inhibitors of cyclin dependent kinases have been hard
to develop because the active sites of many family members are so similar. Now,
a Harvard Medical School team has found a cyclin dependent kinase 7 inhibitor that
covalently binds a cysteine residue outside the enzyme's kinase domain and
suppresses leukemia in mice.1
discover how THZ1 induced cell death, the researchers focused on RNA polymerase, a known target of
CDK7. In cancer cells, THZ1 blocked phosphorylation of RNA polymerase and
decreased the overall mRNA levels compared with the inactive, modified
to Klebl, the most striking finding from the paper was the specificity of THZ1.
Cain, C. SciBX 7(28); doi:10.1038/scibx.2014.817
Published online July 24, 2014
1. Kwiatkowski, N. et al. Nature; published
online June 22, 2014; doi:10.1038/nature13393
Contact: Nathanael S. Gray, Dana-Farber Cancer Institute, Boston, Mass.
Contact: Richard A. Young, Whitehead Institute for Biomedical Research,
2. Lovén, J. et al. Cell 153, 320-334
3. Cain, C. BioCentury 21(15), A12;
April 15, 2013
4. Whyte, W.A. et al. Cell 153, 307-319
AND INSTITUTIONS MENTIONED
Broad Institute of MIT and Harvard, Cambridge, Mass.
Cyclacel Pharmaceuticals Inc. (NASDAQ:CYCC), Berkeley Heights, N.J.
Dana-Farber Cancer Institute, Boston, Mass.
Harvard Medical School, Boston, Mass.
Lead Discovery Center GmbH, Dortmund, Germany
Massachusetts Institute of Technology, Cambridge, Mass.
(Euronext:SAN; NYSE:SNY), Paris, France
Sunesis Pharmaceuticals Inc. (NASDAQ:SNSS), South San Francisco, Calif.
Syros Pharmaceuticals Inc., Watertown, Mass.
Tolero Pharmaceuticals Inc., Lehi, Utah
Whitehead Institute for Biomedical Research, Cambridge, Mass.