4U45

MAP4K4 in complex with inhibitor (compound 25)

4U45 の概要

• エントリーDOI: 10.2210/pdb4u45/pdb
• 関連するPDBエントリー: 4U3Y 4U3Z 4U40 4U41 4U42 4U43 4U44
• 分子名称: Mitogen-activated protein kinase kinase kinase kinase 4, MAGNESIUM ION, 6-(1H-pyrazol-4-yl)-N-(pyridin-4-yl)pyrrolo[2,1-f][1,2,4]triazin-4-amine, ... (5 entities in total)
• 機能のキーワード: kinase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm: O95819
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 76261.29

構造登録者

Harris, S.F.,Wu, P.,Coons, M. (登録日: 2014-07-23, 公開日: 2014-09-03, 最終更新日: 2023-12-27)

主引用文献

Wang, L.,Stanley, M.,Boggs, J.W.,Crawford, T.D.,Bravo, B.J.,Giannetti, A.M.,Harris, S.F.,Magnuson, S.R.,Nonomiya, J.,Schmidt, S.,Wu, P.,Ye, W.,Gould, S.E.,Murray, L.J.,Ndubaku, C.O.,Chen, H.
Fragment-based identification and optimization of a class of potent pyrrolo[2,1-f][1,2,4]triazine MAP4K4 inhibitors.
Bioorg.Med.Chem.Lett., 24:4546-4552, 2014

PubMed Abstract: MAP4K4 has been shown to regulate key cellular processes that are tied to disease pathogenesis. In an effort to generate small molecule MAP4K4 inhibitors, a fragment-based screen was carried out and a pyrrolotriazine fragment with excellent ligand efficiency was identified. Further modification of this fragment guided by X-ray crystal structures and molecular modeling led to the discovery of a series of promising compounds with good structural diversity and physicochemical properties. These compounds exhibited single digit nanomolar potency and compounds 35 and 44 achieved good in vivo exposure.

PubMed: 25139565
DOI: 10.1016/j.bmcl.2014.07.071

実験手法

X-RAY DIFFRACTION (2.58 Å)