englerin A

Englerin A is a natural guaiane-type sesquiterpene glycolate originally isolated from the East African plant *Phyllanthus engleri*. It gained significant attention due to its potent and highly selective cytotoxicity against renal cell carcinoma (RCC) cell lines in the NCI-60 screening panel, often exhibiting IC50 values in the low nanomolar range. Mechanistically, Englerin A acts as a potent agonist of the TRPC4 and TRPC5 (Transient Receptor Potential Canonical) ion channels, leading to a lethal influx of calcium and sodium into sensitive cells. Research also indicates it activates Protein Kinase C (PKC) isoforms, which subsequently inhibits the insulin/PI3K/Akt survival pathway through the inhibitory phosphorylation of Insulin Receptor Substrate 1 (IRS1). While it has shown promising anti-tumor activity in preclinical xenograft models, its development has primarily remained in the research and preclinical stages.

Other names

EA