1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemELY 3000328Cat. No.: HY-15533CAS No.: 1373215-15-6分式: CHFNO分量: 484.52作靶點(diǎn): Cathepsin作通路: Metabolic Enzyme/Protease儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 50 mg/mL (103.19 mM)* means s

2、oluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液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請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。體內(nèi)實(shí)驗(yàn)請根據(jù)您的實(shí)驗(yàn)動物和給藥式選擇適當(dāng)?shù)娜芙獍福渲魄罢埾扰渲瞥吻宓膬湟?，再依次添加助溶?為保證實(shí)驗(yàn)結(jié)果的可靠性，體內(nèi)實(shí)驗(yàn)的作液，建議您現(xiàn)現(xiàn)

3、配，當(dāng)天使；澄清的儲備液可以根據(jù)儲存條件，適當(dāng)保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.16 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (5.16 mM); Clear solution3. 請依序添加每種溶劑： 10% DMSO 90% corn oil1/2 Master of

4、 Small Molecules 您邊的抑制劑師www.MedChemESolubility: 2.5 mg/mL (5.16 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 LY 3000328種有效，選擇性的 Cathepsin S (Cat S) 抑制劑，抑制和Cat S的 IC50 分別為7.7，1.67nM。IC50 & Target IC50: 7.75.85 nM (hCat S), 1.671.17 (mCat S) 1體外研究 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.體內(nèi)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