INCB-024360
(Synonyms: 艾卡哚司他,INCB 024360) 目录号 : GC17968
An IDO1 inhibitor
Cas No.:1204669-58-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Kinase experiment [1]: | |
|
Kinase assays |
The assays were performed at room temperature using 20 nM IDO and 2 mM D-Trp in the presence of 20 mM ascorbate, 3.5 μM methylene blue and 0.2 mg/mL catalase in 50 mM potassium phosphate buffer (pH 6.5). The initial reaction rates were recorded by continuously following the absorbance increase at 321 nm due to the formation of N’-formlylkynurenine. |
| Cell experiment [2]: | |
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Cell lines |
HeLa cells and human T cells |
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Preparation method |
The solubility of this compound in DMSO is >15.7mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
|
Reacting condition |
0.001~2 μM |
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Applications |
IDO1 induction significantly suppressed T-cell proliferation in coculture systems, and the suppression was effectively reversed by INCB024360. IDO1 also increases IFN-γ production, and reduces conversion to regulatory T (Treg)–like cells. |
| Animal experiment [2]: | |
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Animal models |
C57BL/6 mice bearing IDO1-expressing PAN02 pancreatic carcinomas |
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Dosage form |
25 and 100 mg/kg, orally, twice a day for 25 days |
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Application |
The growth of tumors in syngeneic immunocompetent C57BL/6 mice was inhibited in a dose-dependent fashion. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Yue EW1, Douty B, Wayland B, et al. Discovery of potent competitive inhibitors of indoleamine 2,3-dioxygenase with in vivo pharmacodynamic activity and efficacy in a mouse melanoma model. Med Chem. 2009 Dec 10;52(23):7364-7. [2] Liu X, Shin N, Koblish HK, Yang G, Wang Q, Wang K, Leffet L, Hansbury MJ, Thomas B, Rupar M et al: Selective inhibition of IDO1 effectively regulates mediators of antitumor immunity. Blood. 2010 Apr 29;115(17):3520-30. | |
INCB024360 is a potent and selective inhibitor of IDO1 with IC50 value of 10 nM. [1]
IDO means indoleamine-pyrrole 2, 3-dioxygenase. IDO is an enzyme which is encoded by the IDO1 gene. IDO is the rate-limiting and first enzyme of tryptophan which is one amino acid of human catabolism through kynurenine pathway. The decrease of L-tryptophan can cause halted growth of T cells as well as microbes. IDO belongs to immunomodulatory enzyme. It is produced by some activated macrophages and immunoregulatory cells. IDO is overexpressed in a wide range of cancer cells such as lung, prostatic, pancreatic, colorectal cancer. It is indentified to help cancer cells to escape the immune system by reducing the level of L-tryptophan in the microenvironment of cells.[2]
In Hela cells, INCB024360 selectively inhibits the activity of human IDO1 with IC50 values of about 10nM. On the other hand INCB024360demonstrates little inhibition activity against human IDO1 or TDO (tryptophan 2, 3-dioxygenase). In coculture systems of human dendritic cells with allogeneic lymphocytes, INCB024360 inhibit T-cell proliferation and cytokine production and influence the viability of NK cells. INCB024360 also increase CD86 expression and promote activation T cells by DCs.
In mice bearing IDO1-expressing PAN02 pancreatic tumour, ICB024360 significantly inhibit tumour growth in lymphocyte-dependent manner.[1] INCB024360 decreased plasma kynurenine levels by inhibiting the activity of IDO1 at 50 mg/kg in native C57BL/6 mice. INCB024360 also inhibit tumor growth at 100mg/kg in CT26 tumor bearing mice.[3]
References:
[1]. Liu X, Shin N, Koblish HK, Yang G, Wang Q, Wang K, Leffet L, Hansbury MJ, Thomas B, Rupar M et al: Selective inhibition of IDO1 effectively regulates mediators of antitumor immunity. Blood, 115(17):3520-3530.
[2]. Uyttenhove C, Pilotte L, Theate I, Stroobant V, Colau D, Parmentier N, Boon T, Van den Eynde BJ: Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nat Med 2003, 9(10):1269-1274.
[3]. Koblish HK, Hansbury MJ, Bowman KJ, Yang G, Neilan CL, Haley PJ, Burn TC, Waeltz P, Sparks RB, Yue EW et al: Hydroxyamidine inhibitors of indoleamine-2,3-dioxygenase potently suppress systemic tryptophan catabolism and the growth of IDO-expressing tumors. Mol Cancer Ther, 9(2):489-498.
| 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。