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Medicinal chemistry strategies for the development of protein tyrosine phosphatase SHP2 inhibitors and PROTAC degraders.
- Source :
-
European Journal of Medicinal Chemistry . Oct2020, Vol. 204, pN.PAG-N.PAG. 1p. - Publication Year :
- 2020
-
Abstract
- As a non-receptor protein tyrosine phosphatase encoded by the PTPN11 gene, the Src homology 2 domain-containing protein tyrosine phosphatase (SHP2) is involved in mitogen-activated protein kinase (MAPK) signaling pathway and contributes to immune surveillance via programmed cell death pathway (PD-1/PD-L1). To date, numerous SHP2 inhibitors have been developed, some of them have advanced into clinical trials. Moreover, the first PROTAC degrader SHP2-D26 has been proved to effectively induce degradation of SHP2, which may open a new avenue for targeted SHP2 therapies. In this review, we systematically summarized the development of SHP2 inhibitors with a particular focus on the structure-activity relationships (SAR) studies, crystal structures or binding models, and their modes of action. Image 1 • Medicinal chemistry strategies are highlighted for the development of SHP2 inhibitors. • The structures and biological functions of SHP2 are also briefly discussed. • The SHP2 PROTAC degrader SHP2-D26 shows promise for cancer therapy. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 02235234
- Volume :
- 204
- Database :
- Academic Search Index
- Journal :
- European Journal of Medicinal Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 145995372
- Full Text :
- https://doi.org/10.1016/j.ejmech.2020.112657