N-(4-mesityl-1,3-thiazol-2-yl)morpholine-4-carboxamide

Chemical Formula: C17H21N3O2S

Molecular Weight: 331.4398

OTAVAchemicals Catalogue Number: 7070707073

CAS Registry Number: 1134986-24-5

Purity: 95% (HPLC)

Ref. 1. Qiu, Xiao-Long; Li, Guideng; Wu, Guikai; Zhu, et al. Synthesis and Biological Evaluation of a Series of Novel Inhibitor of Nek2/Hec1 Analogues. Journal of Medicinal Chemistry (2009), 52(6), 1757-1767

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.

Abstract 2. QSAR is among the most extensively used computational methodology for analogue-based design. The application of various descriptor classes like quantum chemical, molecular mechanics, conceptual density functional theory (DFT)- and docking-based descriptors for predicting anti-cancer activity is well known. Although in vitro assay for anti-cancer activity is available against many different cell lines, most of the computational studies are carried out targeting insufficient number of cell lines. Hence, statistically robust and extensive QSAR studies against 29 different cancer cell lines and its comparative account, has been carried out.

DOI:

• 10.1021/jm8015969
• 10.1186/2191-2858-1-3