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| 25mg |
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Purity: ≥98%
PD98059 is a novel flavanoid acting as a selective, reversible, and non-ATP competitive MEK inhibitor with potential anti-inflammatory and anticancer activity. It is a flavonoid that specifically inhibits MEK-1-mediated activation of MAPK and does not directly inhibit ERK1 or ERK2. It inhibits MEK with an IC50 of 2 μM in a cell-free assay. Compared to control cells treated with DMSO, the effects of PD98059 treatment on cell morphology and density were clearly discernible. In human leukemic U937 cells, PD98059 either prevented proliferation or brought about cell death.
| Targets |
MEK1 (IC50 = 2-7 μM); MEK2 (IC50 = 50 μM); ERK1; ERK2; Autophagy
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|---|---|
| ln Vitro |
PD98059 inhibits either basal MEK1 or a partially activated MEK created by changing serine at residues 218 and 222 to glutamate (MEK-2E) with an IC50 of 2 M. The MAPK homologues JNK and P38 are not inhibited by PD98059 in any way. 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 are just a few of the additional kinases that PD98059 does not inhibit. With an IC50 of ~10 μM and ~7 μM, respectively, PD98059 blocks PDGF-stimulated MAPK activation and thymidine incorporation into 3T3 cells.[1] PD98059 has an IC50 of 4 μM, which makes it potently inhibit MEK1 activation by Raf or MEK kinase, and an IC50 of 50 μM, which makes it weakly inhibit MEK2 activation by Raf. In KB and PC12 cells as well as in Swiss 3T3 cells, PD98059 does not prevent the activation of the MEK homologues MKK4 and RK kinase, which take part in the stress and interleukin-1-stimulated kinase cascades.[2] PD98059 completely prevents the differentiation of PC12 cells brought on by nerve growth factor (NGF) without affecting cell viability.[3] A dose-dependent inhibition of RAW264.7 cell proliferation in the presence of RANKL by PD98059 causes a visible reduction in TRAP-positive cells in the culture.[4]
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| ln Vivo |
Mice are treated A reduction in infarct volume occurs when PD98059 is administered 30 minutes before focal cerebral ischemia to prevent damage.[5] Based on pancreatic wet weight and histology, PD98059 pretreatment (10 mg/kg per i.v. injection) given 30 minutes prior to hourly cerulein injections for three hours significantly reduces the severity of cerulein-induced acute pancreatitis.[6] A reduction in all the measured parameters of inflammation is brought on by giving mice PD98059 (10 mg/kg) an hour after carrageenan.[7]
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| Enzyme Assay |
In order to measure the incorporation of 32P into myelin basic protein (MBP), glutathione S-transferase (GST) fusion proteins containing either the 44-kDa MAPK (GST-MAPK) or the 45-kDa MEK (GST-MEK1) are used. Assays are carried out in 50 μL of a solution containing 10 μg of GST-MEK1, 0.5 μg of GST-MAPK, and 40 μg of MBP, along with 50 mM Tris, pH 7.4, 10 mM MgCl2, 2 mM EGTA, and 10 μM [γ-32P]ATP. The addition of Laemmli SDS sample buffer stops reactions after 15 minutes of incubation at 30°C. By using SDS/10% PAGE, phosphorylated MBP is resolved.
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| Cell Assay |
Cells are plated into multi-well plates at a density of 10,000–20,000/mL for monolayer growth. The cell growth medium is then supplemented with various concentrations of PD98059 48 hours later, and incubation is then carried out for an additional 3 days. Following trypsin incubation, cells are then extracted from the wells and counted using a Coulter Counter. Cells are seeded into 35-mm dishes at a density of 5,000–10,000 cells per dish with growth medium containing the desired concentrations of PD98059 and 0.3% agar for growth in soft agar. Visible colonies are manually counted using a dissecting microscope after 7–10 days of growth.
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| Animal Protocol |
Male Sprague–Dawley rats with acute pancreatitis
10 mg/kg Injection i.v. |
| References |
[1]. Proc Natl Acad Sci U S A . 1995 Aug 15;92(17):7686-9. [2]. J Biol Chem . 1995 Nov 17;270(46):27489-94. [3]. J Biol Chem . 1995 Jun 9;270(23):13585-8. [4]. J Biol Chem . 2002 Dec 6;277(49):47366-72. [5]. Proc Natl Acad Sci U S A . 1999 Oct 26;96(22):12866-9. [6]. Pancreas . 2002 Oct;25(3):251-9. [7]. Int J Immunopathol Pharmacol . 2009 Oct-Dec;22(4):937-50. [8]. Melanoma Res . 2001 Feb;11(1):11-9. [9]. Int Immunopharmacol . 2007 Jan;7(1):36-45. [10]. Int J Cancer . 2003 Nov 10;107(3):478-85. |
| Molecular Formula |
C16H13NO3
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|---|---|
| Molecular Weight |
267.2793
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| Exact Mass |
267.09
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| Elemental Analysis |
C, 71.90; H, 4.90; N, 5.24; O, 17.96
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| CAS # |
167869-21-8
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| Related CAS # |
167869-21-8
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| Appearance |
Solid powder
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| LogP |
2.9
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| tPSA |
61.6Ų
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| SMILES |
COC1=CC=CC(=C1N)C2=CC(=O)C3=CC=CC=C3O2
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| InChi Key |
QFWCYNPOPKQOKV-UHFFFAOYSA-N
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| InChi Code |
nChI=1S/C16H13NO3/c1-19-14-8-4-6-11(16(14)17)15-9-12(18)10-5-2-3-7-13(10)20-15/h2-9H,17H2,1H3
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| Chemical Name |
2-(2-amino-3-methoxyphenyl)chromen-4-one
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| Synonyms |
PD98059; PD 98059; PD098059; PD-98059
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 33.3~46 mg/mL (124.7~172.1 mM)
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|---|---|
| Solubility (In Vivo) |
4% DMSO+30% PEG 300+5% Tween 80+ddH2O: 1mg/mL (Please use freshly prepared in vivo formulations for optimal results.)
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.7414 mL | 18.7070 mL | 37.4139 mL | |
| 5 mM | 0.7483 mL | 3.7414 mL | 7.4828 mL | |
| 10 mM | 0.3741 mL | 1.8707 mL | 3.7414 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Effect of PD98059 on the development of neuropathic pain symptoms.
Effect of PD98059 on the mRNA and protein level of pro-inflammatory factors (IL-1beta, iNOS, IL-6 and IL-18) and anti-inflammatory factor (IL-10) in neuropathic pain.PLoS One.2015 Oct 1;10(10):e0138583. |
Effect of PD98059 on the p38, ERK1/2, JNK and NF-kappaB protein level in neuropathic pain.PLoS One.2015 Oct 1;10(10):e0138583. |
Effect of PD98059 on opioid analgesia in a naive and neuropathic rats. |
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