959784-89-5Relevant academic research and scientific papers
Hit to Lead optimization of a novel class of squarate-containing polo-like kinases inhibitors
Zhang, Qingwei,Xia, Zhiren,Mitten, Michael J.,Lasko, Loren M.,Klinghofer, Vered,Bouska, Jennifer,Johnson, Eric F.,Penning, Thomas D.,Luo, Yan,Giranda, Vincent L.,Shoemaker, Alexander R.,Stewart, Kent D.,Djuric, Stevan W.,Vasudevan, Anil
, p. 7615 - 7622 (2012)
A high throughput screening (HTS) hit, 1 (Plk1 Ki = 2.2 μM) was optimized and evaluated for the enzymatic inhibition of Plk-1 kinase. Molecular modeling suggested the importance of adding a hydrophobic aromatic amine side chain in order to improve the potency by a classic kinase H-donor-acceptor binding mode. Extensive SAR studies led to the discovery of 49 (Plk1 Ki = 5 nM; EC50 = 1.05 μM), which demonstrated moderate efficacy at 100 mpk in a MiaPaCa tumor model, with no overt toxicity.
INHIBITORS OF POLO-LIKE KINASES
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Page/Page column 50, (2008/06/13)
Compounds that inhibit Plk1, compositions containing the compounds and methods of treating diseases using the compounds are disclosed.
