histone h3 phosphorylation

Ilorasertib (ABT-348) 是一种 ATP 竞争性多靶点激酶抑制剂，可抑制 Aurora A、Aurora B 和Aurora C，IC50值为120 nM、7 nM 和1 nM。它还抑制 RET 酪氨酸激酶、PDGFRβ 和 Flt1，IC50为7 nM、3 nM 和 32 nM。

SJY26 是一种 PI3K/HDAC 双靶点抑制剂，其 IC50 值为 0.59 nM (PI3Kα和PI3Kδ)、2.02 nM (PI3Kγ)、12.69 nM (PI3Kβ) 和 114 nM (HDAC1)。SJY26 展现出强效广谱的抗增殖作用，对 Jurkat 和 PC9R 细胞尤为敏感，并能够抑制 PC9R 细胞的迁移、阻滞细胞周期及诱导细胞凋亡 (apoptosis)。此化合物能够降低 AKT 的磷酸化水平，并减少组蛋白 H3 (Ac-H3) 的去乙酰化。SJY26 可被用于非小细胞肺癌和白血病的研究。

Aurora kinase/HDAC-IN-1 是一种能够口服的 Aurora 激酶与HDAC双靶点抑制剂，其对Aurora A、Aurora B、HDAC1和HDAC2的IC50值分别为116 nM、225 nM、164 nM和346 nM。Aurora kinase/HDAC-IN-1 能够促进组蛋白乙酰化 (Ac-H3)，抑制Aurora A的磷酸化及其下游信号，并通过G2/M期阻滞诱导细胞凋亡 (apoptosis)。该化合物在结直肠癌细胞HCT-116中显示出显著的抗增殖活性，IC50值为30.2 nM，并可在HCT-116结直肠癌异种移植小鼠模型中显著抑制肿瘤生长。

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.