Summary of current small molecule drugs targeting PD-L1 and CD47. Small molecule chemical compounds block the function of key immune checkpoint molecules by (I) competitively binding to immune checkpoint molecules, thus blocking their combination with paired receptors (BMS202, CA-170 and IMMH-010 target PD-L1; NCGC00138783 and 1,2,4-oxadiazole compounds target CD47); (II) inhibiting the level of PD-L1 and CD47 expression (e.g. fraxinellone, RRx-001 and metformin); (III) inhibiting the translation of PD-L1 (e.g. eFT508); (IV) promoting the degradation of PD-L1 (e.g. HIP1R). Source: Cancer biology and medicine (2024). DOI: 10.20892/j.issn.2095-3941.2024.0034
Immunotherapy has revolutionized cancer treatment, with immune checkpoint inhibitors (ICIs) playing a central role. However, current ICIs, mainly monoclonal antibodies, face significant challenges such as poor tissue penetration, high production costs and unwanted side effects. These limitations affect their efficacy and accessibility. Due to these issues, there is an urgent need to explore alternative approaches. Small molecule drugs targeting immune checkpoints offer a promising solution that may overcome these obstacles and enable more effective cancer therapies.
A recent study by researchers from the University of Electronic Science and Technology of China, affiliated with Sichuan Provincial People’s Hospital, appeared in Cancer biology and medicineinvestigates the development of small molecule drugs targeting immune checkpoints. The study presents an innovative approach to cancer therapy by focusing on the efficacy and mechanisms of small molecule ICIs.
The study highlights the advantages of small molecule ICIs over conventional antibody-based therapies. These small molecule drugs exhibit better tissue permeability, better oral bioavailability and favorable pharmacokinetic properties. Important examples include BMS-202, which induces PD-L1 dimerization to block PD-1/PD-L1 interactions, and CA-170, the first oral ICI to be tested in clinical trials. In addition, YPD-29B has shown promising results in promoting PD-L1 degradation and enhancing antitumor immunity.
The research also highlights the potential of combining small molecule ICIs with other therapeutic strategies such as immune regulation and anti-angiogenesis to enhance treatment efficacy. This comprehensive analysis of various small molecule inhibitors demonstrates their potential to revolutionize cancer treatment by overcoming the limitations of antibody-based ICIs and providing patients with more effective and accessible options.
Dr. Chuan Xu, lead researcher, said: “The development of small molecule ICIs represents a significant advance in cancer therapy. These drugs not only overcome the limitations of current antibody-based therapies but also offer new opportunities for combination treatments, thereby improving overall efficacy and outcomes for patients.”
The study’s findings suggest that small molecule ICIs could revolutionize cancer treatment by providing more accessible and cost-effective options. By improving tissue penetration and reducing production costs, these drugs have the potential to bring advanced cancer therapies to a wider audience. The research paves the way for further investigations and clinical trials with the goal of establishing small molecule ICIs as the cornerstone of modern cancer treatment.
Further information:
Luoyi Chen et al., Development of small molecule drugs to target immune checkpoints, Cancer biology and medicine (2024). DOI: 10.20892/j.issn.2095-3941.2024.0034
Provided by the University of Electronic Science and Technology of China
Quote: Small molecules, big impact: advancing immune checkpoint inhibitors against cancer (August 22, 2024), accessed August 22, 2024 from https://medicalxpress.com/news/2024-08-small-molecules-big-impact-advancing.html
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