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Cathepsin S inhibitor

现货
Catalog No.
A3284
抑制MHCII抗原呈递
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 2,500.00
现货
5mg
¥ 2,120.00
现货
10mg
¥ 2,744.00
现货

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Background

Ki: 0.185 nM

Cathepsin S is a lysosomal cysteine protease, playing an important role in antigen presentation. The inhibition of Cathepsin S is expected to result in immunosuppression, which makes this enzyme an attractive target to potentially treat autoimmune and inflammatory diseases. Cathepsin S inhibitor is a novel Cathepsin S inhibitor.

In vitro: Cathepsin S inhibitor was a slow, tight-binding reversible inhibitor of recombinant cathepsin S, exhibiting greater selectivity for cathepsin S compared to cathepsin B [1].

In vivo: No animal in vivo data available currently

Clinical trial: Oral Cathepsin S inhibitor that blocked MHCII antigen presentation could result in a T-cell-selective immunosuppressant agent with improved safety over the current standard of care for the treatment of rheumatoid arthritis, psoriasis, multiple sclerosis and other autoimmune-based inflammatory diseases [2].

References:
[1] Wiener JJ, Sun S, Thurmond RL.  Recent advances in the design of cathepsin S inhibitors. Curr Top Med Chem. 2010;10(7):717-32.
[2] Lee-Dutra A, Wiener DK, Sun S.  Cathepsin S inhibitors: 2004-2010. Expert Opin Ther Pat. 2011;21(3):311-37.

文献引用

1. Steimle A, Gronbach K, et al. "Symbiotic gut commensal bacteria act as host cathepsin S activity regulators." J Autoimmun. 2016 Jul 30. PMID:27484364

Chemical Properties

StorageStore at -20°C
M.Wt484.52
Cas No.1373215-15-6
FormulaC25H29FN4O5
Solubility≥24.25 mg/mL in DMSO, <2.47 mg/mL in EtOH, <2.13 mg/mL in H2O
Chemical Name[(3R,4S)-4-[(4-fluorobenzoyl)amino]-6-[4-(oxetan-3-yl)piperazin-1-yl]-3,4-dihydro-2H-chromen-3-yl] N-methylcarbamate
SDFDownload SDF
Canonical SMILESCNC(=O)OC1COC2=C(C1NC(=O)C3=CC=C(C=C3)F)C=C(C=C2)N4CCN(CC4)C5COC5
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

酶学实验 [1]:

激酶检测

Cat S, mCat S, Cat B 和 Cat L酶学试验通过将待测酶加入到含有FRET(浓度为其Km)的50毫摩尔磷酸钠缓冲液中(pH 6.5)中进行,该缓冲液同时还含有2.5毫摩尔DTT、2.5毫摩尔EDTA以及0.01% Triton X-100。 Cat V 和 Cat K酶学试验的步骤同上,只是缓冲液换成含有2.5毫摩尔DTT、2.5毫摩尔EDTA以及0.01% Triton X-100的0.1摩尔的乙酸钠(pH5.5)。人Cat S, 小鼠Cat S, 人Cat L, 人Cat B, 人Cat K,人Cat V 以及人Cat F 酶的Km值分别为25, 25, 20, 37.5, 35, 35 以及 25 微摩尔。

动物实验 [1]:

动物模型

小鼠腹主动脉瘤模型

剂量

1, 3, 10和 30 mg/kg,口服,一天两次

应用

通过小鼠腹主动脉瘤模型对Cathepsin S inhibitor的疗效进行了考察,结果显示Cathepsin S inhibitor能够在1-30 mg/kg范围内剂量依赖性地减小小鼠主动脉直径。在最低剂量1 mg/kg,Cathepsin S inhibitor能够减少58%的主动脉直径,在3和10 mg/kg可以分别减少83%和87%的主动脉直径。

注意事项

请测试所有化合物在室内的溶解度,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] Jadhav PK, et al. Discovery of Cathepsin S Inhibitor LY3000328 for the Treatment of Abdominal Aortic Aneurysm. ACS Med Chem Lett. 2014 Aug 27;5(10):1138-42.

生物活性

Cathepsin S inhibitor是重组Cathepsin S紧密结合的可逆抑制剂(Ki = 185 pM)。与cathepsin B (Ki = 76 nM)相比,对cathepsin S具有约410倍的更大选择性。
靶点 cathepsin S          
Ki 185pM          

质量控制

化学结构

Cathepsin S inhibitor