brusatol

Brusatol is a natural quassinoid compound primarily extracted from the seeds of Brucea javanica and Brucea sumatrana, plants used in traditional Chinese medicine[2][4][5]. It is best known as a potent inhibitor of nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor that regulates cellular antioxidant responses. By inhibiting Nrf2 signaling, brusatol sensitizes cancer cells to chemotherapeutic agents and promotes apoptosis. Brusatol exhibits broad biological activities including antitumor (notably in colorectal cancer, glioblastoma, pancreatic cancer), antileukemia, anti-inflammatory, antimalarial, antiparasitic (antitrypanosomal), antibacterial and antiviral effects[1][2][3][4][5]. Mechanistically it blocks cell proliferation and cycle progression; induces apoptosis and autophagy; suppresses angiogenesis; inhibits tumor invasion/metastasis; reverses multidrug resistance; inhibits protein synthesis non-selectively[1][3][8]. Recent research also suggests activity against TGF-β signaling via TGFβRII inhibition in some cancers[5], as well as activation of the IL-22/STAT3 pathway for mucosal healing in ulcerative colitis models[5]. Brusatol’s clinical development has been limited by its short-lived effect on Nrf2 and potential toxicity due to non-selective protein synthesis inhibition. Nanoparticle formulations are being explored to improve delivery and reduce toxicity[8].

Other names

brusatolYa-Dan-Zi (Chinese name)quassinoid from Brucea javanica