| Stereochemistry | ACHIRAL |
| Molecular Formula | C28H27NO4S |
| Molecular Weight | 473.583 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
OC1=CC=C(C=C1)C2=C(C(=O)C3=CC=C(OCCN4CCCCC4)C=C3)C5=C(S2)C=C(O)C=C5
InChI
InChIKey=GZUITABIAKMVPG-UHFFFAOYSA-N
InChI=1S/C28H27NO4S/c30-21-8-4-20(5-9-21)28-26(24-13-10-22(31)18-25(24)34-28)27(32)19-6-11-23(12-7-19)33-17-16-29-14-2-1-3-15-29/h4-13,18,30-31H,1-3,14-17H2
| Molecular Formula | C28H27NO4S |
| Molecular Weight | 473.583 |
| Charge | 0 |
| Count |
MOL RATIO
1 MOL RATIO (average) |
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
Raloxifene (marketed as Evista by Eli Lilly and Company) is an oral selective estrogen receptor modulator (SERM) that has estrogenic actions on bone and anti-estrogenic actions on the uterus and breast. Raloxifene binds to estrogen receptors, resulting in differential expression of multiple estrogen-regulated genes in different tissues. Raloxifene produces estrogen-like effects on bone, reducing resorption of bone and increasing bone mineral density in postmenopausal women, thus slowing the rate of bone loss. The maintenance of bone mass by raloxifene and estrogens is, in part, through the regulation of the gene-encoding transforming growth factor-β3 (TGF-β3), which is a bone matrix protein with antiosteoclastic properties. Raloxifene activates TGF-β3 through pathways that are estrogen receptor-mediated but involve DNA sequences distinct from the estrogen response element. The drug also binds to the estrogen receptor and acts as an estrogen agonist in preosteoclastic cells, which results in the inhibition of their proliferative capacity. This inhibition is thought to contribute to the drug's effect on bone resorption. Other mechanisms include the suppression of the activity of the bone-resorbing cytokine interleukin-6 promoter activity. Raloxifene also antagonizes the effects of estrogen on mammary tissue and blocks uterotrophic responses to estrogen. By competing with estrogens for the estrogen receptors in reproductive tissue, raloxifene prevents the transcriptional activation of genes containing the estrogen response element. As well, raloxifene inhibits the estradiol-dependent proliferation of MCF-7 human mammary tumor cells in vitro. The mechanism of action of raloxifene has not been fully determined, but evidence suggests that the drug's tissue-specific estrogen agonist or antagonist activity is related to the structural differences between the raloxifene-estrogen receptor complex (specifically the surface topography of AF-2) and the estrogen-estrogen receptor complex. Also, the existence of at least 2 estrogen receptors (ERα, ERβ) may contribute to the tissue specificity of raloxifene. Raloxifene is indicated for the treatment and prevention of osteoporosis in postmenopausal women. It is also used for reduction of risk and treatment of invasive breast cancer, and it also reduces breast density. For either osteoporosis treatment or prevention, supplemental calcium and/or vitamin D should be added to the diet if daily intake is inadequate. Common adverse events considered to be drug-related were hot flashes and leg cramps.
CNS Activity
Originator
Approval Year
Doses
AEs
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
Drug as perpetrator
Drug as victim
Tox targets
Sourcing
Sample Use Guides
MCF-7 cells were obtained from the ATCC and grown in Growth Medium (GM). The cells are grown to 80% confluency and trypsinized and washed to remove phenol red, then plated at 10,000 cells/well in Starve Medium (SM). After 2 days, the medium is removed from the cells and either fresh SM or SM plus Raloxifene is added (100 mL total volume). The next day the bDNA assay is started by adding Capture Hybridization Buffer to each capture well of the bDNA plate (all solutions supplied with QuantiGene kit). Subsequently, medium is removed from the 96-well plate containing cells and then the solution of lysis buffer and oligomers (designed by ProbeDesigner 1.0 for the gene of interest) is added to the 96-well plate (100 mL/well). The cell and lysis/
oligomer mixture is incubated for 15 min at 53 C and then vortexed for 1 min. The lysate is then transferred to the bDNA capture plate and mixed. The plate is then sealed and incubated at 53 C for 16 h. The next day, the plate is cooled for 10 min at room temperature and the Amplifier Reagent mixture is prepared. The wells are then washed twice with 200 mkL of Wash Solution A. Amplifier Reagent is added (50 mkL/well) and the plate is sealed again and incubated at 53 C for 30 min. The plate is then cooled for 10 min at room temperature (rt) and the Label Probe Reagent is prepared. The plate is washed twice with 200 mkL of Wash Solution A and 50 mkL/well of Label Probe Reagent is added. The plate is sealed and incubated at 53 C for 15 min. The plate is cooled for 10 min at rt and the Substrate Mixture is prepared. The plate is again washed twice with 200 mkL Wash Solution A and then twice with Wash Solution D. The Substrate Mixture is then added (50 mkL) and the plate is sealed. The plate is incubated at 37 C for 30 min and then read on the Quantiplex luminometer. Raloxifene is used as a positive control in this assay, and behaves as a full antagonist of estrogen-induced pS2 expression.
Showing 1 to 5 of 10 entries
