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INCB024360 analogue

现货
Catalog No.
A3493
有效的和选择性的IDO1抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 880.00
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5mg
¥ 700.00
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10mg
¥ 1,050.00
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25mg
¥ 2,100.00
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50mg
¥ 3,150.00
Ship with 10-15 days

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Background

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.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt271.64
Cas No.914471-09-3
FormulaC9H7ClFN5O2
SynonymsINCB-024360;INCB 024360;INCB-24360;indoleamine-2,3-dioxygenase inhibitor INCB024360
Solubility≥13.55mg/mL in DMSO
Chemical Name4-[(3-chloro-4-fluoroanilino)-nitrosomethylidene]-1,2,5-oxadiazol-3-amine
SDFDownload SDF
Canonical SMILESC1=CC(=C(C=C1NC(=C2C(=NON2)N)N=O)Cl)F
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

激酶实验 [1]:

IDO酶活性测定

使用大肠杆菌表达N端被His标记了的人IDO,使其分离纯化至均一。IDO催化色氨酸吲哚核吡咯环的氧化裂解,产生N’-甲酰犬尿氨酸。该测试在室温下,在含20 mM抗坏血酸盐,3.5 μM亚甲蓝和0.2 mg/mL过氧化氢酶的50 mM磷酸钾缓冲液 (pH 6.5) 中,使用20 nM IDO和2 mM D-Trp,在室温下进行测定。在321 nm下,连续记录吸光度的增加(N’-甲酰犬尿氨酸形成),得到其初始反应速率。

细胞实验 [1]:

细胞系

Hela细胞和小鼠B16细胞

制备方法

在DMSO中的溶解度大于10 mM。若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。

反应条件

19 nM(对HeLa细胞的IC50值)以及46 nM(对小鼠B16细胞的IC50值)

实验结果

在HeLa细胞中,INCB024360 analogue选择性地抑制人IDO1的活性,其IC50值为19 nM。在小鼠B16细胞中,INCB024360 analogue抑制IDO,其IC50值为46 nM。

动物实验 [1]:

动物模型

携带分泌GM-CSF的B16肿瘤细胞的小鼠

给药剂量

25、50和75 mg/kg;皮下注射;每日2次,持续14天

实验结果

在携带分泌GM-CSF的B16肿瘤细胞的小鼠中,INCB024360 analogue(75 mg/kg,每日2次)呈剂量依赖性地抑制肿瘤生长。

其它注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

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.

生物活性

Description INCB024360 是一种强效的IDO1抑制剂,IC50值为10 nM。?/td>
靶点 IDO1          
IC50 67 nM          

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