On January 25, 2018, Zhou, Bing; Hu, Jiantao; Xu, Fuming; Chen, Zhuo; Bai, Longchuan; Fernandez-Salas, Ester; Lin, Mei; Liu, Liu; Yang, Chao-Yie; Zhao, Yujun; McEachern, Donna; Przybranowski, Sally; Wen, Bo; Sun, Duxin; Wang, Shaomeng published an article.Product Details of 1949837-12-0 The title of the article was Discovery of a Small-Molecule Degrader of Bromodomain and Extra-Terminal (BET) Proteins with Picomolar Cellular Potencies and Capable of Achieving Tumor Regression. And the article contained the following:
The bromodomain and extra-terminal (BET) family proteins, consisting of BRD2, BRD3, BRD4, and testis-specific BRDT members, are epigenetic “readers” and play a key role in the regulation of gene transcription. BET proteins are considered to be attractive therapeutic targets for cancer and other human diseases. Recently, heterobifunctional small-mol. BET degraders have been designed based upon the proteolysis targeting chimera (PROTAC) concept to induce BET protein degradation Herein, we present our design, synthesis, and evaluation of a new class of PROTAC BET degraders. One of the most promising compounds, 23, effectively degrades BRD4 protein at concentrations as low as 30 pM in the RS4;11 leukemia cell line, achieves an IC50 value of 51 pM in inhibition of RS4;11 cell growth and induces rapid tumor regression in vivo against RS4;11 xenograft tumors. These data establish that compound 23 (BETd-260/ZBC260) is a highly potent and efficacious BET degrader. The experimental process involved the reaction of (2S,4R)-1-((2S)-2-(tert-butyl)-15-((6S)-4-(4-Chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)-4,14-dioxo-6,10-dioxa-3,13-diazapentadecan-1-oyl)-4-hydroxy-N-((S)-1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2-carboxamide(cas: 1949837-12-0).Product Details of 1949837-12-0
The Article related to preparation degrader bromodomain extra terminal protein cancer, Pharmacology: Structure-Activity and other aspects.Product Details of 1949837-12-0
Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics