Read the full paper: Microbial inositol phosphates orchestrate host diurnal metabolism and energy homeostasis via HDAC3

Today's digest has 23 items: medchem led by HDAC3-selective degraders and new carbonic anhydrase IX chemotypes, pharmacology including a Cas9 nickase Huntington's study, one computational paper, and industry news on Roche's pipeline cull and Merck/Moderna's melanoma vaccine at ESMO.

This study was supported by grants from CARIPLO Foundation 2015-0641, EC Marie Curie-ITN 606806 NR-NET, EC FP7-HEALTH-2013-INNOVATION-1 602757 HUMAN, MUR PRIN 2022LHMF43 to M.C, MUR Progetto Eccellenza 2023-2027 to the Department of Pharmacological and Biomolecular Sciences. This work was also partially supported by the Italian Ministry of Health with Ricerca Corrente and “5xmille” funds to N.M. and by the Italian Ministry of Health with Ricerca Corrente to MultiMedica IRCCS to A.L.C.. The graphical abstract was created in BioRender. Crestani, M. (https://BioRender.com/eeq71jf) and is licensed under CC BY 4.0. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need...

Zhang et al. show that gut microbial inositol phosphate metabolism transduces feeding cues into intestinal diurnal rhythms through histone deacetylase 3. This pathway activates PGC-1α and enhances nut...

Sun et al. demonstrate that TBK1 stabilizes HDAC3 via Ser424 phosphorylation during Salmonella Typhimurium infection. HDAC3-mediated NDP52 deacetylation at Lys202 enhances its binding to MAP1LC3A/B and GABARAPL2, thereby facilitating intracellular bacterial clearance and host antibacterial defense.

The HDAC3 Antibody Market is expected to grow from 400 USD Million in 2025 to 1,500 USD Million by 2035. The HDAC3 Antibody Market CAGR (growth rate) is expected to be around 13.4% | Wiseguy Reports

Read the full paper: TBK1 phosphorylates HDAC3 to promote NDP52 deacetylation and accelerate intracellular bacterial clearance

In this study, Xi et al. show that H2BK5ac is essential for establishing inflammatory potential in mouse ESCs during differentiation. H2BK5ac increases upon differentiation and drives inflammatory gene expression. p300 and HDAC3 serve as the corresponding acetyltransferase and deacetylase, respectively, that regulate H2BK5ac levels in mouse ESCs.

This study investigates how HOX gene expression patterns identify therapy-resistant cancer subtypes and demonstrates RUNX1T1-HDAC3 inhibition as a potential

Published in Journal of inflammation research

Penn State researchers discovered that blocking the enzyme HDAC3 improves memory updating in older mice, potentially offering new treatment avenues for age-related cognitive decline and memory disorde...

Oral butyrate exerts therapeutic effects in RA independently of systemic absorption, instead enhancing CST expression within the ileum epithelium. This upregulation of CST is mediated by the inhibiti...

A new study backed by a $3.2M NIMH grant targets the HDAC3 histone modifier and uses CRISPR to erase the amygdala's molecular trauma memory.

To avoid premature death, cells hide a guardian in the cytoplasm: Hdac3 keeps Diap1 stable by deacetylation.

Soft niches in primary tumor microenvironment promote brain metastasis.

Preoperative exercise (PEx) prevents surgical stress-promoted liver metastasis by enhancing anti-tumor immunity. Zhang et al. demonstrate that PEx-induced gut microbiota-derived butyrate accumulates in Kupffer cells, where it inhibits HDAC3 to upregulate CXCL9. This chemokine then recruits and activates CXCR3+ CD8+ T cells, thereby suppressing surgical stress-promoted colorectal cancer liver metastasis.

Dynamic gene regulation requires precise cooperation between transcription factors and chromatin modifiers at regulatory elements to achieve not only activation or repression, but also appropriate tra...

Read the full paper: HDAC3 inhibition stabilizes the IL-37 receptor module to enhance anti-inflammatory signaling in cystic fibrosis airway epithelium