LY 3000328_product_DataBase

Bioactivity

LY 3000328 (Z-FL-COCHO) 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.

Invitro

LY 3000328 maintains excellent in vitro potency and selectivity. LY 3000328 shows low in vitro CYP450 inhibition (4%). At a 100 μM concentration of LY 3000328 there is only 6% displacement of [3H]-astemizole in an assay with HEK293 membrane preparation, indicating low potential of hERG blockade[1]. LY 3000328 is a potent and specific inhibitor of cathepsin S (CatS). Inhibition of CatS activity in plasma would be 50% of maximal when LY 3000328 plasma concentration is approximately 60 ng/mL[2].

In Vivo

The efficacies of LY 3000328 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. LY 3000328 exhibits a dose-responsive aortic diameter reduction at 1, 3, 10, and 30 mg/kg. At the lowest dose of 1 mg/kg of LY 3000328, 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 LY 3000328 are favorable[1].

Name

LY 3000328

CAS

1373215-15-6

Formula

C25H29FN4O5

Molar Mass

484.52

Appearance

Solid

Transport

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Reference

[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.

PeptideDB

LY 3000328

CAS: 1373215-15-6 F: C25H29FN4O5 W: 484.52