Wortmannin
PI3K/AKT pathway inhibitor; Inhibits PI3K and PLKs
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Wortmannin is a fungal metabolite that covalently binds to and inhibits phosphatidylinositol-3-kinases (PI3K) of class I, II, and III. Species-specific differences in the class II PI3Ks determine sensitivity with IC₅₀ = 5, 50, and 450 nM for Drosophila, mouse, and human, respectively (Fruman et al.; Wymann et al.; Okada et al.). Wortmannin also inhibits polo-like kinases (PLK) PLK1 and PLK3 with IC₅₀ = 24 and 49 nM, respectively (Liu et al. 2005; Liu et al. 2007). At high concentrations it can also inhibit other kinases such as mammalian target of rapamycin (mTOR), DNA-dependent protein kinase catalytic subunit (DNA-PKcs), phosphatidylinositol-4-kinase (PI4K), myosin light-chain kinase (MLCK), and mitogen-activated protein kinase (MAPK; Fruman et al.; Meyers & Cantley; Hartley et al.; Brunn et al.; Nakanishi et al.).
CANCER RESEARCH
- Exhibits cytotoxic activity on a number of human tumor cell lines in vitro, and anti-tumor activity in mouse xenografts of C3H mammary carcinoma and BxPC-3 pancreatic carcinoma cells (Schultz et al.; Yuan et al.).
