picropodophyllin

Picropodophyllin is a small molecule cyclolignan alkaloid derived from the mayapple plant family (Podophyllum peltatum) and functions as a potent and selective inhibitor of the insulin-like growth factor 1 receptor (IGF1R). It exhibits antineoplastic activity by specifically inhibiting IGF1R activity and downregulating its cellular expression without affecting other growth factor receptors such as those for insulin, epidermal growth factor, platelet-derived growth factor, fibroblast growth factor, or mast/stem cell growth factor. Picropodophyllin induces apoptosis and mitotic arrest in cancer cells through both IGF-1R-dependent and independent mechanisms. Mechanistically, it suppresses IGF-1R signaling pathways including PI3K/Akt, increases reactive oxygen species (ROS) generation leading to cell cycle arrest at mitosis via interference with microtubule dynamics rather than direct tubulin binding. The drug has been investigated primarily for non-small cell lung cancer (NSCLC), malignant astrocytoma, multiple myeloma, uveal melanoma, rhabdomyosarcoma, and other solid tumors. Axelar has been identified as a developer of this compound.

Other names

picropodophyllotoxin