A patent perspective of antiangiogenic agents

ABSTRACT

Introduction

Angiogenesis plays a crucial role in the development of numerous vascular structures and is involved in a variety of physiologic and pathologic processes, including psoriasis, diabetic retinopathy, and especially cancer. By obstructing the process of angiogenesis, these therapies effectively inhibit the progression of the disease. Consequently, anti-angiogenic agents were subsequently developed.

Areas covered

This review provides a comprehensive summary of the anti-angiogenic inhibitors developed in the past five years in terms of chemical structure, biochemical/pharmacological activity and potential clinical applications. A literature search was conducted using utilizing the databases Web of Science, SciFinder and PubMed with the key word ‘anti-angiogenic agents’ and ‘angiogenesis inhibitor.’

Expert opinion

This is despite the fact that the concept of antiangiogenesis has been proposed for more than 50 years and angiogenesis inhibitors are extensively employed in clinical practice. However, significant challenges continue to confront them. In recent years, there has been a significant increase in the number of patents focusing on angiogenesis inhibitors. These patents aim to enhance the selectivity of drugs against VEGF/VEGFR, explore new targets to overcome drug resistance, and explore potential drug combinations, thereby expanding the therapeutic possibilities in this field.

KEYWORDS:

• Angiogenesis
• antiangiogenic agents
• VEGFR
• small molecule inhibitors
• kinase inhibitor
• drug development

Article highlights

• Significant advancements have been made in the research of tyrosine kinase inhibitors as angiogenesis inhibitors, exemplified by the notable compound anlotinib.

• Structural characteristics of angiogenesis inhibitors reported in patents within the last five years.

• Natural compounds possessing anti-angiogenic activity: analysis of their structures and targets of action.

• Methionine aminopeptidase 2 (MetAp2), Serine arginine protein kinase 1 (SRPK1), the Wnt signaling pathway, the Sphingosine-1-phosphate Receptor (S1P) have been identified as potential new targets for anti-angiogenic therapy.

• A comprehensive examination of prospective avenues for the development of angiogenesis inhibitors.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

Junyu Zhang and Jin Wang conducted the literature search and manuscript writing. Junyu Zhang, Yanchen Li, Xiaoyan Pan and Jingkun Qu prepared the figures. Jie Zhang conceptualized, wrote and edited the manuscript

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (NSFC, No. 82373793 and 82173742), the Science Fund for Distinguished Young Scholars of Shaanxi Province (No. 2022JC-54), the Key Research and Development Program of Shaanxi (No. 2023-YBSF-131) and Medical “basic-clinical” integration and innovation project of Xi ‘an Jiaotong University (YXJLRH2022088).