PD98059（AbMole，M1822）是一種廣泛應(yīng)用于基礎(chǔ)研究中的MEK1/2抑制劑，通過特異性抑制MEK1/2的激酶活性，從而阻斷其下游ERK1/2的磷酸化，在多種細(xì)胞和動(dòng)物模型中被用于解析ERK/MAPK信號(hào)通路的功能。

在體外實(shí)驗(yàn)中，PD98059（AbMole，M1822）常以10–25 μmol/L的濃度使用，例如在RAW 264.7巨噬細(xì)胞、EL-4淋巴細(xì)胞、HK-2近端腎小管上皮細(xì)胞、MDA-MB-231和MCF-7乳腺癌細(xì)胞、C666-1鼻咽癌細(xì)胞、U937單核細(xì)胞以及WJCMSCs和PDLSCs間充質(zhì)干細(xì)胞中，該濃度范圍可有效抑制ERK1/2磷酸化并調(diào)控細(xì)胞增殖、遷移、分化或凋亡等生物學(xué)過程[1-4]。在RAW 264.7細(xì)胞中，25 μmol/L PD98059不僅抑制ERK，還能促進(jìn)破骨細(xì)胞分化[5]。此外，PD98059被發(fā)現(xiàn)能在小鼠神經(jīng)干細(xì)胞中誘導(dǎo)星形膠質(zhì)細(xì)胞生成，提示PD98059（CAS No.：167869-21-8）可用于調(diào)節(jié)神經(jīng)干細(xì)胞的命運(yùn)決定[6]。

在動(dòng)物的體內(nèi)研究中，PD98059（AbMole，M1822）可通過腹腔注射（如10 mg/kg）用于小鼠模型，顯著提高血清IL-5水平，并在大鼠心肺復(fù)蘇模型中以劑量依賴方式抑制腦皮層線粒體凋亡與自噬相關(guān)蛋白LC3-II和Beclin-1的表達(dá)[7, 8]。此外，在高血壓誘導(dǎo)的主動(dòng)脈重構(gòu)小鼠模型中，PD98059被用于干預(yù)血管緊張素II（AngII，Angiotensin II）處理組，單獨(dú)或與SO₂聯(lián)用，結(jié)果發(fā)現(xiàn)PD98059可抑制ERK和磷酸化ERK（P-ERK）的表達(dá)，減輕主動(dòng)脈壁增厚[9]。

綜上，PD98059（AbMole，M1822）作為經(jīng)典MEK1/2抑制工具，在小鼠、大鼠及多種人類和嚙齒類細(xì)胞系中被廣泛用于信號(hào)通路解析，其使用濃度和劑量需根據(jù)具體實(shí)驗(yàn)體系優(yōu)化。

參考文獻(xiàn)及鳴謝
J Nanobiotechnology. 2022 Feb 2;20(1):65.
AbMole的 PD98059（AbMole，M1822）作為ERK1/2信號(hào)通路特異性抑制劑，在本研究中揭示了小鼠脊髓損傷后 ROS 誘導(dǎo)神經(jīng)炎癥的分子機(jī)制：即ROS/MAPK/NFκB P65 信號(hào)通路與上述炎癥反應(yīng)高度相關(guān)，提示該通路可作為脊髓損傷動(dòng)物模型中的新型抑制靶點(diǎn)。
參考文獻(xiàn)及鳴謝
[1] Li, X.; Cao, X.; Zhang, X.; et al. MEK1/2 inhibitors induce interleukin-5 expression in mouse macrophages and lymphocytes. Biochemical and biophysical research communications 2016, 473 (4), 939-946.
[2] Nakamura, T.; Yoshida, E.; Hara, T.; et al. Zn(ii)2,9-dimethyl-1,10-phenanthroline stimulates cultured bovine aortic endothelial cell proliferation. RSC advances 2020, 10 (69), 42327-42337.
[3] Zhang, W.; Obuchi, S.; Teramura, Y. Analysis of cellular responses following interaction with extracellular vesicles derived from HEK293T and human adipose derived stem cells. Scientific reports 2025, 15 (1), 11835.
[4] Hasan, M.; Browne, E.; Guarinoni, L.; et al. Novel Melatonin, Estrogen, and Progesterone Hormone Therapy Demonstrates Anti-Cancer Actions in MCF-7 and MDA-MB-231 Breast Cancer Cells. Breast cancer : basic and clinical research 2020, 14, 1178223420924634.
[5] Agidigbi, T. S.; Kang, I. S.; Kim, C. Inhibition of MEK/ERK upregulates GSH production and increases RANKL-induced osteoclast differentiation in RAW 264.7 cells. Free radical research 2020, 54 (11-12), 894-905.
[6] Lee, H. R.; Lee, J.; Kim, H. J. Differential effects of MEK inhibitors on rat neural stem cell differentiation: Repressive roles of MEK2 in neurogenesis and induction of astrocytogenesis by PD98059. Pharmacological research 2019, 149, 104466.
[7] Hassan, R. M.; Elsayed, N. S.; Assaf, N.; et al. Limettin and PD98059 Mitigated Alzheimer's Disease Like Pathology Induced by Streptozotocin in Mouse Model: Role of p-ERK1/2/p-GSK-3beta/p-CREB/BDNF Pathway. Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology 2025, 20 (1), 55.
[8] Zheng, J. H.; Xie, L.; Li, N.; et al. PD98059 protects the brain against mitochondrial-mediated apoptosis and autophagy in a cardiac arrest rat model. Life sciences 2019, 232, 116618.
[9] Wu, H. J.; Huang, Y. Q.; Chen, Q. H.; et al. Sulfur Dioxide Inhibits Extracellular Signal-regulated Kinase Signaling to Attenuate Vascular Smooth Muscle Cell Proliferation in Angiotensin II-induced Hypertensive Mice. Chinese medical journal 2016, 129 (18), 2226-2232.