SHP099 hydrochloride is a potent, selective, orally bioavailable SHP2 inhibitor with IC50 of 70 nM, which inhibits ERK1/2 activation in cancer cells. [2]

SHP2:70 nM.

METHODS: Cell viability of SMSCs was observed after treatment with different concentrations of SHP099 (5, 10, 15, 20, 25, 30, 40, 50 μM) for 1 week.
RESULTS SHP099 inhibited the cell viability of SMSCs at concentrations greater than 25 μM. [2]

METHODS: The imiquimod (IMQ)-induced mouse psoriasis model was treated with SHP0999 (1, 3, 10 mg/kg), and the effect of SHP099 on the psoriasis-like phenotype in the IMQ-induced mouse model was observed. .
RESULTS SHP099 significantly inhibited IMQ-induced swelling, epidermal acanthosis, keratinocyte proliferation and dermal inflammatory cell infiltration without affecting the skin condition of normal mice; SHP099 also significantly reduced serum IL-23 and IL in the mouse model -17A level. [1]
METHODS: The ability of SHP099 to cross the BBB in C57BL/6J mice was evaluated after a single oral dose of SHP099 at 100 mg/kg in a 400 μL volume.
RESULTS SHP099 concentrations were high in plasma and brain tissue early after oral gavage, and SHP099 levels in brain tissue remained at appreciable levels 24 h after oral gavage. [2]
METHODS: CT-26 and MC-38 cells were subcutaneously inoculated into BALB/c mice to establish a mouse tumor model. The mouse tumor model used SHP099 hydrochloride (5 mg/kg/kg/d, intraperitoneal injection). SHP099 salt was observed. Effects of salt on tumors.
RESULTS The volume and weight of tumors treated with SHP099 were significantly reduced. [3]

The inhibition of SHP2 from the tested compounds (SHP099) concentrations varying from 0.003-100 μM is monitored using an assay in which 0.5 nM of SHP2 is incubated with of 0.5 μM of peptide IRS1_pY1172(dPEG8)pY1222. After 30-60 minutes incubation at the surrogate substrate, DiFMUP is added to the reaction and incubated at 25 °C for 30 minutes. The reaction is then quenched by the addition of 5 μL of a 160 μM solution of bpV(Phen). The fluorescence signal is monitored using a microplate reader using excitation and emission wavelengths of 340 nm and 450 nm, respectively[1].

Cells are plated onto 96-well plates in 100 μL medium. SHP099 with various concentrations (1.25, 2.5, 5, 10, 20 μM) are added 24 h after cell plating. At day 5, 50 μL Celltiter-Glo reagent is added, and the luminescent signal is determined[1].