Details
Stereochemistry | ACHIRAL |
Molecular Formula | C30H34N2O3.C2H4O2 |
Molecular Weight | 530.6545 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CC(O)=O.CC1=C(N(CC2=CC=C(OCCN3CCCCCC3)C=C2)C4=CC=C(O)C=C14)C5=CC=C(O)C=C5
InChI
InChIKey=OMZAMQFQZMUNTP-UHFFFAOYSA-N
InChI=1S/C30H34N2O3.C2H4O2/c1-22-28-20-26(34)12-15-29(28)32(30(22)24-8-10-25(33)11-9-24)21-23-6-13-27(14-7-23)35-19-18-31-16-4-2-3-5-17-31;1-2(3)4/h6-15,20,33-34H,2-5,16-19,21H2,1H3;1H3,(H,3,4)
DescriptionCurator's Comment: description was created based on several sources, including
http://www.ncbi.nlm.nih.gov/pubmed/18457472
Curator's Comment: description was created based on several sources, including
http://www.ncbi.nlm.nih.gov/pubmed/18457472
Bazedoxifene acetate (WAY-140424; TSE-424) is an oral, nonsteroidal, indole-based selective estrogen-receptor modulator developed by Ligand Pharmaceuticals in collaboration with Wyeth Pharmaceuticals (NJ, USA) (now Pfizer) . It was developed using raloxifene as a template with the benzothiophene core substituted by an indole ring in order to obtain favorable effects on the skeleton and lipid metabolism with the additional improvement of a neutral effect on hot flushes and without stimulating the uterus or the breast. The drug is approved as a monotherapy for the prevention and treatment of osteoporosis and in combination with conjugated estrogens for the treatment of menopausal symptoms and prevention of osteoporosis. Bazedoxifene binds to both ERalpha and ERbeta with high affinity. Bazedoxifene acts as both a receptor agonist and/or antagonist, depending upon the cell and tissue type and target genes. Bazedoxifene decreases bone resorption and reduces biochemical markers of bone turnover to the premenopausal range. These effects on bone remodeling lead to an increase in bone mineral density (BMD), which in turn contributes to a reduction in the risk of fractures. Bazedoxifene functions primarily as an estrogen-receptor antagonist in uterine and breast tissues.
CNS Activity
Sources: http://www.ncbi.nlm.nih.gov/pubmed/?term=21071476
Curator's Comment: Bazedoxifene has not been shown to cross the blood brain barrier
Originator
Sources: http://www.ncbi.nlm.nih.gov/pubmed/18457472
Curator's Comment: Bazedoxifene was developed by Ligand Pharmaceuticals in collaboration with Wyeth.Wyeth and Ligand entered into a discovery research collaboration for bazedoxifene in September 1994.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: P03372 Gene ID: 2099.0 Gene Symbol: ESR1 Target Organism: Homo sapiens (Human) Sources: http://www.ncbi.nlm.nih.gov/pubmed/?term=21737572 |
23.0 nM [IC50] | ||
Target ID: Q92731|||O75584 Gene ID: 2100.0 Gene Symbol: ESR2 Target Organism: Homo sapiens (Human) Sources: http://www.ncbi.nlm.nih.gov/pubmed/11356100/ |
89.0 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Palliative | DUAVEE Approved UseDUAVEE is indicated in women with a uterus for: DUAVEE is a combination of conjugated estrogens with an estrogen agonist/antagonist indicated for treatment of the following conditions in women with a uterus: Treatment of moderate to severe vasomotor symptoms associated with menopause (1.1) Prevention of postmenopausal osteoporosis (1.2) Limitation of Use: DUAVEE should be used for the shortest duration consistent with treatment goals and risks for the individual woman. Launch Date2013 |
|||
Preventing | DUAVEE Approved UseDUAVEE is indicated in women with a uterus for: DUAVEE is a combination of conjugated estrogens with an estrogen agonist/antagonist indicated for treatment of the following conditions in women with a uterus: Treatment of moderate to severe vasomotor symptoms associated with menopause (1.1) Prevention of postmenopausal osteoporosis (1.2) Limitation of Use: DUAVEE should be used for the shortest duration consistent with treatment goals and risks for the individual woman. Launch Date2013 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
6.9 ng/mL |
20 mg 1 times / day steady-state, oral dose: 20 mg route of administration: Oral experiment type: STEADY-STATE co-administered: ESTROGENS, CONJUGATED |
BAZEDOXIFENE unknown | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
71 ng × h/mL |
20 mg 1 times / day steady-state, oral dose: 20 mg route of administration: Oral experiment type: STEADY-STATE co-administered: ESTROGENS, CONJUGATED |
BAZEDOXIFENE unknown | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
30 h |
20 mg 1 times / day steady-state, oral dose: 20 mg route of administration: Oral experiment type: STEADY-STATE co-administered: ESTROGENS, CONJUGATED |
BAZEDOXIFENE unknown | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
80 mg 1 times / day multiple, oral Highest studied dose Dose: 80 mg, 1 times / day Route: oral Route: multiple Dose: 80 mg, 1 times / day Sources: |
healthy, 45 - 70 years n = 11 Health Status: healthy Age Group: 45 - 70 years Sex: F Population Size: 11 Sources: |
|
120 mg single, oral Highest studied dose |
healthy, 55.7 yeras (range: 35 - 65 years) n = 84 Health Status: healthy Age Group: 55.7 yeras (range: 35 - 65 years) Sex: F Population Size: 84 Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Page: 5.0 |
no | |||
Page: 5.0 |
no |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Page: 39.0 |
minor | |||
Page: 5.0 |
yes | |||
Page: 39.0 |
yes | |||
Page: 39.0 |
yes |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Page: 38.0 |
PubMed
Title | Date | PubMed |
---|---|---|
Design, synthesis, and preclinical characterization of novel, highly selective indole estrogens. | 2001 May 24 |
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Novel therapies for osteoporosis. | 2003 Apr |
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Selective estrogen receptor modulators protect hippocampal neurons from kainic acid excitotoxicity: differences with the effect of estradiol. | 2004 Nov |
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Bazedoxifene (Wyeth). | 2004 Oct |
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Endometrial effects of bazedoxifene acetate, a novel selective estrogen receptor modulator, in postmenopausal women. | 2005 Jun |
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[Therapeutic agents for disorders of bone and calcium metabolism: Bazedoxifene]. | 2007 Jan |
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Bazedoxifene: bazedoxifene acetate, TSE 424, TSE-424, WAY 140424. | 2008 |
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Efficacy of bazedoxifene in reducing new vertebral fracture risk in postmenopausal women with osteoporosis: results from a 3-year, randomized, placebo-, and active-controlled clinical trial. | 2008 Dec |
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Bazedoxifene: a selective estrogen-receptor modulator. | 2008 Jul |
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Bazedoxifene: a new selective estrogen receptor modulator for the treatment of postmenopausal osteoporosis. | 2009 Jun |
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Modulators of androgen and estrogen receptor activity. | 2010 |
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Treating postmenopausal osteoporosis in women at increased risk of fracture - critical appraisal of bazedoxifene: a review. | 2010 Aug 9 |
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Selective estrogen receptor modulator (SERM) for the treatment of osteoporosis in postmenopausal women: focus on lasofoxifene. | 2010 Feb 2 |
|
Acute administration of non-classical estrogen receptor agonists attenuates ischemia-induced hippocampal neuron loss in middle-aged female rats. | 2010 Jan 8 |
|
Bazedoxifene: a novel selective estrogen receptor modulator for postmenopausal osteoporosis. | 2010 Jun |
|
What is the best balance of benefits and risks among anti-resorptive therapies for postmenopausal osteoporosis? | 2010 Nov |
Sample Use Guides
The recommended dosage is one tablet (containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg) daily.
Route of Administration:
Oral
In Vitro Use Guide
Sources: http://www.ncbi.nlm.nih.gov/pubmed/?term=21737572
The inhibitory effects of BZA (Bazedoxifene acetate) on MCF-7, T47D, MCF-7:5C, and MCF-7:2A cells were determined. MCF-7 and T47D cells were grown in fully estrogenized media, and MCF-7:5C and MCF-7:2A cells were grown in estrogen-free media and then treated with 10^(−12) to 10^(−6) M BZA for 7 days, and cellular DNA was measured as an index of growth.
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Classification Tree | Code System | Code | ||
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EMA ASSESSMENT REPORTS |
CONBRIZA (AUTHORIZED: OSTEOPOROSIS, POSTMENOPAUSAL)
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NCI_THESAURUS |
C1821
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EMA ASSESSMENT REPORTS |
DUAVIVE (AUTHORIZED: OSTEOPOROSIS)
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EU-Orphan Drug |
EU/3/14/1367
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SUB16400MIG
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MM-40
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198481-33-3
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1442171
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DTXSID3048657
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C447119
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C74212
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J70472UD3D
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m2281
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154256
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CHEMBL46740
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100000078576
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J70472UD3D
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ACTIVE MOIETY
SUBSTANCE RECORD