Abstract
Polo-like kinases (Plks) are a family of serine/threonine kinases with a highly conserved N-terminal Ser/Thr kinase catalytic domain and a C-terminal region that play crucial roles in cell cycle progression. Plk1, playing a key role in multiple steps of mitotic progression, is the most studied member of the family. It is overexpressed in a wide spectrum of cancer types and is a promising target in oncology. Most of Plk1 inhibitors competitively bind to the ATP-binding site, which is characterized with unique features. Other inhibitors target regions outside the ATP pocket. In this review some pre-clinical or clinical Plk1 inhibitors are reported, focusing on SAR studies and biological activities, including the kinase activity, in vitro and in vivo anti-tumor efficacy. Those studies exhibited the inhibitors’ significant therapeutic effects. Moreover, combination therapies of these Plk1 inhibitors with other anticancer drugs resulted with synergistic effects.
Keywords: Antitumor activity, clinical, inhibitors, Polo-like kinases, pre-clinical, selectivity, SAR.
Mini-Reviews in Medicinal Chemistry
Title:Developments of Polo-like Kinase 1 (Plk1) Inhibitors as Anti-Cancer Agents
Volume: 13 Issue: 14
Author(s): Shanshan Li, Yingjie Zhang and Wenfang Xu
Affiliation:
Keywords: Antitumor activity, clinical, inhibitors, Polo-like kinases, pre-clinical, selectivity, SAR.
Abstract: Polo-like kinases (Plks) are a family of serine/threonine kinases with a highly conserved N-terminal Ser/Thr kinase catalytic domain and a C-terminal region that play crucial roles in cell cycle progression. Plk1, playing a key role in multiple steps of mitotic progression, is the most studied member of the family. It is overexpressed in a wide spectrum of cancer types and is a promising target in oncology. Most of Plk1 inhibitors competitively bind to the ATP-binding site, which is characterized with unique features. Other inhibitors target regions outside the ATP pocket. In this review some pre-clinical or clinical Plk1 inhibitors are reported, focusing on SAR studies and biological activities, including the kinase activity, in vitro and in vivo anti-tumor efficacy. Those studies exhibited the inhibitors’ significant therapeutic effects. Moreover, combination therapies of these Plk1 inhibitors with other anticancer drugs resulted with synergistic effects.
Export Options
About this article
Cite this article as:
Li Shanshan, Zhang Yingjie and Xu Wenfang, Developments of Polo-like Kinase 1 (Plk1) Inhibitors as Anti-Cancer Agents, Mini-Reviews in Medicinal Chemistry 2013; 13 (14) . https://dx.doi.org/10.2174/13895575113136660103
DOI https://dx.doi.org/10.2174/13895575113136660103 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
Call for Papers in Thematic Issues
Bioprospecting of Natural Products as Sources of New Multitarget Therapies
According to the Convention on Biological Diversity, bioprospecting is the exploration of biodiversity and indigenous knowledge to develop commercially valuable products for pharmaceutical and other applications. Bioprospecting involves searching for useful organic compounds in plants, fungi, marine organisms, and microorganisms. Natural products traditionally constituted the primary source of more than ...read more
Computational Frontiers in Medicinal Chemistry
The thematic issue "Computational Frontiers in Medicinal Chemistry" provides a robust platform for delving into state-of-the-art computational methodologies and technologies that significantly propel advancements in medicinal chemistry. This edition seeks to amalgamate top-tier reviews spotlighting the latest trends and breakthroughs in the fusion of computational approaches, including artificial intelligence (AI) ...read more
Mitochondria as a Therapeutic Target in Metabolic Disorders
Mitochondria are the primary site of adenosine triphosphate (ATP) production in mammalian cells. Moreover, these organelles are an important source of reactive oxygen and nitrogen species in virtually any nucleated cell type. The modulation of a myriad of cellular signaling pathways depends on the mitochondrial physiology. Mitochondrial dysfunction is observed ...read more
Natural Products and Dietary Supplements in Alleviation of Metabolic, Cardiovascular, and Neurological Disorders
Metabolic disorders like diabetes, obesity, inflammation, oxidative stress, cancer etc, cardiovascular disorders like angina, myocardial infarction, congestive heart failure etc as well as neurological disorders like Alzheimer?s, Parkinson?s, Epilepsy, Depression, etc are the global burden. They covered the major segment of the diseases and disorders from which the human community ...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
-
Flavonoids as Sirtuin Modulators
Current Topics in Medicinal Chemistry Recent Advances in Anti-Survivin Treatments for Cancer
Current Medicinal Chemistry Trichomonas Vaginalis Infection Among Women Attending Laboratory Centers in Ilam, Iran
Infectious Disorders - Drug Targets Small Interfering RNA for Effective Cancer Therapies
Mini-Reviews in Medicinal Chemistry Fibroblast Growth Factor Receptor Signaling in Cancer Biology and Treatment
Current Signal Transduction Therapy Phenolic Compounds as Nutraceuticals or Functional Food Ingredients
Current Pharmaceutical Design Metabolic Action of Thyroid Hormones: Insights from Functional and Proteomic Studies
Current Proteomics The Emerging Role of Vascular Endothelial Growth Factor (VEGF) in Vascular Homeostasis: Lessons from Recent Trials with Anti-VEGF Drugs
Current Vascular Pharmacology Physicochemical Characterization of Curcumin Loaded Chitosan Nanoparticles: Implications in Cervical Cancer
Anti-Cancer Agents in Medicinal Chemistry The Role of Toll-Like Receptors in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: A New Promising Therapeutic Approach?
CNS & Neurological Disorders - Drug Targets Thyroid Cancer and Nodules in Graves’ Disease: A Single Center Experience
Endocrine, Metabolic & Immune Disorders - Drug Targets High Throughput Screening Technology and the Small Molecules Modulating Aging Related Signals
Combinatorial Chemistry & High Throughput Screening The Drug Targeting and Delivery Approach Applied to Pt-Antitumour Complexes. A Coordination Point of View
Current Medicinal Chemistry Association Between Chlamydia pneumoniae Antibodies and Lung Cancer: A Meta-Analysis
Current Respiratory Medicine Reviews Signal Transduction and Heavy Ion Radiation Therapy: Biological Mechanisms, Biological Quality Assurance, and New Multimodality Approach
Current Signal Transduction Therapy Risk Factors for Lung Cancer in Never Smokers: A Recent Review Including Genetics
Current Respiratory Medicine Reviews Imaging of Cyclooxygenase-2 (COX-2) Expression: Potential Use in Diagnosis and Drug Evaluation
Current Pharmaceutical Design Nanocarriers for the Effective Treatment of Cervical Cancer: Research Advancements and Patent Analysis
Recent Patents on Drug Delivery & Formulation Virus-Like Particles as Particulate Vaccines
Current HIV Research Predictive Markers for Haematological Toxicity of Pemetrexed
Current Drug Targets