MAP4K
MAP4Ks (Mitogen-activated protein kinase kinase kinase kinases) belong to the mammalian Ste20-like family of serine/threonine kinases. MAP4K family members, including Hematopoietic progenitor kinase 1 (HPK1/MAP4K1), Germinal centre kinase (GCK/MAP4K2), Germinal centre kinase-like kinase (GLK/MAP4K3), HPK/GCK-like kinase (HGK/MAP4K4), Misshapen-like kinase 1 (MINK1/MAP4K6) and TRAF2 and NCK interacting kinase (TNIK/MAP4K7), as potent LATS1/2-activating kinases.
Overexpression or deletion of MAP4Ks affects the phosphorylation and activity of Large tumor suppressor 1/2 (LATS1/2, homologues of Wts) and Yes-associated protein (YAP) /transcriptional co-activator with PDZ-binding motif (TAZ). By acting in a LATS-dependent, but Mammalian Ste20-like kinases 1/2 (MST1/2, homologues of Hpo)-independent manner, MAP4Ks restrict the activity of YAP/TAZ by promoting their phosphorylation and inhibiting target gene expression. MAP4Ks are components of the Hippo pathway by directly phosphorylating and activating the LATS1/2 kinases.MAP4K2/4/6 and MST1/2 both belong to the STE20-like kinase family, and their kinase domains are highly homologous to one another. MAP4K4 acts through LATS to inhibit YAP and cell proliferation.
Targets for MAP4K
Products for MAP4K
- Cat.No. Product Name Information
- GC12151 B-Raf inhibitor
- GC25289 CompK CompK (compound K), a potent and selective hematopoietic progenitor kinase 1 (HPK1 or MAP4K1) small molecule inhibitor, significantly improves human T-cell functions, with enhanced T-cell receptor avidity to recognize tumor-associated antigens and tumor cytolytic activity by CD8+ T cells.
- GC65298 DMX-5804 DMX-5804 is a potent, orally active and selective MAP4K4 inhibitor, with an IC50 of 3 nM, a pIC50 of 8.55 for human MAP4K4, less potent on MINK1/MAP4K6 (pIC50, 8.18), and TNIK/MAP4K7 (pIC50, 7.96).
- GC33123 GNE 220 GNE-220 is a potent and selective inhibitor of MAP4K4 with an IC50 of 7 nM.
- GC34208 GNE 220 Hydrochloride GNE 220 (hydrochloride) is a potent and selective inhibitor of MAP4K4, with an IC50 of 7 nM.
- GC18257 GNE-495 GNE-495 is an orally bioavailable, potent, and selective MAP4K4 inhibitor (IC50 = 3.7 nM).
- GC62514 HPK1-IN-3 HPK1-IN-3 is a potent and selective ATP-competitive hematopoietic progenitor kinase 1 (HPK1; MAP4K1) inhibitor with an IC50 of 0.25 nM.
- GC63569 HPK1-IN-4 HPK1-IN-4 (comp 22) is a HPK1 (MAPK41) inhibitor (IC50 of 0.061 nM) as preclinical immunotherapy tool compound.
- GC63006 HPK1-IN-7 HPK1-IN-7 is a potent, orally active HPK1 (hematopoietic progenitor kinase 1, MAP4K1) inhibitor (IC50=2.6 nM) with excellent family and kinome selectivity. HPK1-IN-7 shows selectivity against IRAK4 (59 nM) and GLK (140 nM). HPK1-IN-7 shows robust efficacy against MC38 syngeneic tumor model in combination with anti-PD1.
- GC63317 HPK1-IN-8 HPK1-IN-8 is an allosteric, inactive conformation-selective inhibitor of full-length HPK1.
- GC63059 MAP4K4-IN-3 MAP4K4-IN-3 (Compound 17) is a potent and selective MAP4K4 inhibitor with an IC50 of 14.9 nM in kinase assay, an IC50 of 470 nM in cell assay.
- GC19260 NCB-0846 NCB-0846 is an orally available TNIK inhibitor with an IC50 of 21 nM.
- GC13514 NG25 An inhibitor of MAP4K2 and TAK1
- GC50252 PF 06260933 dihydrochloride MAP4K4 (HGK) inhibitor; also inhibits MINK and TNIK
- GC31675 PF-06260933 PF-06260933 is an orally active and highly selective inhibitor of MAP4K4 with IC50s of 3.7 and 160 nM for kinase and cell, respectively.
- GC50295 TL4-12 Potent MAP4K2 (GCK) inhibitor