2. Signaling Pathways
  3. MAPK/ERK Pathway
  4. MAP3K
  5. MAP3K8/COT/Tpl2 Isoform

MAP3K8/COT/Tpl2

MAP3K8, also known as COT or Tpl2, is a serine/threonine kinase that regulates MAPK signaling cascades, primarily through activation of MEK1/2 and ERK1/2[1][2]. Mechanistically, MAP3K8 modulates inflammatory responses by controlling the translation and stability of cytokine mRNAs in Toll-like receptor-activated macrophages, including TNFα, IL-6, and KC[2][3]. In immune cells, MAP3K8 influences Th1 differentiation by inhibiting IL-12 production and shaping adaptive responses. Compared with other MAP3Ks, MAP3K8 exhibits isoform-specific regulation of Akt-mTOR-p70 S6k signaling, fine-tuning TLR-mediated responses[3]. Disease models demonstrate MAP3K8’s involvement in cancer, metabolic inflammation, and viral infections; it drives androgen depletion-independent prostate cancer growth, contributes to obesity-induced adipose tissue inflammation, and is transcriptionally repressed during coronavirus infection[4][5][6]. In liver and kidney injury models, MAP3K8 deficiency reduces sterile inflammatory damage and apoptosis, highlighting its pathological significance[7][8]. Pharmacological inhibition of MAP3K8 suppresses pro-inflammatory cytokine production in human cytotoxic T lymphocytes and epithelial cells, though current tool compounds show limited potency, indicating a need for improved inhibitors for therapeutic applications[9][10][11]. Collectively, MAP3K8 serves as a critical node connecting MAPK signaling, inflammatory regulation, and disease-specific cellular responses, distinguishing it functionally from related MAP3K isoforms[12][13].

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MAP3K8/COT/Tpl2 Related Products (4):

Cat. No. Product Name Effect Purity
  • HY-12358
    Tpl2 Kinase Inhibitor 1
    		Inhibitor 99.42%
    Tpl2 Kinase Inhibitor 1 is a 3-pyridylmethylamino analog, and is a selective Tpl2 inhibitor (IC50=50 nM). Tpl2 consists of COT kinase and MAP3K8. Tpl2 Kinase Inhibitor 1 plays an important role in the regulation of the inflammatory response and the progression of some cancers.
  • HY-178726
    Cot-IN-4
    		Inhibitor
    Cot-IN-4 (compound 32) is a potent cancer osaka thyroid (COT) kinase inhibitor with an IC50 of 6 nM. Cot-IN-4 inhibits the phosphorylation of ERK (IC50: 60 nM) and inhibits TNFα release (IC50: 60 nM). Cot-IN-4 also inhibits the formation of the pro-inflammatory cytokine IL-1β (IC50: 0.2 μM) in Uric acid (HY-B2130)-stimulated macrophages. Cot-IN-4 can be used for the study of inflammatory diseases.
  • HY-159074
    Cot-IN-5
    		Inhibitor
    Cot-IN-5 (compound 1) is a potent ATP-competitive inhibitor of cancer osaka thyroid (COT). Cot-IN-5 can block COT kinase autophosphorylation.
  • HY-12358A
    Tpl2 Kinase Inhibitor 1 hydrochloride
    		Inhibitor
    Tpl2 Kinase Inhibitor 1 hydrochloride is a 3-pyridylmethylamino analog, and is a selective Tpl2 inhibitor (IC50=50 nM). Tpl2 consists of COT kinase and MAP3K8. Tpl2 Kinase Inhibitor 1 hydrochloride plays an important role in the regulation of the inflammatory response and the progression of some cancers.