LY-3000328 - Cathepsin S 抑制剂 - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemELY 3000328Cat. No.: HY-15533CAS No.: 1373215-15-6分式: CHFNO分量: 484.52作靶点: Cathepsin作通路: Metabolic Enzyme/Protease储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 50 mg/mL (103.19 mM)* means s

2、oluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.0639 mL 10.3195 mL 20.6390 mL5 mM 0.4128 mL 2.0639 mL 4.1278 mL10 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，并请注意储备液的保存式和期限。体内实验请根据您的实验动物和给药式选择适当的溶解案，配制前请先配制澄清的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的作液，建议您现现

3、配，当天使；澄清的储备液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.16 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (5.16 mM); Clear solution3. 请依序添加每种溶剂： 10% DMSO 90% corn oil1/2 Master of

4、 Small Molecules 您边的抑制剂师www.MedChemESolubility: 2.5 mg/mL (5.16 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 LY 3000328种有效，选择性的 Cathepsin S (Cat S) 抑制剂，抑制和Cat S的 IC50 分别为7.7，1.67nM。IC50 & Target IC50: 7.75.85 nM (hCat S), 1.671.17 (mCat S) 1体外研究 LY3000328 maintains excellent in vitro potency and select

5、ivity. LY3000328 shows low in vitro CYP450inhibition (4%). At a 100 M concentration of LY3000328 there is only 6% displacement of 3H-astemizole inan assay with HEK293 membrane preparation, indicating low potential of hERG blockade 1. LY3000328 isa potent and specific inhibitor of cathepsin S (CatS).

6、 Inhibition of CatS activity in plasma would be 50% ofmaximal when LY3000328 plasma concentration is approximately 60 ng/mL 2.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 su

7、rface. It is shown that features of thedisease state in this model resemble those of human AAA. LY3000328 exhibits a dose-responsive aorticdiameter reduction at 1, 3, 10, and 30 mg/kg. At the lowest dose of 1 mg/kg of LY3000328, the aorticdiameter is reduced by 58%, then 83% at 3 mg/kg, and 87% at 1

8、0 mg/kg. The exposure (AUC) for bothcompounds increased in a dose-dependent manner, suggesting that the drug disposition properties ofLY3000328 are favorable 1.REFERENCES1. 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):1138-42.2. Payne CD, et al. Pharmacokinetics and pharmacodynamics of the cathepsin S inhibitor, LY3000328, in healthy subjects. Br J ClinPharmacol. 2014 Dec;78(6):1334-42.McePdfHeightCaution: Product has not been fully validated for medical ap