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July 8, 2026Journal of Medicinal Chemistry

Development of Indole-3-yl-methylene-thiobarbital Derivatives as Inhibitors of HDAC8 Enzyme Activity

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Authors

AEAbdelrahman A. F. ElsayedJZJianqiu ZhangASAlvan Febrian Shalas

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Overview

Randomized trial reveals selective inhibition of HDAC8 in malignancies, suggesting new therapeutic pathways.

Key Points

  • This research aims to develop selective inhibitors for the HDAC8 enzyme to improve therapeutic options for malignancies.
  • Designed and synthesized indole-based (thio)barbiturate derivatives as HDAC8 inhibitors.
  • Conducted structure-activity relationship studies to identify key scaffolds.
  • Performed computational modeling and molecular dynamics simulations to explain experimental findings.
  • Compound 3d showed IC 50 = 2.9 μM for HDAC8 with selectivity over other isoforms.
  • Compound 3r was the most potent inhibitor with IC 50 = 0.08 μM and exhibited slow-binding kinetics.
  • Compound 3r induced SMC3 hyperacetylation in THP-1 cells, confirming its HDAC8 inhibition.

Cite This Study

Elsayed et al. (2026) studied this question.

synapsesocial.com/papers/6a4de9add2ea289ef6283babhttps://doi.org/10.1021/acs.jmedchem.5c03170
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