PD98059

Catalog No.S1177
5 5 38 Product Citations

PD98059 is a non-ATP competitive MEK inhibitor with IC50 of 2 μM, specifically inhibits MEK-1-mediated activation of MAPK; does not directly inhibit ERK1 or ERK2.

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PD98059 Chemical Structure

PD98059 Chemical Structure
Molecular Weight: 267.28

Validation & Quality Control

Product Citations(38)

Customer Reviews(7)

Quality Control & MSDS

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Product Information

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Product Description

Biological Activity

Description PD98059 is a non-ATP competitive MEK inhibitor with IC50 of 2 μM, specifically inhibits MEK-1-mediated activation of MAPK; does not directly inhibit ERK1 or ERK2.
Targets MEK1 [1]
IC50 2 μM
In vitro PD98059 inhibits either basal MEK1 or a partially activated MEK produced by mutation of serine at residues 218 and 222 to glutamate (MEK-2E) with IC50 of 2 μM. PD98059 does not inhibit the MAPK homologues JNK and P38. PD98059 is highly selective against MEK, as it does not inhibit a number of other kinase activities including Raf kinase, cAMP-dependent kinase, protein kinase C, v-Src, epidermal growth factor (EGF) receptor kinase, insulin receptor kinase, PDGF receptor kinase, and phosphatidylinositol 3-kinase. PD98059 inhibits PDGF-stimulated activation of MAPK and thymidine incorporation into 3T3 cells with IC50 of ~10 μM and ~7 μM, respectively. [1] PD98059 potently prevents the activation of MEK1 by Raf or MEK kinase with IC50 of 4 μM, and weakly inhibits the activation of MEK2 by Raf with IC50 of 50 μM. PD98059 does not inhibit the activation of MEK homologues MKK4 and RK kinase that participate in stress and interleukin-1-stimulated kinase cascades in KB and PC12 cells, and the activation of p70 S6 kinase by insulin or epidermal growth factor in Swiss 3T3 cells. [2] PD98059 completely blocks the nerve growth factor (NGF)-induced differentiation of PC12 cells without altering cell viability. [3] PD98059 inhibits the proliferation of RAW264.7 cells in the culture containing RANKL in a dose-dependent manner, resulting in an apparent decrease of TRAP-positive cells. [4]
In vivo Treatment of mice 30 minutes before focal cerebral ischemia with PD98059 protects against damage, resulting in a decrease in infarct volume. [5] Pretreated with PD98059 (10 mg/kg per i.v. injection) 30 minutes before and then together with hourly cerulein injections for 3 hours significantly ameliorates cerulein-induced acute pancreatitis ipancreatitis on the basis of pancreatic wet weight and histology. [6] Administration of PD98059 (10 mg/kg) in mice 1 hour after carrageenan causes a reduction in all the parameters of inflammation measured. [7]
Features Does not inhibit c-Raf phosphorylated MEK1.

Protocol(Only for Reference)

Kinase Assay:

[1]

In vitro MEK-inhibitory activity Incorporation of 32P into myelin basic protein (MBP) is assayed in the presence of glutathione S-transferase (GST) fusion proteins containing the 44-kDa MAPK (GST-MAPK) or the 45-kDa MEK (GST-MEK1). Assays are conducted in 50 μL of 50 mM Tris, pH 7.4/10 mM MgCl2/2 mM EGTA/10 μM [γ-32P]ATP containing 10 μg of GST-MEK1, 0.5 μg of GST-MAPK, and 40 μg of MBP. After incubation at 30°C for 15 minutes, reactions are stopped by addition of Laemmli SDS sample buffer. Phosphorylated MBP is resolved by SDS/10% PAGE.

Cell Assay:

[1]

Cell lines K-Balb, KNRK, v-raf-3Y1, SRA/3Y1, EGFR/3T3, and K562
Concentrations Dissolved in DMSO, final concentrations ~100 μM
Incubation Time 3 dyas, or 7-10 days
Method

For monolayer growth, cells are plated into multi-well plates at 10,000-20,000/mL. Forty-eight hours later, various concentrations of PD98059 are added to the cell growth medium and incubation is continued for an additional 3 days. Cells are then removed from the wells by incubation with trypsin and enumerated with a Coulter Counter. For growth in soft agar, cells are seeded into 35-mm dishes at 5,000-10,000 cells per dish with growth medium containing 0.3% agar and desired concentrations of PD98059. After 7-10 days of growth, visible colonies are manually enumerated with the aid of a dissecting microscope.

Animal Study:

[7]

Animal Models Male Sprague–Dawley rats with acute pancreatitis
Formulation Dissolved in DMSO, and diluted in saline
Dosages 10 mg/kg
Administration Injection i.v.
Solubility 30% PEG400/0.5% Tween80/5% propylene glycol, 5 mg/mL
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesBaboonDogMonkeyRabbitGuinea pigRatHamsterMouse
Weight (kg)121031.80.40.150.080.02
Body Surface Area (m2)0.60.50.240.150.050.0250.020.007
Km factor202012128653
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Dudley DT, et al. Proc Natl Acad Sci U S A, 1995, 92(17), 7686-7689.

[2] Alessi DR, et al. J Biol Chem, 1995, 270(46), 27489-27494.

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Chemical Information

Download PD98059 SDF
Molecular Weight (MW) 267.28
Formula

C16H13NO3

CAS No. 167869-21-8
Storage 3 years -20℃Powder
6 months-80℃in solvent (DMSO, water, etc.)
Synonyms
Solubility (25°C) * In vitro DMSO 14 mg/mL heating (52.37 mM)
Water <1 mg/mL (<1 mM)
Ethanol <1 mg/mL (<1 mM)
In vivo 30% PEG400/0.5% Tween80/5% propylene glycol 5 mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
Chemical Name 2-(2-amino-3-methoxyphenyl)-4H-chromen-4-one

Research Area

Customer Reviews (7)


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Rating
Source J Natl Cancer Inst 2012 104, 1673-9. PD98059 purchased from Selleck
Method Western Blot
Cell Lines primary human melanocytes
Concentrations 10 μM
Incubation Time 18 h
Results In BRAFV600E melanoma cells, the highly selective BRAFV600E inhibitor GDC-0879 and three selective MEK inhibitors [PD184352/CI-1040, U0126, PD98059] did not suppress c-Jun levels, although they effectively reduced phospho-ERK levels.

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Rating
Source J Biol Chem 2010 285, 32824-32833. PD98059 purchased from Selleck
Method Western blot
Cell Lines Jurkat cells
Concentrations 1-10 μM
Incubation Time 120 min, 240 min
Results Reduction of SRP72 protein expression by MAPK inhibitor was apparent at 120–240 min after culturing with PD98059.

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Rating
Source J Biol Chem 2010 285, 32824-32833. PD98059 purchased from Selleck
Method Immunoprecipitates, Quantification of Protein
Cell Lines Jurkat cells
Concentrations 1-10 μM
Incubation Time 120 min, 240 min
Results PD98059 dramatically reduced the SRP72 phosphorylation in a concentration-dependent manner (Fig. C). Quantification of RUA of the corresponding SRP72 band showed significant reduction (Fig. D).

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Rating
Source J Biol Chem 2010 285, 32824-32833. PD98059 purchased from Selleck
Method Real time RT-PCR
Cell Lines Jurkat cells
Concentrations 1-10 μM
Incubation Time 120 min, 240 min
Results The results did not show significant changes on the mRNA expression of SRP72 mRNA after the treatment with PD98059.

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Rating
Source Microbes Infect 2013 15, 105-14. PD98059 purchased from Selleck
Method Western Blot
Cell Lines MDDC cells
Concentrations 100 uM
Incubation Time 48 h
Results We then evaluated the contribution of ERK1/2 to MDDC activation by using PD98059, a specific inhibitor of ERK1/2. The results obtained showed that ERK1/2 is an important player in the induction of IL-12p70 and IL-10, both the cytokines being reduced by treatment with the inhibitor.

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Rating
Source 2010 Dr. Zhang of Tianjin Medical University. PD98059 purchased from Selleck
Method Western blot
Cell Lines T47D cells
Concentrations 0-20 μM
Incubation Time 3 h
Results PD98059 treatment resulted in a reduction of MAPK phosphorylation.

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Rating
Source J Natl Cancer Inst, 2012, 104(21), 1673-9. PD98059 purchased from Selleck
Method Xenograft
Cell Lines athymic nude Foxn1nu mice
Concentrations 3mg/kg
Incubation Time 13 day
Results CDK2/4 inhibition augmented statistically significant growth reduction of melanoma xenografts in vivo by the BRAF and MEK inhibitors (GDC-0879 and CI1040).

Product Citations (38)

Tech Support & FAQs

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