4I5C

The Jak1 kinase domain in complex with inhibitor

4I5C の概要

• エントリーDOI: 10.2210/pdb4i5c/pdb
• 分子名称: Tyrosine-protein kinase JAK1, 3-oxo-3-[(3R)-3-(pyrrolo[2,3-b][1,2,3]triazolo[4,5-d]pyridin-1(6H)-yl)piperidin-1-yl]propanenitrile, 1,2-ETHANEDIOL, ... (4 entities in total)
• 機能のキーワード: kinase, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Endomembrane system; Peripheral membrane protein: P23458
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 70360.11

構造登録者

Fong, R.,Lupardus, P.J. (登録日: 2012-11-28, 公開日: 2013-05-22, 最終更新日: 2024-10-30)

主引用文献

Hurley, C.A.,Blair, W.S.,Bull, R.J.,Chang, C.,Crackett, P.H.,Deshmukh, G.,Dyke, H.J.,Fong, R.,Ghilardi, N.,Gibbons, P.,Hewitt, P.R.,Johnson, A.,Johnson, T.,Kenny, J.R.,Kohli, P.B.,Kulagowski, J.J.,Liimatta, M.,Lupardus, P.J.,Maxey, R.J.,Mendonca, R.,Narukulla, R.,Pulk, R.,Ubhayakar, S.,van Abbema, A.,Ward, S.I.,Waszkowycz, B.,Zak, M.
Novel triazolo-pyrrolopyridines as inhibitors of Janus kinase 1.
Bioorg.Med.Chem.Lett., 23:3592-3598, 2013

PubMed Abstract: The identification of a novel fused triazolo-pyrrolopyridine scaffold, optimized derivatives of which display nanomolar inhibition of Janus kinase 1, is described. Prototypical example 3 demonstrated lower cell potency shift, better permeability in cells and higher oral exposure in rat than the corresponding, previously reported, imidazo-pyrrolopyridine analogue 2. Examples 6, 7 and 18 were subsequently identified from an optimization campaign and demonstrated modest selectivity over JAK2, moderate to good oral bioavailability in rat with overall pharmacokinetic profiles comparable to that reported for an approved pan-JAK inhibitor (tofacitinib).

PubMed: 23642482
DOI: 10.1016/j.bmcl.2013.04.018

実験手法

X-RAY DIFFRACTION (2.1 Å)