FR 180204

Modify Date: 2024-01-16 18:30:31

FR 180204 Structure
FR 180204 structure
Common Name FR 180204
CAS Number 865362-74-9 Molecular Weight 327.343
Density 1.6±0.1 g/cm3 Boiling Point N/A
Molecular Formula C18H13N7 Melting Point N/A
MSDS Chinese USA Flash Point N/A
Symbol GHS07
GHS07
Signal Word Warning

 Use of FR 180204


FR 180204 is an ATP-competitive, selective ERK inhibitor with Ki of 0.31 μM and 0.14 μM for ERK1 and ERK2, respectively.

 Names

Name 5-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)-1H-pyrazolo[3,4-c]pyridazin-3-amine
Synonym More Synonyms

 FR 180204 Biological Activity

Description FR 180204 is an ATP-competitive, selective ERK inhibitor with Ki of 0.31 μM and 0.14 μM for ERK1 and ERK2, respectively.
Related Catalog
Target

ERK2:0.14 μM (Ki)

ERK1:0.31 μM (Ki)

In Vitro In AP-1-transfected cells, FR180204 dose-dependently inhibits AP-1 transactivation with IC50 of 3.1 μM[1]. FR 180204 inhibits spontaneous mesothelioma cell growth[3]. 
In Vivo FR180204 (100 mg/kg, i.p., b.i.d.) significantly decreases the severity of symptoms and body weight loss in collagen-induced arthritis mice[2]. In a mouse model of dengue virus (DENV) infection, FR180204 limits hepatocyte apoptosis, reduces DENV-induced liver injury, and improves clinical parameters[4].
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 are incubated for 30 min.
Animal Admin In brief, mice are randomized and grouped by body weight immediately before treatment. Bovine CII is dissolved in 0.1mol/Lacetic acid at the concentration of 10 mg/mL and then emulsified in an equal volume of Freund’s complete adjuvant H37Rv. Apart from a naive group, each mouse is immunized with 25 μL of the CII emulsion into the tail base, followed by a boost injection 3 weeks after primary injection (day 0). FR180204 and methylprednisolone are ground and suspended in 0.1% methylcellulose solution to a volume of 5 mL/kg. Drugs are given by twice daily intraperitoneal injection from days 0 to 12 in accordance with pharmacokinetic studies with superior area under the curve and Cmax values of i.p. versus s.c. or p.o. administration. The initial administration is 30 min before the boost CII injection. The clinical score of arthritis is obtained by summing the visual severity grade of each limb, scored as follows: 0, no arthritis; 1, one swollen digit; 2, two or more swollen digits or swelling of the entire paw without ankylosis; 3, gross swelling with ankylosis of the paw. Body weight is measured on day 12.
References

[1]. Ohori M, et al. Identification of a selective ERK inhibitor and structural determination of the inhibitor-ERK2 complex. Biochem Biophys Res Commun. 2005 Oct 14;336(1):357-63.

[2]. Ohori M, et al. FR180204, a novel and selective inhibitor of extracellular signal-regulated kinase, ameliorates collagen-induced arthritis in mice. Naunyn Schmiedebergs Arch Pharmacol. 2007 Jan;374(4):311-6.

[3]. Honda M, et al. Mesothelioma cell proliferation through autocrine activation of PDGF-ββ receptor. Cell Physiol Biochem. 2012;29(5-6):667-74.

[4]. Sreekanth GP, et al. Role of ERK1/2 signaling in dengue virus-induced liver injury. Virus Res. 2014 Aug 8;188:15-26.

 Chemical & Physical Properties

Density 1.6±0.1 g/cm3
Molecular Formula C18H13N7
Molecular Weight 327.343
Exact Mass 327.123230
PSA 98.51000
LogP 0.29
Appearance of Characters faint yellow to dark yellow
Index of Refraction 1.846
Storage condition Store at +4°C
Water Solubility DMSO: ≥10mg/mL

 Safety Information

Symbol GHS07
GHS07
Signal Word Warning
Hazard Statements H302
Hazard Codes Xn
Risk Phrases 22-20
Safety Phrases 20/21
RIDADR NONH for all modes of transport

 Articles11

More Articles
Orthovanadate-Induced Vasoconstriction of Rat Mesenteric Arteries Is Mediated by Rho Kinase-Dependent Inhibition of Myosin Light Chain Phosphatase.

Biol. Pharm. Bull. 38 , 1809-16, (2015)

Orthovanadate (OVA), a protein tyrosine phosphatase inhibitor, induces vasoconstriction in a Rho kinase-dependent manner. The aim of this study was to determine the mechanism underlying OVA-induced va...

Sequential phosphorylation analysis using dye-tethered peptides and microfluidic isoelectric focusing electrophoresis.

Biosens. Bioelectron. 73 , 93-9, (2015)

We report a simple method for analyzing sequential phosphorylation by protein kinases using fluorescent peptide substrates and microfluidic isoelectric focusing (μIEF) electrophoresis. When a dye-labe...

Saturated free fatty acids induce cholangiocyte lipoapoptosis.

Hepatology 60(6) , 1942-56, (2014)

Recent studies have identified a cholestatic variant of nonalcoholic fatty liver disease (NAFLD) with portal inflammation and ductular reaction. Based on reports of biliary damage, as well as increase...

 Synonyms

5-(2-Phenylpyrazolo[1,5-a]pyridin-3-yl)-2H-pyrazolo[3,4-c]pyridazin-3-amine
2H-Pyrazolo[3,4-c]pyridazin-3-amine, 5-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)-
FR 180204
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