The chemical properties of alicyclic heterocycles are similar to those of the corresponding chain compounds. Compound: 11-Bromoundecanoic acid, is researched, Molecular C11H21BrO2, CAS is 2834-05-1, about Discovery of SHP2-D26 as a First, Potent, and Effective PROTAC Degrader of SHP2 Protein, the main research direction is esophageal cancer AML SHP2 PROTAC degrader ERK inhibition phosphorylation.Safety of 11-Bromoundecanoic acid.
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.
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Reference:
Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI