AB029. Boron analogues of α-amino acid-based anti-tumor and anti-rheumatoid arthritis agents for boron neutron capture therapy

Background: Following the latest development and popularization of the neutron sources, boron neutron capture therapy (BNCT) has re-attracted great efforts and interest from both academia and pharmaceutical industry. The Food and Drug Administration (FDA) approved compounds, 4-borono-L-phenylalanine (BPA) and sodium borocaptate (BSH) (Na₂B₁₂H₁₁SH), are currently used in clinical trials. Neither BPA nor BSH has fully achieved the tumor selectivity of boron drug for BNCT treatment, preferentially, with its less accumulation in normal tissues and/or blood. Various boron agents have been explored in the last decades with limited individual successes. Nevertheless, it remained a big challenge to develop the boron drug of choice to meet all of the requirements of BNCT. To address this issue, various α-amino acid analogues were developed and examined as potential BNCT agents. This lecture summarizes recent updates on the development of α-amino acid analogue-based anti-tumor and anti-rheumatoid arthritis agents for BNCT.

Methods: The information summarized in this presentation is based on search results in databases such as PubMed and search engines like Google Scholar, with keywords including boron agent, BNCT, α-amino acid, etc., with English articles from the year of 2010 to 2023.

Results: This report summarizes the syntheses of the boron analogues of α-amino acid-based agents and their unique efficacy in anti-tumor and anti-rheumatoid arthritis through BNCT. The literature suggests that the BNCT agent based on macromolecules may experience pharmacokinetics and/or pharmacodynamics problems. The rational design of a small molecule-based BNCT agent could potentially overcome the clinical limitations of BPA. Until now, the protocol has been proven in vitro. In addition, small molecule-based boron agents typically have a strong druggability and production achievable under the Good Manufacturing Practices (GMP). On the other hand, theranostics have emerged as a frontier in BNCT treatment. Furthermore, the use of individualized BNCT agents seems inevitable for different types of malignant tumors and other diseases. No universal BNCT drug could be available for all types of tumors in clinical applications.

Conclusions: The results suggest that the unprecedented small boron molecules are worthy of further investigation. BNCT is expected to continue to receive attention in the future. With more advancements in various technologies, BNCT can become a competitive cancer treatment plan in the mainstream.

Keywords: α-amino acid analogues; anti-tumor agents; anti-rheumatoid arthritis agents; neutron capture therapy