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Chemical Structure| 167869-21-8 Chemical Structure| 167869-21-8

Structure of PD98059
CAS No.: 167869-21-8

Chemical Structure| 167869-21-8

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

Synonyms: NSC 679828

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Lu, Fen ; Wang, Yuqi ; Li, Kunzhi ; Xu, Huini ;

Abstract: Nitric oxide (NO) is a crucial signaling molecule in plants, but its specific role under low nitrogen (LN) stress remains to be elucidated. In this study, we found that exogenous application of 100 μM NO donor significantly enhanced the growth indicators of tomato seedlings under 0.2 mM LN treatment. Transcriptome analysis revealed 657 differentially expressed genes (DEGs), primarily involving photosynthesis, secondary metabolism, the MAPK signaling pathway, and nitrogen metabolism. Notably, exogenous NO treatment not only alleviated the growth inhibition and chlorophyll reduction caused by LN but also reduced the accumulation of reactive oxygen species (ROS) while enhancing the activity and gene expression of antioxidant enzymes. However, the MAPK inhibitor PD98059 reversed these positive effects. Furthermore, exogenous NO treatment promoted NO accumulation, increased S-nitrosylated proteins, and enhanced the activity and expression of nitrate reductase (SlNR) and glutamine synthetase (SlGS), while PD98059 similarly inhibited these effects. After exogenous NO treatment, the expression of 16 tomato SlMAPKs genes was significantly upregulated. These results indicate that exogenous NO can mitigate oxidative damage and improve nitrogen metabolism in tomato seedlings under low nitrogen stress, and the MAPK signaling pathway involved in this process.

Keywords: NO ; Low nitrogen stress ; Tomato ; MAPK signaling pathway ; Transcriptome analysis

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Xu, Manhua ; Li, Kaiming ; Wang, Yanxi ; Wang, Jie ; Bai, Mengtian ; Kang, Gangjing

Abstract: The objective of this study is to explore the effect of extracellular signal–regulated kinase (ERK) inhibitors on corneal neovascularization induced by alkali burn in mice and its mechanism. A total of 30 standard diet (SD) healthy mice were divided into normal group, alkali burn group, and inhibitor group. Normal group was not treated. Alkali burn group and inhibitor group were used to establish corneal neovascularization model induced by alkali burn. After successful modeling, ERK inhibitor was used to intervene in inhibitor group, and saline of equal volume was used in normal group and alkali burn group. The area of corneal neovascularization was calculated and the expression of vascular endothelial growth factor (VEGF), c-Fos, c-Jun, ERK1/2, and p-ERK1/2 protein in cornea tissue of three groups of mice was detected. The relative expression of vascular area, length, VEGF, c-Fos, c-Jun, ERK1/2, and p-ERK1/2 protein in cornea tissue of mice in alkali burn group was significantly higher than that in normal group and inhibitor group. The relative expression of vascular area, length, VEGF, c-Fos, c-Jun, ERK1/2, and p-ERK1/2 protein in cornea tissue of mice in inhibitor group was higher than that in normal group, and the expression level of PEDF was lower than that in normal group (P<0.05). ERK inhibitors inhibit the formation of corneal neovascularization by inhibiting the expression of VEGF, c-Fos, and c-Jun proteins through the action of ERK signaling pathway.

Keywords: alkali burns ; corneal neovascularization ; ERK inhibitors

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Alternative Products

Product Details of PD98059

CAS No. :167869-21-8
Formula : C16H13NO3
M.W : 267.28
SMILES Code : O=C1C=C(C2=CC=CC(OC)=C2N)OC3=C1C=CC=C3
Synonyms :
NSC 679828
MDL No. :MFCD00671789
InChI Key :QFWCYNPOPKQOKV-UHFFFAOYSA-N
Pubchem ID :4713

Safety of PD98059

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P264-P270-P301+P312-P330-P501

Related Pathways of PD98059

MAPK

Isoform Comparison

Biological Activity

Target
  • MEK1

    MEK1, IC50:2 μM

In Vitro:

Cell Line
Concentration Treated Time Description References
Human intrahepatic biliary epithelial cells (HIBEpiCs) 10 μM 24 h Pretreatment with PD98059 reduced apelin-induced ERK phosphorylation and cholangiocyte proliferation Hepatology. 2021 Jun;73(6):2411-2428.
Y79 cells 0.1 µM, 0.2 µM, 0.39 µM, 0.78 µM, 1.56 µM, 3.12 µM, 6.25 µM, 12.5 µM 22 h To evaluate the effects of PD98059 on the metabolic activity and cytotoxicity of Y79 cells. PD98059 significantly inhibited cellular metabolic activity at a concentration of 3.12 µM or higher, but did not significantly increase cytotoxicity. Theranostics. 2022 Sep 11;12(15):6705-6722.
huPMCs cells 0.1 µM, 0.2 µM, 0.39 µM, 0.78 µM, 1.56 µM, 3.12 µM, 6.25 µM, 12.5 µM 22 h To evaluate the effects of PD98059 on the metabolic activity and cytotoxicity of huPMCs cells. PD98059 did not significantly inhibit cellular metabolic activity at concentrations up to 12.5 µM, nor did it significantly increase cytotoxicity. Theranostics. 2022 Sep 11;12(15):6705-6722.
MIO-M1 cells 0.1 µM, 0.2 µM, 0.39 µM, 0.78 µM, 1.56 µM, 3.12 µM, 6.25 µM, 12.5 µM 22 h To evaluate the effects of PD98059 on the metabolic activity and cytotoxicity of MIO-M1 cells. PD98059 significantly inhibited cellular metabolic activity at a concentration of 1.56 µM or higher, but did not significantly increase cytotoxicity. Theranostics. 2022 Sep 11;12(15):6705-6722.
U87 cells 5 μM 12 h To investigate the effect of PD98059 on RRM2 overexpression in U87 cells, the results showed that PD98059 inhibited the phosphorylation of ERK1/2 and blocked the upregulation of cyclin B1, cyclin D1, and N-cadherin expression induced by RRM2 overexpression. Int J Biol Sci. 2019 Jan 1;15(3):533-543.
Human adipose-derived stem cells (hASCs) 5 μM 48 h To investigate the effect of PD98059 on FGF-2-mediated proliferation of hASCs, results showed that PD98059 significantly inhibited FGF-2-mediated cell proliferation. Stem Cell Res Ther. 2019 Nov 27;10(1):350.
human adipose tissue-derived stem cells (hADSCs) 40 μM 30 min PD98059 abolished the ERK1/2 phosphorylation and proliferation induced by silica NPs Int J Nanomedicine. 2015 Mar 24;10:2261-72.
MIA-PaCa-2 cells 25 µM PD98059 completely blocked KIF15-mediated pancreatic cancer cell proliferation Br J Cancer. 2017 Jul 11;117(2):245-255.
PANC-1 cells 25 µM PD98059 completely blocked KIF15-mediated pancreatic cancer cell proliferation Br J Cancer. 2017 Jul 11;117(2):245-255.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice Photo-oxidative damage model Intravitreal injection 100 µM Single injection, lasting 4 days To evaluate the protective effects of PD98059 on the retina of photo-oxidative damage mice. PD98059 significantly inhibited the phosphorylation of pERK1/2, reduced the expression of the gliotic marker GFAP in Müller cells, and increased the levels of the neuroprotective factor IRBP in photoreceptors. PD98059 also reduced photoreceptor apoptosis in photo-oxidative damage mice and assessed its protective effects on retinal function through OCT and ERG. Theranostics. 2022 Sep 11;12(15):6705-6722.
Balb/c nude mice Orthotopic pancreatic cancer transplantation model Subcutaneous injection 10 mg/kg Once daily for 9 weeks PD98059 blocked KIF15-mediated pancreatic cancer proliferation and prolonged the survival time of mice Br J Cancer. 2017 Jul 11;117(2):245-255.

Protocol

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3.74mL

0.75mL

0.37mL

18.71mL

3.74mL

1.87mL

37.41mL

7.48mL

3.74mL

 

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