CAS 1801747-11-4|SHP099 hydrochloride
Introduction：Basic information about CAS 1801747-11-4|SHP099 hydrochloride, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
| Common Name | SHP099 hydrochloride | ||
|---|---|---|---|
| CAS Number | 1801747-11-4 | Molecular Weight | 388.723 |
| Density | / | Boiling Point | / |
| Molecular Formula | C16H20Cl3N5 | Melting Point | / |
| MSDS | / | Flash Point | / |
Names
| Name | 6-(4-Amino-4-methyl-1-piperidinyl)-3-(2,3-dichlorophenyl)-2-pyrazinamine hydrochloride (1:1) |
|---|---|
| Synonym | More Synonyms |
SHP099 hydrochloride BiologicalActivity
| Description | SHP099 hydrochloride is a potent, selective and orally available SHP2 inhibitor with an IC50 of 70 nM. |
|---|---|
| Related Catalog | Signaling Pathways >>Metabolic Enzyme/Protease >>PhosphataseResearch 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]. Carmine Fedele, et al. SHP2 Inhibition Abrogates MEK inhibitor Resistance in Multiple Cancer Models. bioRxiv. April 25, 2018. |
Chemical & Physical Properties
| Molecular Formula | C16H20Cl3N5 |
|---|---|
| Molecular Weight | 388.723 |
| Exact Mass | 387.078430 |
| InChIKey | KHQHYRFUYAXWOQ-UHFFFAOYSA-N |
| SMILES | CC1(N)CCN(c2cnc(-c3cccc(Cl)c3Cl)c(N)n2)CC1.Cl |
| Storage condition | 2-8℃ |
Synonyms
| 2-Pyrazinamine, 6-(4-amino-4-methyl-1-piperidinyl)-3-(2,3-dichlorophenyl)-, hydrochloride (1:1) |
| 6-(4-Amino-4-methyl-1-piperidinyl)-3-(2,3-dichlorophenyl)-2-pyrazinamine hydrochloride (1:1) |
| SHP099 hydrochloride |
| SHP099 (hydrochloride) |
