4I0R

Crystal structure of spleen tyrosine kinase complexed with 2-(3,4,5-Trimethoxy-phenyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide

Summary for 4I0R

• Entry DOI: 10.2210/pdb4i0r/pdb
• Related: 4I0S 4I0T
• Descriptor: Tyrosine-protein kinase SYK, N-(propan-2-yl)-2-(3,4,5-trimethoxyphenyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (3 entities in total)
• Functional Keywords: kinase inhibitor, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 34254.41

Authors

Kuglstatter, A.,Villasenor, A.G. (deposition date: 2012-11-19, release date: 2013-10-30, Last modification date: 2023-09-20)

Primary citation

Padilla, F.,Bhagirath, N.,Chen, S.,Chiao, E.,Goldstein, D.M.,Hermann, J.C.,Hsu, J.,Kennedy-Smith, J.J.,Kuglstatter, A.,Liao, C.,Liu, W.,Lowrie, L.E.,Luk, K.C.,Lynch, S.M.,Menke, J.,Niu, L.,Owens, T.D.,O-Yang, C.,Railkar, A.,Schoenfeld, R.C.,Slade, M.,Steiner, S.,Tan, Y.C.,Villasenor, A.G.,Wang, C.,Wanner, J.,Xie, W.,Xu, D.,Zhang, X.,Zhou, M.,Lucas, M.C.
Pyrrolopyrazines as selective spleen tyrosine kinase inhibitors.
J.Med.Chem., 56:1677-1692, 2013

PubMed Abstract: We describe the discovery of several pyrrolopyrazines as potent and selective Syk inhibitors and the efforts that eventually led to the desired improvements in physicochemical properties and human whole blood potencies. Ultimately, our mouse model revealed unexpected toxicity that precluded us from further advancing this series.

PubMed: 23350847
DOI: 10.1021/jm301720p

Experimental method

X-RAY DIFFRACTION (2.1 Å)