Definition

The sodium salt dihydrate form of crystalline genistein, a soy-derived isoflavone and phytoestrogen, with potential antineoplastic, chemosensitizing, and antioxidant activities. Upon administration, crystalline genistein formulation AXP107-11 binds to and modulates the activities of the nuclear estrogen receptors ERalpha (ESR1) and ERbeta (ESR2), and activates the G-coupled estrogen receptor 1 (GPER1). In addition, this agent increases the expression of phosphatase and tensin homolog (PTEN), which deactivates protein kinase Akt and mitogen-activated protein kinases (MAPK1 and 3; ERK2 and 1), thereby disrupting PI3K/Akt signal transduction and inducing apoptosis. AXP107-11 also induces antioxidant enzymes through AMP-activated protein kinase (AMPK) activation, inhibits nuclear factor kappa-B (NF-kB) activation and decreases inflammation response, thereby sensitizing tumors to chemotherapy. Compared to genistein itself, which has poor oral availability, this crystalline formulation shows improved solubility and bioavailability.