Single-chain proenzyme form of urokinase, q.v. Produced by the kidney; present in urine and blood. Consists of 411 amino acid residues, mol wt ≈54,000 daltons. Converted by plasmin or kallikrein to active two-chain urokinase by proteolytic cleavage of the Lys 158 - Ile 159 peptide bond. Identification of proenzyme activity from cultured human kidney cells: M. B. Bernik, J. Clin. Invest. 52, 823 (1973). Isoln from culture media: C. Nolan et al., Biochim. Biophys. Acta 496, 384 (1977). Purification from human plasma: T.-C. Wun et al., J. Biol. Chem. 257, 3276 (1982); from human urine: S. S. Husain et al., Arch. Biochem. Biophys. 220, 31 (1983). Amino acid sequence and cleavage site: S. Kasai et al., J. Biol. Chem. 260, 12382 (1985). Clot-specific activity: V. Gurewich et al., J. Clin. Invest. 73, 1731 (1984). Clinical pharmacology: G. Trübestein et al., Haemostasis 17, 238 (1987). Clinical trials in acute myocardial infarction: C. Bode et al., Am. J. Cardiol. 61, 971 (1988); in combination with t-PA: V. Gurewich, J. Am. Coll. Cardiol. 10, 16B (1987). Review of mechanism of action studies: V. Gurewich, R. Pannell, Semin. Thromb. Hemostasis 13, 146-151 (1987); and physicochemical properties: V. Gurewich, ibid. 14, 110-115 (1988).
Nonglycosylated human prourokinase produced in E. coli by recombinant DNA technology. Prepn: H. L. Heyneker et al., EP 92182; eidem, US 5112755 (1983, 1992 both to Genentech); W. E. Holmes et al., Biotechnology 3, 923 (1985). Series of articles on thrombolytic activity: Thromb. Haemostasis 52, 19-33 (1984). Pharmacokinetics: A. de Boer et al., ibid. 70, 320 (1993). Clinical trial: PRIMI Trial Study Group, Lancet 1, 863 (1989); J. Schofer et al., Eur. Heart J. 14, 958 (1993).
Thrombolytic.
Thrombolytic