Histone Deacetylase Inhibitors Research

MYC plus class IIa HDAC inhibition potentiates mitochondrial dysfunction in non-small cell lung cancer

This study identifies that combining MYC inhibition with class IIa HDAC inhibition enhances mitochondrial dysfunction and reduces viability in NSCLC cell lines.

Enzyme-independent functions of HDAC3 in the adult heart

This study shows that HDAC3's cardioprotective role in adult hearts is independent of its enzymatic activity, as enzyme-inactive HDAC3 can rescue gene expression and cardiac function.

Selective molecular inhibition of the HDAC6 ZnF-UBP binding domain impairs multiple myeloma cell proliferation

This study shows that inhibiting the ZnF-UBP domain of HDAC6 in multiple myeloma cells reduces proliferation and aggresome formation, suggesting it as a therapeutic target.

HDAC1 acts as tumor suppressor in ALK-positive anaplastic large-cell lymphoma: Implications for HDAC inhibitor therapy

This study shows HDAC1 suppresses ALK-positive lymphoma growth, but systemic HDAC inhibition can still be therapeutic.

Reversible histone deacetylase activity catalyzes lysine acylation

The paper shows class I HDACs can catalyze beta-hydroxybutyrylation of lysine, a reversible modification, expanding the role of HDACs beyond traditional deacetylation.

Design and Synthesis of Potent First-in-Class Histones Acetyltransferase Modulators.

The paper designs and synthesizes new activators of the p300 histone acetyltransferase enzyme to treat neurodegenerative and cancer disorders.

Class I histone deacetylases catalyze lysine lactylation

This paper identifies class I HDACs as enzymes that catalyze lysine lactylation, showing that this modification is primarily formed through enzymatic action rather than non-enzymatic pathways.

Mechanism-Based Inhibition of Histone Deacetylase 6 by a Selenocyanate is Subject to Redox Modulation

This study investigates how a selenocyanate inhibitor of histone deacetylase 6 is modulated by redox reactions to form an active selenolate anion.

Role of the NuRD complex and altered proteostasis in cancer cell quiescence

This study identifies NuRD complex downregulation and altered proteostasis in quiescent ovarian cancer cells and shows that targeting these mechanisms can synergistically kill cancer cells.

Sodium butyrate is incorporated into central metabolism in fly head while inducing oxygen consumption increase

This study shows that butyrate is metabolized into the TCA cycle in fly heads and increases oxygen consumption without affecting proteome or acetylome.

Dona Flor and her two husbands: Discovery of novel HDAC6/AKT2 inhibitors for myeloid cancer treatment

The paper uses machine learning to identify novel HDAC6/AKT2 inhibitors for myeloid cancer treatment, finding compounds with potent anticancer activity.

Extracellular HDAC6 ZnF UBP domain enhances podosome-mediated neuronal migration

The paper investigates the role of HDAC6 ZnF UBP domain in enhancing podosome-mediated neuronal migration through actin remodelling.

Rapid degradation of Histone Deacetylase 1 (HDAC1) reveals essential roles in both gene repression and active transcription

This study rapidly degrades HDAC1 in ESCs to show its dual role in gene repression and active transcription by modulating histone acetylation at promoters and enhancers.

Histone deacetylase inhibition expands cellular proteostasis repertoires to enhance neuronal stress resilience

This study shows that inhibiting histone deacetylases enhances neuronal resilience to stress by inducing a permissive transcriptional state and activating proteostasis pathways.

HDAC activity is dispensable for repression of cell-cycle genes by DREAM and E2F:RB complexes

This study shows that DREAM and E2F:RB complexes can repress cell-cycle genes without HDAC activity, challenging the canonical role of HDACs in this process.

IPMK regulates HDAC3 activity and histone H4 acetylation in human cells.

This study shows IPMK regulates HDAC3 activity and histone H4 acetylation in human cells through inositol phosphate production.

Genomic analysis reveals HDAC1 regulates clinically relevant transcriptional programs in pancreatic cancer

This study identifies HDAC1's role in promoting multidrug resistance in pancreatic cancer through chromatin remodeling and develops a prognostic gene signature.

Separation of transcriptional repressor and activator functions in HDAC3

This study demonstrates that HDAC3's repressor and activator functions can be genetically separated in Drosophila, revealing distinct roles for catalytic activity and SMRTER interaction in transcriptional regulation.

Mechanism of assembly, activation and lysine selection by the SIN3B histone deacetylase complex

The paper presents the structure of the SIN3B histone deacetylase complex and elucidates its mechanism of substrate recognition and catalysis.

Plasticity of gene expression in the nervous system by exposure to environmental odorants that inhibit HDACs

The paper investigates how exposure to volatile chemicals, like diacetyl, affects gene expression and physiology by inhibiting HDACs in Drosophila and human cells.

Metabolic adaptations underpin resistance to histone acetyltransferase inhibition

This study identifies CoA metabolism dysregulation as a mechanism of resistance to HAT inhibitors in AML, revealing a potential class-wide vulnerability for anti-cancer therapies targeting HATs.

Correlating basal gene expression across chemical sensitivity data to screen for novel synergistic interactors of HDAC inhibitors in pancreatic carcinoma

The paper uses drug-sensitivity and gene expression data to predict synergistic combinations of HDAC inhibitors in pancreatic cancer, identifying novel targets and validating synergistic interactions.

Expanding the HDAC druggable landscape beyond enzymatic activity

This paper identifies a non-enzymatic HDAC inhibitor with anti-tumor and anti-psychedelic effects, showing reduced gene modulation compared to enzymatic inhibitors.

Lactate-derived HDAC6 Lactylation as a new target for neuronal protection in cerebral ischemic reperfusion injury

The paper shows lactate-derived HDAC6 lactylation protects neurons in cerebral ischemic reperfusion injury by disrupting calcium homeostasis through BiP binding.

Structure-based prediction of KDAC6 substrates validated by enzymatic assay reveals determinants of promiscuity and detects new potential substrates

The paper predicts HDAC6 substrates using a structure-based method calibrated by enzymatic assays, identifies new substrates, and highlights structural determinants of HDAC6 promiscuity.

A synthetic lethal screen identifies HDAC4 as a potential target in MELK overexpressing cancers

The paper identifies HDAC4 as a synthetic lethal target in MELK-overexpressing cancers through a yeast screen and mammalian validation.

Interplay between p300 and HDAC1 regulate acetylation and stability of Api5 to regulate cell proliferation

This study identifies p300 and HDAC1 as enzymes regulating Api5 acetylation and deacetylation, showing their impact on Api5 stability and cell cycle progression.

A Knowledge-guided Mechanistic Model of Synthetic Lethality in the HCT116 Vorinostat-resistant Colon Cancer Xenograft Model Cell-line

The paper investigates synthetic lethality in vorinostat-resistant HCT116 colon cancer cells, finding that resistance is linked to rewiring of oncogenic pathways rather than embryonal gene regulation.

Reduction of HDAC2 expression in human induced pluripotent stem cell derived neurons improves neuronal maturation, mitochondrial dynamics and cellular neurodegenerative disease phenotypes.

This study shows that reducing HDAC2 in hiPSC-derived neurons enhances mitochondrial function and reduces neurotoxic amyloid beta, suggesting HDAC2's role in neuronal maturation and disease.

Transcriptional analysis of sodium valproate in a serotonergic cell line reveals gene regulation through both HDAC inhibition-dependent and independent mechanisms