cucurbitacin I

Cucurbitacin I (JSI-124) is a synthetic small molecule that potently and selectively inhibits the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway. It acts as an anticancer agent by downregulating phosphorylated-STAT3 and inhibiting JAK2 activity, which leads to apoptosis, autophagy, and G2/M cell cycle arrest in various tumor types, including glioblastoma, breast cancer, ovarian cancer, anaplastic large cell lymphoma, and malignant pleural mesothelioma. JSI-124 exerts its pro-apoptotic effects via multiple mechanisms, including activation of caspase-3-dependent apoptosis, downregulation of anti-apoptotic proteins like Bcl-2 family members and survivin, inhibition of Aurora kinases, and modulation of the NF-κB pathway. JSI-124 also inactivates cancer-associated fibroblasts, inhibits epithelial-to-mesenchymal transition (EMT), and impairs tumor cell migration and invasion, highlighting its promise as a versatile targeted therapeutic for cancers characterized by STAT3 hyperactivation[1][3][5][6].

Other names

JSI-124JSI124JSI 124cucurbitacin I