On November 4, 2019 Sentinel oncology Limited reported an expansion of it’s collaboration with PhoreMost Limited to accelerate the development of SOL686, a novel allosteric Polo-like kinase 1 (Plk1) inhibitor (Press release, Sentinel Oncology, NOV 4, 2019, View Source [SID1234550397]). The programme adds to Sentinel Oncology’s NeuroOncology pipeline, has started formal preclinical studies and is positioned to enter clinical development as a glioma treatment by 2021.

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Mitotic PLKs are widely recognised 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 programme has demonstrated a promising combination of specific drug-like properties, mode of action and target validation data obtained so far. The programme, which originated from the laboratory of Prof Ashok Venkitaraman at the University of Cambridge, has been optimised by both PhoreMost and Sentinel Oncology to the point where SOL686 was recently identified as a candidate drug for the treatment of glioma. Both PhoreMost and Sentinel Oncology received funding from Innovate UK for the drug discovery programme.