DC Chemicals Limited
China
Product Name: SHP099 free base
Price: $1200.0/500mg $1900.0/1g $3150.0/2g
Purity: 98.0%
Stocking Period: 3 Day
Contact: Tony Cao

1801747-42-1

1801747-42-1 structure

1801747-42-1 structure

Name: SHP099
Chemical Name: 6-(4-Amino-4-methyl-1-piperidinyl)-3-(2,3-dichlorophenyl)-2-pyrazinamine
CAS Number: 1801747-42-1
Molecular Formula: C₁₆H₁₉Cl₂N₅
Molecular Weight: 352.262
Catalog: Signaling Pathways Metabolic Enzyme/Protease Phosphatase
Create Date: 2018-08-23 21:27:31
Modify Date: 2024-01-12 11:32:07
SHP099 is a potent, selective, orally available SHP2 inhibitor with an IC50 of 70 nM.

Name	6-(4-Amino-4-methyl-1-piperidinyl)-3-(2,3-dichlorophenyl)-2-pyrazinamine
Synonyms	6-(4-Amino-4-methyl-1-piperidinyl)-3-(2,3-dichlorophenyl)-2-pyrazinamine 2-Pyrazinamine, 6-(4-amino-4-methyl-1-piperidinyl)-3-(2,3-dichlorophenyl)- SHP099 free base SHP099

Description	SHP099 is a potent, selective, orally available SHP2 inhibitor with an IC50 of 70 nM.
Related Catalog	Signaling Pathways >> Metabolic Enzyme/Protease >> Phosphatase Research Areas >> Cancer
Target	IC50: 70 nM (SHP2)[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].
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].
Kinase Assay	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].
Cell Assay	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].
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. [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. [3]. Kostallari E, et al. Hepatic stellate cell-derived PDGFRα-enriched extracellular vesicles promote liver fibrosis in mice through SHP2. Hepatology. 2018 Jan 23. [4]. Eunhee Choi, et al. Mitotic Regulators and the SHP2-MAPK Pathway Promote Insulin Receptor Endocytosis and Feedback Regulation of Insulin Signaling. bioRxiv. September 17, 2018.

Density	1.3±0.1 g/cm3
Boiling Point	530.4±50.0 °C at 760 mmHg
Molecular Formula	C₁₆H₁₉Cl₂N₅
Molecular Weight	352.262
Flash Point	274.5±30.1 °C
Exact Mass	351.101746
LogP	3.97
Vapour Pressure	0.0±1.4 mmHg at 25°C
Index of Refraction	1.626
Storage condition	-20℃