INCB-024360
(Synonyms: 艾卡哚司他,INCB 024360) 目录号 : GC17968
INCB-024360，又名epacadostat，是一种口服小分子选择性IDO1抑制剂（IC50 = 71.8nM）。
Cas No.:1204669-58-8
Sample solution is provided at 25 µL, 10mM.
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INCB-024360, also known as epacadostat, is an oral small molecule selective IDO1 inhibitor (IC50 = 71.8nM) [1]. INCB-024360 can selectively inhibit IDO1 enzyme activity and block the pathway of tryptophan metabolism to kynurenine [2]. INCB-024360 is mainly used to treat advanced or metastatic solid tumors [3-4].
In SKOV-3 cells, INCB-024360 (10-3-104nM; 24h, 48h, 72h) increases IDO1 protein expression [5]. In HT-29 cells, INCB-024360 (10μM; 96h) reduced cell viability [6]. In 4T1 cells, INCB-024360 (1μM; 24h, 48h) sensitize pulmonary metastases to agents targeting hypoxia/nutrient deprivation survival mechanisms [7].
In colon carcinoma xenograft mice model, INCB-024360 (100mg/kg; ig; 2h) effectively inhibits the metabolism of tryptophan to kynurenine by achieving high drug exposure in areas with high IDO1 expression, significantly reducing the Kyn/Trp ratio, thereby restoring immune activity and enhancing anti-tumor efficacy [8]. In in wild-type and PD-1-negative mice, co-administration of the CTLA-4 blocking antibody 9D9 and/or the IDO1 inhibitor INCB-024360 (300mg/kg; ig; 27d) (to mimic the effects of PD1 blockade) synergistically induced liver injury and immune cell infiltration [9]. In TAC-induced WT mice, INCB-024360 (50mg/kg; sc; 4 weeks) inhibits IDO1 and ameliorates pathological cardiac hypertrophy and remodeling [10].
References:
[1]. Liu X, Shin N, Koblish HK, et al. Selective inhibition of IDO1 effectively regulates mediators of antitumor immunity. Blood, The Journal of the American Society of Hematology. 2010 Apr 29; 115(17): 3520-3230.
[2]. Hao X, Chen Z, Li H, et al. Small-molecule drugs in immunotherapy. Mini Reviews in Medicinal Chemistry. 2023 Jul 1;23(13):1341-1359.
[3]. Alford B, Cox K, Soliman H. IDO1 inhibitors for cancer immunotherapy. Drugs of the Future. 2016 Sep 1; 41(9): 553-559.
[4]. Hellmann MD, Gettinger S, Chow LQ, et al. Phase 1 study of epacadostat in combination with atezolizumab for patients with previously treated advanced nonsmall cell lung cancer. International Journal of Cancer. 2020 Oct 1; 147(7): 1963-1969.
[5]. Rossini S, Ambrosino S, Volpi C, et al. Epacadostat stabilizes the apo-form of IDO1 and signals a pro-tumorigenic pathway in human ovarian cancer cells. Frontiers in Immunology. 2024 Jan 25; 15: 1346686.
[6]. Zhou Y, Tao Q, Luo C, et al. Epacadostat Overcomes Cetuximab Resistance in Colorectal Cancer by Targeting IDO‐Mediated Tryptophan Metabolism. Cancer Science. 2025 Mar 18.
[7]. Shen SC, Dey S, DuHadaway JB, et al. Neovascular pruning by IDO1 inhibitors can potentiate immunogenic cytotoxicity of ischemia-targeted agents to synergistically enhance anti-PD-1 responsiveness. Journal for Immunotherapy of Cancer. 2025 May 30; 13(5): e011398.
[8]. Poncelet L, Ait-Belkacem R, Marillier R, et al. Target exposure and pharmacodynamics study of the indoleamine 2, 3-dioxygenase-1 (IDO-1) inhibitor epacadostat in the CT26 mouse tumor model. Journal of Pharmaceutical and Biomedical Analysis. 2019 Jun 5; 170: 220-227.
[9]. Affolter T, Llewellyn HP, Bartlett DW, et al. Inhibition of immune checkpoints PD-1, CTLA-4, and IDO1 coordinately induces immune-mediated liver injury in mice. PLoS One. 2019 May 21; 14(5): e0217276.
[10]. Wang Y, Song J, Yu K, et al. Indoleamine 2, 3-dioxygenase 1 deletion-mediated kynurenine insufficiency inhibits pathological cardiac hypertrophy. Hypertension. 2023 Oct; 80(10): 2099-2111.
INCB-024360，又名epacadostat，是一种口服小分子选择性IDO1抑制剂（IC50 = 71.8nM） [1]。INCB-024360可以选择性抑制IDO1酶活性，阻断色氨酸代谢为犬尿氨酸的途径 [2]。INCB-024360主要用于治疗晚期或转移性实体瘤 [3-4]。
在SKOV-3细胞中，INCB-024360（10-3-104nM；24h、48h、72h）可增加IDO1蛋白的表达 [5]。在HT-29细胞中，INCB-024360（10μM；96h）可降低细胞活力 [6]。在4T1细胞中，INCB-024360（1μM；24h、48h）可增强肺转移瘤对靶向缺氧/营养剥夺生存机制的药物的敏感性 [7]。
在结肠癌异种移植小鼠模型中，INCB-024360（100mg/kg；ig；2h）通过在IDO1高表达区域实现高药物暴露，有效抑制色氨酸代谢为犬尿氨酸，显著降低犬尿氨酸/色氨酸比例，从而恢复免疫活性并增强抗肿瘤疗效 [8]。在野生型和PD-1阴性小鼠中，联合应用CTLA-4阻断抗体9D9和/或IDO1抑制剂INCB-024360（300mg/kg；ig；27d）（以模拟PD-1阻断的作用）可协同诱导肝损伤和免疫细胞浸润 [9]。在TAC诱导的WT小鼠中，INCB-024360（50mg/kg；sc；4周）抑制IDO1并改善病理性心脏肥大和重塑 [10]。
| Cell experiment [1]: | |
Cell lines | SKOV-3 cells |
Preparation Method | The cell viability of SKOV-3 cells exposed to INCB-024360 was analyzed by MTT assay. Cells were seeded at the final concentration of 5 x 103 cells/100µL/well in a 96-well plate, and treated with INCB-024360 for 24, 48, and 72 hours. Vehicle-treated cells were used as control. At each time point, the stimulus was removed and cells were provided with 110µL/well of complete medium containing MTT at the final concentration of 0.45mg/mL. After 4 hours at 37℃, 100µL/well of the solubilization buffer (SDS 10% in HCl 0.01M) were added and cells were incubated overnight at 37℃. The day after, cell viability was determined by measuring the absorbance at 570nm, by using a UV/visible spectrophotometer. |
Reaction Conditions | 10-3-104nM; 24h, 48h, 72h |
Applications | INCB-024360 increases IDO1 protein expression in SKOV-3 cells. |
| Animal experiment [2]: | |
Animal models | Colon carcinoma xenograft mice model |
Preparation Method | Colon carcinoma CT26 cell line was subcutaneously grafted into BALB/c mice (Charles River Laboratories, France). Mice were randomized and treatment was started when tumors had an average size of 70-120mm3. Mice were treated by oral gavage with the IDO1 inhibitor, INCB-024360 at 100mg/kg, and then sacrificed 2h later. |
Dosage form | 100mg/kg; ig; 2h |
Applications | INCB-024360 effectively inhibits the metabolism of tryptophan to kynurenine by achieving high drug exposure in areas with high IDO1 expression, significantly reducing the Kyn/Trp ratio, thereby restoring immune activity and enhancing anti-tumor efficacy. |
References: | |
| Cas No. | 1204669-58-8 | SDF | |
| 别名 | 艾卡哚司他,INCB 024360 | ||
| 化学名 | (E)-N'-(3-bromo-4-fluorophenyl)-N-hydroxy-4-((2-(sulfamoylamino)ethyl)amino)-1,2,5-oxadiazole-3-carboximidamide | ||
| Canonical SMILES | BrC1=C(F)C=CC(/N=C(NO)\C2=NON=C2NCCNS(N)(=O)=O)=C1 | ||
| 分子式 | C11H13BrFN7O4S | 分子量 | 438.23 |
| 溶解度 | ≥ 17.1mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.2819 mL | 11.4095 mL | 22.8191 mL |
| 5 mM | 0.4564 mL | 2.2819 mL | 4.5638 mL |
| 10 mM | 0.2282 mL | 1.141 mL | 2.2819 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
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- Purity: >99.50%
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