Fragment-based approach to identify IDO1 inhibitor building blocks

Alice Coletti, Francesca Camponeschi, Elisa Albini, Francesco Antonio Greco, Vincenzo Maione, Chiara Custodi, Federica Iannia, Ursula Grohmann, Ciriana Orabona, Francesca Cantini, Antonio Macchiarulo

European Journal of Medicinal Chemistry
2017 vol: 141 pp: 169-177 doi: 10.1016/j.ejmech.2017.09.044

Indoleamine 2,3-dioxygenase 1 (IDO1) is attracting a great deal of interest as drug target in immune-oncology being highly expressed in cancer cells and participating to the tumor immune-editing process. Although several classes of IDO1 inhibitors have been reported in literature and patent applications, only few compounds have proved optimal pharmacological profile in preclinical studies to be advanced in clinical trials. Accordingly, the quest for novel structural classes of IDO1 inhibitors is still open. In this paper, we report a fragment-based screening campaign that combines Water-LOGSY NMR experiments and microscale thermophoresis approach to identify fragments that may be helpful for the development of novel IDO1 inhibitors as therapeutic agents in immune-oncology disorders.

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Topics: Tryptophan, IDO, Inhibitor, Immune, Cancer, Fragment-based, Water-LOGSY, Monolith – MicroScale Thermophoresis, MST, Proteins, Publications