5IIS

Design, synthesis and structure activity relationship of potent pan-PIM kinase inhibitors derived from the pyridyl-amide scaffold

Summary for 5IIS

• Entry DOI: 10.2210/pdb5iis/pdb
• Descriptor: Serine/threonine-protein kinase pim-1, DI(HYDROXYETHYL)ETHER, 3-amino-N-(2'-amino-6'-methyl[4,4'-bipyridin]-3-yl)-6-(2-fluorophenyl)pyridine-2-carboxamide, ... (4 entities in total)
• Functional Keywords: pim1, moloney murine leukemia, pim447, kinase inhibitor, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (Human)
• Cellular location: Isoform 2: Cytoplasm. Isoform 1: Cell membrane: P11309
• Total number of polymer chains: 1
• Total formula weight: 32534.76

Authors

Bellamacina, C.,Bussiere, D.,Burger, M. (deposition date: 2016-03-01, release date: 2016-04-06, Last modification date: 2016-05-04)

Primary citation

Nishiguchi, G.A.,Burger, M.T.,Han, W.,Lan, J.,Atallah, G.,Tamez, V.,Lindvall, M.,Bellamacina, C.,Garcia, P.,Feucht, P.,Zavorotinskaya, T.,Dai, Y.,Wong, K.
Design, synthesis and structure activity relationship of potent pan-PIM kinase inhibitors derived from the pyridyl carboxamide scaffold.
Bioorg.Med.Chem.Lett., 26:2328-2332, 2016

PubMed Abstract: The Pim proteins (1, 2 and 3) are serine/threonine kinases that have been found to be upregulated in many hematological malignancies and solid tumors. As a result of overlapping functions among the three isoforms, inhibition of all three Pim kinases has become an attractive strategy for cancer therapy. Herein we describe our efforts in identifying potent pan-PIM inhibitors that are derived from our previously reported pyridyl carboxamide scaffold as part of a medicinal chemistry strategy to address metabolic stability.

PubMed: 26995528
DOI: 10.1016/j.bmcl.2016.03.037

Experimental method

X-RAY DIFFRACTION (2.1 Å)