Targeting MCL-1 with APG-3526: Unveiling a Potent Inhibitor for Cancer Therapy

3 June 2024
The research focuses on MCL-1, a protein that prevents cell death in various cancers, including prostate, lung, and breast. This protein is often overexpressed and contributes to resistance to common treatments. The study introduces APG-3526, a new compound that has shown significant antitumor effects in vitro and in vivo.

APG-3526 was synthesized through a multistep process and its binding to MCL-1 was measured using a fluorescence polarization assay. The compound's impact on cell viability was assessed with the CCK-8 assay, and its antitumor efficacy was tested in multiple myeloma xenograft models in mice.

The results indicate that APG-3526 has a high affinity for MCL-1 and is effective in inhibiting the growth of MCL-1-dependent cancer cells. Treatment with APG-3526 led to complete tumor regression in the tested models. Pharmacodynamic studies showed that the compound induced apoptosis by activating caspase 3 and cleaving PARP. Furthermore, APG-3526 was found to disrupt the MCL-1:BIM complex, initiating the apoptotic process.

In summary, APG-3526 is a novel and potent MCL-1 inhibitor with favorable pharmacokinetic properties, demonstrating strong antiproliferative and antitumor activities. The compound is considered a promising candidate for further clinical development as an MCL-1 inhibitor.

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The transational medicine section of the Synapse database supports searches based on fields such as drug, target, and indication, covering the T0-T3 stages of translation. Additionally, it offers a historical conference search function as well as filtering options, view modes, translation services, and highlights summaries, providing you with a unique search experience.

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Taking obesity as an example, select "obesity" under the indication category and click search to enter the Translational Medicine results list page. By clicking on the title, you can directly navigate to the original page.

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By clicking the analysis button, you can observe that GLP-1R treatment for obesity has gained significant attention over the past three years, with preclinical research still ongoing in 2023. Additionally, there are emerging potential targets, such as GDF15, among others.

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