SHP099,SHP-099|SHP2 inhibitor

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].

Cat. No.	Product name	Field of application
DC71995	PSB-06126	PSB-06126 is a selective nucleoside triphosphate diphosphohydrolase (NTPDase) inhibitor, with the Ki values of 0.33 μM for rat NTPDase 1, 19.1 μM for NTPDase 2 and 2.22 μM for NTPDase 3, respectively.
DC70739	RMC-4630	RMC-4630 is a potent and selective inhibitor of SHP2, a central node in the RAS signaling pathway.
DC70502	IACS-15414	IACS-15414 (IACS 15414) is a potent, selective, orally bioavailable SHP2 inhibitor with IC50 of 122 nM; IACS-15414 potently suppressed the mitogen-activated protein kinase (MAPK) pathway signaling and tumor growth in RTK-activated and KRASmut xenograft models in vivo. IACS-15414 potently suppressed the mitogen-activated protein kinase (MAPK) pathway signaling and tumor growth. IACS-15414 had excellent PK properties across species but a narrow hERG window.
DC11021	KY-226	KY-226 (KY226) is a potent, allosteric, orally active inhibitor of protein tyrosine phosphatase 1B (PTP1B) with IC50 of 0.28 uM (human PTP1B), does not exhibit PPARγ agonist activity.
DC10088	TPI-1	TPI-1 is a potent and selective SHP-1 inhibitor effective at low nanomolar levels.
DC9737	SHP099 hydrochloride	SHP099 is a selective, orally bioavailable, and efficacious SHP2 inhibitor with IC50 =0.07 μM and p-ERK modulation in cells IC50 = 0.250 μM.
DC10004	SHP099 free base	SHP099 is a selective, orally bioavailable, and efficacious SHP2 inhibitor with IC50 =0.07 μM and p-ERK modulation in cells IC50 = 0.250 μM.
DC12051	RMC-4550	RMC-4550 (RMC4550) is a potent, selective, allosteric inhibitor of SHP2 with IC50 of 0.58 nM (full-length SHP2 enzyme), suppresses pERK signaling in Calu-1 cells with IC50 of 7 nM.
DC10878	Raphin1	Raphin1 is an orally available selective phosphatase inhibitor improves proteostasis and diminishes deficits in a mouse model of Huntington’s disease.
DC9999	NQ301	NQ301 is a selective CD45 inhibitor (IC50 = 200 nM). Exhibits >200-fold selectivity for CD45 over six related protein tyrosine phosphatases.

SHP099 hydrochloride