histone h3 phosphorylation

Ilorasertib (ABT-348) (ABT-348) is an ATP-competitive multitargeted kinase inhibitor, which inhibits Aurora A/Aurora B/Aurora C (IC50s: 120 nM/7 nM/1 nM). It also suppresses RET tyrosine kinase, PDGFRβ, and Flt1 (IC50s: 7 nM, 3 nM, and 32 nM).

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.

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.

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.

Fostriecin (free base) is an inhibitor of the serine/threonine protein phosphatases 2A (PP2A) and 4 (PP4) (IC50s = 3.2 and 3 nM, respectively). It less effectively inhibits topoisomerase II and PP1 (IC50s = 40 and 131 μM, respectively) and does not inhibit PP2B. Through its effects on protein phosphatases, fostriecin increases the level of histone H3 phosphorylation and may alter epigenetic regulation of cell proliferation. On a related note, fostriecin was first identified as an antitumor antibiotic.