gamabufotalin

Gamabufotalin is a major bufadienolide isolated from the Traditional Chinese Medicine *Chansu* (toad venom). It exhibits potent anti-cancer activity by inhibiting cancer cell growth, promoting apoptosis, and suppressing angiogenesis. Mechanistically, it inhibits COX-2 expression by targeting IKKβ at the ATP-binding site, thereby blocking NF-κB-mediated transcriptional activation. It also induces apoptosis via the cytochrome c and caspase-dependent pathway. Additionally, gamabufotalin blocks VEGF-induced angiogenesis by interacting with and inhibiting the kinase domain of vascular endothelial growth factor receptor 2 (VEGFR-2)[1][3][4][6]. It shows synergistic effects when combined with temozolomide in glioblastoma models, partially through activating ATP1A3 and affecting the ATP1A3/AQP4 axis[6]. Other studied targets include c-Myc degradation (via WWP2 induction)[3]. Primary indications studied in preclinical models are cancers such as multiple myeloma, breast cancer, lung cancer, and glioblastoma.

Other names

gamabufagingamabufogeningammabufotalin3,11,14-trihydroxybufa-20,22-dienolide3β,11α,14-Trihydroxy-5β-bufa-20,22-dienolide