Preclinical and Toxicology Studies of BRD5529, a Selective Inhibitor of CARD9.

ABSTRACT:

Background

The caspase recruitment domain-containing protein 9 (CARD9) inhibitor BRD5529 has been shown to be an effective in vitro inhibitor of Pneumocystis β-glucan-induced proinflammatory signaling, suggesting its viability as a candidate for preliminary anti-Pneumocystis drug testing in the rodent Pneumocystis pneumonia (PCP) model.

Methods

Mice were injected intraperitoneally (IP) daily with either vehicle or BRD5529 at 0.1 or 1.0 mg/kg for 2 weeks. Mouse weights were taken daily. At day 14, mice were euthanized, weighed, and analyzed by flexiVent™ for lung stiffness. Lungs, liver, and kidney were then harvested for hematoxylin and eosin (H&E) staining and pathology scoring. Lung samples were further analyzed for proinflammatory cytokines via enzyme-linked immunosorbent

SUBMITTER: Kottom TJ 

PROVIDER: S-EPMC9167333 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature