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详细内容
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AZD7986 is a Dipeptidyl peptidase 1 (DPP1) inhibitor with pIC50s of 6.85, 7.6, 7.7, 7.8, and 7.8 in human, mouse, rat, dog and rabbit, respectively.
Results from cell assay show that AZD7986 is a Dipeptidyl peptidase 1 (DPP1) inhibitor with pIC50s of 6.85, 7.6, 7.7, 7.8, and 7.8 in human, mouse, rat, dog and rabbit, respectively. AZD7986 is stable in the propionaldehyde reactivity assay, with a half-life over 50 h. After differentiation in the presence of AZD7986 (38 pM to 10 uM), concentration-dependent decreases in cell lysate enzyme activity are observed for DPP1, as well as for all of the three NSPs, NE, Pr3, and CatG. AZD7986 inhibits activation of all three NSPs in a concentration dependent manner, with pIC50 values of around 7 for all three NSPs. The reduction of the activities is almost complete, with NE, Pr3, and CatG activities reduced to 4 to 10% of control at 10 uM AZD7986[1].
AZD7986 shows good stability in plasma, with a half life of >10 h. AZD7986 inhibits activation of NE and Pr3, but not CatG, in bone marrow cell lysates in a dose dependent manner in vivo[1].
References:
[1]. Doyle K, et al. Discovery of Second Generation Reversible Covalent DPP1 Inhibitors Leading to an Oxazepane Amidoacetonitrile Based Clinical Candidate (AZD7986). J Med Chem. 2016 Oct 27;59(20):9457-9472.
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