Immunotherapy is one of the recent advances in cancer treatment. Cancer immunotherapy makes use of the body’s immune system to help fight cancer. The amino acid tryptophan is an important regulator of the immune system by regulating the activation of T cells. Tumor cells express enzymes that oxidize tryptophan, thereby dampening the local T cell immune response against cancer cells. These two enzymes are indoleamine 2,3-dioxygenase (IDO1) and tryptophan 2,3-dioxygenase (TDO).

NTRC has developed a new fluorescent probe (NFK Green™) to measure the enzymatic activity of IDO1 and TDO and has applied the assay technology for high-throughput screening of small molecule compound libraries. The results are described in an article in the Journal of Biomolecular Screening, the leading journal of the drug discovery and screening community.

“Previous methods for screening of tryptophan metabolizing enzymes involved harsh assay conditions, toxic reagents, and heating of the reaction to 65 °C,” explains Dr. Suzanne van Gerwen, Sales Manager NTRC Services. “NFK GreenScreen™ uses ambient reaction conditions, and is a simple, addition-only assay. It can be used at the laboratory bench or in an automated setting.”

The NFK GreenScreen™ assay was validated for IDO1 and TDO by screening a library of 87,000 compounds at the Pivot Park Screening Centre, a neighboring company at the Pivot Park life sciences park in Oss.

“Screening of this library has revealed several new and interesting scaffolds,” Dr. Rogier Buijsman, Managing Director & Head of Chemistry said. Current, most advanced clinical IDO1 inhibitors show significant cross-reactivity with TDO, as demonstrated in the article. “This leaves room for improved, more selective compounds,” Buijsman adds.

The NFK GreenScreen™ assay technology was also validated for use in cell-based assays.

NFK GreenScreen™ is a commercial product that can be ordered at the website of NTRC.

NTRC is a privately-owned biotech company based at the Pivot Park, in Oss, The Netherlands. NTRC (Netherlands Translational Research Center B.V.) translates novel ideas in disease biology into small molecule drug candidates, using its proprietary technology platforms Oncolines™, SynergyFinder™, and ResidenceTimer™ . These technologies can be applied in an integrated drug discovery service, or ordered separately. For more information: E-mail: info@ntrc.nl ; or visit website: www.ntrc.nl