Abstract
The Kinase insert Domain containing Receptor (KDR), alternatively referred to as VEGFR-2, is a receptor for Vascular Endothelial Growth Factors (VEGFs) and functions as a key regulator of angiogenesis, the process by which new capillaries are created from preexisting blood vessels. The induction of angiogenesis, or the “angiogenic switch,” is a critical step in tumor progression, and inhibitors of KDR have been demonstrated both to induce tumor regression and reduce metastatic potential in preclinical models. In the last few years, medicinal chemists have expanded the kinase selectivity profile of known inhibitor classes to include KDR, and also identified novel classes of KDR inhibitors. This review presents structure activity relationships (SAR) of small molecule inhibitors of KDR, with an emphasis on the pharmacophore elements of the scaffolds employed. Binding hypotheses based on X-ray crystallographic analyses will also be described. Additionally, the efficacy of representative compounds in in vitro and in vivo models of tumor progression and angiogenesis are discussed.
Keywords: (vegfr-2), structure activity relationships, vasculogenesis, endostatin and angiostatin, cancer chemotherapy, heterocycles, streptomyces
Current Topics in Medicinal Chemistry
Title: Small Molecule Inhibitors of KDR (VEGFR-2) Kinase: An Overview of Structure Activity Relationships
Volume: 2 Issue: 9
Author(s): Stephen J. Boyer
Affiliation:
Keywords: (vegfr-2), structure activity relationships, vasculogenesis, endostatin and angiostatin, cancer chemotherapy, heterocycles, streptomyces
Abstract: The Kinase insert Domain containing Receptor (KDR), alternatively referred to as VEGFR-2, is a receptor for Vascular Endothelial Growth Factors (VEGFs) and functions as a key regulator of angiogenesis, the process by which new capillaries are created from preexisting blood vessels. The induction of angiogenesis, or the “angiogenic switch,” is a critical step in tumor progression, and inhibitors of KDR have been demonstrated both to induce tumor regression and reduce metastatic potential in preclinical models. In the last few years, medicinal chemists have expanded the kinase selectivity profile of known inhibitor classes to include KDR, and also identified novel classes of KDR inhibitors. This review presents structure activity relationships (SAR) of small molecule inhibitors of KDR, with an emphasis on the pharmacophore elements of the scaffolds employed. Binding hypotheses based on X-ray crystallographic analyses will also be described. Additionally, the efficacy of representative compounds in in vitro and in vivo models of tumor progression and angiogenesis are discussed.
Export Options
About this article
Cite this article as:
Boyer J. Stephen, Small Molecule Inhibitors of KDR (VEGFR-2) Kinase: An Overview of Structure Activity Relationships, Current Topics in Medicinal Chemistry 2002; 2 (9) . https://dx.doi.org/10.2174/1568026023393273
DOI https://dx.doi.org/10.2174/1568026023393273 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
AlphaFold in Medicinal Chemistry: Opportunities and Challenges
AlphaFold, a groundbreaking AI tool for protein structure prediction, is revolutionizing drug discovery. Its near-atomic accuracy unlocks new avenues for designing targeted drugs and performing efficient virtual screening. However, AlphaFold's static predictions lack the dynamic nature of proteins, crucial for understanding drug action. This is especially true for multi-domain proteins, ...read more
Artificial intelligence for Natural Products Discovery and Development
Our approach involves using computational methods to predict the potential therapeutic benefits of natural products by considering factors such as drug structure, targets, and interactions. We also employ multitarget analysis to understand the role of drug targets in disease pathways. We advocate for the use of artificial intelligence in predicting ...read more
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Chronic Kidney Disease
The scope of the special thematic issue includes but not limited to the mechanism of chronic kidney disease (CKD), the treatment of renal fibrosis and early diagnosis of CKD and so on. We also welcome manuscripts from other scientific research area with respect to internal medicine. Cell death has been ...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
- Announcements
Related Articles
-
Pyrazolo-Triazolo-Pyrimidine Derivatives as Adenosine Receptor Antagonists: A Possible Template for Adenosine Receptor Subtypes?
Current Pharmaceutical Design Alogliptin: a Novel Molecule for Improving Glycemic Control in Type II Diabetes Mellitus
Current Diabetes Reviews Recent Advances in Small Molecule Inhibitors of VEGFR and EGFR Signaling Pathways
Current Topics in Medicinal Chemistry An Effective QWBA/UHPLC-MS/Tissue Punch Approach: Solving a Pharmacokinetic Issue via Quantitative Met-ID
Drug Metabolism Letters Elucidating the Drug Repurposing Spectra of COVID-19 with its Analogues SARS and MERS
Mini-Reviews in Medicinal Chemistry A Rationale for the Use of Proton Pump Inhibitors as Antineoplastic Agents
Current Pharmaceutical Design Editorial [Hot Topic: Recent Advances in Antiviral Agents (Executive Editor: Shin-Ru Shih)]
Current Pharmaceutical Design New Zinc Binding Motifs in the Design of Selective Carbonic Anhydrase Inhibitors
Mini-Reviews in Medicinal Chemistry Combined Dyslipidemia: Should the Focus be LDL Cholesterol or Atherogenic Dyslipidemia?
Current Pharmaceutical Design The Therapeutic use of the Zonulin Inhibitor AT-1001 (Larazotide) for a Variety of Acute and Chronic Inflammatory Diseases
Current Medicinal Chemistry Association between Statin Use and Poor Outcomes in COVID-19 Patients with Diabetes Mellitus: A Systematic Review
Current Diabetes Reviews Current Advances in Antitubercular Drug Discovery: Potent Prototypes and New Targets
Current Medicinal Chemistry Multivalent Agents: A Novel Concept and Preliminary Practice in Anti-HIV Drug Discovery
Current Medicinal Chemistry Reversine: A Synthetic Purine with a Dual Activity as a Cell Dedifferentiating Agent and a Selective Anticancer Drug
Current Medicinal Chemistry Antitumor Effects of Celastrol and Semi-Synthetic Derivatives
Mini-Reviews in Organic Chemistry Synthesis and In Vitro Evaluation of Tropane Halogenated-derivatives Against Malaria, Sleeping Sickness, Chagas Disease and Leishmaniasis
Medicinal Chemistry Thymosin α1; Potential Therapeutic Implications of an Immunoregulatory Drug in the Treatment of Lymphocytopenia Associated with COVID-19
Current Immunology Reviews (Discontinued) Quality of Experience: A New Paradigm for Resource Management in Wireless Multimedia Networks
Recent Patents on Computer Science Primary Tumors of the Sacrum: Imaging Findings
Current Medical Imaging The Emirates Medical Association (EMA) Celebrates the “Emirates Medical Day” as the First Inventiveness at the National Level: “<i>The UAE Appreciates you</i>”
New Emirates Medical Journal