Neutrophil serine proteases are activated early in the promyelocyte stage of neutrophil development via cleavage of a dipeptide, by the cysteine protease dipeptidyl peptidase 1 (DPP1, also known as cathepsin C ).
Only two potent and selective DPP1 inhibitors, AZD7986 (NCT02303574, ClinTrials.gov) and GSK2793660 (NCT02058407, ClinTrials.gov), have entered clinical development.
In conclusion, targeting the neutrophil weaponry by blocking the activation of proteases via DPP1 inhibition, or neutrophil-mediated NETosis, or multiple neutrophil functions via dual blockade of PI3K[gamma]S may show promise as future therapies to address such pressing unmet medical needs.
Kack et al., "Discovery of second generation reversible covalent DPP1 inhibitors leading to an oxazepane amidoacetonitrile based clinical candidate (AZD7986)," Journal of Medicinal Chemistry, vol.
It was reported yesterday that the contract has been signed for global exclusive rights to AZD7986, a novel oral inhibitor of dipeptidyl peptidase I (DPP1
, also known as cathepsin C).
AZD7986 is a novel oral inhibitor of dipeptidyl peptidase I (DPP1, also known as cathepsin C).
In preclinical studies, AZD7986 was shown to effectively and reversibly inhibit DPP1 and the activation of NSPs within maturing neutrophils.