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].
References:
- [1]. Katz P, et al. Differential expression of a novel protein kinase in human B lymphocytes. Preferential localization in the germinal center. J Biol Chem. 1994 Jun 17;269(24):16802-9. [Content Brief]
- [2]. Pombo CM, et al. Activation of the SAPK pathway by the human STE20 homologue germinal centre kinase. Nature. 1995 Oct 26;377(6551):750-4. [Content Brief]
- [3]. Chadee DN, et al. Direct activation of mitogen-activated protein kinase kinase kinase MEKK1 by the Ste20p homologue GCK and the adapter protein TRAF2. Mol Cell Biol. 2002 Feb;22(3):737-49. [Content Brief]
- [4]. Meng Z, et al. MAP4K family kinases act in parallel to MST1/2 to activate LATS1/2 in the Hippo pathway. Nat Commun. 2015 Oct 5;6:8357. [Content Brief]
- [5]. Matthews JM, et al. Pathophysiological significance and therapeutic targeting of germinal center kinase in diffuse large B-cell lymphoma. Blood. 2016 Jul 14;128(2):239-48. [Content Brief]
- [6]. Chuang HC, et al. MAP4K2 suppresses antitumor immunity in a pancreatic cancer model by promoting Treg differentiation. J Clin Invest. 2026 Jan 29;136(6):e196379. [Content Brief]
- [7]. Tan L, et al. Discovery of type II inhibitors of TGFβ-activated kinase 1 (TAK1) and mitogen-activated protein kinase kinase kinase kinase 2 (MAP4K2). J Med Chem. 2015 Jan 8;58(1):183-96. [Content Brief]
All Product Categories
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MAP4K2/GCK Related Products (10)
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NG25
0 ImagesNG25 is a potent dual TAK1 and MAP4K2 inhibitor, with IC50s of 149 nM and 21.7 nM, respectively. -
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DMX-5804
0 ImagesDMX-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. -
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TAK1/MAP4K2 inhibitor 1
0 ImagesTAK1/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. -
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DB1113
0 ImagesDB1113 (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. -
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SB1-G-187
0 ImagesSB1-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. -
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HPK1-IN-62
0 ImagesCat. No.: HY-178097HPK1-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. -
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HPK1-IN-56
0 ImagesCat. No.: HY-172107CAS No.: 2901054-39-3HPK1-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. -
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HPK1-IN-52
0 ImagesCat. No.: HY-168110CAS No.: 2994298-66-5HPK1-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. -
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- Multi kinase ligand 4
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