| CAS |
No.1204669-58-8 |
| 中文名称 |
艾卡哚司他 |
| 英文名称 |
Epacadostat |
| 别名 |
;INCB24360;INCB024360; |
| 分子式 |
C11H13BrFN7O4S |
| 分子量 |
438.23 |
| 溶解性 |
Soluble in DMSO ≥5mg/mL(Need ultrasonic) |
| 纯度 |
≥98% |
| 外观(性状) |
White to off-white Solid |
| 储存条件 |
Powder:2-8℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year |
| MDL |
MFCD26142934 |
| SMILES |
O=S(NCCNC1=NON=C1/C(NC2=CC=C(F)C(Br)=C2)=N/O)(N)=O |
| 靶点 |
Indoleamine 2,3-Dioxygenase (IDO) |
| 通路 |
Immunology & Inflammation;Metabolic Enzyme&Protease |
| 背景说明 |
Epacadostat是一种有效,选择性的 IDO1 抑制剂。 |
| 生物活性 |
Epacadostat (INCB 024360) is a potent and selective indoleamine 2，3-dioxigenase 1 (IDO1) inhibitor with an IC50 of 71.8 nM.[1-3] |
| In Vitro |
在细胞测定中，Epacadostat (INCB 024360) 选择性抑制人 IDO1，IC50 值约为 10 nM，表明对其他相关酶 (例如 IDO2 或色氨酸 2，3-双加氧酶 (TDO)) 几乎没有活性。Epacadostat (INCB 024360) 也对小鼠 IDO1 表现出显著活性，IC50 值为 52.4 nM±15.7 nM，在使用小鼠 IDO1 转染的 HEK293/MSR 细胞的类似测定中[1]。 |
| In Vivo |
携带 CT26 肿瘤的雌性 Balb/c 小鼠用 100 mg/kg 的 Epacadostat 口服处理，每天两次，持续 12 天。Epacadostat (INCB 024360) 在血浆、肿瘤和淋巴结中等效地抑制犬尿氨酸。在初始 C57BL/6 小鼠中，50 mg/kg Epacadostat (INCB 024360) 可在 1 小时内降低血浆犬尿氨酸水平，并且这些水平在 8 小时的时间过程中保持至少 50% 的抑制[2]。 |
| 细胞实验 |
To determine Epacadostat activity against IDO in recombinant cells， HEK293/MSR cells are transiently transfected with full-length human or mouse IDO1， or mouse IDO2 cDNA， with Transit-293 transfection reagent or Lipofectamine 2000 reagents. Epacadostat (INCB 024360) at different concentrations is added to the recovered transfected cells seeded at 2×104 cells per well in a 96-well plate (200 μL/well). The cells are incubated for 2 days， and kyn in the supernatants is measured as described in the HeLa cell assay. The tryptophan 2，3-dioxygenase (TDO) assay is performed similarly with HEK293/MSR cells transfected with a human TDO expression vector[1]. |
| 动物实验 |
Mice[2] The female C57BL/6 mice are dosed orally with 50 mg/kg Epacadostat. C57BL/6 wild-type or Ido1-/--deficient mice are administered a single oral dose of Epacadostat (INCB 024360)， at which point food is removed from the cages until after the 8-h time point. At various time points after dosing， mice are euthanized and blood is collected by cardiac puncture. Plasma is analyzed for the presence of Epacadostat (INCB 024360)， tryptophan， and kynurenine according to the methods below. |
| 数据来源文献 |
[1]. Liu X， et al. Selective inhibition of IDO1 effectively regulates mediators of antitumor immunity. Blood. 2010 Apr 29;115(17):3520-30.
[2]. Koblish HK， et al. Hydroxyamidine inhibitors of indoleamine-2，3-dioxygenase potently suppress systemic tryptophan catabolism and the growth of IDO-expressing tumors. Mol Cancer Ther. 2010 Feb;9(2):489-98.
[3]. Fu R， et al. LW106， a novel indoleamine 2，3-dioxygenase 1 inhibitor， suppresses tumour progression by limiting stroma-immune crosstalk and cancer stem cell enrichment in tumour micro-environment. Br J Pharmacol. 2018 Jul;175(14):3034-3049. |
| 规格 |
5mg 10mg 25mg 50mg 100mg |
| 单位 |
瓶 |
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