Novel selective mTORC1 inhibitors

Project Information

inhibiTOR

Grant agreement ID: 875610

DOI

10.3030/875610

Project closed

EC signature date 19 December 2019

Start date 1 January 2020

End date 31 December 2021

Funded under

• EXCELLENT SCIENCE - European Research Council (ERC)

Total cost

No data

EU contribution

€ 150 000,00

Coordinated by

UNIVERSITAT BASEL
Switzerland

Periodic Reporting for period 1 - inhibiTOR (Novel selective mTORC1 inhibitors)

Reporting period: 2020-01-01 to 2021-12-31

Summary of the context and overall objectives of the project

Hepatocellular carcinoma (HCC) is the predominant form of liver cancer. The multikinase inhibitor sorafenib is the only approved drug to treat HCC and, on average, enhances survival by three months. Thus, the efficacy of current HCC treatment options is very limited. mTORC1 is a protein complex involved in cellular signaling. mTORC1 inhibitors are approved for some advanced cancers, but not HCC, partially due to their limited efficacy and specificity. Novel classes of mTORC1 targeting drugs may provide a novel therapeutic regimen for treating HCC, either alone or in combination with currently approved treatment.

In this EU-funded inhibiTOR project, we have successfully conducted a high-throughput screen of highly diverse compound libraries. We i) identified and validated hits using biophysical assays, ii) improved their in vitro potency by testing derivatives, and iii) developed several compound classes that selectively inhibit mTORC1 in vitro with a novel mode of action. These compound classes are highly promising candidates for further chemical and pharmaceutical development as mTORC1 inhibitors for the treatment of HCC.