6I5I

Crystal structure of CLK1 in complexed with furo[3,2-b]pyridine compound 12h

6I5I の概要

• エントリーDOI: 10.2210/pdb6i5i/pdb
• 分子名称: Dual specificity protein kinase CLK1, 5-(1-methylpyrazol-4-yl)-3-[1-(phenylmethyl)pyrazol-4-yl]furo[3,2-b]pyridine, 1,2-ETHANEDIOL, ... (4 entities in total)
• 機能のキーワード: splicing kinase, furopyridine, inhibitor, clk, structural genomics, structural genomics consortium, sgc, transferase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 40681.72

構造登録者

Chaikuad, A.,Arrowsmith, C.H.,Edwards, A.M.,Bountra, C.,Paruch, K.,Knapp, S.,Structural Genomics Consortium (SGC) (登録日: 2018-11-13, 公開日: 2019-01-09, 最終更新日: 2024-01-24)

主引用文献

Nemec, V.,Hylsova, M.,Maier, L.,Flegel, J.,Sievers, S.,Ziegler, S.,Schroder, M.,Berger, B.T.,Chaikuad, A.,Valcikova, B.,Uldrijan, S.,Drapela, S.,Soucek, K.,Waldmann, H.,Knapp, S.,Paruch, K.
Furo[3,2-b]pyridine: A Privileged Scaffold for Highly Selective Kinase Inhibitors and Effective Modulators of the Hedgehog Pathway.
Angew. Chem. Int. Ed. Engl., 58:1062-1066, 2019

PubMed Abstract: Reported is the identification of the furo[3,2-b]pyridine core as a novel scaffold for potent and highly selective inhibitors of cdc-like kinases (CLKs) and efficient modulators of the Hedgehog signaling pathway. Initially, a diverse target compound set was prepared by synthetic sequences based on chemoselective metal-mediated couplings, including assembly of the furo[3,2-b]pyridine scaffold by copper-mediated oxidative cyclization. Optimization of the subseries containing 3,5-disubstituted furo[3,2-b]pyridines afforded potent, cell-active, and highly selective inhibitors of CLKs. Profiling of the kinase-inactive subset of 3,5,7-trisubstituted furo[3,2-b]pyridines revealed sub-micromolar modulators of the Hedgehog pathway.

PubMed: 30569600
DOI: 10.1002/anie.201810312

実験手法

X-RAY DIFFRACTION (1.6 Å)