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 Date1.38075845E12 |
|||
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 Date1.38075845E12 |
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 |
|
Bazedoxifene (Wyeth). | 2004 Oct |
|
Management of age-related osteoporosis and prevention of associated fractures. | 2006 Sep |
|
Update on bazedoxifene: a novel selective estrogen receptor modulator. | 2007 |
|
Effect of estrogens on skin aging and the potential role of SERMs. | 2007 |
|
Selective estrogen receptor modulators for postmenopausal osteoporosis: current state of development. | 2007 |
|
Bazedoxifene: a third-generation selective estrogen receptor modulator for treatment of postmenopausal osteoporosis. | 2007 May |
|
Bazedoxifene and bazedoxifene combined with conjugated estrogens for the management of postmenopausal osteoporosis. | 2007 Oct |
|
Bazedoxifene: bazedoxifene acetate, TSE 424, TSE-424, WAY 140424. | 2008 |
|
The pairing of a selective estrogen receptor modulator, bazedoxifene, with conjugated estrogens as a new paradigm for the treatment of menopausal symptoms and osteoporosis prevention. | 2008 Dec |
|
Bazedoxifene: a selective estrogen-receptor modulator. | 2008 Jul |
|
Selective estrogen receptor modulators: an update on recent clinical findings. | 2008 Mar |
|
Lasofoxifene for the prevention and treatment of postmenopausal osteoporosis. | 2009 |
|
Clinical issues regarding cardiovascular disease and selective estrogen receptor modulators in postmenopausal women. | 2009 |
|
Vitamin D status, parathyroid function, bone turnover, and BMD in postmenopausal women with osteoporosis: global perspective. | 2009 Apr |
|
Advances in the treatment of menopausal symptoms. | 2009 Jul |
|
Designing the ideal selective estrogen receptor modulator--an achievable goal? | 2009 May-Jun |
|
Bazedoxifene effects on the reproductive tract in postmenopausal women at risk for osteoporosis. | 2009 Nov-Dec |
|
The effects of bazedoxifene on mammographic breast density in postmenopausal women with osteoporosis. | 2009 Nov-Dec |
|
Modulators of androgen and estrogen receptor activity. | 2010 |
|
Aprela, a single tablet formulation of bazedoxifene and conjugated equine estrogens (Premarin) for the potential treatment of menopausal symptoms. | 2010 Apr |
|
Effects of bazedoxifene/conjugated estrogens on quality of life in postmenopausal women with symptoms of vulvar/vaginal atrophy. | 2010 Apr |
|
Treating postmenopausal osteoporosis in women at increased risk of fracture - critical appraisal of bazedoxifene: a review. | 2010 Aug 9 |
|
Long-term safety and efficacy of raloxifene in the prevention and treatment of postmenopausal osteoporosis: an update. | 2010 Aug 9 |
|
Bazedoxifene when paired with conjugated estrogens is a new paradigm for treatment of postmenopausal women. | 2010 Dec |
|
Management of osteoporosis in patients hospitalized for hip fractures. | 2010 Dec |
|
Selective estrogen receptor modulator (SERM) for the treatment of osteoporosis in postmenopausal women: focus on lasofoxifene. | 2010 Feb 2 |
|
Gene expression profiling studies of three SERMs and their conjugated estrogen combinations in human breast cancer cells: insights into the unique antagonistic effects of bazedoxifene on conjugated estrogens. | 2010 Jan |
|
Efficacy and safety of bazedoxifene, a novel selective estrogen receptor modulator for the prevention and treatment of postmenopausal osteoporosis. | 2010 Jul |
|
Bazedoxifene: a novel selective estrogen receptor modulator for postmenopausal osteoporosis. | 2010 Jun |
|
Lasofoxifene: Evidence of its therapeutic value in osteoporosis. | 2010 Jun 15 |
|
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 |
|
Evidence-based guidelines for the pharmacological treatment of postmenopausal osteoporosis: a consensus document by the Belgian Bone Club. | 2010 Oct |
|
Tissue-selective agents: selective estrogen receptor modulators and the tissue-selective estrogen complex. | 2010 Sep |
|
Assessment of individual fracture risk: FRAX and beyond. | 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
by
admin
on
Edited
Fri Dec 15 16:03:05 UTC 2023
by
admin
on
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Record UNII |
Q16TT9C5BK
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Record Status |
Validated (UNII)
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Record Version |
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Classification Tree | Code System | Code | ||
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LIVERTOX |
NBK548475
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WHO-ATC |
G03CC07
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NDF-RT |
N0000175826
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NCI_THESAURUS |
C1821
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WHO-VATC |
QG03XC02
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WHO-ATC |
G03XC02
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DTXSID70173593
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C447119
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DB06401
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Q16TT9C5BK
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BAZEDOXIFENE
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154257
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C73598
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198481-32-2
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SUB26694
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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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