Raloxifene HCl (also known as LY-156758; LY-139481; trade names: Evista; Keoxifene; RALOX), the hydrochloride salt of Raloxifene, is a selective estrogen antagonist or estrogen strogen receptor modulator (SERM) that has been approved as a medication to prevent and treat osteoporosis in postmenopausal women. It inhibits human cytosolic aldehyde oxidase-catalyzed phthalazine oxidation activity with an IC50 of 5.7 nM. Raloxifene belongs to the benzothiophene class of estrogen strogen receptor modulator (SERM). Raloxifene binds to estrogen receptors as a mixed estrogen agonist/antagonist; it displays both an ER-α-selective partial agonist/antagonist effect and a pure ER-ss-selective antagonist effect.
理化性质和储存条件
| Molecular Weight (MW) | 510.04 |
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| Formula | C28H27NO4S.HCl |
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| CAS No. | 82640-04-8 |
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| Storage | -20℃ for 3 years in powder form |
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| -80℃ for 2 years in solvent |
| Solubility (In vitro) | DMSO: 100 mg/mL (196.1 mM) |
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| Water: <1 mg/mL |
| Ethanol: <1 mg/mL |
| Solubility (In vivo) | 1% methylcellulose: 30mg/mL |
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| Synonyms | LY-156758; LY-139481; LY 156758; LY139481; LY156758 (Keoxifene) HCl; LY 139481; trade names: Evista; Keoxifene; RALOX
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实验参考方法
| In Vitro | In vitro activity: Raloxifene, has been demonstrated as a potent uncompetitive inhibitor of human liver aldehyde oxidase-catalyzed oxidation of phthalazine, vanillin, and nicotine-Delta1'(5')-iminium ion, with Ki values of 0.87 nM, 1.2 nM and 1.4 nM. Raloxifene has also been shown to be a noncompetitive inhibitor of an aldehyde oxidase-catalyzed reduction reaction of a hydroxamic acid-containing compound, with a Ki of 51 nM. Raloxifene activates TGF beta 3 promoter as a full agonist at nanomolar concentrations, and raloxifene inhibits the estrogen response element-containing vitellogenin promoter expression as a pure estrogen antagonist in transient transfection assays. |
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| In Vivo | Raloxifene restores both bone mineral density and TGF beta 3 messenger RNA expression in the femur to levels measured in intact rats. Raloxifene (0.1 mg/kg-10 mg/kg, orally for 5 weeks) increases bone mineral density in the distal femur and proximal tibia in ovariectomized (OVX) rat. Raloxifene reduces serum cholesteroloral with ED50 of 0.2 mg/kg in ovariectomized (OVX) rat. Raloxifene diverges dramatically from estrogen in its lack of significant estrogenic effects on uterine tissue. Raloxifene prevents cancellous osteopenia as well as the changes in radial bone growth, bone resorption, and blood cholesterol, but is less effective in reducing cancellous bone formation and does not prevent uterine atrophy in ovariectomized (OVX) rats. Raloxifene (3 mg/kg/day) has potent estrogenic activity on bone resorption and serum cholesterol, a lesser effect on bone formation, and minimal activity on uterine wet weight in ovariectomized (OVX) rats. |
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| Animal model | Ovariectomized (OVX) rat |
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| Formulation & Dosage | Dissolved in 1.5% carboxymethylcellulose; 10 mg/kg; Oral gavage |
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| References | Drug Metab Dispos. 2004 Jan;32(1):89-97; Endocrinology. 1996 May;137(5):2075-84. |
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