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:
[1] Cherney E C, Zhang L, Nara S, et al. Discovery and preclinical evaluation of BMS-986242, a potent, selective inhibitor of indoleamine-2, 3-dioxygenase 1[J]. ACS Medicinal Chemistry Letters, 2021, 12(2): 288-294.
[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.
BMS-986205是一种选择性的不可逆的吲哚胺2,3-双加氧酶1（IDO1）的抑制剂，在过表达人IDO1的HEK293细胞中，IC50值为1.1μM[1, 2]。BMS-986205具有免疫调节和抗肿瘤活性，已进入多种癌症类型的临床试验，包括膀胱癌、头颈癌、子宫内膜癌、胃癌、黑色素瘤、肝癌、非小细胞肺癌和实体瘤等[3, 4]。BMS-986205能够通过抑制IDO1逆转Taprenepag的抗自闭症效果[5]。BMS-986205能够抑制呼吸链复合物I的泛醌还原位点，从而损害线粒体ATP的生成，同时干扰糖酵解和氧化磷酸化（OXPHOS）[6]。
在体外，BMS-986205（0-100µM）处理Jurkat细胞72h，以剂量依赖性方式诱导了细胞死亡，IC50值为6.3μM[7]。
在体内，BMS-986205（10mg/kg）通过每日两次腹腔注射给药治疗单侧输尿管梗阻（UUO）小鼠7天，减轻了小鼠肾脏胶原沉积[8]。