AI Article Synopsis
- Aberrant epigenetic modifications contribute significantly to blood cancers, making epigenetic modulators like HDAC and EZH2 inhibitors crucial in treatment.
- A combination therapy using these inhibitors has shown effectiveness, but new dual inhibitors designed from SAHA and GSK126 exhibit even better results.
- The newly developed compound demonstrated strong inhibition of HDAC1 and EZH2 while effectively suppressing tumor growth, indicating it could be a promising candidate for treating hematological malignancies.
Article Abstract
Aberrance of epigenetic modification is one of the important factors leading to hematological malignancies. Histone deacetylase (HDAC) inhibitors and enhancers of zeste homologue 2 (EZH2) inhibitors are demonstrated to be significant epigenic modulators. Cocktail therapy of HDAC inhibitors and EZH2 inhibitors was demonstrated to be a promising strategy in hematological malignancies. We designed HDAC and EZH2 dual inhibitors based on the strong synergistic effect of SAHA and GSK126. Compound exhibited excellent inhibitory activity against HDAC1 (IC = 0.12 μM) and EZH2 (IC = 0.059 μM), it also showed good antiproliferation activity against MV4-11 (IC = 0.17 μM), which has more potential than the cocktail therapy of SAHA and GSK126 (IC = 0.40 μM). suppressed tumor growth in vivo, which was as good as the combination therapy. These results suggested that may be a promising drug candidate for treating hematological malignancies.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/acs.jmedchem.2c00673 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!