histone acetylation

R306465 (JNJ-16241199) is an orally active and selective class I histone deacetylase (HDAC 1) inhibitor with an IC50 of 3.3 nM. R306465 has a broad spectrum of antitumor activity, can induce histone 3 acetylation, and induce apoptosis, and can be used to study solid tumors and hematological malignancies.

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.

Triciferol acts as a multiple ligand with combined VDR agonist and HDAC antagonist activities. Triciferol binds directly to the VDR ( IC 50 =87 nM), and functions as an agonist with 1,25D-like potency on several 1,25D target genes. Triciferol induces marked tubulin hyperacetylation, and augments histone acetylation. Triciferol also exhibits efficacious antiproliferative and cytotoxic activities in cancer cell models in vitro [1].

Histone Acetyltransferase Inhibitor II is a selective and cell permeable inhibitor of p300 histone acetyltransferase(IC50 : 5 μM).with anti-acetylase activity in mammalian cells.

L002, a potent, cell-permeable, reversible, and specific acetyltransferase p300 (KAT3B) inhibitor with an IC50 of 1.98 μM, directly binds the acetyl-CoA pocket and competitively inhibits the FATp300 catalytic domain. By blocking histone acetylation, p53 acetylation, and STAT3 activation, L002 shows potential in the treatment of hypertension‐induced cardiac hypertrophy and fibrogenesis.

1-Naphthohydroxamic acid (Compound 2) is a potent and selective HDAC8 inhibitor with an IC50 of 14 μM, demonstrating greater selectivity for HDAC8 than class I HDAC1 and class II HDAC6 (IC50 >100 μM). It does not increase global histone H4 acetylation or reduce total intracellular HDAC activity but can induce tubulin acetylation[1][2].

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].

PSF-IN-1 (Compound No.10-3) is an inhibitor of the RNA-binding protein (PSF), effectively blocking PSF-RNA interactions with an IC50 of 2.2 pM. It enhances histone acetylation, suppresses tumor cell proliferation, and induces apoptosis. PSF-IN-1 exhibits antitumor activity.

HDAC-IN-27 dihydrochloride (Compound 11h) is a potent, orally active, HDACI class-selective inhibitor, with IC50 values ranging from 0.43 to 3.01 nM for HDAC1-3. This compound exhibits both in vivo and in vitro anticancer activity. HDAC-IN-27 shows significant antiproliferative effects against acute myeloid leukemia (AML) cell lines by inducing apoptosis and histone acetylation (AcHH3 and AcHH4). It is useful for research on acute myeloid leukemia (AML).

CS4 is a selective HDAC inhibitor, with IC50 values for HDAC1, HDAC6, HDAC8, HDAC4, and HDAC11 reported as 38 nM, 12 nM, 5.8 μM, 19 μM, and 61 μM, respectively. It enhances the acetylation of α-tubulin and histone 3 (histone 3). Additionally, CS4 activates PPARγ and blocks glycolysis (glycolysis). It induces cell cycle arrest at the G2 phase and triggers apoptosis (apoptosis), exhibiting anticancer effects both in vitro and in vivo.

EGFR/HDAC-IN-1 (Compound 22c2) is a potent dual inhibitor of epidermal growth factor receptor (EGFR) and histone deacetylase (HDAC), exhibiting IC50 values of 4.81 nM for EGFR, 119.4 nM for HDAC1, and 354.8 nM for HDAC3. It disrupts the EGFR signaling pathway and alters histone acetylation status, thereby inhibiting tumor cell proliferation. EGFR/HDAC-IN-1 is a promising candidate for research in non-small cell lung cancer (NSCLC).

NU 9056 is an effective and selective inhibitor of KAT5 histone acetyltransferase with an IC50 of 2 µM. NU 9056 blocks DNA damage response and inhibits protein acetylation in prostate cancer cell lines.

HDAC3-IN-T247 (HDAC3 inhibitor T247) is a selective and potent histone deacetylase 3 (HDAC3) inhibitor with anticancer and antiviral activities.HDAC3-IN-T247 induces NF-κB acetylation in human colon cancer HCT116 cells in a dose-dependent manner.HDAC3-IN-T247 inhibits cancer cell proliferation. HDAC3-IN-T247 inhibits cancer cell proliferation.

AC-93253 iodide is a selective inhibitor of SIRT2. It significantly enhances the acetylation of tubulin p53 and histone H4.

CAY10669 is an inhibitor of the histone acetyltransferase PCAF (p300 CREB-binding protein-associated factor; IC50 = 662 μM), displaying a 2-fold improvement in inhibitory potency over anacardic acid . At 30-60 μM, CAY10669 can dose-dependently inhibit histone H4 acetylation in HepG2 cells in vitro.

Trichostatin C is a glycosylated derivative of trichostatin A , the antifungal antibiotic that reversibly inhibits histone deacetylase. Trichostatin C is reported to be the first example of a glucopyranosyl hydroxamate identified in nature. It has been shown to induce the differentiation of a mouse erythroleukemia cell line and to increase histone H4 acetylation in B cells, though at higher concentrations than trichostatin A.

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 H2B (108-125) is a peptide fragment of histone H2B that corresponds to amino acid residues 109-126 of the human histone H2B sequence. It contains an N-terminal biotinylated lysine followed by a tryptophan linker. Histone H2B can be modified by addition of an O-linked N-acetylglucosamine (GlcNAc) moiety to the serine residue at position 112, which promotes monoubiquitination of the lysine at position 120.1 Both of these modifications are associated with active transcription. Histone H2B also has lysine residues at positions 108, 116, and 120 that are subject to acetylation.2References1. Fujiki, R., Hashiba, W., Sekine, H., et al. GlcNAcylation of histone H2B facilitates its monoubiquitination. Nature 480(7378), 557-560 (2011).2. Portela, A., and Esteller, M. Epigenetic modifications and human disease. Nat. Biotechnol. 28(10), 1057-1068 (2010). Histone H2B (108-125) is a peptide fragment of histone H2B that corresponds to amino acid residues 109-126 of the human histone H2B sequence. It contains an N-terminal biotinylated lysine followed by a tryptophan linker. Histone H2B can be modified by addition of an O-linked N-acetylglucosamine (GlcNAc) moiety to the serine residue at position 112, which promotes monoubiquitination of the lysine at position 120.1 Both of these modifications are associated with active transcription. Histone H2B also has lysine residues at positions 108, 116, and 120 that are subject to acetylation.2 References1. Fujiki, R., Hashiba, W., Sekine, H., et al. GlcNAcylation of histone H2B facilitates its monoubiquitination. Nature 480(7378), 557-560 (2011).2. Portela, A., and Esteller, M. Epigenetic modifications and human disease. Nat. Biotechnol. 28(10), 1057-1068 (2010).

Selective p300 histone acetyltransferase (HAT) inhibitor (IC50 = 50-500 nM). Exhibits approximately 100-fold selectivity for p300 over PCAF (IC50 = 200 μM). Inhibits p300-dependent transcription. Active in vivo. Lau et al (2000) HATs off: selective synthetic inhibitors of the histone acetyltransferases p300 and PCAF. Mol.Cell. 5 589 PMID:10882143 |Liu et al (2008) The structural basis of protein acetylation by the p300/CBP transcriptional coactivator. Nature. 451 846 PMID:18273021 |Burns et al (2005) Iso-coenzyme A. J.Biol.Chem. 280 16550 PMID:15708855 |Cebrat et al (2003) Synthesis and analysis of potential prodrugs of coenzyme A analogues for the inhibition of the histone acetyltransferase p300. Bioorg.Med.Chem. 11 3307 PMID:12837541

Givinostat (ITF-2357) is an HDAC inhibitor with IC50 values of 198 nM for HDAC1 and 157 nM for HDAC3.

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.

CXD101 is a novel class I-selective HDACi (HDAC1 (IC50 : 63nM), HDAC2 (IC50 :570nM), HDAC3 (IC50 :550nM)). CXD101(CXD-101) has no activity against HDAC class II

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]