MAP4K2 inhib 
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  • ||||||||||  Mekinist (trametinib) / Novartis, BeiGene, BAY-61-3606 / Bayer
    Dual targeting of the RAS-MAPK pathway as a personized medicine approach in RASMut multiple myeloma (Exhibit Hall, Pavilion 3) -  Sep 26, 2024 - Abstract #IMW2024IMW_555;    
    Our data lay the foundation for personalized treatment of RASMut MM patients, particularly relevant for patients who have failed immunotherapy. The synergistic treatment approach of targeting MAP4K2 and MEK in RASMut MM warrants further investigation in an in vivo setting to validate our findings and potentially translate them into clinical practice.
  • ||||||||||  Journal:  Baicalin restore intestinal damage after early-life antibiotic therapy: the role of the MAPK signaling pathway. (Pubmed Central) -  May 30, 2024   
    Conversely, baicalin supplementation not only counteracted these effects but also enhanced beneficial metabolites and regulated genes within the MAPK signaling pathway (MAP3K11, MAP4K2, MAPK7, MAPK13) and calcium channel proteins (ORA13, CACNA1S, CACNA1F and CACNG8), suggesting a mechanism through which baicalin mitigates antibiotic-induced intestinal and microbial disturbances. These findings highlight baicalin's potential as a plant extract-based intervention for preventing antibiotic-related intestinal injury and offer new targets for therapeutic strategies.
  • ||||||||||  Journal:  MAP4K2 connects the Hippo pathway to autophagy in response to energy stress. (Pubmed Central) -  Mar 11, 2024   
    Moreover, MAP4K2 is highly expressed in head and neck cancer, while MAP4K2 and its mediated autophagy are required for head and neck cancer development. Taken together, our study not only reveals a noncanonical role of the Hippo pathway in energy stress response, but also suggests Hippo kinase MAP4K2 as a potential therapeutic target for head and neck cancer treatment.
  • ||||||||||  Journal:  Stressed Hippo kinase turns to autophagy. (Pubmed Central) -  Sep 30, 2023   
    Taken together, our study not only reveals a noncanonical role of the Hippo pathway in energy stress response, but also suggests Hippo kinase MAP4K2 as a potential therapeutic target for head and neck cancer treatment. The Hippo kinase MAP4K2 takes a YAP-independent path to tolerating energy stress.
  • ||||||||||  Journal:  Potent and Selective Biaryl Amide Inhibitors of Hematopoietic Progenitor Kinase 1 (HPK1). (Pubmed Central) -  Jan 20, 2023   
    Structure-activity relationship development, aided by molecular modeling, identified indazole 5b as a core for further exploration because of its outstanding enzymatic and cellular potency coupled with encouraging kinome selectivity. Late-stage manipulation of the right-hand aryl and amine moieties surmounted issues of selectivity over TRKA, MAP4K2, and STK4 as well as generating compounds with balanced in vitro ADME profiles and promising pharmacokinetics.
  • ||||||||||  Journal:  CircRNA PDE3B regulates tumorigenicity via the miR-136-5p/MAP3K2 axis of esophageal squamous cell carcinoma. (Pubmed Central) -  Dec 20, 2022   
    Late-stage manipulation of the right-hand aryl and amine moieties surmounted issues of selectivity over TRKA, MAP4K2, and STK4 as well as generating compounds with balanced in vitro ADME profiles and promising pharmacokinetics. In conclusion, circ_PDE3B acted as oncogenic circRNA in ESCC and accelerated ESCC progression by adsorption of miR-136-5p and activation of MAP3K2, supporting circ_PDE3B as a potential therapeutic target for ESCC.
  • ||||||||||  Journal:  E3 ubiquitin ligase NEDD4L negatively regulates inflammation by promoting ubiquitination of MEKK2. (Pubmed Central) -  Nov 9, 2022   
    Importantly, Nedd4l-deficient mice show increased susceptibility to IL-17-induced inflammation and aggravated symptoms of experimental autoimmune encephalomyelitis (EAE) in IL-17R signaling-dependent manner. These data suggest that NEDD4L acts as an inhibitor of IL-17R signaling, which ameliorates the pathogenesis of IL-17-mediated autoimmune diseases.
  • ||||||||||  iberdomide (CC-220) / BMS
    Overcoming IMiDs-resistance in multiple myeloma by targeting MAP4K2 () -  Aug 13, 2022 - Abstract #IMW2022IMW_345;    
    Taken together, our findings demonstrate that MAP4K2 is a novel therapeutic target to bypass IMiDs resistance in RAS mutated MM. The combination of MAP4K2 inhibition with Iberdomide results in synergetic anti-cancer effects in MM, therefore could be a potential novel therapeutic regimen for patients with relapsed/refractory multiple myeloma.
  • ||||||||||  Journal:  MAP3K2 augments Th1 cell differentiation via IL-18 to promote T cell-mediated colitis. (Pubmed Central) -  Dec 30, 2021   
    At the molecular level, we showed that MAP3K2-mediated Th1 cell differentiation in the intestine was regulated by IL-18 and required specific JNK activation. Together, our study reveals a novel regulatory role of MAP3K2 in intestinal T cell immunity via the IL-18-MAP3K2-JNK axis and may provide a novel target for intervention in T cell-mediated colitis.
  • ||||||||||  Journal:  miR‑3613‑3p/MAP3K2/p38/caspase‑3 pathway regulates the heat‑stress‑induced apoptosis of endothelial cells. (Pubmed Central) -  Dec 16, 2021   
    Taken together, the results of the present study demonstrated that HS suppressed miR‑3613‑3p expression, which activated the MAP3K2/p38/caspase‑3 pathway, leading to the apoptosis of HUVECs. In conclusion, the miR‑3613‑3p/MAP3K2/p38/caspase‑3 pathway may serve an indispensable role in regulating the progression of apoptosis, indicating a regulatory role of miR‑3613‑3p in the pathophysiology of HS‑exposed endothelial cells.
  • ||||||||||  lenalidomide / Generic mfg.
    MAP4K2 Silencing Overcomes IMiDs-Resistance in Multiple Myeloma (GWCC - Hall B5, Level 1) -  Nov 5, 2021 - Abstract #ASH2021ASH_4302;    
    Previous biochemical and structural studies demonstrated that Iberdomide binds to cereblon with a higher affinity than lenalidomide or pomalidomide...To address the combination effects, Tet-on sh-MAP4K2 RAS Mut MM cells were treated with doxycycline and different dosages of iberdomide...Taken together, our findings demonstrate that MAP4K2 is a novel therapeutic target to bypass IMiDs resistance in RAS mutated MM. Combination of MAP4K2 inhibition with Iberdomide results in synergetic anti-cancer effects in MM, therefore could be a potent novel therapeutic regimen for patients with relapsed/refractory multiple myeloma.
  • ||||||||||  Revlimid (lenalidomide) / BMS
    Targeting GCK in RAS-mutant multiple myeloma offer a promising therapeutic approach () -  Aug 21, 2021 - Abstract #IMW2021IMW_214;    
    Importantly, GCK inhibition downregulates IKZF1 via a CRBN-independent mechanism. Our findings thus provide a rationale for the clinical evaluation of targeting GCK in RASmut MM patients and further mechanistic insight into the role of GCK in MM tumorigenesis as well as drug resistance.
  • ||||||||||  Votrient (pazopanib) / Novartis
    Journal:  Pazopanib ameliorates acute lung injuries via inhibition of MAP3K2 and MAP3K3. (Pubmed Central) -  Jul 14, 2021   
    This myeloid MAP3K2/MAP3K3-p47 pathway acted via paracrine HO to enhance pulmonary vasculature integrity and promote lung epithelial cell survival and proliferation, leading to increased pulmonary barrier function and resistance to ALI. Thus, pazopanib has the potential to be effective for treating ALI.
  • ||||||||||  Clinical, Journal:  Machine Learning for Building Immune Genetic Model in Hepatocellular Carcinoma Patients. (Pubmed Central) -  Apr 2, 2021   
    The immune-risk model, based on expression of SPP1, BRD8, NDRG1, KITLG, HSPA4, TRAF3, ITGAV, and MAP4K2, can better differentiate patients into high and low immune-risk groups. Combined nomogram, using immune-risk score and tumor stages, could make accurate prediction of 1-, 3- and 5-year survival in HCC patients.