PD98059 (Synonyms: NSC 679828) |
カタログ番号GC12819
One-Click Copy Product Info
|
PD98059は、IC50が2μMの強力で選択的なMEK阻害剤である。
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 167869-21-8
Sample solution is provided at 25 µL, 10mM.
PD98059は、IC50が2μMの強力で選択的なMEK阻害剤である。PD98059は不活性型のMEKに結合し、それにより上流のキナーゼがMEK1/2を活性化するのを防ぐ。また、PD98059はAHRのリガンドであり、AHRアンタゴニストとして機能する[1-3]。
PD98059(10μM PD98059;14日)をTGF-β1と組み合わせることで、ヒトUDSC(hUDSC)を平滑筋細胞(SMC)に形質転換する[4]。PD98059 (10μM PD98059 ;24 h)は、低用量シスプラチン耐性卵巣癌細胞(SKOV-3/DDP)のERK経路と上皮間葉転換過程(EMT)プロセスを抑制する[5]。G0/G1期でHec50co細胞が停止PD98059、PTX処理との組み合わせにより、G0/G1期とG2/M期の両方で蓄積が増加した[6]。PD98059(1、5、10、20、50μM;24時間)は、用量依存的にMCF-7およびMDA-MB-231細胞の増殖を阻害した[7]。
PD98059(5mg/kg/日; i.p; 2 週間)治療により、EAEモデルにおける小核 (MN)形成、脂質過酸化、グルタチオン(GSH)酸化などの副作用が軽減された[8]。PD98059(0.15/0.3mg/kg PD98059; i.v. gtt)は、心停止/心肺蘇生法(CA/CPR)を受けたラットにおいて、蘇生後24時間でミトコンドリアを介したアポトーシスおよびオートファジーから脳を保護する。これは、ダイナミン関連タンパク質1(Drp1)発現のダウンレギュレーションと関連している[9]。マウスにPD98059(10mg/kg; i.p; ボーラス)を投与すると、ザイモサンによる腹膜滲出と多形核細胞の遊走が弱まった[10]。
References:
[1]. Reiners JJ Jr, Lee JY, Clift RE, et.al. PD98059 is an equipotent antagonist of the aryl hydrocarbon receptor and inhibitor of mitogen-activated protein kinase kinase. Mol Pharmacol. 1998 Mar;53(3):438-45. doi: 10.1124/mol.53.3.438. PMID: 9495809.
[2]. Dudley DT, Pang L, et.al. A synthetic inhibitor of the mitogen-activated protein kinase cascade. Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7686-9. doi: 10.1073/pnas.92.17.7686. PMID: 7644477; PMCID: PMC41210.
[3]. Attia SM, Ahmad SF, et.al.The MAP kinase inhibitor PD98059 reduces chromosomal instability in the autoimmune encephalomyelitis SJL/J-mouse model of multiple sclerosis. Mutat Res Genet Toxicol Environ Mutagen. 2021 Jan-Feb;861-862:503278. doi: 10.1016/j.mrgentox.2020.503278. Epub 2020 Oct 29. PMID: 33551096.
[4]. Hwang Y, Cha SH, et.al.Combination of PD98059 and TGF-β1 Efficiently Differentiates Human Urine-Derived Stem Cells into Smooth Muscle Cells. Int J Mol Sci. 2021 Sep 29;22(19):10532. doi: 10.3390/ijms221910532. PMID: 34638875; PMCID: PMC8508912.
[5]. Hou L, Hou X, et.al.PD98059 impairs the cisplatin-resistance of ovarian cancer cells by suppressing ERK pathway and epithelial mesenchymal transition process. Cancer Biomark. 2017 Dec 12;21(1):187-194. doi: 10.3233/CBM-170644. PMID: 29103028.
[6].Wiwatchaitawee K, Mekkawy AI, et.al. The MEK 1/2 inhibitor PD98059 exhibits synergistic anti-endometrial cancer activity with paclitaxel in vitro and enhanced tissue distribution in vivo when formulated into PAMAM-coated PLGA-PEG nanoparticles. Drug Deliv Transl Res. 2022 Jul;12(7):1684-1696. doi: 10.1007/s13346-021-01065-7. Epub 2021 Oct 11. PMID: 34635984; PMCID: PMC8995400.
[7]. Zhao Y, Ge CC, et.al. MEK inhibitor, PD98059, promotes breast cancer cell migration by inducing β-catenin nuclear accumulation. Oncol Rep. 2017 Nov;38(5):3055-3063. doi: 10.3892/or.2017.5955. Epub 2017 Sep 13. PMID: 29048617.
[8]. Attia SM, Ahmad SF, et.al.The MAP kinase inhibitor PD98059 reduces chromosomal instability in the autoimmune encephalomyelitis SJL/J-mouse model of multiple sclerosis. Mutat Res Genet Toxicol Environ Mutagen. 2021 Jan-Feb;861-862:503278. doi: 10.1016/j.mrgentox.2020.503278. Epub 2020 Oct 29. PMID: 33551096.
[9]. Zheng JH, Xie L, et.al. PD98059 protects the brain against mitochondrial-mediated apoptosis and autophagy in a cardiac arrest rat model. Life Sci. 2019 Sep 1;232:116618. doi: 10.1016/j.lfs.2019.116618. Epub 2019 Jun 29. PMID: 31265854.
[10].Di Paola R, Galuppo M, et.al.PD98059, a specific MAP kinase inhibitor, attenuates multiple organ dysfunction syndrome/failure (MODS) induced by zymosan in mice. Pharmacol Res. 2010 Feb;61(2):175-87. doi: 10.1016/j.phrs.2009.09.008. Epub 2009 Oct 9. PMID: 19819333.
| 細胞実験[1]: | |
細胞株 | MCF-7およびMDA-MB-231細胞 |
準備方法 | 細胞は96ウェルプレートに播種した。細胞が細胞培養プレートの底部の30%まで増殖した後、細胞に様々な濃度のPD980589(1、5、10、20、50μM)を添加し、24時間インキュベーションを行った。 |
反応条件 | 1、5、10、20、50 μM;24時間 |
アプリケーション | PD98059、MCF-7およびMDA-MB-231細胞の増殖を用量依存的に阻害した。 |
| 動物実験 [2]: | |
動物モデル | SJL/Jマウス(実験的自己免疫性脳脊髄炎(EAE)モデル) |
準備方法 | マウスは、神経学的障害スコアが>2に達したら、PD98059の腹腔内注射、または同量の1%DMSOの偽注射を1日1回受けた(i.e，14日目)。マウスは、PD98059による最後の注射の24時間後に安楽死させ、骨髄細胞と脊髄組織を採取した。 |
投与形態 | 5 mg/kg/日; i.p;2週間 |
アプリケーション | PD98059治療により、EAEモデルにおける小核(MN)形成、脂質過酸化、グルタチオン(GSH)酸化などの副作用が軽減された。 |
| キナーゼ実験 [3]: | |
準備方法 | ミエリン塩基性タンパク質(MBP)への32Pの取り込みは、44-kDa MAPK(GST-MAPK)または45-kDa MEK(GST-MEK1)を含むグルタチオンS-トランスフェラーゼ(GST)融合タンパク質の存在下でアッセイしたPD98059(または有無)。アッセイは、50μlの50mM Tris、pH 7.4.10mM MgCl2、2mM EGTA、10μgのGST-MEK1、0.5μgのGST-MAPK、および 40μgの MBPを含む10μM [y-32P]ATPで実施した。30°Cで15分間インキュベートした後、Laemmli SDSサンプルバッファーを添加して反応を停止した。リン酸化MBPはSDS/PAGE(10%)で分離した。 |
反応条件 | |
アプリケーション | D98059は、IC50が2μMの非ATP競合MEK阻害剤である。 |
参考文献: [1]. Dudley DT, Pang L, et.al. A synthetic inhibitor of the mitogen-activated protein kinase cascade. Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7686-9. doi: 10.1073/pnas.92.17.7686. PMID: 7644477; PMCID: PMC41210. [2]. Zhao Y, Ge CC, et.al.MEK inhibitor, PD98059, promotes breast cancer cell migration by inducing β-catenin nuclear accumulation. Oncol Rep. 2017 Nov;38(5):3055-3063. doi: 10.3892/or.2017.5955. Epub 2017 Sep 13. PMID: 29048617. [3]. Attia SM, Ahmad SF, et.al. The MAP kinase inhibitor PD98059 reduces chromosomal instability in the autoimmune encephalomyelitis SJL/J-mouse model of multiple sclerosis. Mutat Res Genet Toxicol Environ Mutagen. 2021 Jan-Feb;861-862:503278. doi: 10.1016/j.mrgentox.2020.503278. Epub 2020 Oct 29. PMID: 33551096. | |
| Cas No. | 167869-21-8 | SDF | |
| 同義語 | NSC 679828 | ||
| Chemical Name | 2-(2-amino-3-methoxyphenyl)chromen-4-one | ||
| Canonical SMILES | COC1=CC=CC(=C1N)C2=CC(=O)C3=CC=CC=C3O2 | ||
| Formula | C16H13NO3 | M.Wt | 267.28 |
| 溶解度 | ≥ 40.23 mg/mL in DMSO | Storage | 4°C, protect from light |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 3.7414 mL | 18.707 mL | 37.4139 mL |
| 5 mM | 748.3 μL | 3.7414 mL | 7.4828 mL |
| 10 mM | 374.1 μL | 1.8707 mL | 3.7414 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
-
Related Biological Data
Inhibition of p-STAT3 (Ser727) augments the effects of CPX on the autophagy of GC cells.b Western blotting analysis of p-STAT3 (Ser727), p-STAT3 (Tyr705), STAT3, p-ERK (Thr202/Tyr204), and ERK1/2 in GC cells treated with a serial concentration of PD98059 for 24 h.
Western blotting analysis of p-STAT3 (Ser727), p-STAT3 (Tyr705), STAT3, p-ERK (Thr202/Tyr204), and ERK1/2 in GC cells treated with a serial concentration of PD98059 （Glpbio）for 24 h.
Cell Death & Disease 13.11 (2022): 1007. PMID: PMID: 36443287 IF: 9.0002 -
Related Biological Data
tBHQ induces the Nrf2-dependent antioxidant responses in glutamate-induced R28 cells A. Expression of Nrf2 in R28 cells under fluorescence microscopy.B. Effects of pretreatment with inhibitors of intermediate proteins on cell viability.
We pretreated cells for 30 min with inhibitors of ERK (PD98059)（Glpbio）, JNK (SP600125), p38 (SB203580) or Akt (MK-2206) to determine if tBHQ affects these intermediate proteins .
Biomedicine & Pharmacotherapy 152 (2022): 113117. PMID: 35653886 IF: 6.5298 -
Related Biological Data
Effects of 5-HT and 5-HT7R selective agonist LP-12 combined with SB269970 on melanin contents, dendrite, or migration in B16F10 cells. B16F10 cells were pre-incubated with SP600125 (10 μM) and PD98059 (10 μM) for 2 h prior to the addition of LP-12 (200 nM), and then incubated for 72 h for the measurement of melanin content.
B16F10 cells were pre-incubated with PD98059（Glpbio） (10 μM) for 2 h prior to the addition of LP-12(200 nM), and then incubated for 72 h for the measurement of melanin content.
The FASEB Journal 37.4 (2023): e22893. PMID: 36961387 IF: 5.8339
Average Rating: 5 (Based on Reviews and 22 reference(s) in Google Scholar.)