Ask about this productRelated genes to: MAP4K4 antibody
- Gene:
- MAP4K4 NIH gene
- Name:
- mitogen-activated protein kinase kinase kinase kinase 4
- Previous symbol:
- -
- Synonyms:
- HGK, NIK, FLH21957
- Chromosome:
- 2q11.2
- Locus Type:
- gene with protein product
- Date approved:
- 1999-09-07
- Date modifiied:
- 2016-10-05
Related products to: MAP4K4 antibody
Related articles to: MAP4K4 antibody
- Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting side effect of cancer treatment, yet the lack of predictive human models continues to hinder therapeutic progress. Here, we establish a scalable and reproducible model of paclitaxel-induced axon degeneration and neurotoxicity in human iPSC-derived sensory neurons, suitable for high-throughput identification of neuroprotective compounds. Using this platform, we screen a library of 192 kinase inhibitors and identify 19 hits that commonly inhibit three STE20 kinases-MAP4K4, MINK1, and TNIK. Genetic knockdown studies reveal that multi-kinase inhibition of these kinases is required for neuroprotection against paclitaxel. Consistently, selective pharmacological inhibition of the identified STE20 kinases rescues paclitaxel-induced axon degeneration in iPSC-derived sensory neurons and primary human dorsal root ganglia (DRG) and preserves intraepidermal nerve fiber density in a mouse model of CIPN. Together, these findings establish a translational human sensory neuron platform that enables target validation and drug discovery for CIPN. - Source: PubMed
Publication date: 2026/05/06
Petrova VeselinaMills Caitlin EHug ClemensCetinkaya-Fisgin AyselSplaine JenniferFouladzadeh SepidehHakim SaraPowell RasheenZhen ShannonChung MirraBradshaw Gary ADeng TaoSingec IlyasWang QingKawaguchi RikiJonnagaddala HarathiBarrett Lee BSmith Jennifer AKalocsay MarianGyori Benjamin MHoke AhmetSorger Peter KWoolf Clifford J - Metabolic dysfunction-associated steatotic liver disease (MASLD) is a progressive condition and a leading driver of global liver-related morbidity. Its advanced form, metabolic dysfunction-associated steatohepatitis (MASH), is characterized by hepatic steatosis, inflammation, hepatocellular ballooning, and fibrosis. This study aimed to define the significance of MAP4K4 (mitogen-activated protein kinase kinase kinase kinase 4) as a therapeutic target and to evaluate a novel small-molecule inhibitor, glucosyl pyrrolo-pyrimidinone (GPPD), for the mitigation of MASH. - Source: PubMed
Publication date: 2026/05/04
Ampadu FelixPatil NikhilEeda VenkateswararaoRus IuliaJung WoncheolAbu Shukair Hassan MAli AnzaAguilar-Sanchez YurianaOh Tae GyuAwasthi VibhuduttaJoshi Aditya D - The incidence of obesity and male infertility continues to rise, and a complex pathophysiological association exists between the two. However, the comorbid molecular mechanisms remain incompletely elucidated. In this study, bioinformatics and machine learning methods were integrated to systematically explore the shared mechanisms of obesity and male infertility, and to predict natural compounds and TCMs with therapeutic potential based on multi-omics data. Datasets of male infertility and obesity were obtained from the GEO database, and 43 intersecting genes were identified through differential expression analysis. Using three machine learning algorithms, including random forest, least absolute shrinkage and selection operator(LASSO) regression, and support vector machine(SVM), five Hub genes(MAP4K4, GPT2, ADSSL1, PAIP2, and GINS3) were screened. The combined diagnostic model achieved an area under the curve(AUC) greater than 0.8, indicating good diagnostic performance. Functional enrichment analysis revealed that these genes are mainly involved in key biological processes such as amino acid metabolism, cell migration, and DNA replication. Immune infiltration analysis showed a significant upregulation of central memory CD4~+ T cells in both diseases, suggesting that chronic immune activation is an important basis for their comorbidity. Single-cell sequencing and pseudotime analyses demonstrated disordered cell differentiation trajectories in the adipose tissue of obese patients and the testicular tissue of infertile patients. Based on the connectivity map(CMap) database, ten natural compounds, including berberine, curcumin, and ginsenosides, were predicted and further validated by molecular docking to have strong binding affinities with the Hub genes. Integration with the traditional Chinese medicine systems pharmacology(TCMSP) platform enabled the construction of a "target-natural compound-herbal medicine" interaction network, identifying 38 corresponding herbal medicines. Property and meridian analysis indicated a predominance of warm nature, sweet flavor, and liver meridian tropism, consistent with the TCM therapeutic principles of "resolving phlegm and dampness, strengthening the spleen, and tonifying the kidney". This study reveals, at the molecular level, the comorbid mechanisms of obesity and male infertility in immune-inflammatory regulation and cell differentiation dysfunction, providing a theoretical basis and potential drug targets for precise TCM intervention in obesity-related male infertility. - Source: PubMed
Gong Zhuo-ZhiFeng Qiu-JianGao Qing-HeWang FuGuo JunLiu Sheng-Jing - Alternative splicing (AS) is increasingly recognized as a hallmark of cancer, contributing to tumor progression and therapeutic resistance. Zinc finger MYND-type containing 11 (ZMYND11), a critical reader of the histone modification H3.3K36me3, is frequently downregulated in various cancers. However, its specific role in regulating AS in prostate cancer (PCa) remains unclear. This study aimed to elucidate the mechanisms by which ZMYND11 modulates AS in PCa and evaluate its potential as a therapeutic target. - Source: PubMed
Publication date: 2025/02/14
Lian ChengWang ZixianGao XuWei Gong-Hong - The c-Jun N-terminal kinase (JNK) pathway is a central driver of fibrosis, inflammation, and neurodegeneration. While direct JNK inhibitors have shown therapeutic promise, achieving high isoform selectivity remains a significant medicinal chemistry challenge. Furthermore, targeting the upstream 'gatekeepers' MKK4 and MKK7 offers a distinct mechanism to modulate pathway output with greater precision. Consequently, medicinal chemistry efforts have shifted upstream to the dual-specificity kinases MKK4 and MKK7. This review critically evaluates the structural biology and pharmacological evolution of small-molecule inhibitors targeting these nodes. We contrast the distinct therapeutic landscapes of the two kinases: while MKK4 inhibition has emerged as a breakthrough strategy for unlocking liver regeneration (exemplified by the first-in-class clinical candidate HRX215), MKK7 inhibition is primarily pursued for its anti-fibrotic and anti-inflammatory potential. Special attention is given to structure-based design strategies, including the exploitation of the unique hinge-region cysteine (Cys218) for MKK7-specific covalent targeting and the optimization of scaffold selectivity against off-targets like BRAF. Finally, we discuss emerging modalities, such as PROTACs and dual inhibitors, outlining a roadmap for the next generation of precision therapeutics targeting the MKK-JNK axis. - Source: PubMed
Publication date: 2026/02/15
Zhao MinLi BaojianGao YingLiang YanShao NanqiShi XinboLi Jie