Epigenetics


Epigenetics research delves into the molecular mechanisms that control gene expression and cellular traits without altering the underlying DNA sequence. One crucial aspect of this field is the role of small molecules, which act as powerful regulators of epigenetic modifications. These small compounds, typically comprising a few dozen to a few hundred atoms, have emerged as essential tools in understanding and manipulating the epigenome.
- DNA Methylation Inhibitors: Small molecules like 5-azacytidine and 5-aza-2'-deoxycytidine are DNA methyltransferase inhibitors. They block the addition of methyl groups to DNA, leading to DNA demethylation. This can reactivate silenced genes, potentially offering therapeutic avenues for conditions like cancer.
- HDAC inhibitors: HDACs remove acetyl groups from histone proteins, contributing to gene repression. Small molecule HDAC inhibitors, such as Vorinostat and Romidepsin, can reverse this process by increasing histone acetylation, allowing genes to be more accessible for transcription. These inhibitors are being explored for cancer therapy and other conditions.
- Histone Methyltransferase Inhibitors: Small molecules like GSK126 inhibit specific histone methyltransferases, affecting histone methylation patterns. This can alter gene expression, making them promising candidates for cancer and other diseases with epigenetic dysregulation.
- RNA Modulators: Small molecules can also target non-coding RNAs involved in epigenetic regulation. For instance, small molecules called small interfering RNAs (siRNAs) can be designed to target and degrade specific long non-coding RNAs, influencing gene expression.
- Epigenetic Reader Domain Inhibitors: These small molecules target proteins that recognize and bind to specific epigenetic marks. Examples include inhibitors of bromodomain-containing proteins (BET inhibitors), which can disrupt gene regulation by interfering with protein-DNA interactions.
Small molecules in epigenetics research not only provide insights into the fundamental biology of gene regulation but also hold immense promise for developing novel therapeutics. Their ability to selectively modulate specific epigenetic marks and pathways has led to ongoing clinical trials and drug development efforts for various diseases, including cancer, neurological disorders, and inflammatory conditions. Understanding and harnessing the power of these small molecules is at the forefront of modern epigenetics research, offering new hope for precision medicine and targeted therapies.
3 key components involved in the regulation of epigenetic modifications
Epigenetics Writer
Epigenetics writers are enzymes responsible for adding chemical marks or modifications to DNA or histone proteins. These marks include DNA methylation (addition of methyl groups to DNA) and histone modifications (such as acetylation, methylation, phosphorylation, etc.).
Epigenetics Reader
Function: Epigenetics readers are proteins that can recognize and bind to specific epigenetic marks on DNA or histones. These reader proteins interpret the epigenetic code and facilitate downstream cellular processes, such as gene activation or repression.
Epigenetics Eraser
Function: Epigenetics erasers are enzymes responsible for removing or reversing epigenetic marks on DNA or histones. This process allows for the dynamic regulation of gene expression and the resetting of epigenetic states during various stages of development and in response to environmental changes.
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cyt-PTPε 抑制剂
cyt-PTPε Inhibitor-1 是一种强效的细胞质蛋白酪氨酸磷酸酶ε(cyt-PTPε)抑制剂,它与 cyt-PTPε 的催化域结合,阻断 c-Src 激活(c-Src 的去磷酸化),并表现出抗破骨细胞活性。 -
Aurora A kinase 抑制剂
Aurora Kinase Inhibitor 3 是一种强效且选择性的 Aurora A kinase 抑制剂,其 IC50 为 42 nM,对 EGFR 的抑制作用较弱,IC50 大于 10 μM。 -
virion mRNA(guanine-7-)-methyltransferase 抑制剂
Sinefungin 是一种强效的 病毒mRNA(鸟嘌呤-7-)-甲基转移酶、mRNA(核苷酸-2'-)-甲基转移酶 和 病毒增殖 抑制剂。 -
EHMT 抑制剂
EHMT2-IN-2 是一种强效的 EHMT 抑制剂,对 EHMT1 肽、EHMT2 肽和细胞内 EHMT2 的 IC50 均小于 100 nM。用于血液病或癌症的研究。 -
Aurora 抑制剂
Aurora inhibitor 1 是一种强效的 Aurora 抑制剂,其 IC50 分别为 4 nM 和 13 nM,针对 Aurora A 和 Aurora B 激酶。 -
KDM2A/7A 抑制剂
KDM2A/7A-IN-1 是首创的、选择性的、细胞渗透性的组蛋白赖氨酸去甲基化酶 KDM2A/7A 抑制剂,对 KDM2A 的 IC50 为 0.16 μM,对其他 JmjC 赖氨酸去甲基化酶具有 75 倍的选择性,并且对甲基转移酶和组蛋白乙酰转移酶无活性。 -
SYK/JAK 抑制剂
Gusacitinib (ASN-002) 是一种强效的双重抑制剂,针对脾脏酪氨酸激酶(SYK)和雅努斯激酶(JAK),其半抑制浓度(IC50)值为5-46纳摩尔(nM)。