Chemical Properties
Light-Yellow Solid
Uses
A nonsteroidal estrogen receptor mixed agonist/antagonist
Definition
ChEBI: A member of the class of 1-benzothiophenes that is 1-benzothiophene in which the hydrogens at positions 2, 3, and 6 have been replaced by p-hydroxyphenyl, p-[2-(piperidin-1-yl)ethoxy]benzoyl, and hydroxy groups, respectively.
Indications
Raloxifene (Evista) is a new SERM approved for
use in the treatment and prevention of osteoporosis because
it has estrogenic activity in bone. Raloxifene is an
estrogen antagonist in both breast and endometrial tissues.
The estrogenlike properties of raloxifene result in
the maintenance of a favorable serum lipid profile (decreased
low-density lipoprotein levels with no change
in either high-density lipoproteins or triglycerides).
Raloxifene is 95% bound to plasma proteins. Absorption
of raloxifene is impaired by cholestyramine.
Brand name
Evista (Lilly).
General Description
Raloxifene, [6-hydroxy-2-(4-hydroxyphenyl)benzo[b]thien-3-yl][4-[2-(1-piperidinyl)ethoxy]phenyl]methanone (Evista), is a benzothiophene derivativethat differs slightly from the triphenylethyleneSERMs. A key structural difference is the carbonyl “hinge”that connects the modified phenolic side chain to the benzothiophenering system. This hinge is the key structural elementthat leads to the differing actions at the ERs.Raloxifene, unlike tamoxifen and toremifene, has antagonistproperties on the endometrium and breast tissue and agonistproperties on bone and the cardiovascular system. The lackof agonist action on endometrial tissue has been suggestedas a reason for the lack of endometrial cancer associatedwith raloxifene use. Raloxifene is approved for the preventionand treatment of osteoporosis in postmenopausalwomen. It has also been investigated for preventing breastcancer in comparison with tamoxifen. Recent studies indicatesthat it has similar effectiveness to tamoxifen, but has apreferable side effect profile.
Biological Activity
Selective estrogen receptor modulator (SERM) that binds to ER α and ER β , and tissue-dependently activates or blocks estrogen-induced transcription. Acts as an antiestrogen in breast and uterine tissue, but displays estrogen agonist activity in bone. In D12 rat hypothalamic cells, inhibits progesterone receptor induction by estrogen with an IC 50 of 1 nM.
Clinical Use
Raloxifene, the first SERM
approved for the prevention of osteoporosis in postmenopausal women, acts as an estrogen agonist on
receptors in osteoblasts and osteoclasts but as an antagonist at breast and uterine estrogen receptors.
