4TWC

2-Benzamido-N-(1H-benzo[d]imidazol-2-yl)thiazole-4- carboxamide derivatives as potent inhibitors of CK1d/e

Summary for 4TWC

• Entry DOI: 10.2210/pdb4twc/pdb
• Descriptor: Casein kinase I isoform delta, SULFATE ION, GLYCEROL, ... (7 entities in total)
• Functional Keywords: ck1d, ck1e, phosphorylation, small molecule inhibitor, transferase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 71359.66

Authors

Bischof, J.,Leban, L.,Zaja, M.,Grothey, A.,Radunsky, B.,Othersen, O.,Strobl, S.,Vitt, D.,Knippschild, U. (deposition date: 2014-06-30, release date: 2014-10-08, Last modification date: 2023-12-20)

Primary citation

Bischof, J.,Leban, J.,Zaja, M.,Grothey, A.,Radunsky, B.,Othersen, O.,Strobl, S.,Vitt, D.,Knippschild, U.
2-Benzamido-N-(1H-benzo[d]imidazol-2-yl)thiazole-4-carboxamide derivatives as potent inhibitors of CK1d/e.
Amino Acids, 43:1577-1591, 2012

PubMed Abstract: In this study we identified two heterocyclic compounds (5 and 6) as potent and specific inhibitors of CK1δ (IC(50) = 0.040 and 0.042 μM, respectively). Whereas compound 5 exhibited fivefold higher affinity towards CK1δ than to CK1ε (IC(50) CK1ε = 0.199 μM), compound 6 also inhibited CK1ε (IC(50) = 0.0326 μM) in the same range as CK1δ. Selected compound 5 was screened over 442 kinases identifying 5 as a highly potent and selective inhibitor of CK1δ. X-ray analysis of 5 bound to CK1δ demonstrated its binding mode. In addition, characterization of 5 and 6 in a cell biological approach revealed the ability of both compounds to inhibit proliferation of tumor cell lines in a dose and cell line specific manner. In summary, our optimizations lead to the development of new highly selective CK1δ and ε specific inhibitors with biological activity.

PubMed: 22331384
DOI: 10.1007/s00726-012-1234-x

Experimental method

X-RAY DIFFRACTION (1.7 Å)