h3 acetylation

BRD73954, an effective and specific HDAC inhibitor, which is with IC50 of 36 nM and 120 nM for HDAC6 and HDAC8, respectively.

Crebinostat is a potent histone deacetylase (HDAC) inhibitor, targeting HDAC1, HDAC2, HDAC3, and HDAC6 with IC50s of 0.7 nM, 1.0 nM, 2.0 nM, and 9.3 nM, respectively. It increases the density of synapsin-1 punctae along dendrites in neurons in vitro, modulates chromatin-mediated neuroplasticity, and enhances memory in mice. Additionally, Crebinostat induces histone H3 and H4 acetylation and enhances the expression of Egr1, a cAMP-responsive element binding protein (CREB) target gene.

HDAC-IN-7, an analogue of Tucidinostat (Chidamide), is a HDAC inhibitor. HDAC-IN-7 inhibits acetylation of histone protein H3 and induces apoptosis in human colon cancer cell lines[1].

PI3Kδ/HDAC6-IN-1 (Compound 22E) is an orally active dual inhibitor of PI3Kδ and HDAC6, with IC50 values of 2.4 nM and 6.2 nM, respectively. It exhibits potent antiproliferative effects against non-Hodgkin's lymphoma (NHL) cells and demonstrates antitumor activity in vivo without significant toxicity. PI3Kδ/HDAC6-IN-1 induces cell cycle arrest at the G0/G1 phase and triggers apoptosis. Additionally, it inhibits the PI3K/AKT/mTOR signaling pathway and enhances the acetylation levels of α-tubulin and histone H3.

LSD1/HDAC-IN-3 is an inhibitor targeting class I HDACs and LSD1. It effectively inhibits HDAC1, HDAC2, HDAC3, and LSD1 with IC50 values of 1702 nM, 842 nM, 358 nM, and 1074 nM, respectively. Demonstrating antioxidant properties, it increases acetylation and methylation of histone H3 in H2O2-treated ARPE-19 and 661W retinal cells. In the rd10 mouse model of retinitis pigmentosa, LSD1/HDAC-IN-3 enhances photoreceptor survival. It is applicable for studying hereditary retinal diseases such as retinitis pigmentosa (RP).

SJY26 is a dual-target inhibitor of PI3K/HDAC, exhibiting IC50 values of 0.59 nM for PI3Kα and PI3Kδ, 2.02 nM for PI3Kγ, 12.69 nM for PI3Kβ, and 114 nM for HDAC1. It has potent antiproliferative activity across a broad spectrum, particularly affecting Jurkat and PC9R cells. SJY26 inhibits the migration of PC9R cells, induces cell cycle arrest, and triggers apoptosis. It also reduces AKT phosphorylation and decreases acetylation of histone H3 (Ac-H3). SJY26 is applicable for research in non-small cell lung cancer and leukemia.

HDAC6-IN-67 is a selective HDAC6 inhibitor with an IC50 of 17.15 nM, demonstrating 19-fold selectivity over HDAC1. It selectively inhibits HDAC6 by interacting with Ser531 and His614. HDAC6-IN-67 induces apoptosis by cleaving caspase9, 8, 3 and PARP, upregulating Bax expression, and downregulating Bcl-2 expression. It effectively acetylates α-tubulin in MCF-7/ADR cells without affecting histone H3 acetylation. HDAC6-IN-67 is applicable in breast cancer research.

HDAC6-IN-66 is a potent and selective inhibitor of histone deacetylase (HDAC) 6, with an IC50 value of 1.2 nM. It induces acetylation of α-tubulin more effectively than that of histone H3. HDAC6-IN-66 is applicable in cancer-related research.

Aurora kinase/HDAC-IN-1 is an orally active dual-target inhibitor of Aurora kinase and HDAC. It inhibits Aurora A (IC50 = 116 nM), Aurora B (IC50 = 225 nM), HDAC1 (IC50 = 164 nM), and HDAC2 (IC50 = 346 nM). This compound enhances histone acetylation (Ac-H3), inhibits phosphorylation of Aurora A and its downstream signaling, and induces apoptosis through G2/M phase arrest. In colorectal cancer cells HCT-116, Aurora kinase/HDAC-IN-1 shows significant antiproliferative activity with an IC50 of 30.2 nM and effectively suppresses tumor growth in HCT-116 colorectal cancer xenograft mouse models.

HDAC1-IN-12 is an inhibitor of the malignant malaria parasite (Plasmodium falciparum) HDAC1 (PfHDAC1), with an IC50 of 4.1 nM. This inhibitor functions by inhibiting PfHDAC1, increasing histone H3 acetylation in the P. falciparum parasite, and reducing the expression of genes associated with malaria invasion. It exhibits favorable safety profiles, improved physicochemical properties, and effective in vivo antimalarial activity, making HDAC1-IN-12 a valuable tool for malaria research.

HDAC/HSP90-IN-1 (compound 20) is a potent dual inhibitor targeting HDAC (IC50 = 194 nM) and HSP90 (HSP90α IC50 = 153 nM). It induces the expression of HSP70, downregulates HSP90 substrate proteins, and enhances the acetylation of α-tubulin and histone H3 in cancer cells. Additionally, HDAC/HSP90-IN-1 reduces PD-L1 expression in IFN-γ-treated H1975 cells. This compound is applicable in research on cancers such as lung and colon cancer.

HDAC/HSP90-IN-2 (compound 26) is a potent dual inhibitor of HDAC (IC50= 194 nM) and HSP90 (HSP90α IC50= 153 nM). It induces HSP70 expression, downregulates HSP90 substrate proteins, and promotes the acetylation of α-tubulin and histone H3 in cancer cells. Additionally, HDAC/HSP90-IN-2 reduces PD-L1 expression in H1975 cells treated with IFN-γ and is applicable in the research of cancers such as lung cancer and colon cancer.

Histone H3 (21-44)-GK-biotin is a peptide fragment of histone H3 that corresponds to amino acid residues 22-45 of the human histone H3.1 and 3.2 sequences and is biotinylated via a C-terminal GK linker. Histone H3 (21-44) contains a lysine residue at position 23 that is subject to acetylation, an arginine at position 26 subject to methylation, and a serine at position 28 subject to phosphorylation, as well as lysine residues at positions 27 and 36 that are subject to methylation and acetylation. Histone H3 (21-44)-GK-biotin has been used as a substrate for the primate-specific histone methyltransferase PR domain-containing protein 7 (PRDM7) to determine substrate specificity.

Histone H3 (21-44)-GK-biotin is a peptide fragment of histone H3 that corresponds to amino acid residues 22-45 of the human histone H3.3 sequence and is biotinylated via a C-terminal GK linker. Unlike histone H3.1 and H3.2, the histone H3.3 variant contains a serine residue at position 31 that is phosphorylated during late prometaphase and metaphase of mitosis. Histone H3 (21-44) also contains lysine residues at positions 23, 27, and 36 that are subject to methylation and acetylation, all of which have a role in the regulation of gene expression, and a serine residue at position 28 that is subject to phosphorylation during mitosis.

Histone H3 (23-34) is a peptide composed of amino acid residues 23 to 34 of the histone H3 protein, including lysine residues at positions 23 and 27, which are subject to methylation and acetylation modifications.

HDAC-IN-27 is a highly potent and orally bioavailable class I HDAC-selective inhibitor with IC₅₀ values ranging from 0.43 to 3.01 nM against HDAC1–3. It shows significant anti-tumor activity in vitro and in vivo, exerts prominent anti-proliferative effects on acute myeloid leukemia (AML) cell lines, and achieves its biological effects by inducing apoptosis and promoting acetylation of histones H3 and H4 (AcHH3, AcHH4), making it applicable in acute myeloid leukemia research.

HDAC1-IN-5, a potent inhibitor of HDAC1 with an IC50 value of 15 nM, also exhibits inhibitory activity towards HDAC6 with an IC50 value of 20 nM. In cancer cells, HDAC1-IN-5 enhances the acetylation of both histone H3 and α-tubulin, leading to the activation of caspase 3 and induction of apoptosis. Additionally, HDAC1-IN-5 binds with DNA, causing chromatin damage. Furthermore, it demonstrated strong inhibitory activity against tumor growth in xenograft mice. [1]

CPTH6, a thiazole derivative, selectively inhibits the lysine acetyltransferase activity of Gcn5 and pCAF without affecting p300 or CBP. It effectively blocks the acetylation of H3/H4 histones and α-tubulin in various leukemia cell lines, leading to reduced cell viability by arresting the cell cycle in the G0/G1 phase and inducing apoptosis. Additionally, CPTH6 disrupts autophagy across several tumor cell lines, primarily by interfering with ATG7-mediated autophagosomal membrane elongation.

PI3K/HDAC-IN-3 (36) acts as a dual inhibitor targeting PI3K and HDAC, exhibiting respective IC50 concentrations of 0.23 nM for PI3Kα and 172 nM for HDAC1. In MV4-11 cells, it inhibits AKT phosphorylation while enhancing H3 acetylation. Furthermore, PI3K/HDAC-IN-3 (36) demonstrates substantial, dose-dependent anticancer effects in an MV4-11 xenograft model [1].