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