Raloxifene 4′-β-D-Glucuronide Lithium Salt (CAS 182507-22-8 (free base))

Raloxifene 4′-Glucuronide (4′-RG) is a glucuronide metabolite derived from raloxifene, a selective estrogen receptor modulator (SERM) utilized in the prevention and treatment of osteoporosis in postmenopausal women. 4′-RG, the primary metabolite of raloxifene in humans, is believed to contribute significantly to the drug′s pharmacological effects. It acts as a potent agonist at the estrogen receptor β (ERβ) and exhibits various biochemical and physiological impacts. By binding to and activating the ERβ, 4′-RG initiates downstream signaling pathways involved in diverse cellular processes, including cell proliferation, apoptosis, and gene expression. It exerts notable effects on bone metabolism, promoting bone formation and inhibiting bone resorption. Additionally, it possesses anti-inflammatory, antioxidant, and anti-atherogenic properties. Raloxifene 4′-glucuronide is formed through the action of UDP-glucuronosyltransferase (UGT) isoforms, namely UGT1A1, UGT1A8, and UGT1A10, which convert raloxifene into its metabolite. It binds to the estrogen receptor with an IC50 value of 370 nM. Moreover, it demonstrates inhibitory effects on the voltage-gated potassium channel Kv4.3, reducing its activity by 6.2% and 20.1% at concentrations of 10 µM and 30 µM, respectively.