AZD-5904

Description	AZD5904 is a potent orally bioavailable MPO inhibitor. In preclinical studies, AZD5904 inhibited the isolated MPO enzyme with an IC50 of 140 nM and was approximately equipotent in assays of rat and mouse MPO enzyme activity. Cross over to other species has not been investigated. AZD5904 was > 10-fold selective for the related peroxide enzymes lactoperoxidase (LPO) and thyroid peroxidase (TPO) and > 70-fold selective against a panel of other targets. AZD5904 dose dependently reduced MPO activity in a rat peritonitis model with an estimated plasma IC50 of 5 μmol/L (~1.3 μg/mL) and elicited protective effects at comparable plasma exposures in a mouse Experimental Autoimmune Encephalomyelitis (EAE) model, although effects were not consistently reproduced. AZD5904 was in development for multiple sclerosis and COPD and has been evaluated in single and multiple dose studies in healthy volunteers.
Pathways	Protease/Metabolic Enzyme

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