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7B9L

MEK1 in complex with compound 23

Summary for 7B9L
Entry DOI10.2210/pdb7b9l/pdb
DescriptorDual specificity mitogen-activated protein kinase kinase 1,Dual specificity mitogen-activated protein kinase kinase 1, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, ~{N}-(4-methoxyphenyl)-2-[(2~{S})-3-oxidanylidenethiomorpholin-2-yl]ethanamide, ... (7 entities in total)
Functional Keywordskinase, allosteric, fragments, transferase
Biological sourceHomo sapiens (Human)
More
Total number of polymer chains2
Total formula weight74925.85
Authors
Kack, H.,Oster, L. (deposition date: 2020-12-14, release date: 2021-03-03, Last modification date: 2024-01-31)
Primary citationDi 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
Cited by
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
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (1.7 Å)
Structure validation

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