2. Signaling Pathways
  3. MAPK/ERK Pathway
  4. MAP4K
  5. MAP4K2/GCK Isoform

MAP4K2/GCK

MAP4K2/GCK encodes a serine/threonine kinase preferentially expressed in germinal center B cells and other tissues[1]. Mechanistically, GCK activates the mammalian SAPK/JNK pathway and links inflammatory stimuli such as TNF and interleukin-1 to c-Jun signaling[2]. In TNF signaling, GCK associates with TRAF2 and MEKK1, providing a route from receptor-adaptor complexes to stress-activated MAPK signaling[3]. In the Hippo pathway, MAP4K family kinases, including MAP4K2/GCK, directly activate LATS1/2 and regulate YAP/TAZ phosphorylation in parallel with MST1/2[4]. In disease models, GCK has been evaluated as a molecular therapeutic target in diffuse large B-cell lymphoma, while MAP4K2 promotes FOXP3 expression and Treg differentiation in pancreatic cancer models[5][6]. Compared with related MAP4K isoforms, MAP4K2 is distinguished by its original germinal-center localization, TRAF2-MEKK1 coupling, and inclusion among MAP4K1/2/3 LATS1/2-activating kinases[1][3][4]. For experimental applications, type II kinase-inhibitor studies identified 4-substituted 1H-pyrrolo[2,3-b]pyridines with potent activity against TAK1 and MAP4K2[7].

MAP4K2/GCK Related Products (8):

Cat. No. Product Name Effect Purity
  • HY-15434
    NG25
    		Inhibitor 98.68%
    NG25 is a potent dual TAK1 and MAP4K2 inhibitor, with IC50s of 149 nM and 21.7 nM, respectively.
  • HY-111754
    DMX-5804
    		Inhibitor 99.83%
    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). DMX-5804 enhances cardiomyocyte survival, and reduces ischemia-reperfusion injury in mice.
  • HY-77251
    TAK1/MAP4K2 inhibitor 1
    		Inhibitor 99.91%
    TAK1/MAP4K2 inhibitor 1 is a potent dual TGFβ-activated kinase 1 (TAK1) and mitogen-activated protein kinase kinase kinase kinase 2 (MAP4K2) inhibitor, with IC50s of 41.1 nM and 18.2 nM, respectively.
  • HY-148061
    DB1113
    		99.86%
    DB1113 (Example 24) is a bifunctional compound targeted protein degradation of kinases. DB1113 degrades ABL1, ABL2, BLK, CDK11B, CDK4, CSK, EPHA3, FER, GAK, LIMK1, MAP3K20, MAP4K1, MAP4K2, MAP4K3, MAP4K5, MAPK14, MAPK7, MAPK8, MAPK9, MAPKAPK2, MAPKAPK3, NLK, PDIK1L, PTK2B, RIPK1, RPS6KA1, RPS6KA3, SIK2, SIK3, STK35, TNK2, and ULK1. DB1113 can be used for research of disease or disorder mediated by aberrant kinase activity.
  • HY-137342
    SB1-G-187
    		Degrader 98.70%
    SB1-G-187 is a multi-target kinase PROTAC degrader with activity against various kinases including GCK, YES1, IRAK1 and LYN. SB1-G-187 induces degradation of target kinases via a p97-dependent pathway, and forms ternary complexes with CRBN and specific functional kinases. SB1-G-187 can be used in tumor-related research. (Pink: multi-target kinase ligand (HY-125142); Blue: CRBN ligand (HY-A0003); Black: linker).
  • HY-178097
    HPK1-IN-62
    		Inhibitor
    HPK1-IN-62 is a selective and orally active HPK-1 inhibitor with an IC50 of 1.22 nM. HPK1-IN-62 significantly improves GLK selectivity (> 665-fold) and LCK selectivity (> 1095-fold). HPK1-IN-62 enhances T-cell activation and demonstrated synergistic effects when combined with anti-mPD-1 therapy in the MC38 tumor model, inhibiting a tumor growth. HPK1-IN-62 can be used in the researchs of colon cancer and cancer immunotherapy.
  • HY-172107
    HPK1-IN-56
    		Inhibitor
    HPK1-IN-56 (Compound A29) is a HPK1 inhibitor (IC50: 2.70 nM). HPK1-IN-56 inhibits downstream p-SLP76 (IC50: 8.1 nM in Jurkat T cells). HPK1-IN-56 induces the production of IL-2 in human PBMCs. HPK1-IN-56 has anticancer effect, enhances T-cell killing ability and the antitumor efficacy of anti-PD-1 antibody.
  • HY-168110
    HPK1-IN-52
    		Inhibitor
    HPK1-IN-52 is a potent and orally active hematopoietic progenitor kinase 1 (HPK1) inhibitor with an IC50 value of 10.4 nM. HPK1-IN-52 exhibits anti-tumor activities.