product name FR 180204
Description: FR 180204 is a novel, selective and ATP-competitive ERK inhibitor with Ki of 0.31 μM and 0.14 μM for ERK1 And ERK2, respectively. FR180204 may serve as a potential new therapy for rheumatoid arthritis. It displays 30-fold selectivity for ERK over p38α (IC50 = 10 μM); and it displays no activity against human recombinant MEK1, MKK4, IKKα, PKCα, Src, Syc and PDGFα at concentrations less than 30 μM. Also inhibits TGFβ-induced AP-1 activation in Mv1Lu cells (IC50 = 3.1 μM).
References: Biochem Biophys Res Commun. 2005 Oct 14;336(1):357-63; Cell Physiol Biochem. 2012;29(5-6):667-74.
327.34
Formula
C18H13N7
CAS No.
865362-74-9
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 65 mg/mL (198.6 mM)
Water: <1 mg/mL
Ethanol: 2 mg/mL warmed (6.1 mM)
Solubility (In vivo)
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19415358
| In Vitro |
In vitro activity: In AP-1-transfected cells, FR180204 dose-dependently inhibits AP-1 transactivation with IC50 of 3.1 μM. FR 180204 inhibits spontaneous mesothelioma cell growth. Kinase Assay: Nunc-Immuno MaxiSorp plates are coated with 20 μg/ml MBP solution in phosphate-buffered saline (PBS). After washing with PBS containing 0.05% Tween 20 (T-PBS), blocking buffer (T-PBS containing 3% BSA) is added to each well and the plates are incubated for 10 min at room temperature. After washing with T-PBS, chemical compounds, ATP and recombinant ERK2 diluted in assay dilution buffer (20 mM Mops, pH 7.2, 25 mM β-glycerol phosphate, 5 mM EGTA, 1 mM sodium orthovanadate, 1 mM dithiothreitol, and 50 μg/ml BSA) and are added to each well. Vehicle groups (containing 0.1% DMSO) and kinase-withdrawal groups are used for the control and basal determinations. After incubation for 1 h at room temperature, plates are washed twice with T-PBS. Anti-phospho MBP antibody (0.2 μg/ml) is added to each well, and the plates are incubated for 1 h at room temperature. After washing, anti-mouse HRP-conjugated polyclonal antibodies are added and the plates were incubated for 30 min. SuperSignal chemiluminescent substrate is used for the measurement of HRP activity according to the manufacturer’s instructions. Prism 4.0 software is used for the Lineweaver–Burk plot analysis, IC50 and Ki determinations. Cell Assay: Cell viability is assayed by the method using MTT. MTT-reactive cells are quantified at an absorbance of 570 nm using a micro-plate reader. |
|---|---|
| In Vivo | In collagen-induced arthritis mice, FR180204 (100 mg/kg, i.p., b.i.d.) significantly decreases the severity of symptoms and body weight loss. In a mouse model of dengue virus (DENV) infection, FR180204 limits hepatocyte apoptosis, reduces DENV-induced liver injury, and improves Clinical parameters. |
| Animal model | Collagen-induced arthritis mouse model |
| Formulation & Dosage | Suspended in 0.1% methylcellulose solution; 100 mg/kg; i.p. injection |
| References | Naunyn Schmiedebergs Arch Pharmacol. 2007 Jan;374(4):311-6. |
