ArticleJournal of medicinal chemistry2024
Discovery of a Highly Potent and Selective HDAC8 Degrader: Advancing the Functional Understanding and Therapeutic Potential of HDAC8.
Article in Journal of medicinal chemistry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
7 citing papers in PubMed.
- Article
- Histone Deacetylase Meets Protein Degradation: Accelerating Anticancer Drug Discovery.Medicinal research reviews · 2026Review
- Dual PROTACs Versus Dual Inhibitors in Oncology: A Medicinal Chemistry and Linker Design Perspective.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Targeted Degradation of Histone Deacetylase 8 Using Proteolysis Targeting Chimeras Technology: A Promising Approach for Glioblastoma Treatment.Drug design, development and therapy · 2026Article
- Advancements in Hydrazide-Based HDAC Inhibitors: A Review of Recent Developments and Therapeutic Potential.Journal of medicinal chemistry · 2025Review
- Epigenetic therapy meets targeted protein degradation: HDAC-PROTACs in cancer treatment.Future medicinal chemistry · 2025Review
- Development of Ethyl-Hydrazide-Based Selective Histone Deacetylase 6 (HDAC6) PROTACs.ACS medicinal chemistry letters · 2025Article
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
HDAC8 plays crucial roles in biological processes, from gene regulation to cell motility, making it a highly desirable target for therapeutic intervention. HDAC8 also has deacetylase-independent activity which cannot be blocked by a conventional inhibitor. In this study, we report the discovery of YX862, a highly potent and selective hydrazide-based HDAC8-proteolysis targeting chimera (PROTAC) degrader. The selectivity is achieved through rational design of the warhead to spare HDAC3 activity from the previous HDAC3/8 dual degrader YX968. We demonstrate that the degradation of HDAC8 by YX862 increases acetylation levels of its nonhistone substrates such as SMC3 without significantly triggering histone PTM, supporting HDAC8's major role in nonhistone PTM regulation. YX862 exhibits promising on-target antiproliferative activity against DLBCL cells with higher potency than the HDAC8 selective inhibitor PCI-34051. As a selective HDAC8 degrader that avoids pan-HDAC inhibition, YX862 represents a valuable tool for exploring the biological and therapeutic potential of HDAC8.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.