7B3M

MEK1 in complex with compound 6

7B3M の概要

• エントリーDOI: 10.2210/pdb7b3m/pdb
• 分子名称: Dual specificity mitogen-activated protein kinase kinase 1,Dual specificity mitogen-activated protein kinase kinase 1, MAGNESIUM ION, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, ... (6 entities in total)
• 機能のキーワード: kinase, allosteric, fragments, transferase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 74717.56

構造登録者

Kack, H.,Oster, L. (登録日: 2020-12-01, 公開日: 2021-03-03, 最終更新日: 2024-01-31)

主引用文献

Di Fruscia, P.,Edfeldt, F.,Shamovsky, I.,Collie, G.W.,Aagaard, A.,Barlind, L.,Borjesson, U.,Hansson, E.L.,Lewis, R.J.,Nilsson, M.K.,Oster, L.,Pemberton, J.,Ripa, L.,Storer, R.I.,Kack, H.
Fragment-Based Discovery of Novel Allosteric MEK1 Binders.
Acs Med.Chem.Lett., 12:302-308, 2021

PubMed Abstract: The MEK1 kinase plays a critical role in key cellular processes, and as such, its dysfunction is strongly linked to several human diseases, particularly cancer. MEK1 has consequently received considerable attention as a drug target, and a significant number of small-molecule inhibitors of this kinase have been reported. The majority of these inhibitors target an allosteric pocket proximal to the ATP binding site which has proven to be highly druggable, with four allosteric MEK1 inhibitors approved to date. Despite the significant attention that the MEK1 allosteric site has received, chemotypes which have been shown structurally to bind to this site are limited. With the aim of discovering novel allosteric MEK1 inhibitors using a fragment-based approach, we report here a screening method which resulted in the discovery of multiple allosteric MEK1 binders, one series of which was optimized to sub-μM affinity for MEK1 with promising physicochemical and ADMET properties.

PubMed: 33603979
DOI: 10.1021/acsmedchemlett.0c00563

実験手法

X-RAY DIFFRACTION (2.3 Å)