2. Signaling Pathways
  3. MAPK/ERK Pathway
  4. MAP4K

MAP4K

MAPK Kinase Kinase Kinase

MAP4K

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MAP kinase kinase kinase kinases (MAP4Ks) belong to the mammalian Ste20-like family of serine/threonine kinases. MAP4Ks including MAP4K1/HPK1, MAP4K2/GCK, MAP4K3/GLK, MAP4K4/HGK, MAP4K5/KHS, and MAP4K6/MINK have been reported to induce JNK activation through activating the MAP3K-MAP2K cascade. MAP4Ks play important roles in the regulation of cell apoptosis, cell survival, cell autophagy, and cell migration. Several studies reported that MAP4Ks are involved in the regulation of immune-cell responses through JNK-independent pathways.

MAP4K1/HPK1 and MAP4K4/HGK play negative roles in T-cell activation and inflammatory responses. In contrast, MAP4K3/GLK plays a positive role in T-cell activation and autoimmune responses. Moreover, MAP4K1 downregulation and MAP4K3 overexpression in T cells are involved in human autoimmune diseases such as psoriatic arthritis, rheumatoid arthritis (RA), adult-onset Still’s disease, and SLE.

MAP4K Isoform Specific Products:

MAP4K Isoform Comparison
Cat. No. Product Name Effect Purity Chemical Structure
  • HY-149206
    HPK1-IN-33
    		Inhibitor
    HPK1-IN-33 (compound 21) is a potent Hematopoietic Progenitor Kinase 1 (HPK1) inhibitor with a Ki value of 1.7 nM. HPK1-IN-33 inhibits the produce of IL-2 with EC50s of 286, >10000 nM in Jurkat WT and Jurkat HPK1 KO cells, respectively.
    HPK1-IN-33
  • HY-100830A
    NCB-0970
    		Control
    NCB-0970 is the negative control of NCB-0846 (HY-100830). NCB-0846 is an orally active, selective inhibitor for Wnt, that inhibits Traf2- and Nck-interacting kinase (TNIK) with an IC50 of 21 nM. NCB-0846 blocks TGF-β signaling pathway by inhibiting SMAD2/3 phosphorylation and nuclear translocation.
    NCB-0970
  • HY-170365
    HPK1-IN-55
    		Inhibitor
    HPK1-IN-55 (compound 19) is a selective and orally active hematopoietic progenitor kinase 1 (HPK1) inhibitor with an IC50 of <0.51 nM. HPK1-IN-55 shows excellent kinase selectivity (>637-fold vs GCK-like kinase and >1022-fold vs LCK). HPK1-IN-55 has anticancer effects.
    HPK1-IN-55
  • HY-160218
    HPK1-IN-42
    		Inhibitor
    HPK1-IN-42 (compound 185) ia a HPK1 inhibitor with the IC50 50 of 0.24 nM.
    HPK1-IN-42
  • HY-159905
    HPK1-IN-54
    		Inhibitor
    HPK1-IN-54 is a potent HPK1 (Hematopoietic Progenitor Kinase 1) inhibitor that enhances T cell activation and proliferation by inhibiting HPK1 activity, thereby exhibiting antitumor effects. Its IC50 value against HPK1 is 2.67 nM, with excellent selectivity over the MAP4K family (>100-fold) and other selected kinases (>300-fold). HPK1-IN-54 displayed moderate in vivo clearance and reasonable oral exposure in mice and rats. Additionally, HPK1-IN-54 demonstrated strong antitumor efficacy in a CT26 murine colon cancer model and synergistic effects when combined with anti-PD-1 (HY-P9902A). HPK1-IN-54 shows promise for research in the field of immunotherapy.
    HPK1-IN-54
  • HY-163717
    HPK1-IN-48
    		Inhibitor
    HPK1-IN-48 (compound 14g) is a potent Hematopoietic Progenitor Kinase 1 (HPK1) inhibitor with a IC50 of 0.15 nM. HPK1-IN-48 significantly suppresses the phosphorylation of SLP76 with a IC50 of 27.92 nM.
    HPK1-IN-48
  • HY-161335
    HPK1-IN-43
    		Inhibitor
    HPK1-IN-43 (compound 9f) is a HPK1 kinase inhibitor with the IC50 value of 0.32 nM. HPK1-IN-43 inhibits the phosphorylation of the downstream protein SLP-76 and enhances the secretion of interleukin-2 (IL-2) and interferon-γ (IFN-γ). HPK1-IN-43 can be used in cancer research.
    HPK1-IN-43
  • HY-19562A
    PF-06260933 hydrochloride
    		Inhibitor
    PF-06260933 hydrochloride is the hydrochloride form of PF-06260933 (HY-19562). PF-06260933 hydrochloride is an orally active and highly selective inhibitor of MAP4K4 with IC50s of 3.7 and 160 nM for kinase and cell, respectively.
    PF-06260933 hydrochloride
  • HY-168119
    HPK1-IN-53
    		Inhibitor
    HPK1-IN-53 (compund 3a) is the potent HPK1 inhibitor (IC50=48 nM).
    HPK1-IN-53
MAP4K Isoform Comparison

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