Wang, S; Shen, DD; Zhao, LJ; Yuan, XH; Cheng, JL; Yu, B; Zheng, YC; Liu, HM in [Yu, Bin; Zheng, Yichao; Liu, Hongmin] Zhengzhou Univ, Key Lab Technol Drug Preparat, Minist Educ China, Zhengzhou 450001, Peoples R China; Zhengzhou Univ, Sch Pharmaceut Sci, Zhengzhou 450001, Peoples R China published Discovery of [1,2,4]triazolo[1,5-a]pyrimidine derivatives as new bromodomain-containing protein 4 (BRD4) inhibitors in 2020, Cited 47. Computed Properties of C2H4N4. The Name is 1H-1,2,4-Triazol-5-amine. Through research, I have a further understanding and discovery of 61-82-5.
Targeting bromodomain-containing protein 4 (BRD4) has been proved to be an effective strategy for cancer therapy. To date, numerous BRD4 inhibitors and degraders have been identified, some of which have advanced into clinical trials. In this work, a focused library of new [1,2,4]triazolo[1,5-a]pyrimidine derivatives were discovered to be able to inhibit BRD4. WS-722 inactivated BRD4 (BD1/BD2), BRD2 (BD1 BD2) and BRD3 (BD1/BD2) broadly with the IC50 values less than 5 mu mol/L. Besides, WS-722 inhibited growth of THP-1 cells with an IC50 value of 3.86 mu mol/L. Like (+)-JQ1, WS-722 inhibited BRD4 in a reversible manner and enhanced protein stability. Docking studies showed that WS-722 occupied the central acetyl-lysine (Kac) binding cavity and formed a hydrogen bond with Asn140. In THP-1 cells, WS-722 showed target engagement to BRD4. Cellular effects of WS-722 on THP-1 cells were also examined, showing that WS-722 could block c-MYC expression, induce G0/G1 phase arrest and p21 up-regulation, and promote differentiation of THP-1 cells. BRD4 inhibition by WS-722 resulted in cell apoptosis and up-regulated expression of cleaved caspased-3/7 and PARP in THP-1 cell lines. The [1,2,4]triazolo[1,5-a] pyrimidine is a new template for the development of new BRD4 inhibitors. (C) 2019 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.
Computed Properties of C2H4N4. Bye, fridends, I hope you can learn more about C2H4N4, If you have any questions, you can browse other blog as well. See you lster.
Reference:
Article; Safari, Niloufar; Shirini, Farhad; Tajik, Hassan; Journal of Molecular Structure; vol. 1201; (2020);,
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics