Estrogen receptor modulators, selective

More recently, another SERM, known as raloxifene (Evista), was developed. Raloxifene is similar to tamoxifen except that it blocks estrogen receptors on breast and uterine tissues and may therefore produce beneficial effects (inhibiting breast cancer, improving bone and cardiovascular function) without increasing the risk of endometrial cancers.30,51,57 Raloxifene is currently approved for treating osteoporosis, and the use of this drug is associated with increased vertebral bone density and a reduced risk of vertebral fractures.30,77 

As indicated, raloxifene may also reduce the incidence of breast and uterine cancers.20,57 This drug may cause several bothersome side effects, including hot flashes, joint or muscle pain, depression, insomnia, and gastrointestinal disturbances. More serious problems with raloxifene may be indicated by symptoms 

Efforts continue to develop other SERMs that will capitalize on the beneficial effects of estrogen while minimizing or even reducing the carcinogenic effects of estrogen on other tissues. As newer agents are developed, SERMs may have an expanded role in the treatment of various diseases and perhaps provide a safer and more effective method of estrogen replacement.54,59 

---

Selective estrogen receptor modulators (SERMs) are synthetic compounds with partially agonistic and partially antagonistic estrogenic properties. In bone, SERMs inhibit bone resorption via the mechanisms known for estrogens. Major SERMs are tamoxifen, a triphenylethylene compound, and raloxifene. In postmenopausal women, the latter has been shown to prevent bone loss and to reduce fracture risk by 40%. 

BRZEZiNSKi A and DEBI A (1999) Ph)4oestrogens the natural selective estrogen receptor modulators Eur J Obstet Gynecol Reprod Biol. 85 (1) 47-51. 

SETCHELL K D (2001) Soy isoflavones-benefits and risks from nature s selective estrogen receptor modulators (SERMs). J Am Coll Nutr. 20 (5 Suppl) 354S-362S. 

Liu, H. Liu, J. van Breemen, R. B. Thatcher, G. R. Bolton, J. L. Bioactivation of the selective estrogen receptor modulator desmethylated arzoxifene to quinoids 4 -fhioro substitution prevents quinoid formation. Chem. Res. Toxicol. 2005, 18, 162-173. 

DVT, deep vein thrombosis HIT, heparin-induced thrombocytopenia PAI-I, plasminogen activator inhibitor PE, pulmonary embolism SERM, selective estrogen receptor modulator VTE, venous thromboembolism. 

GP glycoprotein SERM selective estrogen receptor modulator... 

SERM, selective estrogen receptor modulator SERD, selective estrogen receptor down regulator LHRH, luteinizing hormone-releasing hormone. 

In conclusion, we have developed an efficient asymmetric synthesis of the selective estrogen receptor modulator 1. This process was scaled up in the pilot plant for the early steps in the synthetic route and in kilo laboratory scale for the later steps and finally 4 kg of the final product was made. The key process development and project support milestones are summarized below ... 

Zajchowski DA et al. Identification of selective estrogen receptor modulators by their gene expression fingerprints. J Biol Chem 2000 275 15885-15894. 

Hypercoagulable states include malignancy activated protein C resistance deficiency of protein C, protein S, or antithrombin factor VIII or XI excess antiphospholipid antibodies and other situations. Estrogens and selective estrogen receptor modulators have been linked to venous thrombosis, perhaps due in part to increased serum clotting factor concentrations. Although a thrombus can form in any part of the venous circulation, the majority of thrombi begin in the lower extremities. Once formed, a venous... 

Selective estrogen-receptor modulators prevent bone loss and vertebral ... 

---