SHP099 HCl

Description: SHP099 HCl, the HCl salt of SHP099 which is identified through HTS and structure-based drug design, is a potent, selective, orally available, and highly efficacious allosteric inhibitor of SHP2 Src homology-2 domain containing protein tyrosine phosphatase-2 with an IC50 of 70 nM. SHP2 is a nonreceptor protein tyrosine phosphatase (PTP) encoded by the PTPN11 gene involved in cell growth and differentiation via the MAPK signaling pathway. SHP2 also purportedly plays an important role in the programmed cell death pathway (PD-1/PD-L1). As an allosteric modulator (inhibitor) of SHP2, SHP099 stabilizes the autoinhibited conformation of SHP2. The X-ray crystallography revealed the location of binding in a previously undisclosed allosteric binding pocket.

References: J Med Chem. 2016 Sep 8; 59(17):7773-82; Nature. 2016 Jul 7; 535(7610):148-52; Leukemia. 2018 Jan 30. doi: 10.1038/s41375-018-0020-5.

Related CAS#:1801747-42-1 (free base)