Abstract
Urokinase-type plasminogen activator (uPA) is one of the two physiological serine proteases responsible for the activation of plasminongen to plasmin. uPA activity is regulated by its inhibitors (PAI-1 and PAI-2) and its receptor (uPAR), and an expanding list of their interacting proteins. In addition to plasminogen activation, this system also plays important roles in the regulation of many cellular processes including cell proliferation, adhesion and migration. It is beyond reasonable doubt that this enzyme system plays a central role in tumor biology and represents a high potential target for therapeutic intervention of tumor growth and metastasis. During the past fifteen years, crystal structures of uPA and its inhibitors have facilitated the development of uPA inhibitors. Many crystal structures of proteins in the uPA/uPAR system have also been reported recently, especially a series of structures of uPAR and its complexes with vitronectin and uPA, facilitating the development and evaluation of uPAR inhibitors. Recent progress on uPA inhibitors will be summarized in this article. The unique structural features and the druggable potentials of these new structures will also be discussed.
Keywords: uPA, uPAR, SMB crystal structures, inhibitors, crystal structures, inhibitors, serine proteases, plasminogen activation, antagonist, tumor, signaling
Current Drug Targets
Title: Structural Basis for Therapeutic Intervention of uPA/uPAR System
Volume: 12 Issue: 12
Author(s): Jacky Chi Ki Ngo, Longguang Jiang, Zhonghui Lin, Cai Yuan, Zhuo Chen, Xu Zhang, Haiyang Yu, Jundong Wang, Lin Lin and Mingdong Huang
Affiliation:
Keywords: uPA, uPAR, SMB crystal structures, inhibitors, crystal structures, inhibitors, serine proteases, plasminogen activation, antagonist, tumor, signaling
Abstract: Urokinase-type plasminogen activator (uPA) is one of the two physiological serine proteases responsible for the activation of plasminongen to plasmin. uPA activity is regulated by its inhibitors (PAI-1 and PAI-2) and its receptor (uPAR), and an expanding list of their interacting proteins. In addition to plasminogen activation, this system also plays important roles in the regulation of many cellular processes including cell proliferation, adhesion and migration. It is beyond reasonable doubt that this enzyme system plays a central role in tumor biology and represents a high potential target for therapeutic intervention of tumor growth and metastasis. During the past fifteen years, crystal structures of uPA and its inhibitors have facilitated the development of uPA inhibitors. Many crystal structures of proteins in the uPA/uPAR system have also been reported recently, especially a series of structures of uPAR and its complexes with vitronectin and uPA, facilitating the development and evaluation of uPAR inhibitors. Recent progress on uPA inhibitors will be summarized in this article. The unique structural features and the druggable potentials of these new structures will also be discussed.
Export Options
About this article
Cite this article as:
Chi Ki Ngo Jacky, Jiang Longguang, Lin Zhonghui, Yuan Cai, Chen Zhuo, Zhang Xu, Yu Haiyang, Wang Jundong, Lin Lin and Huang Mingdong, Structural Basis for Therapeutic Intervention of uPA/uPAR System, Current Drug Targets 2011; 12 (12) . https://dx.doi.org/10.2174/138945011797635911
DOI https://dx.doi.org/10.2174/138945011797635911 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
Call for Papers in Thematic Issues
New drug therapy for eye diseases
Eyesight is one of the most critical senses, accounting for over 80% of our perceptions. Our quality of life might be significantly affected by eye disease, including glaucoma, diabetic retinopathy, dry eye, etc. Although the development of microinvasive ocular surgery reduces surgical complications and improves overall outcomes, medication therapy is ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Intravitreal Bevacizumab (Avastin®) for Diabetic Retinopathy at 24-months: The 2008 Juan Verdaguer-Planas Lecture
Current Diabetes Reviews Trends in Nanotechnology Patents Applied to the Health Sector
Recent Patents on Nanotechnology Extraction of Quantitative Anatomical Information from Coronary Angiographies
Current Bioinformatics Reacting to Stress: Radical Cellular Pathways for Novel Drug Development
Current Neurovascular Research Pathophysiology of the Vascular Wall and its Relevance for Cerebrovascular Disorders in Aged Rodents
Current Neurovascular Research Novel Therapeutic Approaches Targeting Matrix Metalloproteinases in Cardiovascular Disease
Current Topics in Medicinal Chemistry Continuous Elevation of Intracellular Ca2+ Is Essential for the Development of Cerebral Vasospasm
Current Vascular Pharmacology Cell Immunity in Inflammatory Vasculitis
Current Immunology Reviews (Discontinued) Congenital Heart Disease: The Crossroads of Genetics, Epigenetics and Environment
Current Genomics Matrix Metalloproteinases as Valid Clinical Target
Current Pharmaceutical Design The Genetics of Vascular Complications in Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Current Hypertension Reviews Peri-Procedural Care of Renal Nerve Ablation Candidates
Current Clinical Pharmacology Contributory Role of Matrix Metalloproteinases in Cardiovascular Remodeling
Current Drug Targets - Cardiovascular & Hematological Disorders Drainage of Cerebral Abscesses Prior to Valve Replacement in Stable Patients with Acute Left-Sided Infective Endocarditis
CNS & Neurological Disorders - Drug Targets Cellular Mechanisms of Bypass Vein Graft Arterialization and Approaches to Attenuate Graft Remodeling
Vascular Disease Prevention (Discontinued) Interleukin-1 and Occlusive Arterial Diseases
Cardiovascular & Hematological Agents in Medicinal Chemistry Contemporary Review of Drugs Used to Treat Obesity
Cardiovascular & Hematological Agents in Medicinal Chemistry Regulation and Function of Rankl in Arterial Calcification
Current Pharmaceutical Design Indications, Implications and Applications of Renal Denervation. Have we Discovered Something new?
Current Hypertension Reviews Editorial (Thematic Issue: Frontiers in Atherosclerosis, Heart Disease and Diabetes)
Cardiovascular & Hematological Disorders-Drug Targets