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Details

Stereochemistry ACHIRAL
Molecular Formula C30H34N2O3.C2H4O2
Molecular Weight 530.6557
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of BAZEDOXIFENE ACETATE

SMILES

Cc1c2cc(ccc2n(Cc3ccc(cc3)OCCN4CCCCCC4)c1-c5ccc(cc5)O)O.CC(=O)O

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)

HIDE SMILES / InChI

Molecular Formula C30H34N2O3
Molecular Weight 470.6037
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C2H4O2
Molecular Weight 60.052
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
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

Curator's Comment:: Bazedoxifene has not been shown to cross the blood brain barrier

Originator

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

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P03372
Gene ID: 2099.0
Gene Symbol: ESR1
Target Organism: Homo sapiens (Human)
23.0 nM [IC50]
Target ID: Q92731|||O75584
Gene ID: 2100.0
Gene Symbol: ESR2
Target Organism: Homo sapiens (Human)
89.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
DUAVEE

Approved Use

DUAVEE 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 Date

1.38075845E12
Preventing
DUAVEE

Approved Use

DUAVEE 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 Date

1.38075845E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
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

AUC

ValueDoseCo-administeredAnalytePopulation
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

T1/2

ValueDoseCo-administeredAnalytePopulation
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

Doses

DosePopulationAdverse 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
Dose: 120 mg
Route: oral
Route: single
Dose: 120 mg
Sources:
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

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer






Drug as perpetrator​Drug as victimTox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
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 acetate: a selective estrogen receptor modulator with improved selectivity.
2005 Sep
Emerging selective estrogen receptor modulators: special focus on effects on coronary heart disease in postmenopausal women.
2006
Developments in the pharmacotherapeutic management of osteoporosis.
2006 Aug
Update on bazedoxifene: a novel selective estrogen receptor modulator.
2007
In silico elucidation of the molecular mechanism defining the adverse effect of selective estrogen receptor modulators.
2007 Nov
Bazedoxifene and bazedoxifene combined with conjugated estrogens for the management of postmenopausal osteoporosis.
2007 Oct
Effects of bazedoxifene on BMD and bone turnover in postmenopausal women: 2-yr results of a randomized, double-blind, placebo-, and active-controlled study.
2008 Apr
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
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
[Newly developed drugs for osteoporosis in overseas and their future roles for the therapy].
2008 Oct
Lasofoxifene for the prevention and treatment of postmenopausal osteoporosis.
2009
Progress in osteoporosis and fracture prevention: focus on postmenopausal women.
2009
Clinical issues regarding cardiovascular disease and selective estrogen receptor modulators in postmenopausal women.
2009
Bazedoxifene acetate: a novel selective estrogen receptor modulator for the prevention and treatment of postmenopausal osteoporosis.
2009 Jul
Metabolic disposition of [14C]bazedoxifene in healthy postmenopausal women.
2009 Jun
Bazedoxifene reduces vertebral and clinical fractures in postmenopausal women at high risk assessed with FRAX.
2009 Jun
Emerging drugs for postmenopausal osteoporosis.
2009 Mar
Designing the ideal selective estrogen receptor modulator--an achievable goal?
2009 May-Jun
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
The effects of bazedoxifene on mammographic breast density in postmenopausal women with osteoporosis.
2009 Nov-Dec
Modulators of androgen and estrogen receptor activity.
2010
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
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
Selective estrogen receptor modulators decrease the production of interleukin-6 and interferon-gamma-inducible protein-10 by astrocytes exposed to inflammatory challenge in vitro.
2010 Jan 1
Acute administration of non-classical estrogen receptor agonists attenuates ischemia-induced hippocampal neuron loss in middle-aged female rats.
2010 Jan 8
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
What is the best balance of benefits and risks among anti-resorptive therapies for postmenopausal osteoporosis?
2010 Nov
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
In vitro metabolism, permeability, and efflux of bazedoxifene in humans.
2010 Sep
New treatment modalities in osteoporosis.
2010 Sep-Oct
Patents

Sample Use Guides

The recommended dosage is one tablet (containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg) daily.
Route of Administration: Oral
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 Sat Jun 26 06:32:51 UTC 2021
Edited
by admin
on Sat Jun 26 06:32:51 UTC 2021
Record UNII
J70472UD3D
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
BAZEDOXIFENE ACETATE
JAN   MART.   MI   USAN   WHO-DD  
USAN  
Official Name English
BAZEDOXIFENE ACETATE [ORANGE BOOK]
Common Name English
WAY-140424
Code English
CONBRIZA
Brand Name English
BAZEDOXIFEN ACETATE
Common Name English
DUAVIVE
Brand Name English
BAZEDOXIFENE ACETATE [MART.]
Common Name English
1-(P-(2-(HEXAHYDRO-1H-AZEPIN-1-YL)ETHOXY)BENZYL)-2-(P-HYDROXYPHENYL)-3-METHYLINDOL-5-OL MONOACETATE (SALT)
Common Name English
BAZEDOXIFENE ACETATE [WHO-DD]
Common Name English
BAZEDOXIFENE ACETATE [JAN]
Common Name English
BAZEDOXIFENE ACETATE [MI]
Common Name English
1H-INDOL-5-OL, 1-((4-(2-(HEXAHYDRO-1H-AZEPIN-1-YL)ETHOXY)PHENYL)METHYL)-2-(4-HYDROXYPHENYL)-3-METHYL-, MONOACETATE (SALT)
Common Name English
BAZEDOXIFENE ACETATE [USAN]
Common Name English
Classification Tree Code System Code
EMA ASSESSMENT REPORTS CONBRIZA (AUTHORIZED: OSTEOPOROSIS, POSTMENOPAUSAL)
Created by admin on Sat Jun 26 06:32:51 UTC 2021 , Edited by admin on Sat Jun 26 06:32:51 UTC 2021
NCI_THESAURUS C1821
Created by admin on Sat Jun 26 06:32:51 UTC 2021 , Edited by admin on Sat Jun 26 06:32:51 UTC 2021
EMA ASSESSMENT REPORTS DUAVIVE (AUTHORIZED: OSTEOPOROSIS)
Created by admin on Sat Jun 26 06:32:51 UTC 2021 , Edited by admin on Sat Jun 26 06:32:51 UTC 2021
EU-Orphan Drug EU/3/14/1367
Created by admin on Sat Jun 26 06:32:51 UTC 2021 , Edited by admin on Sat Jun 26 06:32:51 UTC 2021
Code System Code Type Description
EVMPD
SUB16400MIG
Created by admin on Sat Jun 26 06:32:51 UTC 2021 , Edited by admin on Sat Jun 26 06:32:51 UTC 2021
PRIMARY
CAS
198481-33-3
Created by admin on Sat Jun 26 06:32:51 UTC 2021 , Edited by admin on Sat Jun 26 06:32:51 UTC 2021
PRIMARY
RXCUI
1442171
Created by admin on Sat Jun 26 06:32:51 UTC 2021 , Edited by admin on Sat Jun 26 06:32:51 UTC 2021
PRIMARY RxNorm
EPA CompTox
198481-33-3
Created by admin on Sat Jun 26 06:32:51 UTC 2021 , Edited by admin on Sat Jun 26 06:32:51 UTC 2021
PRIMARY
MESH
C447119
Created by admin on Sat Jun 26 06:32:51 UTC 2021 , Edited by admin on Sat Jun 26 06:32:51 UTC 2021
PRIMARY
NCI_THESAURUS
C74212
Created by admin on Sat Jun 26 06:32:51 UTC 2021 , Edited by admin on Sat Jun 26 06:32:51 UTC 2021
PRIMARY
MERCK INDEX
M2281
Created by admin on Sat Jun 26 06:32:51 UTC 2021 , Edited by admin on Sat Jun 26 06:32:51 UTC 2021
PRIMARY Merck Index
PUBCHEM
154256
Created by admin on Sat Jun 26 06:32:51 UTC 2021 , Edited by admin on Sat Jun 26 06:32:51 UTC 2021
PRIMARY
ChEMBL
CHEMBL46740
Created by admin on Sat Jun 26 06:32:51 UTC 2021 , Edited by admin on Sat Jun 26 06:32:51 UTC 2021
PRIMARY
DRUG BANK
DBSALT001296
Created by admin on Sat Jun 26 06:32:51 UTC 2021 , Edited by admin on Sat Jun 26 06:32:51 UTC 2021
PRIMARY
FDA UNII
J70472UD3D
Created by admin on Sat Jun 26 06:32:51 UTC 2021 , Edited by admin on Sat Jun 26 06:32:51 UTC 2021
PRIMARY
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PARENT -> SALT/SOLVATE
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ACTIVE MOIETY