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Feasibility study: Development of a lead compound for specific mTORC1 inhibition

Research Project
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01.09.2018
 - 29.02.2020

mTORC1 is a master regulator of cell growth and metabolism. mTORC1 is an important pharmacological target as its deregulation is implicated in multiple diseases. However, the clinical applicability of the currently available mTORC1 inhibitors (rapamycin and its derivatives) is limited by their specificity, effectiveness, and safety. Chronic and systemic administration of current mTORC1 inhibitors is often associated with undesirable side effects on metabolism, including hyperglycemia, hyperlipidemia, and insulin resistance. This hinders the use of mTORC1 inhibition as a pharmacologic strategy to treat multiple conditions with unmet therapeutic needs. They include cancer, epilepsy, depression, autism and stroke, obesity and diabetes, autoimmunity, age-related pathologies. We aim to generate a lead compound that justifies its further development into a drug to treat diseases arising from unbridled mTORC1 activity. Initially, we intend to focus on the lifelong tumor syndrome TSC (tuberous sclerosis complex) and, in the long term, to other conditions mentioned above. mTORC1 substrate recruitment is an unexplored pharmacological target. We provided a structural basis for analyzing this process. Based on this study, we established a biophysical assay to identify novel compounds that block mTORC1 substrate recruitment. We expect such compounds to be more specific, effective and safer than the currently available mTORC1 inhibitors, possibly allowing for higher dose or prolonged treatment. The clinical potential of these novel compounds would be immense and readily testable. This project displays a considerable innovation potential. It involves an experienced, highly committed, and cross-disciplinary team at the forefront of knowledge in the relevant fields. This project may form the basis for establishment of a start-up company in Switzerland to further develop the lead compound and bring it to clinical trials and to market.

Funding

Feasibility study: Development of a lead compound for specific mTORC1 inhibition

Innosuisse Projekt (GrantsTool), 09.2018-02.2020 (18)
PI : Maier, Timm.
CI : Hall, Michael N..

Members (4)

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Timm Maier

Principal Investigator
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Michael N. Hall

Co-Investigator
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Asier Gonzalez Sevine

Project Member
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Stefan Imseng

Project Member