3R22

Design, synthesis, and biological evaluation of pyrazolopyridine-sulfonamides as potent multiple-mitotic kinase (MMK) inhibitors (Part I)

Summary for 3R22

• Entry DOI: 10.2210/pdb3r22/pdb
• Related: 3R21
• Descriptor: Serine/threonine-protein kinase 6, N-{5-[(1-cycloheptyl-1H-pyrazolo[3,4-d]pyrimidin-6-yl)amino]pyridin-2-yl}methanesulfonamide (3 entities in total)
• Functional Keywords: kinase domain, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm, cytoskeleton, centrosome: O14965
• Total number of polymer chains: 1
• Total formula weight: 31748.42

Authors

Zhang, L.,Fan, J.,Chong, J.-H.,Cesana, A.,Tam, B.,Gilson, C.,Boykin, C.,Wang, D.,Marcotte, D.,Le Brazidec, J.-Y.,Aivazian, D.,Piao, J.,Lundgren, K.,Hong, K.,Vu, K.,Nguyen, K. (deposition date: 2011-03-11, release date: 2011-08-10, Last modification date: 2023-09-13)

Primary citation

Zhang, L.,Fan, J.,Chong, J.H.,Cesena, A.,Tam, B.Y.,Gilson, C.,Boykin, C.,Wang, D.,Aivazian, D.,Marcotte, D.,Xiao, G.,Le Brazidec, J.Y.,Piao, J.,Lundgren, K.,Hong, K.,Vu, K.,Nguyen, K.,Gan, L.S.,Silvian, L.,Ling, L.,Teng, M.,Reff, M.,Takeda, N.,Timple, N.,Wang, Q.,Morena, R.,Khan, S.,Zhao, S.,Li, T.,Lee, W.C.,Taveras, A.G.,Chao, J.
Design, synthesis, and biological evaluation of pyrazolopyrimidine-sulfonamides as potent multiple-mitotic kinase (MMK) inhibitors (part I).
Bioorg.Med.Chem.Lett., 21:5633-5637, 2011

PubMed Abstract: A novel class of pyrazolopyrimidine-sulfonamides was discovered as selective dual inhibitors of aurora kinase A (AKA) and cyclin-dependent kinase 1 (CDK1). These inhibitors were originally designed based on an early lead (compound I). SAR development has led to the discovery of potent inhibitors with single digit nM IC(50)s towards both AKA and CDK1. An exemplary compound 1a has demonstrated good efficacy in an HCT116 colon cancer xenograft model.

PubMed: 21798738
DOI: 10.1016/j.bmcl.2011.06.129

Experimental method

X-RAY DIFFRACTION (2.9 Å)