deguelin

Deguelin is a naturally occurring rotenoid compound classified as a **small molecule** isoflavone derivative within the rotenone family, primarily extracted from plants of the genera Derris, Lonchocarpus, and Tephrosia in the Fabaceae family[5][7]. It has demonstrated significant **anticancer activity** in preclinical studies, exerting its effects by inducing apoptosis, arresting the cell cycle, and inhibiting angiogenesis in a range of cancer types, including lung, gastric, breast, gallbladder, and colorectal carcinomas as well as B-cell chronic lymphocytic leukemia[1][4][7]. Deguelin functions mainly by **inhibiting the PI3K/AKT pathway** and acts as a specific **heat shock protein 90 (Hsp90) inhibitor**, binding to its ATP pocket and suppressing client protein function, notably affecting survivin and Cdk4[1][4][6]. It also inhibits **mTOR signaling**, decreases androgen receptor (AR) levels and nuclear localization in AR-expressing cancer cells, and suppresses glycolysis by inhibiting mitochondrial hexokinase-2 (HK2)[3][6]. Furthermore, deguelin is an inhibitor of mitochondrial complex I (ubiquinone oxidoreductase), contributing to mitochondrial dysfunction and cellular apoptosis[7]. Deguelin and its derivatives have shown effectiveness in various animal models for chemoprevention and treatment of malignancies; however, preclinical toxicology studies reveal a risk of neurotoxicity (including Parkinsonian-like effects at high concentrations), and potential toxicity to heart, lungs, and nerves, which has limited clinical development for human use[4][7][5]. To date, deguelin is used exclusively in research and preclinical studies; it is not approved for human therapeutic use.

Other names

(-)-deguelin(-)-cis-deguelin