Biological Activity
inh6 is a potent inhibitor of hec1/nek2 [1].hec1 is an oncogene that involved in spindle checkpoint signaling and is overexpressed in many human cancers. nek2 is a serine/threonine-protein kinase that phosphorylates hec1, which is critical for its mitotic function and cell survival [1].inh6 is a potent hec1/nek2 inhibitor. inh6 inhibited hec1/nek2 function through protein degradation that led to chromosome mis-segregation and cell death. in mda-mb468 and mda-mb231 human breast cancer cell lines, hela human cervical cancer line and k562 human erythromyeloblastoid leukemia cell line, inh6 exhibited significantly anti-proliferation activities with ic50 values of 2.1, 1.7, 2.4 and 2.5 μm, respectively. in hela cell extract, inh6-conjugated matrix selectively co-precipitated with cellular hec1, which suggested that inh6 bound to cellular hec1. in hela cells, inh6 (6.25 μm) reduced nek2 by 50% at 8-11 h. in addition, inh6 slightly reduced hec1 over time. also, inh6 increased mitotic population with multipolar spindle configurations. in hela cells expressing the chromosome marker protein h2b-gfp, inh6 increased chromosome misalignment. in hela cells, inh6 exhibited progressive morphological changes of dying cells and induced apoptosis by 20% [1].
References
[1]. qiu xl, li g, wu g, et al. synthesis and biological evaluation of a series of novel inhibitor of nek2/hec1 analogues. j med chem, 2009, 52(6): 1757-1767.
