排序方式: 共有93条查询结果,搜索用时 125 毫秒
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Storm Hassell-Hart Sarah Picaud Raphael Lengacher Joshua Csucker Regis Millet Gilles Gasser Roger Alberto Hannah Maple Robert Felix Zbigniew J. Leśnikowski Helen J. S. Stewart Timothy J. Chevassut Simon Morley Panagis Filippakopoulos John Spencer 《Helvetica chimica acta》2021,104(3):e2000214
A series of bulky organometallic and organic analogues of the bromodomain (BRD) inhibitor (+)-JQ1 have been prepared. The most potent, N-[(adamantan-1-yl)methyl]-2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetraazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetamide, 2e , showed excellent potency with an KD=ca. 130 nm vs. BRD4(1) and a ca. 2-fold selectivity over BRD4(2) (KD=ca. 260 nm ). Its binding to the first bromodomain of BRD4 was determined by a protein cocrystal structure. 相似文献
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核酸碱基的表观遗传修饰是生命体实现表观遗传功能的重要组成部分,可以直接参与调控细胞分化、基因表达等重要的生理过程。然而,核酸碱基的光稳定性会受表观遗传修饰的影响,相应的碱基可能成为紫外线诱导皮肤癌产生的重要突变位点。因此,研究表观遗传修饰对核酸碱基的光物理与光化学性质的影响具有十分重要的意义。本文综述了近年来本课题组利用超快时间光谱技术结合高精度的量子化学理论计算对一系列表观遗传修饰的核酸碱基激发态动力学性质的研究。研究表明,表观遗传修饰对碱基激发态性质的影响主要分为三个方面:显著增长ππ∗1态的寿命、引入分子内电荷转移态、有效促进单重态到三重态系间窜跃。 相似文献
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Alain Aguirre-Vzquez Luis A. Salazar-Olivo Xchitl Flores-Ponce Ana L. Arriaga-Guerrero Dariela Garza-Rodríguez María E. Camacho-Moll Ivn Velasco Fabiola Castorena-Torres Nidheesh Dadheech Mario Bermúdez de Len 《Molecules (Basel, Switzerland)》2021,26(7)
A generation of induced pluripotent stem cells (iPSC) by ectopic expression of OCT4, SOX2, KLF4, and c-MYC has established promising opportunities for stem cell research, drug discovery, and disease modeling. While this forced genetic expression represents an advantage, there will always be an issue with genomic instability and transient pluripotency genes reactivation that might preclude their clinical application. During the reprogramming process, a somatic cell must undergo several epigenetic modifications to induce groups of genes capable of reactivating the endogenous pluripotency core. Here, looking to increase the reprograming efficiency in somatic cells, we evaluated the effect of epigenetic molecules 5-aza-2′-deoxycytidine (5AZ) and valproic acid (VPA) and two small molecules reported as reprogramming enhancers, CHIR99021 and A83-01, on the expression of pluripotency genes and the methylation profile of the OCT4 promoter in a human dermal fibroblasts cell strain. The addition of this cocktail to culture medium increased the expression of OCT4, SOX2, and KLF4 expression by 2.1-fold, 8.5-fold, and 2-fold, respectively, with respect to controls; concomitantly, a reduction in methylated CpG sites in OCT4 promoter region was observed. The epigenetic cocktail also induced the expression of the metastasis-associated gene S100A4. However, the epigenetic cocktail did not induce the morphological changes characteristic of the reprogramming process. In summary, 5AZ, VPA, CHIR99021, and A83-01 induced the expression of OCT4 and SOX2, two critical genes for iPSC. Future studies will allow us to precise the mechanisms by which these compounds exert their reprogramming effects. 相似文献
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Corrigendum: Crowdsourcing Natural Products Discovery to Access Uncharted Dimensions of Fungal Metabolite Diversity 下载免费PDF全文
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Dr. Hong Zong Dhavan Shah Katherine Selwa Ryan E Tsuchida Dr. Rahul Rattan Jay Mohan Dr. Adam B Stein James B Otis Dr. Sascha N Goonewardena 《ChemistryOpen》2015,4(3):335-341
Histone deacetylase inhibitors (HDACi) are promising therapeutics for cancer. HDACi alter the epigenetic state of tumors and provide a unique approach to treat cancer. Although studies with HDACi have shown promise in some cancers, variable efficacy and off-target effects have limited their use. To overcome some of the challenges of traditional HDACi, we sought to use a tumor-specific dendrimer scaffold to deliver HDACi directly to cancer cells. Here we report the design and evaluation of tumor-specific dendrimer–HDACi conjugates. The HDACi was conjugated to the dendrimer using an ester linkage through its hydroxamic acid group, inactivating the HDACi until it is released from the dendrimer. Using a cancer cell model, we demonstrate the functionality of the tumor-specific dendrimer–HDACi conjugates. Furthermore, we demonstrate that unlike traditional HDACi, dendrimer–HDACi conjugates do not affect tumor-associated macrophages, a recently recognized mechanism through which drug resistance emerges. We anticipate that this new class of cell-specific epigenetic therapeutics will have tremendous potential in the treatment of cancer. 相似文献
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