LY 3000328
目录号 : KM8771 CAS No. : 1373215-15-6 纯度 : 98%

LY 3000328 是一种有效,选择性的 Cathepsin S (Cat S) 抑制剂,抑制人和小鼠Cat S的 IC50 分别为7.7,1.67 nM。

规格 价格 是否有货 数量
2mg
In-stock
5mg
In-stock
10mg
In-stock
50mg
In-stock
100mg 询价 In-stock

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生物活性

LY 3000328 is a potent and selective Cathepsin S (Cat S) inhibitor with IC50s of 7.7 and 1.67 nM for hCat S and mCat S, respectively.

体外研究

LY3000328 maintains excellent in vitro potency and selectivity. LY3000328 shows low in vitro CYP450 inhibition (<15% at 10 μM for CYP3A4, CYP2D6, and CYP2C9); low in vitro metabolism in mouse, rat, dog, and human liver microsomes (<20% after 30 min incubation at 4 μM); and good permeability (MDCK A-B>4%). At a 100 μM concentration of LY3000328 there is only 6% displacement of [H]-astemizole in an assay with HEK293 membrane preparation, indicating low potential of hERG blockade. LY3000328 is a potent and specific inhibitor of cathepsin S (CatS). Inhibition of CatS activity in plasma would be 50% of maximal when LY3000328 plasma concentration is approximately 60 ng/mL.

体内研究

The efficacies of LY3000328 is studied in a mouse model of abdominal aortic aneurysm (AAA). In this model, inflammation is induced using CaCl2 applied to the ablumenal surface. It is shown that features of the disease state in this model resemble those of human AAA. LY3000328 exhibits a dose-responsive aortic diameter reduction at 1, 3, 10, and 30 mg/kg. At the lowest dose of 1 mg/kg of LY3000328, the aortic diameter is reduced by 58%, then 83% at 3 mg/kg, and 87% at 10 mg/kg. The exposure (AUC) for both compounds increased in a dose-dependent manner, suggesting that the drug disposition properties of LY3000328 are favorable.

分子式
C24H28N2O5.H2O
分子量
484.52
CAS号
1373215-15-6
运输条件

Room temperature in continental US; may vary elsewhere.

储存方式
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
溶解性数据
In Vitro: 

DMSO : ≥ 50 mg/mL (103.19 mM)

* "≥" means soluble, but saturation unknown.

配制储备液
浓度 溶剂体积 质量 1 mg 5 mg 10 mg
1 mM 2.0639 mL 10.3195 mL 20.6390 mL
5 mM 0.4128 mL 2.0639 mL 4.1278 mL
10 mM 0.2064 mL 1.0319 mL 2.0639 mL
*

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, 6 months; -20°C, 1 month。-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。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液,再依次添加助溶剂:

——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议您现用现配,当天使用; 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶

  • 1.

    请依序添加每种溶剂: 10% DMSO    40% PEG300    5% Tween-80    45% saline

    Solubility: ≥ 2.5 mg/mL (5.16 mM); Clear solution

    此方案可获得 ≥ 2.5 mg/mL (5.16 mM,饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀;向上述体系中加入50 μL Tween-80,混合均匀;然后继续加入 450 μL生理盐水定容至 1 mL。

  • 2.

    请依序添加每种溶剂: 10% DMSO    90% (20% SBE-β-CD in saline)

    Solubility: ≥ 2.5 mg/mL (5.16 mM); Clear solution

    此方案可获得 ≥ 2.5 mg/mL (5.16 mM,饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中,混合均匀。

  • 3.

    请依序添加每种溶剂: 10% DMSO    90% corn oil

    Solubility: ≥ 2.5 mg/mL (5.16 mM); Clear solution

    此方案可获得 ≥ 2.5 mg/mL (5.16 mM,饱和度未知) 的澄清溶液,此方案不适用于实验周期在半个月以上的实验。

    以 1 mL 工作液为例,取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中,混合均匀。

临床试验
科研文献
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