PD98059
PD98059 is a selective and reversible inhibitor of MAPK-activating enzyme, MAPK/ERK kinase (MEK) that inhibits either basal MEK (GST-MEK1) or a partially activated MEK produced by mutation of serine to glutamate at 218 and 222 residues (GST-MEK-2E) with IC50 values of 10uM [1].
PD98059 treatment resulted in distinct changes in cell morphology and density compared to control cells treated with DMSO. PD98059 inhibited proliferation or induced cell death in human leukemic U937 cells. Additionally, PD98059 dose-dependently inhibited the ERK1/2 phosphorylation as well as down-regulated cyclin E/Cdk2 and cyclin D1/Cdk4 levels, resulting in G1 phase arrest and apoptosis induction in U937 cells [2].
References:
[1] Dudley DT1, Pang L, Decker SJ, Bridges AJ, Saltiel AR. A synthetic inhibitor of the mitogen-activated protein kinase cascade. Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7686-9.
[2] Moon DO1, Park C, Heo MS, Park YM, Choi YH, Kim GY. PD98059 triggers G1 arrest and apoptosis in human leukemic U937 cells through downregulation of Akt signal pathway. Int Immunopharmacol. 2007 Jan;7(1):36-45. Epub 2006 Sep 8.
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| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 267.28 |
| Cas No. | 167869-21-8 |
| Formula | C16H13NO3 |
| Solubility | insoluble in EtOH; insoluble in H2O; ≥40.23 mg/mL in DMSO |
| Chemical Name | 2-(2-amino-3-methoxyphenyl)chromen-4-one |
| SDF | Download SDF |
| Canonical SMILES | COC1=CC=CC(=C1N)C2=CC(=O)C3=CC=CC=C3O2 |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment: [1] | |
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Cell lines |
C-81 LNCaP cells (LNCaP cells with 80–120 passage numbers) |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
10 μM, 3 days |
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Applications |
Treatment of C-81 LNCaP cells with 10 μM PD98059 as a single agent resulted in a 5-fold elevation of Bax protein, while 1.2 nM docetaxel alone caused only a 2-fold elevation. A combination of 10 μM PD98056 with 1.2 nM docetaxel led to a 15-fold elevated expression of Bax in addition to the phosphorylation inactivation of Bcl-2 and diminished elevation of Bcl-XL. These combined effects were associated with a great increase of apoptotic cells, which may contribute to the approximately 20% additional suppression of cell growth. |
| Animal experiment: [2] | |
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Animal models |
Male SV-129 mice |
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Dosage form |
Intracerebroventricular injection, 200 μM |
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Applications |
Mice were treated with PD98059 and 30 min later, ischemia was induced. Pretreatment with PD98059 reduced phospho-ERK1/2 immunostaining in the cortex within the MCA territory after 2 hr of ischemia and 3 min of reperfusion. PD98059 also attenuated infarct size by 55%. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Zelivianski S, Spellman M, Kellerman M, et al. ERK inhibitor PD98059 enhances docetaxel-induced apoptosis of androgen-independent human prostate cancer cells. International journal of cancer, 2003, 107(3): 478-485. [2] Alessandrini A, Namura S, Moskowitz M A, et al. MEK1 protein kinase inhibition protects against damage resulting from focal cerebral ischemia. Proceedings of the National Academy of Sciences, 1999, 96(22): 12866-12869. |
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| Description | PD98059 is a selective and reversible inhibitor of MAPK-activating enzyme with IC50 values of both about 10 μM for basal MEK (GST-MEK1) and a partially activated MEK produced by mutation of serine to glutamate at 218 and 222 residues (GST-MEK-2E). | |||||
| Targets | GST-MEK1 | GST-MEK-2E) | ||||
| IC50 | 10 μM | 10 μM | ||||
Quality Control & MSDS
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