Bischof, Joachim; Leban, Johann; Zaja, Mirko; Grothey, Arnhild; Radunsky, Barbara; Othersen, Olaf; Strobl, Stefan; Vitt, Daniel; Knippschild, Uwe published the artcile< 2-Benzamido-N-(1H-benzo[d]imidazol-2-yl)thiazole-4-carboxamide derivatives as potent inhibitors of CK1δ/ε>, Electric Literature of 162046-61-9, the main research area is benzamidobenzoimidazolylthiazolecarboxamide derivative preparation inhibition casein kinase 1 isoenzyme antitumor; crystal structure casein kinase isoenzyme inhibitor complex.
In this study two heterocyclic compounds (5 and 6) were identified as potent and specific inhibitors of CK1δ (IC50 = 0.040 and 0.042 μM, resp.). Whereas compound 5 exhibited 5-fold higher affinity toward CK1δ than to CK1ε (IC50 CK1ε = 0.199 μM), compound 6 also inhibited CK1ε (IC50 = 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 anal. of 5 bound to CK1δ demonstrated its binding mode. In addition, characterization of 5 and 6 in a cell biol. approach revealed the ability of both compounds to inhibit proliferation of tumor cell lines in a dose and cell line specific manner. In summary, these optimizations lead to the development of new highly selective CK1δ and ε specific inhibitors with biol. activity.
Amino Acids published new progress about Antitumor agents. 162046-61-9 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H4ClF3O2, Electric Literature of 162046-61-9.
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics