7B9L
MEK1 in complex with compound 23
Summary for 7B9L
| Entry DOI | 10.2210/pdb7b9l/pdb |
| Descriptor | Dual 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 Keywords | kinase, allosteric, fragments, transferase |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 2 |
| Total formula weight | 74925.85 |
| Authors | |
| Primary citation | 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 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: 33603979DOI: 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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