Saxagliptin hydrate

Saxagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor which is used in combination with diet and exercise in the therapy of type 2 diabetes, either alone or in combination with other oral hypoglycemic agents. Saxagliptin is a relatively new medication and has yet to be implicated in causing clinically apparent liver injury.
While liraglutide targets the incretin system as a GLP-1 analog for therapeutic intervention in T2DM, saxagliptin enhances GLP-1 plasma concentrations by inhibiting the DPP-4 enzyme responsible for degradation of GLP-1 by cleavage of the two N-terminal amino acids adjacent to alanine (or proline), thereby rendering the hormone inactive. Similarto vildagliptin, saxagliptin is a cyanopyrrolidine substrate-based inhibitor. The proline mimetic occupies the small S1-pocket while the nitrile’s trajectory aligns with the scissile bond of the substrate. The slow dissociation kinetics of saxagliptin is attributed to a reversible, covalent reaction between the nitrile and the catalytically active serine hydroxyl (Ser630). The steric bulk provided by the adamantyl moiety and the constrained cyclopropyl ring stabilizes the trans-rotamer of the amide, thereby preventing the problematic intramolecular cyclization, via the amino group attacking the nitrile, which is favored in the cis-conformation.Since metabolism of saxagliptin is primarily mediated by CYP3A4/5, there is a potential for drug interactions with concomitant administration of strong inducers or inhibitors of these cytochrome P450 enzymes. The most common adverse events (>5% of patients) included upper respiratory tract infection, urinary tract infection, and headache.
ChEBI: Saxagliptin hydrate is a hydrate that is the monohydrate form of anhydrous saxagliptin. Used for the treatment of Type II diabetes. It has a role as a hypoglycemic agent and an EC 3.4.14.5 (dipeptidyl-peptidase IV) inhibitor. It contains a saxagliptin.