SHP099 hydrochloride

Cas No.:	1801747-11-4
Chemical Name:	6-(4-amino-4-methylpiperidin-1-yl)-3-(2,3-dichlorophenyl)pyrazin-2-amine hydrochloride
Synonyms:	SHP099,SHP 099,SHP-099
SMILES:	NC1=NC(N2CCC(C)(N)CC2)=CN=C1C3=CC=CC(Cl)=C3Cl.HCl
Formula:	C16H20Cl3N5
M.Wt:	388.72
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	SHP099 hydrochloride is a potent, selective and orally available SHP2 inhibitor with an IC50 of 70 nM.
In Vivo:	After a single doses of 30 and 100 mg/kg (red and blue lines, respectively), dose-dependent exposure and modulation of the pharmacodynamic marker p-ERK is observed in the xenografts. A daily oral dose of 10 or 30 mg/kg yield 19% and 61% tumor growth inhibition, respectively. Tumor stasis is achieved at 100 mg/kg[1].
In Vitro:	The X-ray co-crystal for SHP099 with SHP2 reveals a new interaction with the basic amine and the Phe113 backbone carbonyl. SHP099 shows inhibition of cell proliferation (KYSE-520 model) with an IC50 of 1.4 μM. SHP099 shows high solubility and high permeability with no apparent efflux in Caco-2 cells[1]. SHP099 concurrently binds to the interface of the N-terminal SH2, C-terminal SH2, and protein tyrosine phosphatase domains, thus inhibiting SHP2 activity through an allosteric mechanism. SHP099 suppresses RAS–ERK signalling to inhibit the proliferation of receptor-tyrosine-kinase-driven human cancer cells[2].