Unveiling DN-016: A Potent and Selective IDO1 Inhibitor for Cancer Immunotherapy

The abstract discusses the significance of Indoleamine-2,3-dioxygenase (IDO1) as a target for cancer immunotherapy. There is a surge of interest in inhibiting the Trp-to-Kyn pathway to manage immunosuppression in various cancers. Pharmaceutical entities are actively pursuing clinical trials for IDO1 inhibitors such as INCB024360, GDC-0919, indoximod, and BMS-986205. Notably, at the 2017 ASCO Annual Meeting, it was highlighted that head and neck squamous cell carcinoma patients showed positive responses to combinations involving epacadostat with pembrolizumab and nivolumab. Furthermore, epacadostat was found to be highly effective in combination with PD-1 inhibitors for solid tumors. The 32nd SITC annual meeting revealed promising early clinical trial results for BMS-986205 combined with Opdivo. The authors previously reported on the dual IDO1/TDO inhibitor DN131 and now introduce DN-016, a more potent and selective IDO1 inhibitor with superior drug-like characteristics. DN-016, a novel heterocyclic compound, showed exceptional in vitro potency against hela IDO1 cells and favorable ADME properties. It also demonstrated high oral bioavailability in rat pharmacokinetic studies and is currently under preclinical evaluation both as a standalone treatment and in combination with a PD-1 inhibitor. The abstract concludes by emphasizing DN-016's remarkable in vitro potency, selectivity, and pharmacokinetic profile, with further preclinical data to be presented.

Reference: Chen S, Liu F, Guo H, et al. Discovery of DN-016: A highly potent, selective and orally available IDO1 inhibitor for treating cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5555.