BMS-986205 is a selective, irreversible inhibitor of indoleamine 2,3-dioxygenase 1 (IDO1), with an IC50 of 1.1μM in HEK293 cells overexpressing human IDO1[1, 2]. BMS-986205 possesses immunomodulatory and antitumor activities and has entered clinical trials for various cancer types, including bladder cancer, head and neck cancer, endometrial cancer, gastric cancer, melanoma, liver cancer, non-small cell lung cancer, and solid tumors[3, 4]. BMS-986205 can reverse the anti-autistic effects of Taprenepag by inhibiting IDO1[5]. BMS-986205 can inhibit the ubiquinone reduction site of respiratory chain complex I, thereby impairing mitochondrial ATP production and interfering with glycolysis and oxidative phosphorylation (OXPHOS)[6].
In vitro, treatment of Jurkat cells with BMS-986205 (0-100µM) for 72h induced cell death in a dose-dependent manner, with an IC50 value of 6.3μM[7].
In vivo, treatment of mice with unilateral ureteral obstruction (UUO) with BMS-986205 (10mg/kg) via intraperitoneal injection twice daily for 7 days reduced collagen deposition in the kidneys[8].
References:
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[2] Wang X X, Sun S Y, Dong Q Q, et al. Recent advances in the discovery of indoleamine 2, 3-dioxygenase 1 (IDO1) inhibitors[J]. Medchemcomm, 2019, 10(10): 1740-1754.
[3] Safdarian A R, Farhangnia P, Rezaei N. Indoleamine 2, 3-dioxygenase (IDO) and cancerous cells[M]//Cancerous Cells: Immunobiology of Tumors and Metastasis. Cham: Springer Nature Switzerland, 2025: 475-497.
[4] Le Naour J, Galluzzi L, Zitvogel L, et al. Trial watch: IDO inhibitors in cancer therapy[J]. Oncoimmunology, 2020, 9(1): 1777625.
[5] Wang K, Zhang S, Wang Y, et al. Taprenepag restores maternal–fetal interface homeostasis for the treatment of neurodevelopmental disorders[J]. Journal of Neuroinflammation, 2024, 21(1): 307.
[6] Dreute J, Stengel J, Becher J, et al. Synergistic targeting of cancer cells through simultaneous inhibition of key metabolic enzymes[J]. Cell Death & Differentiation, 2025: 1-18.
[7] Richards T, Brin E. Cell Based Functional Assays for IDO1 Inhibitor Screening and Characterization. Oncotarget, 9, 30814-30820[EB/OL].(2018)
[8] Jensen C G, Jensen M S, Tingskov S J, et al. Local inhibition of indoleamine 2, 3-dioxygenase mitigates renal fibrosis[J]. Biomedicines, 2021, 9(8): 856.