New selective estrogen receptor modulators (SERMs) in development.
Selective estrogen receptor modulators (SERMs) or estrogen agonists/antagonists have shown promise in osteoporosis in that they have the potential to reduce the risk of fracture, and also reduce the risk of breast cancer. SERMs maybe classified according to their core structure, which is typically a variation of the 17 beta-estradiol template and subclassified according to the side chain at the helix 12 affector region. The best known are the triphenylethylenes such as tamoxifen, used in the management of breast cancer. However, the clinical application of this class of SERMs has been limited due to endometrial stimulation. A second class is the benzothiophenes such as raloxifene and arzoxifene, which have skeletal benefit with little, if any, uterine stimulation. Indole-based SERMs such as bazedoxifene have a 2-phenyl ring system that serves as a core binding unit. Other classes include benzopyrans and naphthalenes (eg, lasofoxifene). In this review article, I will discuss raloxifene and three new SERMs--arzoxifene, bazedoxifene, and lasofoxifene--that have been recently studied. I will discuss their effect on bone, breast, and the cardiovascular system, as well as on safety.
Silverman
Stuart L
SL
Cedars-Sinai/UCLA, 8641 Wilshire Boulevard, Suite 301, Beverly Hills, CA 90211, USA. stuarts@omcresearch.org
D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000453:epidemiology / Q000517:prevention & control; D005260:Female; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use; D010024:Osteoporosis / Q000188:drug therapy*; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use; D011759:Pyrrolidines / Q000009:adverse effects / Q000627:therapeutic use; D012307:Risk Factors; D020845:Selective Estrogen Receptor Modulators / Q000009:adverse effects / Q000627:therapeutic use*; D013764:Tetrahydronaphthalenes / Q000009:adverse effects / Q000627:therapeutic use; D013876:Thiophenes / Q000009:adverse effects / Q000627:therapeutic use
D050071:Bone Density Conservation Agents; D007211:Indoles; D010880:Piperidines; D011759:Pyrrolidines; D020845:Selective Estrogen Receptor Modulators; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; C111332:Lasofoxifene; C115121:LY 353381; C447119:bazedoxifene