chromatin remodeling

Citarinostat (ACY241) 是一种强效、选择性和口服组蛋白脱乙酰酶 (HDAC) 抑制剂，具有抗肿瘤活性，对 HDAC1、HDAC2、HDAC3、HDAC6 和 HDAC8 的 IC50分别为 35、45、46、2.6 和 137 nM。

Mivebresib (ABBV-075) 是一种有效的，口服活性的溴结构域和末端结构域 (BET) 抑制剂，结合BRD4的Ki 值是 1.5 nM。

TH5427 hydrochloride is a potent and selective inhibitor of NUDT5 with an IC50 of 29 nM. It demonstrates a remarkable 690-fold selectivity towards NUDT5 compared to MTH1. Moreover, TH5427 hydrochloride effectively inhibits progestin-dependent, PAR-derived nuclear ATP synthesis in breast cancer cells, thereby impeding chromatin remodeling, gene regulation, and ultimately suppressing proliferation.

JQ-1 (carboxylic acid) 是一种细胞渗透性 BRD4 抑制剂，对 BRD4(1) 和 BRD4(2) 的 IC50 分别为 77 和 33 nM。它是一种 (+)-JQ1 衍生物，可作为合成 PROTACs 的前体。

FT-1101 is an orally bioavailable, potent and selective BET inhibitor. FT-1101 binds to the acetylated lysine recognition motifs in the bromodomain sites of BET proteins, thereby preventing the interaction between the BET proteins and acetylated histones. This disrupts chromatin remodeling and gene expression. Prevention of the expression of certain growth-promoting genes may lead to the inhibition of tumor cell growth. BET proteins, comprised of BRD2, BRD3, BRD4 and BRDT, are transcriptional regulators that play an important role during development and cellular growth.

Bisthianostat, also known as CF367 or CF367;-C, is a novel Orally Efficacious Pan-HDAC Inhibitor. Bisthianostat selectively binds to and inhibits HDACs, which inhibits deacetylation of histone proteins and leads to the accumulation of highly acetylated histones. This may result in an induction of chromatin remodeling, the inhibition of tumor oncogene transcription, and the selective transcription of tumor suppressor genes. This prevents cell division, induces cell cycle arrest and apoptosis. This may inhibit the proliferation of susceptible tumor cells. HDACs, upregulated in many tumor cell types, are a family of enzymes that deacetylate histone proteins.

Nanatinostat, also known as Tractinostat, CHR-3996 and VRx-3996, is an orally bioavailable, second-generation hydroxamic acid-based inhibitor of histone deacetylase (HDAC) with potential antineoplastic activity. HDAC inhibitor CHR-3996 inhibits HDAC, resulting in an accumulation of highly acetylated histones, the induction of chromatin remodeling, and the selective transcription of tumor suppressor genes; these events may result in the inhibition of tumor cell division and the induction of tumor cell apoptosis. This agent may upregulate HSP70 and downregulate anti-apoptotic Bcl-2 proteins more substantially than some first-generation HDAC inhibitors. HDACs, upregulated in many tumor cell types, are a family of metalloenzymes responsible for the deacetylation of chromatin histone proteins.

SMARCA2-IN-8(Compound 13)是针对SWI/SNF染色质重塑复合物中的SMARCA2(Brahma 同源物,BRM)和SMARCA4(Brahma 相关基因1,BRG1)的口服有效抑制剂,其IC50值分别为5 nM和6 nM.此化合物能有效抑制携带SMARCA2突变的癌细胞SKMEL5的增殖,AAC50为5 nM,并能下调依赖SMARCA2的KRT80基因的表达,AAC50为10 nM.在小鼠模型中,SMARCA2-IN-8展现出抗肿瘤活性以及良好的药物代谢动力学属性.

SMARCA2-IN-4(Compound 26)作为一种抑制剂,专门针对SWI/SNF染色质重塑复合物中的SMARCA的溴结构域.该化合物对PB1(5)、SMARCA2B及SMARCA4展示出较高的亲和性,Kd 值分别为124 nM、262 nM 和 417 nM.

SMARCA2-IN-1 (Compound I-19),作为SWI/SNF染色质重塑复合物SMARCA2的抑制剂,在H1299细胞中展示出IC50值超过1000 nM.

DCSM06 作为 SWI/SNF 染色质重塑复合物 SMARCA2 的溴结构域抑制剂表现出效力,其半抑制浓度 (IC50) 为 9.7 μM.

NAD+ lithium (β-DPN lithium) 是一种烟酰胺腺嘌呤二核苷酸锂盐，作为氧化还原反应的辅酶，NAD+ 能直接或间接影响多种重要细胞功能，包括代谢途径、DNA 修复、染色质重塑、细胞衰老及免疫细胞功能。