Oss, December, 9th, 2015 – NTRC today announced that they have identified a series of IDO1 inhibitors with best-in-class properties by screening at the European Lead Factory (ELF). IDO1 is an important target in cancer immunotherapy.
The aim of immunotherapy is to restore the body’s own immune response against cancer cells. Recently approved immunotherapies are based on antibodies that block the immune checkpoints PD-1 and CTLA-4, while most experimental immune-therapeutics are also based on biologics. Synthetic small chemicals provide the potential of oral route of administration, and lower costs of manufacturing. IDO1 and TDO are two structurally unrelated proteins that both catalyse the degradation of the amino acid tryptophan and regulate the T cell response. Thus, inhibition of IDO1 or TDO restore the body’s immune response against cancer cells. IDO1 and TDO inhibitors may also increase the efficacy of immunotherapy with immune checkpoint inhibitors.
‘Current most advanced inhibitors lack selectivity over TDO and have suboptimal drug-like properties,’ Dr. Rogier Buijsman, Head of Chemistry of NTRC said. ‘This was the reason to embark on a screening project with the European Lead Factory, which gave us access to a library of more than 300,000 compounds collated from the libraries of seven pharmaceutical companies in the ELF consortium. Indeed screening at the ELF revealed several novel chemotypes that have never been linked to activity on tryptophan metabolizing enzymes and are derived from high-quality pharmaceutical compound collections.’
‘The IDO1 project complements our TDO project,’ Guido Zaman, Head of Biology of NTRC said. ‘IDO1 and TDO are expressed in different cancer cells. Both enzymes also have different roles in normal physiology. TDO is mainly expressed in the liver where it regulates systemic tryptophan levels, while expression of IDO1 is induced by interferon-gamma at sites of immune activity. Based on these differences, we have optimized our series on either being IDO1 or TDO selective.’
Originally, NTRC’s IDO1 and TDO inhibitor series were identified by ultra-high throughput screening at the Pivot Park Screening Centre using NTRC’s NFK GreenScreen™ technology. After transfer and optimization by NTRC chemists, selective IDO1 and TDO inhibitors with best-in-class properties have been identified.
NTRC is a precision medicine company dedicated to the development of new anti-cancer drugs. NTRC facilitates the development of novel therapies by providing cancer cell line profiling services (Oncolines™, SynergyFinder™ and OncolinesProfiler™), target residence time measurements for protein kinases (ResidenceTimer™), and developing new enabling technologies, such as NFK GreenScreen™. In addition, NTRC develops own novel targeted therapies based on small molecules, such as selective inhibitors of TTK (Mps1) protein kinase for chromosomal unstable tumours and inhibitors of the tryptophan metabolizing enzymes IDO1 and TDO for cancer immunotherapy. For more information please visit www.ntrc.nl or contact [email protected]