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更新于：2025-05-07

MAP3K3

更新于：2025-05-07

基本信息

别名

MAP/ERK kinase kinase 3、MAP3K3、MAPK/ERK kinase kinase 3

+ [5]

简介

Component of a protein kinase signal transduction cascade. Mediates activation of the NF-kappa-B, AP1 and DDIT3 transcriptional regulators.

关联

项与 MAP3K3 相关的药物

QXT-101

靶点

MAP3K2 x MAP3K3

作用机制

MAP3K2抑制剂 [+1]

在研机构-

原研机构

Qx Therapeutics, Inc.

在研适应症-

非在研适应症

新型冠状病毒感染 [+1]

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 MAP3K3 相关的临床结果

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100 项与 MAP3K3 相关的转化医学

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0 项与 MAP3K3 相关的专利（医药）

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332

项与 MAP3K3 相关的文献（医药）

2025-05-01·Molecular Neurobiology

Sodium Danshensu Inhibits Macrophage Inflammation in Atherosclerosis via the miR-200a-3p/MEKK3/NF-κB Signaling Pathway

Article

作者: Zhang, Yilin ; Wang, Yijing ; Zhang, Xiaolu ; Jiang, Xijuan ; Yu, Qun ; Gan, Jiali ; Zeng, Miao

Macrophages are fundamental cellular components of atherosclerotic plaques, and inhibition of macrophage inflammation can delay the development of atherosclerotic plaques. Sodium danshensu (SDSS) can inhibit inflammatory responses and thus delay atherosclerosis, but the specific mechanism remains unclear. The effect of SDSS in inhibiting atherosclerosis was confirmed by observing and detecting atherosclerotic plaque area, morphology and lipid levels in the aorta. The mechanism by which SDSS attenuated atherosclerotic plaques was elucidated by in vivo and in vitro detection of inflammation-related mRNA and protein expression. In addition, bioinformatics analysis, RT-qPCR and dual-luciferase assays were used to predict and validate the potential miRNAs of SDSS to attenuate atherosclerosis. miR-200a-2p mimic and inhibitor were then compared for their effects on the efficacy of SDSS. SDSS inhibited atherosclerotic plaque formation and suppressed the expression of MEKK3, TNF-α, and IL-1β as well as nuclear factor-κB (NF-κB) phosphorylation and nuclear translocation to attenuate inflammatory responses. Bioinformatic predictions combined with RT-qPCR results and dual-luciferase assays indicated that miR-200a-3p negatively regulated MEKK3 expression by directly targeting the 3'UTR region of MEKK3, thereby blocking MEKK3. Further studies showed that miR-200a-3p inhibitor, but not miR-200a-3p mimic, reversed the beneficial effects of SDSS on inflammation. SDSS inhibited macrophage inflammation by modulating the miR-200a-3p/MEKK3/NF-κB signaling pathway.

2025-04-01·Stroke

Map3k3 ^I441M Knock-In Mouse Model of Cerebral Cavernous Malformations

Article

作者: Sun, Yingfan ; Yang, Yingxi ; Zhao, Shaozhi ; Xu, Hongyuan ; Cao, Yong ; Wang, Jiguang ; Zhou, Qiuxia ; Wang, Jie ; He, Qiheng ; Tang, Jinyi ; Jiao, Yuming ; Yu, Qifeng ; Huo, Ran

BACKGROUND: Cerebral cavernous malformations (CCMs) refer to vascular dysplasia primarily found in the brain, affecting ≈0.5% of the population. A somatic Map3k3I441M mutation has been found in ≈40% of patients with sporadic CCMs, which were typically accompanied by somatic gain-of-function mutations in PIK3CA . Although mouse models of adeno-associated virus-BR1–mediated mutant overexpression have been reported, these models have limitations in representing clinical specimens of CCMs, which typically harbor single allele mutation in Map3k3 . A Map3k3I441M knock-in murine model of CCMs has not yet been established. METHODS: The Map3k3I441M knock-in mice were crossed with Cdh5 -creER T2 mice to induce mutant gene expression specifically in endothelial cells. Subsequently, Map3k3I441M mice were bred with Ptenfl/fl mice to generate Map3k3I441M ; Ptenfl/fl mice. In both murine models, CCM lesions were examined using magnetic resonance imaging, while single-cell RNA sequencing and immunostaining were utilized to investigate the pathomechanism of the mutation. Finally, we administered an mTOR (mechanistic target of rapamycin) inhibitor to explore its therapeutic effect on lesions of both murine models. RESULTS: Both endothelial Map3k3I441M mutant juvenile mice and Map3k3I441M ; Ptenfl/fl mice developed abnormal lesions with human CCM characteristics. In Map3k3I441M mice, the mutant promoted endothelial apoptosis, while activation of the PI3K (phosphatidylinositol 3-kinase) pathway was able to activate the downstream AKT (protein kinase B)/mTOR/p-S6 (phosphorylated S6 ribosomal protein) pathway and upregulate VEGFA (vascular endothelial growth factor A) expression, counteracting apoptosis, and facilitating lesion progression. The activation of PI3K signaling is required for Map3k3I441M to generate CCM-like lesions in adult mice. Finally, we demonstrated that rapamycin effectively inhibited the formation of lesions in the Map3k3I441M mice and Map3k3I441M ; Ptenfl/fl mice. CONCLUSIONS:Map3k3I441M heterozygous is sufficient to induce lesions in juvenile mice, while the additional activation of PI3K signaling is required for the effective formation of CCMs at the adult stage. The Map3k3I441M murine model provides a preclinical model for further mechanistic and therapeutic studies of CCMs.

2025-04-01·Histopathology

Low‐grade myxoid spindle cell neoplasm with novel gene fusions involving MAP3K3 and MAP3K8 kinases: a report of two cases

Letter

作者: Weiss, Kurt R. ; Schoedel, Karen ; Hahn, Elan ; Karunamurthy, Arivarasan ; Naous, Rana ; Rosenbaum, Joel ; Mohebnasab, Mana ; Chiosea, Simion I ; Neyaz, Azfar ; da Gama Lobo, Lucas ; John, Ivy

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