Members of the Plk family of Ser/Thr protein kinases play important roles in the entry to, progression through, and exit from cell mitosis. Plk1 is overexpressed in a variety of cancers and these high expression levels often correlate with poor prognosis. Plk1 is therefore considered to be a good target for the development of novel antimitotic cancer therapies. As part of our efforts to discover new cancer therapeutics, we developed a high throughput screen (HTS) against Plk1. This led to the identification of a series of pan-Plk inhibitors based on the pyrrolopyridine scaffold.  A structure based drug design approach enabled us to optimize the HTS hits to obtain a series of inhibitors that were selective for Plk1 against other members of the Plk family. These compounds demonstrated potent inhibition of cellular proliferation in vitro and tumour growth in animals following oral administration.

Discovery of orally active selective inhibitors of Plk1

243rd National Meeting (2012)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.