product name VX-11e
Description: VX-11e is a potent, selective, and orally bioavailable ERK2 inhibitor with Ki of <2 nM, which is more than 200-fold selective over other kinases tested. ERK is extracellular signal-regulated kinases. The Ras/Raf/MEK/ERK signal transduction is an oncogenic pathway related to a variety of human cancers. In both rats and mice, VX-11e shows good oral bioavailability. In NSG mice bearing human melanoma RPDX tumors, VX-11e (50 mg/kg, p.o.) results in robust inhibition of pRSK, and inhibits tumor growth. When used in combination with BKM120, VX-11e results in significantly improved tumor growth inhibition.
References: J Med Chem. 2009 Oct 22;52(20):6362-8; Clin Cancer Res. 2016 Apr 1;22(7):1592-602.
500.35
Formula
C24H20Cl2FN5O2
CAS No.
896720-20-0
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 100 mg/mL (199.9 mM)
Water: <1 mg/mL
Ethanol: 16 mg/mL (32.0 mM)
Solubility (In vivo)
Synonyms
VTX-11e, Vertex-11e
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19415450
| In Vitro |
In vitro activity: In HT29 cells, VX-11e potently inhibits cell proliferation with IC50 of 48 nM. Kinase Assay: Compounds were assayed for the inhibition of ERK2 by a spectophotometric coupled-enzyme assay. In this assay, a fixed concentration of activated ERK2 (10 nM) was incubated with various concentrations of the compounds in DMSO (2.5%) for 10 mins at 30 ℃ in 0.1 M HEPES buffer, pH = 7.5, containing 10 mM MgCl2, 2.5 mM phosphoenolpyruvate, 200 μM NADH, 150 μg/mL pyruvate kinase, 50 μg/mL lactate dehydrogenase and 200 μM erktide peptide. The reaction was initiated by the addition of 65 μM ATP. The rate of decrease of absorbance at 340 nM was monitored. The IC50 was evaluated from the data as a function of inhibitor concentration. Cell Assay: Cell proliferation is measured by 3H-thymidine incorporation. The cells are plated at a concentration of 10,000 cells/well in a 96-well plate using growth media, RPMI 1640 containing 10% FBS. Serially diluted compounds are added. The cells and compounds are incubated for 48 hours at 37°C incubator. After 48 hours, 0.4 μCi of 3H-thymidine is added to each wells for 8 hours and returned to the 37°C incubator. The cells are harvested using a Tomtec 96-well cell harvester and the CPM is determined using the Wallac 1205 BETAPLATE liquid scintillation counter. |
|---|---|
| In Vivo | In both rats and mice, VX-11e shows good oral bioavailability. In NSG mice bearing human melanoma RPDX tumors, VX-11e (50 mg/kg, p.o.) results in robust inhibition of pRSK, and inhibits tumor growth. When used in combination with BKM120, VX-11e results in significantly improved tumor growth inhibition |
| Animal model | NSG mice bearing human melanoma RPDX tumors |
| Formulation & Dosage | Formulated in 5% ethanol, 20% propylene glycol, 7.4% Tween80; 50 mg/kg; p.o. |
| References | J Med Chem. 2009 Oct 22;52(20):6362-8; Clin Cancer Res. 2016 Apr 1;22(7):1592-602. |
