PhoreMost Limited and Sentinel Oncology announced an expansion of their collaboration to accelerate the progression of SOL686, a novel allosteric Polo-like kinase 1 (PLK1) inhibitor through preclinical development and IND enabling studies for the treatment of glioma.
Mitotic PLKs are widely recognized as playing crucial roles in disease causing pathways, including K-Ras mutant cancers. Traditional approaches to drugging PLK enzymes have focused on targeting their active site; however, this tactic has been hindered by toxicity-associated adverse events. Sentinel Oncology’s allosteric PLK1 inhibitor takes the novel approach of targeting the Polo-box domain (PBD) of the PLKs, thereby aiming to mitigate adverse events seen by active site inhibitors.
The program has demonstrated a promising combination of specific drug-like properties, mode of action and target validation data obtained so far. Originating from the laboratory of Prof Ashok Venkitaraman at the University of Cambridge, PhoreMost subsequently developed the lead chemical series. Sentinel Oncology then optimized drug-like properties for the series and guided therapeutic positioning.