JDB153

JDB153 is a novel small molecule that acts as a dual inhibitor of mitogen-activated protein kinase-interacting kinases (MNK) and vascular endothelial growth factor receptor 2 (VEGFR2). By targeting the MNK-eIF4E axis, JDB153 inhibits the phosphorylation of the eukaryotic initiation factor 4E (eIF4E), a key regulator of ribosomal protein translation that is frequently dysregulated in oncogenic processes. Simultaneously, its inhibition of VEGFR2 suppresses tumor angiogenesis, a critical component of cancer progression and metastasis. Preclinical studies and exploratory clinical trials have investigated its efficacy in treating solid tumors, including non-small cell lung cancer (NSCLC), hepatocellular carcinoma (HCC), and pancreatic ductal adenocarcinoma (PDAC), particularly as a sensitizing agent for chemotherapy and immune checkpoint inhibitors such as PD-1 antibodies.