5USQ

ALK-5 kinase inhibitor complex

5USQ の概要

• エントリーDOI: 10.2210/pdb5usq/pdb
• 分子名称: TGF-beta receptor type-1, N-[2-(5-chloro-2-fluorophenyl)pyridin-4-yl]-2-[(piperidin-4-yl)methyl]-2H-pyrazolo[4,3-b]pyridin-7-amine (3 entities in total)
• 機能のキーワード: tgf-beta receptor type i, serine/threonine-protein kinase receptor r4, activin receptor-like kinase 5, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cell membrane ; Single-pass type I membrane protein : P36897
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 34702.31

構造登録者

Dougan, D.R.,Lawson, J.D. (登録日: 2017-02-13, 公開日: 2017-04-12, 最終更新日: 2024-03-06)

主引用文献

Sabat, M.,Wang, H.,Scorah, N.,Lawson, J.D.,Atienza, J.,Kamran, R.,Hixon, M.S.,Dougan, D.R.
Design, synthesis and optimization of 7-substituted-pyrazolo[4,3-b]pyridine ALK5 (activin receptor-like kinase 5) inhibitors.
Bioorg. Med. Chem. Lett., 27:1955-1961, 2017

PubMed Abstract: A series of potent ALK5 inhibitors were designed using a SBDD approach and subsequently optimized to improve drug likeness. Starting with a 4-substituted quinoline screening hit, SAR was conducted using a ALK5 binding model to understand the binding site and optimize activity. The resulting inhibitors displayed excellent potency but were limited by high in vitro clearance in rat and human microsomes. Using a scaffold morphing strategy, these analogs were transformed into a related pyrazolo[4,3-b]pyridine series with improved ADME properties.

PubMed: 28359790
DOI: 10.1016/j.bmcl.2017.03.026

実験手法

X-RAY DIFFRACTION (2.55 Å)