Histone deacetylase inhibitor

• Interrogation of macrophage-related prognostic signatures reveals a potential immune-mediated therapy strategy by histone deacetylase inhibition in glioma
• Inhibition of histone deacetylase 6 activity mitigates neurological impairment and post-hemorrhagic hydrocephalus after intraventricular hemorrhage by modulating pyroptosis and autophagy pathways
• Targeting the HLA-E-NKG2A axis in combination with MS-275 enhances NK cell-based immunotherapy against DMG
• Generation and validation of a novel multitarget small molecule in glioblastoma
• Vorinostat attenuates UVB-induced skin senescence by modulating NF-κB and mTOR signaling pathways
• Targeting the SP/KLF Transcriptional Regulatory Network Synergizes with HDAC Inhibition to Impede Progression of H3K27M Diffuse Intrinsic Pontine Glioma
• Characterization of an Enhancer RNA Signature Reveals Treatment Strategies for Improving Immunotherapy Efficacy in Cancer
• Efficacy and Safety of Sulforaphane Added to Antipsychotics for the Treatment of Negative Symptoms of Schizophrenia: A Randomized Controlled Trial

Histone deacetylase inhibitors (HDAC inhibitors, HDACi, HDIs) are chemical compounds that inhibit histone deacetylases.

HDIs have a long history of use in psychiatry and neurology as mood stabilizers and anti-epileptics. More recently they are being investigated as possible treatments for cancers, parasitic and inflammatory diseases.

HDAC inhibitors that induce acetylation of nuclear histones play a crucial role in gene expression ¹⁾.

HDAC inhibitors have radiosensitizing effects in established cancer cell lines, and antiproliferative agents that could be developed into drugs to treat cancer.

The deacetylase inhibitor sodium butyrate (NaBT) has been shown to induce cell cycle arrest or differentiation in various tumor cells ²⁾.

GBM cell growth was significantly inhibited by ACY-1215, a specific HDAC6 inhibitor. Further analyses show that HDAC6 may promote growth of GBM cells through inhibition of SMAD2 phosphorylation to downregulate p21. Thus, the data demonstrate a previously unrecognized regulation pathway in that HDAC6 increases GBM growth through attenuating transforming growth factor β (TGFβ) receptor signaling ³⁾.

A study demonstrated that histone deacetylase (HDAC) inhibitors enable the heat shock response in cultured spinal motor neurons, in a stress-dependent manner, and can improve the efficacy of HSP-inducing drugs in murine spinal cord cultures subjected to thermal or proteotoxic stress. The effect of particular HDAC inhibitors differed with the stress paradigm. The HDAC6 (class IIb) inhibitor, tubastatin A, acted as a co-inducer of Hsp70 (HSPA1A) expression with heat shock, but not with proteotoxic stress induced by expression of mutant SOD1 linked to familial ALS. Certain HDAC class I inhibitors (the pan inhibitor, SAHA, or the HDAC1/3 inhibitor, RGFP109) were HSP co-inducers comparable to the hydroxyamine arimoclomol in response to proteotoxic stress, but not thermal stress. Regardless, stress-induced Hsp70 expression could be enhanced by combining an HDAC inhibitor with either arimoclomol or with an HSP90 inhibitor that constitutively induced HSPs. HDAC inhibition failed to induce Hsp70 in motor neurons expressing ALS-linked mutant FUS, in which the heat shock response was suppressed; yet SAHA, RGFP109, and arimoclomol did reduce loss of nuclear FUS, a disease hallmark, and HDAC inhibition rescued the DNA repair response in iPSC-derived motor neurons carrying the FUSP525Lmutation, pointing to multiple mechanisms of neuroprotection by both HDAC inhibiting drugs and arimoclomol ⁴⁾.

Histone deacetylase inhibitor for glioma