Pharmacokinetics of Recserpins

Inhibitors of proteolytic enzymes have multiple roles in limiting the causes of inflammation, whichcontrolled, would result in acute and chronic tissue damage. Human neutrophil elastase (HNE) and othproteases are controlled by plasma proteins belonging to the serine protease inhibitor (serpin) famiinsufficient production of serpins can result in life-threatening diseases. Lexin has constructed athe ability to inhibit HNE, cathepsin G and chymotrypsin. LEX032 has been shown to be an efficaciousneutrophil recruitment. The data obtained from the study of LEX032, e.g., high resolution crystal stkinetic scheme of serpin/enzyme reactions, was used to guide the design and construction of severalserpins. Since these proteins are being produced in E. coli they are, unlike their wild-type counterThe purpose of this project is to determine if the pharmacokinetic and biodistribution patterns of sserpins, especially those which are non-glycosylated, are consistent with the patterns needed for efobtain data to guide the design of dosing regimes to be used in both preclinical (efficacy and toxicThis is a critical step on the path to determine the feasibility of using human recombinant serpinsdisease. In phase two, the data obtained will be applied to the toxicity and clinical evaluation ofdrugs for the treatment of the destructive inflammatory processes in pulmonary inflammation, acute pinjury and other neutrophil related disorders.