histones

LP99 is an epigenetic probe. LP99 disrupts the binding of BRD7 and BRD9 to chromatin in cells. LP99 is an effective and selective inhibitor of the BRD7 and BRD9 bromodomains (Kd: 99 nM against BRD9).

Trichostatin A (TSA), a natural derivative of diene isohydroxamic acids, is a specific and reversible histone deacetylase inhibitor (IC50=1.8 nM) that induces hyperacetylation of core histones to regulate chromatin structure.

Patamostat mesylate (E-3123) is a potent protease inhibitor with IC50 values of 39 nM for trypsin, 950 nM for plasmin, and 1.9 μM for thrombin. This compound demonstrates promising potential in suppressing the pathogenesis and development of acute pancreatitis.

Chlorambucil (CB-1348) is an orally-active antineoplastic aromatic nitrogen mustard. Chlorambucil alkylates and cross-links DNA during all phases of the cell cycle, resulting in disruption of DNA function, cell cycle arrest, and apoptosis.

Nanatinostat, also known as Tractinostat, CHR-3996 and VRx-3996, is an orally bioavailable, second-generation hydroxamic acid-based inhibitor of histone deacetylase (HDAC) with potential antineoplastic activity. HDAC inhibitor CHR-3996 inhibits HDAC, resulting in an accumulation of highly acetylated histones, the induction of chromatin remodeling, and the selective transcription of tumor suppressor genes; these events may result in the inhibition of tumor cell division and the induction of tumor cell apoptosis. This agent may upregulate HSP70 and downregulate anti-apoptotic Bcl-2 proteins more substantially than some first-generation HDAC inhibitors. HDACs, upregulated in many tumor cell types, are a family of metalloenzymes responsible for the deacetylation of chromatin histone proteins.

N-myristoyl-RKRTLRRL is a compound that impedes the binding of protein kinase C (PKC) substrates and inhibits calcium (Ca2+)- and phosphatidylserine (PS)-dependent phosphorylation of histones, exhibiting an IC50 of 5 μM. Additionally, it demonstrates an inhibitory effect on histone phosphorylation with an IC50 of 80 μM [1] [2].

FT-1101 is an orally bioavailable, potent and selective BET inhibitor. FT-1101 binds to the acetylated lysine recognition motifs in the bromodomain sites of BET proteins, thereby preventing the interaction between the BET proteins and acetylated histones. This disrupts chromatin remodeling and gene expression. Prevention of the expression of certain growth-promoting genes may lead to the inhibition of tumor cell growth. BET proteins, comprised of BRD2, BRD3, BRD4 and BRDT, are transcriptional regulators that play an important role during development and cellular growth.

Mivebresib (ABBV-075), also known as ABBV-075, is a potent BET inhibitor (bromodomain (BRD)-containing protein) with potential antineoplastic activity. Upon administration, the bromodomain inhibitor ABBV-075 binds to the acetyl-lysine binding site in the BRD of certain BRD-containing protein(s), thereby preventing the interaction between those proteins and acetylated histones. This disrupts chromatin remodeling, prevents the expression of certain growth-promoting genes, and leads to an inhibition of cell growth in susceptible tumors. Also a potent inhibitor of MYC and the TMPRSS2-ETS fusion proteins.

TCEP-biotin is biotinylated form of the reducing agent TCEP and an affinity probe for protein lysine crotonylation. Covalent addition of the TCEP moiety to crotonylated lysine residues results in adduct formation that allows for detection or immobilization of crotonylated proteins through interaction with the biotin ligand. It has been used in the detection and isolation of crotonylated histones in HEK293 cells.

(+)-Biotin 4-amidobenzoic acid is a substrate of biotinidase, which cleaves biotin amide to give biotin in vivo. Biotin is an essential coenzyme for certain carboxylases and is used to modify histones and regulate gene transcription. Biotinidase has key roles in intestinal absorption of biotin, the transport of biotin in plasma, and in the regulation of histone biotinylation. (+)-Biotin 4-amidobenzoic acid is hydrolyzed by biotinidase to release 4-aminobenzoic acid (PABA), which can be quantified by either fluorescent or colorimetric methods. This approach is used in biotinidase activity assays in newborn screening protocols to evaluate biotinidase deficiency.

PI3Kα HDAC6-IN-1 (compound 21j) is a dual inhibitor of PI3Kα and HDAC6, with IC50 values of 2.9 nM and 26 nM, respectively. It hinders AKT(Ser473) phosphorylation and promotes the accumulation of acetylated α-tubulin without affecting acetylated histones H3 and H4. The compound exhibits potent anti-cancer efficacy, inhibiting the L-363 cell line with an IC50 of 0.17 μM [1].

BRD9539 is an inhibitor of euchromatin histone methyltransferase 2 (EHMT2), also known as G9a, with an IC50 value of 6.3 μM

ACY-241, also known as Citarinostat (ACY241), is a potent, selective and orally available histone deacetylase (HDAC) inhibitor, with potential antineoplastic activity. Upon oral administration, ACY-241 inhibits the activity of HDACs; this results in an accumulation of highly acetylated chromatin histones, the induction of chromatin remodeling and an altered pattern of gene expression. This leads to the inhibition of tumor oncogene transcription, and the selective transcription of tumor suppressor genes, which inhibit tumor cell division and induce tumor cell apoptosis.

TDI-11055 is an orally available inhibitor of chromatin reader 11-19 leukemia (ENL) that works by blocking the interaction of its YEATS domain with acylated histones. TDI-11055 can be used to study acute myeloid leukemia (AML).

Histone H3 (1-35) is a 35-residue peptide derived from histone H3, a crucial component of the five main histones involved in chromatin formation within eukaryotic cells.

2-(Propyl-3,3,3-d3)pentanoic-5,5,5-d3 Acid is a deuterated compound of 2-pentanoic Acid. 2-pentanoic Acid has a CAS number of 99-66-1. Valproic Acid is a branched chain fatty acid which potentially enhances central GABAergic neurotransmission and inhibits Na+ channels. Currently, the various molecular mechanisms of action of Valproic Acid have not been completely elucidated. Valproic Acid has been reported to be a potent inhibitor of histone deacetylases (HDACs) in vitro. Valproic Acid is also noted to relieve HDAC-dependent transcriptional repression and causes the hyperacetylation of histones in cultured cells. Additionally, Valproic Acid is reported to activate Wnt-dependent gene expression and to mimic trichostatin A (sc-3511) in the inhibition of histone deacetylase.

Valproic Acid-d4 is a deuterated compound of Valproic Acid. Valproic Acid has a CAS number of 99-66-1. Valproic Acid is a branched chain fatty acid which potentially enhances central GABAergic neurotransmission and inhibits Na+ channels. Currently, the various molecular mechanisms of action of Valproic Acid have not been completely elucidated. Valproic Acid has been reported to be a potent inhibitor of histone deacetylases (HDACs) in vitro. Valproic Acid is also noted to relieve HDAC-dependent transcriptional repression and causes the hyperacetylation of histones in cultured cells. Additionally, Valproic Acid is reported to activate Wnt-dependent gene expression and to mimic trichostatin A (sc-3511) in the inhibition of histone deacetylase.

Competitive inhibitor of cGMP-dependent protein kinase (PKG); analog of a substrate peptide corresponding to a phosphorylation site of histone H2B. Competes with synthetic substrates (Ki = 86 mM) but does not inhibit phosphorylation of intact histones by

STC314 is an anti-infective agent that reverses organ damage caused by excessive immune response by neutralizing extracellular histones and neutrophil trapping networks, and can be used in the study of sepsis and acute respiratory distress syndrome (ARDS).STC314 protects the stability of lipid bilayers, and inhibits platelet activation and erythrocyte damage.STC314 is also used in the study of prostate cancer.Nardeterol HCl is a selective kappa agonist with analgesic activity.

HDAC3-IN-2 (compound 4i), a pyrazinyl hydrazide-based HDAC3 inhibitor with an IC50 of 14 nM, effectively targets triple-negative breast cancer cells. Demonstrating cytotoxic activity, HDAC3-IN-2 exhibits an IC50 of 0.55 μM against 4T1 cells and 0.74 μM against MDA-MB-231 cells. In vivo, it shows anti-tumor efficacy in tumor-bearing mouse models by selectively elevating acetylation of histones H3K9, H3K27, and H4K12, enhancing apoptosis-inducing proteins caspase-3, caspase-7, and cytochrome c, and diminishing proliferation markers Bcl-2, CD44, EGFR, and Ki-67 [1].

The methylation of lysine residues on histones plays a central role in determining euchromatin structure and gene expression. The histone methyltransferase (HMTase) G9a can mono- or dimethylate lysine 9 on histone 3 (H3), contributing to early embryogenesis, genomic imprinting, and lymphocyte development. BIX01294 (hydrochloride hydrate) is a selective inhibitor of G9a HMTase (IC50 = 1.7 μM). It less effectively inhibits the HMTase G9a-like protein (GLP; IC50 = 38 μM) and has no effect on other known HMTases. BIX01294 has been used in combination with the calcium channel activator BayK8644 to facilitate the generation of induced pluripotent stem cells from somatic cells in vitro.

Suberoyl bis-hydroxamic acid (SBHA) is a Histone deacetylase (HDAC) inhibitor. HDAC is required for transcriptional modulation, cell cycle regulation and development. It is an enzyme that deacetylates lysine residues on the N-terminal of the core histones.

Histone-H2A-(107-122)-Ac-OH is a peptide with the sequence Ac-Gly-Val-Leu-Pro-Asn-Ile-Gln-Ala-Val-Leu-Leu-Pro-Lys-Lys-Thr-Glu-OH, MW= 1762.1. Histone H2A is one of the five main histone proteins involved in the structure of chromatin in eukaryotic cells.

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.