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IDO inhibitors

The indoleamine 2,3-dioxygenase (IDO) contributes to tumoral immune resistance. Blocking this enzyme by inhibitors is a promising approach in the development of new anticancer drugs

Description

Tryptophan catabolism mediated by indoleamine 2,3-dioxygenase (IDO) is an important mechanism of peripheral immune tolerance contributing to tumoral immune resistance. IDO inhibition is thus an active area of research in drug development. Recently, our group has shown that tryptophan 2,3-dioxygenase (TDO), an unrelated hepatic enzyme also catalyzing the first step of tryptophan degradation, is also expressed in many tumors and that this expression prevents tumor rejection by locally depleting tryptophan.

The aim is to design new specific inhibitors of TDO and characterize their interactions with the enzyme using theoretical and experimental approaches.

The first series is based on 3-(2-(pyridyl)ethenyl)indoles and more than 70 derivatives were synthesized and evaluated on TDO. This series led to the identification of very promising compound displaying good TDO inhibition (Ki = 5.5 microM).

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