LY3000328 is a non-covalent, non-peptidic and selective Cathepsin S inhibitor with IC50 values of 7.7nM and 1.67nM for hCathepsin S and mCathepsin S, respectively. Oral administration of LY3000328, BID, for 28 days reduced aortic diameter induced by CaCl2 by 58%, 83% and 87% at dose of 1, 3 and 10mg/kg[1]. LY3000328 showed cleared quickly from plasma. A Phase 1 study of LY-3000328 has been completed.[2].
作用机制
LY3000328 binds to the S2 and S3 subsites of Cathepsin S without interacting with the active site Cys25.[1]
LY 3000328 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Human corneal epithelial cells (HCECs)
Human corneal epithelial cells (HCECs)
Prevented CTSS-induced loss of tight junction proteins ZO-1 and occludin
Exp Eye Res. 2022 Jan;214:108895.
LY 3000328 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
APP/PS1 transgenic mice
Hippocampal stereotactic injection
0.2 mg/kg
5 consecutive days, once daily
LY3000328 significantly alleviated the neuroinflammatory response, decreased Aβ deposition, and rescued learning and memory deficits in APP/PS1 mice via the CX3CL1-CX3CR1 axis and JAK2-STAT3 pathway
Aging Cell. 2025 Feb;24(2):e14393
BALB/c mice
TDI or OVA/CFA-induced mixed granulocytic asthma model
Intraperitoneal injection
30 mg/kg
Administered 30 minutes after each challenge, for a total of 3 times
LY3000328 significantly alleviated airway hyperresponsiveness and neutrophilic inflammation induced by TDI or OVA/CFA, but had no effect on eosinophils and levels of IL-4 and IL-5
Respir Res. 2024 Dec 24;25(1):441
Mouse
CaCl2-induced AAA model
Oral
1, 3, 10, 30 mg/kg
Twice daily for 28 days
Evaluate the effect of LY3000328 on aortic diameter in AAA model, showing dose-dependent reduction in aortic diameter
ACS Med Chem Lett. 2014 Aug 27;5(10):1138-42
Sprague Dawley (SD) rats
IBS-like rat model
Intrathecal injection
1, 3, and 10 μg
Once daily for 3 consecutive days
LY3000328 dose-dependently down-regulated EMG amplitude and FKN expression, indicating that Cat S regulated visceral hypersensitivity via activating FKN in IBS-like rats.
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