
| 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 | 72102.58 |
| 構造登録者 | |
| 主引用文献 | Deng, W.,Chen, X.,Yan, L.,Xiang, S.,Song, X.,Zhang, L.,Li, X.,Zhu, W.,Pei, J.,Lin, X.,Patterson, A.V.,Smaill, J.B.,Li, B.,Tu, Z.,Zhou, Y.,Chen, Y.,Lu, X. Design, Synthesis and Biological Evaluation of 7-(1-Methyl-1 H -indole-3-yl)-5 H -pyrrolo[2,3- b ]pyrazine Derivatives as Novel Covalent pan-FGFR Inhibitors to Overcome Clinical Resistance. J.Med.Chem., 68:19415-19437, 2025 Cited by PubMed Abstract: Aberrant activation of fibroblast growth factor receptors (FGFRs) plays a critical role in tumorigenesis across multiple cancer types, driving the development of various FGFR inhibitors. Despite clinical advances, therapeutic efficacy remains limited by the emergence of drug resistance, primarily mediated by gatekeeper mutations in FGFRs. To overcome this challenge, we designed and synthesized a novel series of 7-(1-methyl-1-indole-3-yl)-5-pyrrolo[2,3-]pyrazine derivatives as covalent pan-FGFR inhibitors targeting both wild-type and gatekeeper mutants. Compound demonstrated potent nanomolar inhibitory activity against FGFR1-3 and gatekeeper mutants in biochemical and cellular assays. Structural characterization using matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS) and X-ray crystallography confirmed covalent binding of to FGFR1. Additionally, showed significant in vivo antitumor efficacy in nude mice bearing the RT112 bladder cancer xenograft model. These findings establish as a promising lead for further development of FGFR-targeted anticancer therapies. PubMed: 40921092DOI: 10.1021/acs.jmedchem.5c01594 主引用文献が同じPDBエントリー |
| 実験手法 | X-RAY DIFFRACTION (1.88 Å) |
構造検証レポート
検証レポート(詳細版)
をダウンロード
をダウンロード
