Description

SHP099 is a potent, selective, orally bioavailable, and efficacious SHP2 inhibitor with IC50 =0.07 μM and p-ERK modulation in cells IC50 = 0.250 μM. SHP099 exhibits dose-dependent pathway inhibition and antitumor activity in xenograft models. 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). Because it is an oncoprotein associated with multiple cancer-related diseases, as well as a potential immunomodulator, controlling SHP2 activity is of significant therapeutic interest.

Uses

SHP099 hydrochloride is a potent, selective and orally available SHP2 inhibitor with an IC50 of 70 nM[1].

in vivo

target

SHP2 inhibitor with IC50 =0.07 μM.

References

[1] Garcia Fortanet J, et al. Allosteric Inhibition of SHP2: Identification of a Potent, Selective, and Orally Efficacious Phosphatase Inhibitor. J Med Chem. 2016 Sep 8;59(17):7773-82. DOI:10.1021/acs.jmedchem.6b00680
[2] Chen YN, et al. Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinases. Nature. 2016 Jul 7;535(7610):148-52. DOI:10.1038/nature18621
[3] Carmine Fedele, et al. SHP2 Inhibition Abrogates MEK inhibitor Resistance in Multiple Cancer Models. bioRxiv. April 25, 2018.