N-[4-(2,4,6-Trimethylphenyl)-2-thiazolyl]-benzamide

A cell-permeable INH1 analog exhibits significantly improved antiproliferative activity against MB231, MB468, HeLa, and K562 cells (IC50 = 1.7, 2.1, 2.4, and 2.5 µM, respectively)

OTAVAchemicals Catalogue Number: 7070707071
CAS Registry Number: 1001753-24-7
Purity: 97%+

Ref. 1: Qiu et al. Synthesis and Biological Evaluation of a Series of Novel Inhibitor of Nek2/Hec1 Analogues. Journal of Medicinal Chemistry (2009), 52, 1757-1767Ref. 1. 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;

Ref. 2: Zhu, Yongxia; Wei, Wei; Ye, Tinghong; Liu, Zhihao; Liu, Li; Luo, Yong; Zhang, Lidan; Gao, Chao; Wang, Ningyu; Yu, Luoting. Small Molecule TH-39 Potentially Targets Hec1/Nek2 Interaction and Exhibits Antitumor Efficacy in K562 Cells via G0/G1 Cell Cycle Arrest and Apoptosis Induction. Cellular Physiology and Biochemistry (2016), 40(1-2), 297-308;

Abstract 1. 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.