| Description | LY 3000328 (Cathepsin S inhibitor) is a potent, highly selective Cathepsin S (Cat S) inhibitor (IC50s: 7.7 and 1.67 nM for hCat S and mCat S). |
| In vitro | LY3000328在体外对CYP450的抑制作用低(4%) [1]。LY3000328是一种强效且特异性的cathepsin S (CatS)抑制剂。当LY3000328的血浆浓度大约为60 ng/mL时，可将CatS在血浆中的活性抑制50% [2]。 |
| In vivo | LY3000328的效用在腹主动脉瘤（AAA）的小鼠模型中进行了研究。在该模型中，通过将CaCl2应用于非腔内表面来诱导炎症。研究显示，该模型中的疾病状态特征与人类AAA的特征相似。LY3000328（1, 3, 10, 30 mg/kg）显示出剂量反应性的主动脉直径减少效果。当LY3000328的最低剂量为1 mg/kg时，主动脉直径减少了58%，在3 mg/kg时减少了83%，在10 mg/kg时减少了87%。两种化合物的暴露量（AUC）随着剂量的增加而增加，表明LY3000328的药物配置特性是有利的[1]。 |
| Target activity | Cathepsin S (mouse):1.67 nM, Cathepsin S (human):7.7 nM |
| Synonyms | Cathepsin S inhibitor |
| molecular weight | 484.52 |
| Molecular formula | C25H29FN4O5 |
| CAS | 1373215-15-6 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| Solubility | DMSO: 48 mg/mL (99.06 mM) |
| 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. 2. Payne CD, et al. Pharmacokinetics and pharmacodynamics of the cathepsin S inhibitor, LY3000328, in healthy subjects. Br J Clin Pharmacol. 2014 Dec;78(6):1334-42. |