3R04

The discovery of novel benzofuran-2-carboxylic acids as potent Pim-1 inhibitors

Summary for 3R04

• Entry DOI: 10.2210/pdb3r04/pdb
• Related: 3R00 3R01 3R02
• Descriptor: Proto-oncogene serine/threonine-protein kinase pim-1, 5-{6-[(trans-4-aminocyclohexyl)amino]pyrazin-2-yl}-1-benzofuran-2-carboxylic acid, IMIDAZOLE, ... (4 entities in total)
• Functional Keywords: kinae, pim1, 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: 35040.74

Authors

Xiang, Y.,Hirth, B.,Asmussen, G.,Biemann, H.-P.,Good, A.,Fitzgerald, M.,Gladysheva, T.,Jancsics, K.,Liu, J.,Metz, M.,Papoulis, A.,Skerlj, R.,Stepp, D.J.,Wei, R.R. (deposition date: 2011-03-07, release date: 2011-05-11, Last modification date: 2024-02-21)

Primary citation

Xiang, Y.,Hirth, B.,Asmussen, G.,Biemann, H.P.,Bishop, K.A.,Good, A.,Fitzgerald, M.,Gladysheva, T.,Jain, A.,Jancsics, K.,Liu, J.,Metz, M.,Papoulis, A.,Skerlj, R.,Stepp, J.D.,Wei, R.R.
The discovery of novel benzofuran-2-carboxylic acids as potent Pim-1 inhibitors.
Bioorg.Med.Chem.Lett., 21:3050-3056, 2011

PubMed Abstract: Novel benzofuran-2-carboxylic acids, exemplified by 29, 38 and 39, have been discovered as potent Pim-1 inhibitors using fragment based screening followed by X-ray structure guided medicinal chemistry optimization. The compounds demonstrate potent inhibition against Pim-1 and Pim-2 in enzyme assays. Compound 29 has been tested in the Ambit 442 kinase panel and demonstrates good selectivity for the Pim kinase family. X-ray structures of the inhibitor/Pim-1 binding complex reveal important salt-bridge and hydrogen bond interactions mediated by the compound's carboxylic acid and amino groups.

PubMed: 21507633
DOI: 10.1016/j.bmcl.2011.03.030

Experimental method

X-RAY DIFFRACTION (1.7 Å)