Small molecule inhibitors of mTOR kinase featuring sub-nanomolar potency and a high level of selectivity over the rest of the kinome. The novel drug candidates display excellent PK properties and highly potent antiproliferative activity in a range of cell lines representing different cancer types.
Application
Treatment of solid and blood cancers, metabolic disorders, fibrosis, ageing, neurodegenerative disorders and other immune-related diseases.
Development Status
Undergoing preclinical development in state-of-the-art cancer models
IP Status
PCT/GB2025/052680 filed December 2025
Commercial Offering
Licence opportunity
Opportunity
Mechanistic Target Of Rapamycin (mTOR), a Serine/Threonine kinase, is a master regulator of key oncogenic processes central to cancer, including cell migration (responsible for metastases), protein synthesis and cell proliferation. mTOR exerts its effects as a core unit of two multimeric protein complexes, mTORC1 and mTORC2, which are both highly implicated in haematological, solid cancers and many other therapeutic indications. In addition, the role of mTOR is well established in other pathologies such as ageing, fibrosis, neurodegenerative disorders and immune-related diseases, opening up opportunities for therapeutic intervention in these indications.
The patented set of drug candidates displays superb inhibition of mTOR kinase activity. Thus, unlike rapalogs which only inhibit the mTORC1 complex, the novel drugs disrupt both mTORC1 and mTORC2. These molecules are currently in pre-clinical development with efficacy obtained in cancer models. The University of Edinburgh is looking for a partner with the experience and capital to progress this IP towards IND-enabling studies and clinical trials.
Technology
The novel inhibitors display sub-nanomolar IC50
values both in biochemical assays and in cell culture (Fig 1). Notably, at 1 μM, full kinome profiling (364 kinases) shows that the compounds inhibit 50 % of the enzymatic activity of less than 10 kinases (Fig 2). The lead compound, eALM1396 is >50-fold less potent against the second-most inhibited kinase (the PIKK family member DNA-PK) in the panel and features optimal PK properties in murine models, including excellent oral bioavailability (>70%).
Once daily administration of eALM1396 (2.5, 5, and 10mg/kg) to mice bearing SW48 xenografts resulted in total inhibition of mTOR activity. pAKT Ser473 was used as readout for mTORC2 activity inhibition in these models (Fig3b). Similar results were obtained using the SW48 cell line in culture where the phosphorylation of AKT on Ser473 was fully inhibited at concentrations above 1nM (Fig3a).
In vivo, eALM1396 induced a dose-dependent reduction of tumour growth in an SW48 Xenograft model achieving >70% TGI at day 14 of treatment by once daily oral dosing (Fig 4). The results correlated with the reduced cell proliferation observed in vitro for this model.
Benefits
Publications
Over 20 analogues, which are more potent and selective than Sapanisertib, have been discovered and patented. Examples include the tool compound eALM1137, which was shown to strongly suppress Glioblastoma Multiform Cell growth recently published in J Med Chem.
Álvaro Lorente-Macias, Jonathon Mok, John C. Dawson, Ana Juan-Albuquerque, Neil O. Carragher, Margaret C. Frame, and Asier Unciti-Broceta. Discovery of a Highly Potent and Selective mTOR Inhibitor that Strongly Suppresses Glioblastoma Multiforme Cell Growth. Journal of Medicinal Chemistry 2026, 69, 8, 9680-9712.
Quote: TEC1104782
Technology Transfer Manager
The Institute of Genetics and Cancer
The Usher Institute
Researchers at the Institute of Genetics and Cancer have developed highly potent, superselective mTOR inhibitors for the treatment of solid and blood cancers. The University of Edinburgh seeks partners to progress this IP towards IND-enabling studies and clinical trials.
