Prourokinase in Acute Ischemic Stroke: A Review of Current Evidence

Saini V, Guada L, Yavagal DR. Global epidemiology of stroke and access to acute ischemic stroke interventions. Neurology. 2021;97(20 Suppl 2):S6–16. https://doi.org/10.1212/WNL.0000000000012781.

Article  PubMed  Google Scholar 

Fekadu G, Chelkeba L, Kebede A. Risk factors, clinical presentations and predictors of stroke among adult patients admitted to stroke unit of Jimma university medical center, south west Ethiopia: prospective observational study. BMC Neurol. 2019;19: 187. https://doi.org/10.1186/s12883-019-1409-0.

Article  PubMed  PubMed Central  Google Scholar 

Berge E, Whiteley W, Audebert H, et al. European stroke organisation (ESO) guidelines on intravenous thrombolysis for acute ischaemic stroke. Eur Stroke J. 2021;6(1):I–LXII. https://doi.org/10.1177/2396987321989865.

Article  PubMed  PubMed Central  Google Scholar 

Jadhav AP, Desai SM, Jovin TG. Indications for mechanical thrombectomy for acute ischemic stroke: current guidelines and beyond. Neurology. 2021;97(20 Suppl 2):S126–36. https://doi.org/10.1212/WNL.0000000000012801.

Article  PubMed  Google Scholar 

Lijnen HR, Collen D. Fibrinolytic agents: mechanisms of activity and Pharmacology. Thromb Haemost. 1995;74(1):387–90. PMID: 8578491.

Article  CAS  PubMed  Google Scholar 

Miller SE, Warach SJ. Evolving thrombolytics: from alteplase to tenecteplase. Neurotherapeutics. 2023;20(3):664–78. https://doi.org/10.1007/s13311-023-01391-3. Epub 2023 Jun 5. PMID: 37273127; PMCID: PMC10275840.

Article  PubMed  PubMed Central  Google Scholar 

Song H, Wang Y, Ma Q, et al. Efficacy and safety of Recombinant human prourokinase in the treatment of acute ischemic stroke within 4.5 hours of stroke onset: A phase 3 randomized clinical trial. JAMA Netw Open. 2023;6(7):e2325415. https://doi.org/10.1001/jamanetworkopen2023.25415.

Article  PubMed  PubMed Central  Google Scholar 

Credo RB, Burke SE. Fibrinolytic mechanism, biochemistry, and preclinical pharmacology of recombinant prourokinase. J Vasc Interv Radiol. 1995;6:8S-18S. https://doi.org/10.1016/s1051-0443(95)71242-8.

Article  CAS  PubMed  Google Scholar 

Lo KM, Gilles SD. High-level expression of human proteins in murine hybridoma cells: induction by methotrexate in the absence of gene amplification. Biochim Biophys Acta. 1991;1088:217–24.

Article  CAS  PubMed  Google Scholar 

Kasai S, Arimura H, Nishida M, Suyama T. Proteolytic cleavage of single-chain pro-urokinase induces conformational change which follows activation of the zymogen and reduction of its high affinity for fibrin. J Biol Chem. 1985;260:12377–81.

Article  CAS  PubMed  Google Scholar 

Nolan C, Hall LS, Barlow GH, Tribby II. Plasminogen activator from human embryonic kidney cell cultures: evidence for a proactivator. Biochim Biophys Acta. 1977;496:384–400.

Article  CAS  PubMed  Google Scholar 

Loza JP, Gurewich V, Johnstone M, Pannell R. Platelet-bound prekallikrein promotes pro-urokinase-induced clot lysis: a mechanism for targeting the factor XII-dependent intrinsic pathway of fibrinolysis. Thromb Haemost. 1994;71:347–52.

Article  CAS  PubMed  Google Scholar 

Kobayashi H, Schmitt M, Goretzki L, et al. Cathepsin B efficiently activates the soluble and the tumor cell, receptor-bound form of the proenzyme urokinase-type plasminogen activator (pro-uPA). J Biol Chem. 1991;266:5147–52.

Article  CAS  PubMed  Google Scholar 

Berkenpas M, Quigley JP. Secretion of two-chain active plasminogen activator from rsv-transformed chicken embryo fibroblasts: evidence for a plasmin-independent converting activity. Fibrinolysis. 1989;3(Suppl 1):3.

Article  Google Scholar 

Gurewich V, Pannell R, Louie S, Kelley P, Suddith RL, Greenlee R. Effective and fibrin-specific clot lysis by a zymogen precursor form of urokinase (pro-urokinase): a study in vitro and two animal species. J Clin Invest. 1984;73:1731–9.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Takano K, Carano RA, Tatlisumak T, Meiler M, Sotak CH, Kleinert HD, Fisher M. Efficacy of intra-arterial and intravenous prourokinase in an embolic stroke model evaluated by diffusion-perfusion magnetic resonance imaging. Neurology. 1998;50(4):870-5. https://doi.org/10.1212/wnl50.4.870

Collen D, Stassen JM, Blaber M, Winker M, Verstraete M. Biological and thrombolytic properties of proenzyme and active forms of human urokinase. III. Thrombolytic properties of natural and recombinant urokinase in rabbits with experimental jugular vein thrombosis model. Thromb Haemost. 1984;52:27–30.

Article  CAS  PubMed  Google Scholar 

Brott T, Adams HP Jr, Olinger CP, et al. Measurements of acute cerebral infarction: a clinical examination scale. Stroke. 1989;20:864–70.

Article  CAS  PubMed  Google Scholar 

Del Zoppo GJ, Higashida RT, Furlan AJ, et al. PROACT: a phase II randomized trial of recombinant pro-urokinase by direct arterial delivery in acute middle cerebral artery stroke. Stroke. 1998;29:4–11.

Article  PubMed  Google Scholar 

Kasai S, Arimura H, Nishida M, Suyama T. Primary structure of single-chain pro-urokinase. J Biol Chem. 1985;260:12382–9.

Article  CAS  PubMed  Google Scholar 

Li S, Gu HQ, Feng B, et al. Safety and efficacy of intravenous recombinant human prourokinase for acute ischaemic stroke within 4·5 h after stroke onset (PROST-2): a phase 3, open-label, non-inferiority, randomised controlled trial. Lancet Neurol. 2025;24(1):33–41. https://doi.org/10.1016/S1474-4422(24)00436-8.

Article  CAS  PubMed  Google Scholar 

Song H, Wang Y, Ma Q, et al. Thrombolysis with recombinant human prourokinase 4.5-6 h after acute ischemic stroke: a phase iia, randomized, and open-label multicenter clinical trial. CNS Drugs. 2024;38(1):67–75. https://doi.org/10.1007/s40263-023-01051-2.

Article  CAS  PubMed  Google Scholar 

Xiong Y, Hao M, Pan Y, et al. Rationale and design of prourokinase in mild ischemic stroke (PUMICE): a multicentre, prospective, randomised, open-label, blinded-endpoint controlled trial. Stroke Vascular Neurol. 2024;9:e002673. https://doi.org/10.1136/svn-2023-002673.

Article  Google Scholar 

Furlan A, Higashida R, Wechsler L, Gent M, Rowley H, Kase C, Pessin M, Ahuja A, Callahan F, Clark WM, Silver F, Rivera F. Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study: a randomized controlled trial. Prolyse in Acute Cerebral Thromboembolism. JAMA. 1999;282(21):2003-11. https://doi.org/10.1001/jama282.21.2003.

Dey M, Stadnik A, Awad IA. Thrombolytic evacuation of intracerebral and intraventricular hemorrhage. Curr Cardiol Rep. 2012;14(6):754–60. https://doi.org/10.1007/s11886-012-0316-4.

Article  PubMed  PubMed Central  Google Scholar 

Song H, Wang Y, Ma Q, Feng W, Liu R, Lv X, et al. PROST collaborative group. Efficacy and safety of Recombinant human prourokinase in the treatment of acute ischemic stroke within 4.5 hours of stroke onset: A phase 3 randomized clinical trial. JAMA Netw Open. 2023;6(7):e2325415. https://doi.org/10.1001/jamanetworkopen2023.25415.

Article  PubMed  PubMed Central  Google Scholar 

Intravenous Thrombolysis NOAC. [Internet] [Phase 3 Clinical trial]. [China]: Second Affiliated Hospital, School of Medicine, Zhejiang University; Available from: https://clinicaltrials.gov/study/NCT06749834?cond=Acute%20Ischemic%20Stroke&term=Cerebrovascular%20Accident&intr=Prourokinase&aggFilters=status:not%20rec&rank=3#more-information. A prospective cohort study on Intravenous Thrombolytic Therapy in Acute Ischemic Stroke Patients on New Oral Anticoagulants.

ISC 2025 Session Report: New and Alternative Thrombolytic Therapies (a Stroke Journal session), March 7. 2025. Available from: https://www.ahajournals.org/do/10.1161/blog.20250306.382323/full/. The topic was delivered at the International Stroke Conference 2025 held in Los Angeles, California, USA.

Yang Y, Gu B, Xu XY. In silico study of combination thrombolytic therapy with Alteplase and mutant pro-urokinase for fibrinolysis in ischemic stroke. Comput Biol Med. 2024;171: 108141. https://doi.org/10.1016/j.compbiomed.2024.108141.

Article  CAS  PubMed  Google Scholar 

n Der Ende NAM, Roozenbeek B, Smagge LEM, Luijten SPR, Aerden LAM, Kraayeveld P et al. Safety and Efficacy of Dual Thrombolytic Therapy With Mutant Prourokinase and Small Bolus Alteplase for Ischemic Stroke: A Randomized Clinical Trial. JAMA Neurol [Internet]. 2023 [cited 2025 Mar 13];80:714 22. Available from: https://pure.eur.nl/en/publications/safety-and-efficacy-of-dual-thrombolytic-therapy-with-mutant-prou

Ali MR. Aspect of thrombolytic therapy: a review. Sci World J. 2014. https://doi.org/10.1155/2014/586510.

Article  Google Scholar 

Shen M, Wang Y, Hu F, Lv L, Chen K, Xing G. Thrombolytic agents: nanocarriers in targeted release. Molecules. 2021;26(22):6776. https://doi.org/10.3390/molecules26226776. PMID: 34833868; PMCID: PMC8619279.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Aderinto N, Olatunji G, Kokori E, et al. Stem cell therapies in stroke rehabilitation: a narrative review of current strategies and future prospects. Egypt J Neurol Psychiatry Neurosurg. 2024;60:79. https://doi.org/10.1186/s41983-024-00851-7.

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