2019年9月1日 · Here, we report the novel anti-prion activity of SGI-1027 and its meta/meta analogue (M/M), previously known only as potent inhibitors of DNA methyltransferases (DNMTs). These compounds effectively decreased the level of PrPSc in cultured cells with permanent prion infection, without affecting PrP C at the transcriptional or translational levels.

2019年4月18日 · Here, we report the novel anti-prion activity of SGI-1027 and its meta/meta analogue (M/M), previously known only as potent inhibitors of DNA methyltransferases (DNMTs). These compounds effectively decreased the level of PrP Sc in cultured cells with permanent prion infection, without affecting PrP C at the transcriptional or translational levels.

DNA methyltransferases (DNMTs) is involved for DNA methylation, which are responsible for adding a methyl group to the fifth carbon atom of the cytosine residues within cytosine-phosphate-guanine (CpG) and non-CpG dinuclotide sites. Five DNMT enzymes have been identified in mammals including DNMT1, DNMT2, DNMT3A, DNMT3B, and DNMT3L.

dna 甲基转移酶 (dnmt) 是一类“写入”酶，负责 dna 甲基化，即将甲基添加到胞嘧啶的第五碳原子 (c5) 上。 哺乳动物编码五种 DNMT：DNMT1、DNMT2、DNMT3A-DNMT3B（从头甲基转移酶）和 DNMTL。

2016年7月28日 · We provide evidence for G-quadruplex formation within imprinted gene promoters, and report high-affinity binding of recombinant human DNMTs to such DNA G-quadruplexes in vitro. These observations suggest a potential interaction of G-quadruplexes with the DNA methylation machinery, which may be of epigenetic and biological significance.

DNA甲基化是在DNA甲基转移酶（DNA methyltransferase， DNMTs）的催化下进行的。 该反应以S-腺苷甲硫氨酸（SAM）为甲基供体将胞嘧啶核苷酸第5位碳原子进行甲基化生成5-mC： 5-mC可以后续被 TET家族双加氧酶 氧化，依次生成5-hmC、5-fC、5-caC，5-caC进而可以通过TDG等途径被转化为没有修饰的C，从而完成整个甲基化修饰的循环： DNMTs家族的成员包括DNMT1、DNMT2、DNMT3a、DNMT3b、DNMT3L等蛋白，它们的结构如下图所示。 但请注 …

DNA methyltransferase-1 (DNMT1) plays a crucial role in the maintenance of genomic methylation patterns. The crystal structure of DNMT1 was determined in two different states in which the helix that follows the catalytic loop was either kinked (designated helix-kinked) or well folded (designated helix-straight state).

2023年2月7日 · dnmt在癌症发病机制中的调控机制 探索基因的功能和信号通路通常是探索疾病分子机制的一种实用方法。 癌症肿瘤的发生、发展、转移、侵袭等过程涉及复杂的分子机制，而目前对它们的理解是不完整的，这导致癌症的治愈率较低。

GSK3685032 是一种强效的 DNMT1 选择性抑制剂，通过晶体学研究表明，它与DNMT1的活性位环竞争，以渗透到两个 CpG碱基对 之间的半甲基化DNA。 在体外诱导强有力的DNA甲基化丧失、转录激活和癌细胞生长抑制。 2021年9月27日，美国葛兰素史克的Michael T. McCabe博士等人在《Nature Cancer》上发表了一篇“Discovery of a first-in-class reversible DNMT1-selective inhibitor with improved tolerability and efficacy in acute myeloid leukemia”的文章。 DNA甲基化是一种 …

2023年7月1日 · DNMT抑制剂 (DNMT inhibitors, DNMTis) 可以抑制DNMT的活性，从而阻止甲基从s-腺苷蛋氨酸转移SAM转化为胞嘧啶。 目前， 治疗TECs最可行的方法是研发新型DNMTis以及将DNMTis与其他治疗方法进行协同治疗，提高治疗效果，减少药物毒性。