INCB024360 analogue
(Synonyms: 4-氨基-N-(3-氯-4-氟苯基)-N'-羟基-1,2,5-恶二唑-3-甲脒,INCB-024360;INCB 024360;INCB-24360;indoleamine-2,3-dioxygenase inhibitor INCB024360) 目录号 : GC15846
A selective IDO1 inhibitor
Cas No.:914471-09-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Kinase experiment [1]: | |
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IDO enzyme assays |
Human IDO with an N-terminal His tag was expressed in E.coli and purified to homogeneity. IDO catalyzed the oxidative cleavage of the pyrrole ring of the indole nucleus of tryptophan to yield N’-formylkynurenine. 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 [1]: | |
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Cell lines |
Hela cells and murine B16 cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. 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. |
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Reaction Conditions |
19 nM (the IC50 value for Hela cells) and 46 nM (the IC50 value for murine B16 cells) |
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Applications |
In Hela cells, INCB024360 analogue selectively inhibited the activity of human IDO1 with an IC50 value of 19 nM. In murine B16 cells, INCB024360 analogue inhibited IDO with an IC50 value of 46 nM. |
| Animal experiment [1]: | |
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Animal models |
Mice bearing GM-CSF-secreting B16 tumors |
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Dosage form |
25, 50 and 75 mg/kg; s.c.; b.i.d, for 14 days |
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Applications |
In mice bearing GM-CSF-secreting B16 tumors, INCB024360 analogue (75 mg/kg, b.i.d.) inhibited tumor growth in a dose-dependent manner. |
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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. J Med Chem. 2009 Dec 10;52(23):7364-7. | |
INCB024360 analogue is a potent and selective inhibitor of IDO1 with IC50 value of 67 nM. [1]
IDO (indoleamine-pyrrole 2, 3-dioxygenase) 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 analogue selectively inhibited the activity of human IDO1 with IC50 value of 19 nM. On the other hand, INCB024360 analogue demonstrated little inhibition activity against TDO (tryptophan 2, 3-dioxygenase). In murine B16 cells, INCB024360 analogue inhibited IDO with IC50 value of 46 nM [1].
In naive C57BL/6 mice, 100 mg/kg INCB024360 analogue injected subcutaneously reduced kynurenine levels by >50% via inhibition of IDO activity. In C57BL/6 mice bearing GM-CSF- secreting B16 tumors, INCB024360 analogue (25, 50, and 75 mg/kg b.i.d.) injected subcutaneously for 14 days dose-dependently inhibited tumor growth [1].
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. J Med Chem. 2009 Dec 10;52(23):7364-7.
[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.
| Cas No. | 914471-09-3 | SDF | |
| 别名 | 4-氨基-N-(3-氯-4-氟苯基)-N'-羟基-1,2,5-恶二唑-3-甲脒,INCB-024360;INCB 024360;INCB-24360;indoleamine-2,3-dioxygenase inhibitor INCB024360 | ||
| 化学名 | 4-[(3-chloro-4-fluoroanilino)-nitrosomethylidene]-1,2,5-oxadiazol-3-amine | ||
| Canonical SMILES | C1=CC(=C(C=C1NC(=C2C(=NON2)N)N=O)Cl)F | ||
| 分子式 | C9H7ClFN5O2 | 分子量 | 271.64 |
| 溶解度 | ≥ 13.55mg/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 | 3.6813 mL | 18.4067 mL | 36.8134 mL |
| 5 mM | 0.7363 mL | 3.6813 mL | 7.3627 mL |
| 10 mM | 0.3681 mL | 1.8407 mL | 3.6813 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。