Small molecule inhibitors of mTOR kinase featuring subnanomolar potency and unprecedented selectivity over the rest of the kinome. The novel drug candidates display excellent PK properties and highly potent antiproliferative activity against cancer cell lines, including colorectal cancer.
Application
Treatment of solid and blood cancers
Development Status
Undergoing preclinical development in state-of-the-art cancer models
IP Status
UK application filed
Commercial Offering
Licence opportunity
Opportunity
Mechanistic Target Of Rapamycin (mTOR), a Serine/Threonine kinase, is a central master regulator of key oncogenic processes central to cancer, regulating pathways ranging from cell migration responsible for metastases, to its main function of protein synthesis and cell proliferation, responsible for initial tumour colonisation. mTOR exerts its effects through its dimeric complexes, mTORC1 and mTORC2, which are exploited by both liquid and solid cancers.
The patented set of drug candidates displays superb inhibition of mTOR kinase, a pathway frequently upregulated in a multitude of difficult-to-treat malignancies, including colorectal cancer. Unlike rapalogs, which only inhibit the mTORC1 complex, the novel drugs inhibit mTOR kinase activity, which is the essential enzymatic unit of both mTORC1 and mTORC2. The novel drugs are currently being developed preclinically in state-of-the-art cancer models. The University of Edinburgh seeks a partner with the experience and capital to progress this IP towards IND-enabling studies and clinical trials.
Technology
The novel inhibitors display subnanomolar IC50 values both in biochemical assays and in cell culture (Western blot). Notably, at 1 μM, full kinome profiling shows that the compounds inhibit 50 % of the enzymatic activity of less than 10 kinases. The lead compounds exhibit >50-fold lower activity against the second-ranked most inhibited kinase (the PIKK family member DNA-PK) and feature optimal PK properties in murine models, including oral bioavailability (>70 %).
Benefits
Quote: TEC1104782
Technology Transfer Manager
The Institute of Genetics and Cancer
The Usher Institute
