N-[4-(2,4-Dimethylphenyl)-2-thiazolyl]-4-pyridinecarboxamide

An inhibitor of Nek2/Hec1 exhibits significantly improved antiproliferative activity against MB231, MB468, HeLa, and K562 cells (IC50 = 1.1, 3.4, 1.6, and 1.2 µM, respectively)

OTAVAchemicals Catalogue Number: 7070707072 
CAS Registry Number: 560103-80-2
Purity: 97%+

 
Ref.: Qiu et al. Synthesis and Biological Evaluation of a Series of Novel Inhibitor of Nek2/Hec1 Analogues. Journal of Medicinal Chemistry (2009), 52, 1757-1767

Abstract: High expression in cancer 1 (Hec1) is an oncogene overly expressed in many human cancers. Small molecule inhibitor of Nek2/Hec1 (INH) targeting the Hec1 and its regulator, Nek2, in the mitotic pathway, was identified to inactivate Hec1/Nek2 function mediated by protein degradation that subsequently leads to chromosome mis-segregation and cell death. To further improve the efficacy of INH, a series of INH analogues were designed, synthesized, and evaluated. Among these 33 newly synthesized analogues, three of them, 6, 13, and 21, have 6-8 fold more potent cell killing activity than the previous lead compound INH1. Compounds 6 and 21 were chosen for analyzing the underlying action mechanism. They target directly the Hec1/Nek2 pathway and cause chromosome mis-alignment as well as cell death, a mechanism similar to that of INH1. This initial exploration of structural/functional relationship of INH may advance the progress for developing clinically applicable INH analogue.

DOI: 10.1021/jm8015969