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I-BET-762

现货
Catalog No.
B1498
BET抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 950.00
现货
5mg
¥ 880.00
现货
10mg
¥ 1,350.00
现货
50mg
¥ 4,500.00
现货

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Background

I-BET-762 is a highly potent inhibitor of BET with IC50 values of 32.5–42.5 nM [1].

I-BET-762 is found to have high affinity with BET (Kd of 50.5–61.3 nM). It binds to the acetyl-lysine (AcK)-binding pocket of BET and competes with AcK. The structure of I-BET-762 allows it to bind with BET in ratio of 2:1 results in the high affinity of it. I-BET-762 also has high selectivity, it has no interaction with other bromodomain-containing proteins. I-BET-762 is reported to downregulate the expression of the genes which are induced by LPS, thus causing the decreased expression of LPS-inducible cytokines and chemokines. In vivo assay shows that I-BET-762 has the anti-inflammatory potential. Treatment of I-BET-762 can cure the mice which have started to develop symptoms of inflammatory disease [1].

References:
[1] Nicodeme E, Jeffrey KL, Schaefer U, Beinke S, Dewell S, Chung CW, Chandwani R, Marazzi I, Wilson P, Coste H, White J, Kirilovsky J, Rice CM, Lora JM, Prinjha RK, Lee K, Tarakhovsky A. Suppression of inflammation by a synthetic histone mimic. Nature. 2010 Dec 23;468 (7327):1119-23.

文献引用

1. Yang R, Wu Y, et al. "A super-enhancer maintains homeostatic expression of Regnase-1." Gene. 2018 May 16. pii: S0378-1119(18)30542-0. PMID:29777912
2. Kim SR, Lewis JM, et al. "BET inhibition in advanced cutaneous T cell lymphoma is synergistically potentiated by BCL2 inhibition or HDAC inhibition." Oncotarget. 2018 Jun 26;9(49):29193-29207. PMID:30018745
3. Fontanals-Cirera B, Hasson D, et al. "Harnessing BET Inhibitor Sensitivity Reveals AMIGO2 as a Melanoma Survival Gene." Mol Cell. 2017 Nov 16;68(4):731-744.e9. PMID:29149598
4. Ronald M. Evans,Michael Downes,et al. "Increasing storage of vitamin a, vitamin d and/or lipids." US Patent App. 15, 2016.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt423.9
Cas No.1260907-17-2
FormulaC22H22ClN5O2
Solubility≥21.195mg/mL in DMSO
Chemical Name2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide
SDFDownload SDF
Canonical SMILESCCNC(=O)CC1C2=NN=C(N2C3=C(C=C(C=C3)OC)C(=N1)C4=CC=C(C=C4)Cl)C
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]:

荧光共振能量转移(FRET)滴定

在有四乙酰化的组蛋白H4肽(200 nM)存在的条件下,在50 mM HEPES pH7.5, 50 mM NaCl, 0.5 mM CHAPS中对BRD2 (200 nM), BRD3 (100 nM) 和 BRD4 (50 nM) 进行I-BET滴定。平衡1小时后,在含0.05% (v/v) BSA 和 400 mM KF的实验缓冲液中加入2nM 铕穴状化合物标记的链霉亲和素和10 nM XL-665标记的anti-6His 抗体,使用FRET检测溴区蛋白:肽相互作用。使用Envision酶标仪(激发菠长320 nm,发射波长615 nm和665 nm)对实验板进行读数。

细胞实验 [2]:

细胞系

CD4+ T细胞

溶解方法

该化合物在DMSO中的溶解度> 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。

反应时间

125、250和500 nmol/L 处理120 h;

应用

I-BET-762处理CD4+ T细胞,诱导细胞中细胞因子的差异化变化,表现为上调抗炎基因(IL-10、Lag3与Egr2)的表达而抑制炎症因子(GM-CSF与IL-17)的表达。

动物实验 [1, 2]:

动物模型

C57BL/6小鼠模型

剂量

30 mg/kg、尾静脉注射给药、一天两次、持续2天;或500 nM

应用

I-BET-762 (30 mg/kg、尾静脉注射给药) 对内毒素休克和败血症的发生有显著的治疗效果,并且抑制体内炎症的发生;同时用I-BET-762处理自身反应性Th1T细胞,能干扰抑制自身反应性Th1T细胞诱导的体内病理学的改变。

注意事项

请于室内测试所有化合物的溶解度。实际溶解度和理论值可能略有不同,这是由实验系统的误差引起的,属于正常现象。

References:

1. Nicodeme, E., Jeffrey, K. L., Schaefer, U., Beinke, S., Dewell, S., Chung, C. W., Chandwani, R., Marazzi, I., Wilson, P., Coste, H., White, J., Kirilovsky, J., Rice, C. M., Lora, J. M., Prinjha, R. K., Lee, K. and Tarakhovsky, A. (2010) Suppression of inflammation by a synthetic histone mimic. Nature. 468, 1119-1123

2. Bandukwala, H. S., Gagnon, J., Togher, S., Greenbaum, J. A., Lamperti, E. D., Parr, N. J., Molesworth, A. M., Smithers, N., Lee, K., Witherington, J., Tough, D. F., Prinjha, R. K., Peters, B. and Rao, A. (2012) Selective inhibition of CD4+ T-cell cytokine production and autoimmunity by BET protein and c-Myc inhibitors. Proc Natl Acad Sci U S A. 109, 14532-14537

生物活性

描述 I-BET-762是一种有效的溴和额外C端结构域(BET)家族抑制剂,IC50值介于32.5-42.5 nM之间。
靶点 BET          
IC50 32.5–42.5 nM          

质量控制

化学结构

I-BET-762

相关生物数据

I-BET-762

相关生物数据

I-BET-762

相关生物数据

I-BET-762