Details
Stereochemistry | ACHIRAL |
Molecular Formula | C30H34N2O3 |
Molecular Weight | 470.6026 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CC1=C(N(CC2=CC=C(OCCN3CCCCCC3)C=C2)C4=CC=C(O)C=C14)C5=CC=C(O)C=C5
InChI
InChIKey=UCJGJABZCDBEDK-UHFFFAOYSA-N
InChI=1S/C30H34N2O3/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/h6-15,20,33-34H,2-5,16-19,21H2,1H3
Molecular Formula | C30H34N2O3 |
Molecular Weight | 470.6026 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
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 |
|
Novel therapies for osteoporosis. | 2003 Apr |
|
Selective estrogen receptor modulators protect hippocampal neurons from kainic acid excitotoxicity: differences with the effect of estradiol. | 2004 Nov |
|
Bazedoxifene (Wyeth). | 2004 Oct |
|
Lasofoxifene: CP 336156, CP-336156. | 2005 |
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Bazedoxifene acetate: a selective estrogen receptor modulator with improved selectivity. | 2005 Sep |
|
Estrogen receptors as therapeutic targets in breast cancer. | 2006 |
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Developments in the pharmacotherapeutic management of osteoporosis. | 2006 Aug |
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Update on bazedoxifene: a novel selective estrogen receptor modulator. | 2007 |
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Effect of estrogens on skin aging and the potential role of SERMs. | 2007 |
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Selective estrogen receptor modulators for postmenopausal osteoporosis: current state of development. | 2007 |
|
Estrogen receptor ligands. Part 16: 2-Aryl indoles as highly subtype selective ligands for ERalpha. | 2007 Apr 15 |
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[Therapeutic agents for disorders of bone and calcium metabolism: Bazedoxifene]. | 2007 Jan |
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The future of the new selective estrogen receptor modulators. | 2007 Mar |
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Bazedoxifene: a third-generation selective estrogen receptor modulator for treatment of postmenopausal osteoporosis. | 2007 May |
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Bazedoxifene and bazedoxifene combined with conjugated estrogens for the management of postmenopausal osteoporosis. | 2007 Oct |
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Selective estrogen receptor modulators: an update on recent clinical findings. | 2008 Mar |
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[Newly developed drugs for osteoporosis in overseas and their future roles for the therapy]. | 2008 Oct |
|
Vitamin D status, parathyroid function, bone turnover, and BMD in postmenopausal women with osteoporosis: global perspective. | 2009 Apr |
|
Effects of various selective estrogen receptor modulators with or without conjugated estrogens on mouse mammary gland. | 2009 Apr |
|
Bazedoxifene acetate: a novel selective estrogen receptor modulator for the prevention and treatment of postmenopausal osteoporosis. | 2009 Jul |
|
Advances in the treatment of menopausal symptoms. | 2009 Jul |
|
Bazedoxifene, a selective estrogen receptor modulator: effects on the endometrium, ovaries, and breast from a randomized controlled trial in osteoporotic postmenopausal women. | 2009 Nov-Dec |
|
Cross-geographic region differences in quality of life in women with and without vertebral fracture. | 2009 Oct |
|
Aprela, a single tablet formulation of bazedoxifene and conjugated equine estrogens (Premarin) for the potential treatment of menopausal symptoms. | 2010 Apr |
|
Disposition of bazedoxifene in rats. | 2010 Aug |
|
FRAX and its applications in health economics--cost-effectiveness and intervention thresholds using bazedoxifene in a Swedish setting as an example. | 2010 Aug |
|
The utility and limitations of FRAX: A US perspective. | 2010 Dec |
|
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 |
|
SERMs in the prevention and treatment of postmenopausal osteoporosis: an update. | 2010 Mar |
|
Endometrial safety: a key hurdle for selective estrogen receptor modulators in development. | 2010 May-Jun |
|
What is the best balance of benefits and risks among anti-resorptive therapies for postmenopausal osteoporosis? | 2010 Nov |
|
In vitro metabolism, permeability, and efflux of bazedoxifene in humans. | 2010 Sep |
|
New treatment modalities in osteoporosis. | 2010 Sep-Oct |
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.
Substance Class |
Chemical
Created
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on
Edited
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Record UNII |
Q16TT9C5BK
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Record Status |
Validated (UNII)
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LIVERTOX |
NBK548475
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WHO-ATC |
G03CC07
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N0000175826
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C1821
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WHO-VATC |
QG03XC02
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G03XC02
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BAZEDOXIFENE
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Related Record | Type | Details | ||
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BINDER->LIGAND |
BINDING
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METABOLIC ENZYME -> SUBSTRATE | |||
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SALT/SOLVATE -> PARENT | |||
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METABOLIC ENZYME -> SUBSTRATE | |||
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TARGET -> INHIBITOR | |||
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TRANSPORTER -> SUBSTRATE | |||
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METABOLIC ENZYME -> SUBSTRATE |
Related Record | Type | Details | ||
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METABOLITE -> PARENT |
MINOR
FECAL
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METABOLITE -> PARENT |
MINOR
PLASMA
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METABOLITE -> PARENT |
MINOR
PLASMA
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METABOLITE -> PARENT |
MAJOR
PLASMA
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Related Record | Type | Details | ||
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ACTIVE MOIETY |
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Biological Half-life | PHARMACOKINETIC |
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Tmax | PHARMACOKINETIC |
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MULTIPLE DOSE ADMINISTRATION |
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Volume of Distribution | PHARMACOKINETIC |
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