《Discovery of SHP2-D26 as a First, Potent, and Effective PROTAC Degrader of SHP2 Protein》 was written by Wang, Mingliang; Lu, Jianfeng; Wang, Mi; Yang, Chao-Yie; Wang, Shaomeng. Application of 14660-52-7 And the article was included in Journal of Medicinal Chemistry in 2020. The article conveys some information:
Src homol. 2 domain-containing phosphatase 2 (SHP2) is an attractive therapeutic target for human cancers and other human diseases. Herein, we report our discovery of potent small-mol. SHP2 degraders whose design is based upon the proteolysis-targeting chimera (PROTAC) concept. This work has led to the discovery of potent and effective SHP2 degraders, exemplified by SHP2-D26. SHP2-D26(I) achieves DC50 values of 6.0 and 2.6 nM in esophageal cancer KYSE520 and acute myeloid leukemia MV4;11 cells, resp., and is capable of reducing SHP2 protein levels by >95% in cancer cells. SHP2-D26 is >30-times more potent in inhibition of phosphorylation of extracellular signal-regulated kinase (ERK) and of cell growth than SHP099, a potent SHP2 inhibitor, in KYSE520 and MV4;11 cancer cell lines. This study demonstrates that induced SHP2 degradation is a very effective approach to inhibit the function of SHP2. Further optimization of these SHP2 degraders may lead to the development of a new class of therapies for cancers and other human diseases. The experimental process involved the reaction of Ethyl 5-bromovalerate(cas: 14660-52-7Application of 14660-52-7)
Ethyl 5-bromovalerate(cas: 14660-52-7) belongs to bromides. A variety of minor organobromine compounds are found in nature, but none are biosynthesized or required by mammals. Organobromine compounds have fallen under increased scrutiny for their environmental impact.Application of 14660-52-7
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary