3I5Z

Crystal structure of ERK2 bound to (S)-N-(2-hydroxy-1-phenylethyl)-4-(5-methyl-2-(phenylamino)pyrimidin-4-yl)-1H-pyrrole-2-carboxamide

Summary for 3I5Z

• Entry DOI: 10.2210/pdb3i5z/pdb
• Related: 3I60
• Descriptor: Mitogen-activated protein kinase 1, SULFATE ION, N-[(1S)-2-hydroxy-1-phenylethyl]-4-[5-methyl-2-(phenylamino)pyrimidin-4-yl]-1H-pyrrole-2-carboxamide, ... (4 entities in total)
• Functional Keywords: kinase, inhibitor, atp-binding, cell cycle, host-virus interaction, nucleotide-binding, phosphoprotein, serine/threonine-protein kinase, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm, cytoskeleton, spindle : P28482
• Total number of polymer chains: 1
• Total formula weight: 44413.73

Authors

Jacobs, M.D.,Xie, X. (deposition date: 2009-07-06, release date: 2010-01-12, Last modification date: 2024-04-03)

Primary citation

Aronov, A.M.,Tang, Q.,Martinez-Botella, G.,Bemis, G.W.,Cao, J.,Chen, G.,Ewing, N.P.,Ford, P.J.,Germann, U.A.,Green, J.,Hale, M.R.,Jacobs, M.,Janetka, J.W.,Maltais, F.,Markland, W.,Namchuk, M.N.,Nanthakumar, S.,Poondru, S.,Straub, J.,ter Haar, E.,Xie, X.
Structure-guided design of potent and selective pyrimidylpyrrole inhibitors of extracellular signal-regulated kinase (ERK) using conformational control.
J.Med.Chem., 52:6362-6368, 2009

PubMed Abstract: The Ras/Raf/MEK/ERK signal transduction, an oncogenic pathway implicated in a variety of human cancers, is a key target in anticancer drug design. A novel series of pyrimidylpyrrole ERK inhibitors has been identified. Discovery of a conformational change for lead compound 2, when bound to ERK2 relative to antitarget GSK3, enabled structure-guided selectivity optimization, which led to the discovery of 11e, a potent, selective, and orally bioavailable inhibitor of ERK.

PubMed: 19827834
DOI: 10.1021/jm900630q

Experimental method

X-RAY DIFFRACTION (2.2 Å)