PROTAC分子通常由两个部分组成:一个配体(ligand)和一个肽类毒素(peptidebasedtoxins)。配体与目标蛋白结合后,肽类毒素会被释放出来,进而诱导目标蛋白发生构象变化或降解。PROTAC分子的药代动力学特征主要取决于配体与目标蛋白之间的结合亲和力、肽类毒素的活性以及目标蛋白的稳定性等因素。 PROTAC分子的药代动力学特征...
PROTACs主要由3部分组成,POI Ligand,E3泛素连接酶配体以及中间的Linker。POI Ligand主要由和靶蛋白具有结合力的小分子配体,多肽以及核酸等组成。由于小分子抑制剂具有稳定的理化性质,生物利用度高,且上市或者处于前期研究阶段的小分子均可作为目标蛋白配体等优势,目前广泛用于构建PROTAC分子库。据PROTACs数据库报道,目前超...
Naito, Y. HashimotoProtein knockdown using methyl bestatin-ligand hybrid molecules: design and synthesis of inducers of ubiquitination-mediated degradation of cellular retinoic acid-binding proteins J. Am. Chem. Soc., 132 (2010), pp. 5820-5826 CrossRefView Record in ScopusGoogle Scholar Jacobsen ...
be recognized and degraded by the proteasome. ROTACs are designed primarily on the basis of E3 ubiquitin ligase peptide ligands, but because of inherent defects such as poor metabolic stability and difficulty in crossing cell membranes, pROTACS currently uses the small E 3 ubiquitin ligase ligand....
Discovery of a Keap1-dependent peptide PROTAC to knockdown Tau by ubiquitination-proteasome degradation pathway. Eur. J. Med. Chem. 146, 251–259 (2018). CAS PubMed Google Scholar Wang, W. et al. A novel small-molecule PROTAC selectively promotes tau clearance to improve cognitive ...
Abstract Proteolysis-targeting chimeras (PROTACs) have emerged as effective tools to selectively degrade disease-related proteins by using the ubiquitin-proteasome system. Developing PROTACs involves extensive tests and trials to explore the vast chemical space. To accelerate this process, we propose a no...
表:用于开发PROTAC分子的E3连接酶举例 表:常用E3连接酶配体及其参数 E3连接酶 结合配体 代表性临床药物 参数 CRBN ligand VHL ligand IAP ligand CRBN IMiDs ARV-110、ARV-471 VHL VHL peptidomimetics DT-2216 MDM2 idasanutlin 暂无 结构式 β-TRCP phosphorylated peptide 暂无 bestatin esters 暂无 clAP MV-1 ...
产品名称：Fmoc-NH-pentanoic acid-NHS-SO3Na 英文名称：Fmoc-NH-pentanoic acid-NHS-SO3Na 状态：固体/粉末/溶液 产品规格：mg 保存：冷藏 储藏条件：-20℃ 储存时间：1年 用途：科研 温馨提醒：仅供科研，不能用于人体实验 相关产品：ERRα Ligand-Linker Conjugates 1 Fmoc-aminooxy-PEG12-acid Fmoc-aminooxy...
Von Hippel-lindau (VHL) is an E3 ubiquitin ligase used in the design of PROTACs. VHL can polymerize HIFLA and cause HIF1 α degradation. A small-molecule compound that inhibits VHL-HIFla interactions, a VHL ligand that can bind to the recognition site of the HIF1 α peptide in VHL, 7...
There is more space for the improvement of the working efficacy of xStAx-VHLL. The VHL peptide ligand inserted in this study consists of natural amino acids, which could be degraded once the PROTAC peptide enters the cell. Non-natural residues substitution instead of original ones, such as ...