更新于：2024-11-01

ERK1 x ERK5

更新于：2024-11-01

基本信息

关联

项与 ERK1 x ERK5 相关的药物

ADTL-EI-1712

靶点

ERK1 x ERK5

作用机制

ERK1抑制剂 [+1]

在研机构

西南交通大学 [+1]

原研机构

西南交通大学

在研适应症

肿瘤

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 ERK1 x ERK5 相关的临床结果

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100 项与 ERK1 x ERK5 相关的转化医学

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0 项与 ERK1 x ERK5 相关的专利（医药）

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项与 ERK1 x ERK5 相关的文献（医药）

2021-06-01·Journal of Neuroscience Research3区 · 医学

Extracellular signal‐regulated kinases 2 (Erk2) and Erk5 in the central nervous system differentially contribute to central sensitization in male mice

3区 · 医学

Article

作者: Terashima, Hayato ; Satoh, Yasushi ; Ishizuka, Toshiaki ; Ikeda, Takehiko ; Wang, Xin ; Iwanaga, Koji ; Kawaguchi, Masanori ; Kobayashi, Yasushi ; Morohashi, Toru ; Itakura, Sayako ; Matsuura, Fumihiro ; Endo, Shogo ; Takahashi, Tetsuya

AbstractNervous systems are designed to become extra sensitive to afferent nociceptive stimuli under certain circumstances such as inflammation and nerve injury. How pain hypersensitivity comes about is key issue in the field since it ultimately results in chronic pain. Central sensitization represents enhanced pain sensitivity due to increased neural signaling within the central nervous system (CNS). Particularly, much evidence indicates that underlying mechanism of central sensitization is associated with the change of spinal neurons. Extracellular signal‐regulated kinases have received attention as key molecules in central sensitization. Previously, we revealed the isoform‐specific function of extracellular signal‐regulated kinase 2 (Erk2) in spinal neurons for central sensitization using mice with Cre‐loxP‐mediated deletion of Erk2 in the CNS. Still, how extracellular signal‐regulated kinase 5 (Erk5) in spinal neurons contributes to central sensitization has not been directly tested, nor is the functional relevance of Erk5 and Erk2 known. Here, we show that Erk5 and Erk2 in the CNS play redundant and/or distinct roles in central sensitization, depending on the plasticity context (cell types, pain types, time, etc.). We used male mice with Erk5 deletion specifically in the CNS and found that Erk5 plays important roles in central sensitization in a formalin‐induced inflammatory pain model. Deletion of both Erk2 and Erk5 leads to greater attenuation of central sensitization in this model, compared to deletion of either isoform alone. Conversely, Erk2 but not Erk5 plays important roles in central sensitization in neuropathic pain, a type of chronic pain caused by nerve damage. Our results suggest the elaborate mechanisms of Erk signaling in central sensitization.

2021-06-01·Translational Oncology

Diverse and converging roles of ERK1/2 and ERK5 pathways on mesenchymal to epithelial transition in breast cancer

Article

作者: Miele, Lucio ; Cavanaugh, Jane E ; Flaherty, Patrick T ; Ucar, Deniz A ; Wright, Thomas D ; Chakrabarty, Suravi ; Barnes, Van ; Bhatt, Akshita B ; Lexner, Erin ; Burow, Matthew E ; Matossian, Margarite D

The epithelial to mesenchymal transition (EMT) is characterized by a loss of cell polarity, a decrease in the epithelial cell marker E-cadherin, and an increase in mesenchymal markers including the zinc-finger E-box binding homeobox (ZEB1). The EMT is also associated with an increase in cell migration and anchorage-independent growth. Induction of a reversal of the EMT, a mesenchymal to epithelial transition (MET), is an emerging strategy being explored to attenuate the metastatic potential of aggressive cancer types, such as triple-negative breast cancers (TNBCs) and tamoxifen-resistant (TAMR) ER-positive breast cancers, which have a mesenchymal phenotype. Patients with these aggressive cancers have poor prognoses, quick relapse, and resistance to most chemotherapeutic drugs. Overexpression of extracellular signal-regulated kinase (ERK) 1/2 and ERK5 is associated with poor patient survival in breast cancer. Moreover, TNBC and tamoxifen resistant cancers are unresponsive to most targeted clinical therapies and there is a dire need for alternative therapies. In the current study, we found that MAPK3, MAPK1, and MAPK7 gene expression correlated with EMT markers and poor overall survival in breast cancer patients using publicly available datasets. The effect of ERK1/2 and ERK5 pathway inhibition on MET was evaluated in MDA-MB-231, BT-549 TNBC cells, and tamoxifen-resistant MCF-7 breast cancer cells. Moreover, TU-BcX-4IC patient-derived primary TNBC cells were included to enhance the translational relevance of our study. We evaluated the effect of pharmacological inhibitors and lentivirus-induced activation or inhibition of the MEK1/2-ERK1/2 and MEK5-ERK5 pathways on cell morphology, E-cadherin, vimentin and ZEB1 expression. Additionally, the effects of pharmacological inhibition of trametinib and XMD8-92 on nuclear localization of ERK1/2 and ERK5, cell migration, proliferation, and spheroid formation were evaluated. Novel compounds that target the MEK1/2 and MEK5 pathways were used in combination with the AKT inhibitor ipatasertib to understand cell-specific responses to kinase inhibition. The results from this study will aid in the design of innovative therapeutic strategies that target cancer metastases.

2020-09-26·Oxidative Medicine and Cellular Longevity2区 · 生物学

In VitroStudies on the Immunomodulatory Effects ofPulicaria crispaExtract on Human THP-1 Monocytes

2区 · 生物学

ArticleOA

作者: Alnasser, Moonerah M. ; ALKahtani, Muneera D. ; Al-Qahtani, Ahmed A. ; Albrahim, Tarfa ; Alkahtani, Saad ; Al-Anazi, Mashael R.

Background.Pulicaria crispa(P. crispa) is a plant from the Compositae family that exhibits antioxidant, anti-inflammatory, antibacterial, and cytotoxic activities.Objective. The current study aimed at investigating the immunomodulatory effects ofP. crispaextract in lipopolysaccharide- (LPS-) stimulated human monocytic THP-1 cells.Methods. To induce macrophage differentiation, THP-1 cell lines were treated with phorbol-12-myristate 13-acetate, followed by exposure to LPS with or without 50 or 100 μg/ml ofP. crispaextract. The following tests were employed to test the immunomodulatory effects of the extract: MTT assay, ELISA, Western blotting analysis, cell migration and phagocytosis assays, and Annexin V staining method.Results. Exposure to 100 μg/mlP. crispaextract significantly reduced THP-1 cell proliferation, migration, and phagocytosis (in LPS-stimulated cells, but not in unstimulated cells). Moreover, the extract alone significantly reduced the rate of THP-1 cell apoptosis, while it increased the rate of late apoptosis. Molecular investigations showed that treatment withP. crispaextract significantly upregulated the expression of ERK1, p-MAPK, P-P38, and Bcl2, while it significantly reduced the expression of ERK5, Bax, NF-κB, P-NF-κB, CCL1, CCL2, CCL5, CCL22, CXCL1, and CXCL10.Conclusion.Pulicaria crispaextract exhibited anti-inflammatory, antiproliferative, antimigratory, and antiphagocytic effects in LPS-stimulated THP-1 cells. Future studies should investigate these mechanisms in animal models with chronic inflammatory diseases.