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Details

Stereochemistry ACHIRAL
Molecular Formula C30H34N2O3
Molecular Weight 470.6037
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of BAZEDOXIFENE

SMILES

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

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

HIDE SMILES / InChI

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
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
[Next generation selective estrogen receptor modulators].
2006 Jan
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
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
Bazedoxifene: bazedoxifene acetate, TSE 424, TSE-424, WAY 140424.
2008
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
Bazedoxifene for the prevention of postmenopausal osteoporosis.
2008 Dec
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
[Newly developed drugs for osteoporosis in overseas and their future roles for the therapy].
2008 Oct
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
Bazedoxifene: a new selective estrogen receptor modulator for the treatment of postmenopausal osteoporosis.
2009 Jun
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 effects on the reproductive tract in postmenopausal women at risk for osteoporosis.
2009 Nov-Dec
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
Cross-geographic region differences in quality of life in women with and without vertebral fracture.
2009 Oct
FRAX and its applications in health economics--cost-effectiveness and intervention thresholds using bazedoxifene in a Swedish setting as an example.
2010 Aug
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
Selective estrogen receptor modulator (SERM) for the treatment of osteoporosis in postmenopausal women: focus on lasofoxifene.
2010 Feb 2
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
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
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.
Name Type Language
BAZEDOXIFENE
DASH   EMA EPAR   INN   MI   VANDF   WHO-DD  
INN  
Official Name English
BAZEDOXIFENE [MI]
Common Name English
AK-R215 COMPONENT BAZEDOXIFENE
Common Name English
AK R215 COMPONENT BAZEDOXIFENE
Common Name English
BAZEDOXIFENE [WHO-DD]
Common Name English
1H-INDOL-5-OL, 1-((4-(2-(HEXAHYDRO-1H-AZEPIN-1-YL)ETHOXY)PHENYL)METHYL)-2-(4-HYDROXYPHENYL)-3-METHYL-
Systematic Name English
BAZEDOXIFENE [VANDF]
Common Name English
BAZEDOXIFENE [INN]
Common Name English
BZA
Common Name English
1-(P-(2-(HEXAHYDRO-1H-AZEPIN-1-YL)ETHOXY)BENZYL)-2-(P-HYDROXYPHENYL)-3-METHYLINDOL-5-OL
Common Name English
BAZEDOXIFENE [EMA EPAR]
Common Name English
Classification Tree Code System Code
LIVERTOX NBK548475
Created by admin on Sat Jun 26 02:37:45 UTC 2021 , Edited by admin on Sat Jun 26 02:37:45 UTC 2021
WHO-ATC G03CC07
Created by admin on Sat Jun 26 02:37:45 UTC 2021 , Edited by admin on Sat Jun 26 02:37:45 UTC 2021
NDF-RT N0000175826
Created by admin on Sat Jun 26 02:37:45 UTC 2021 , Edited by admin on Sat Jun 26 02:37:45 UTC 2021
NCI_THESAURUS C1821
Created by admin on Sat Jun 26 02:37:45 UTC 2021 , Edited by admin on Sat Jun 26 02:37:45 UTC 2021
WHO-VATC QG03XC02
Created by admin on Sat Jun 26 02:37:45 UTC 2021 , Edited by admin on Sat Jun 26 02:37:45 UTC 2021
WHO-ATC G03XC02
Created by admin on Sat Jun 26 02:37:45 UTC 2021 , Edited by admin on Sat Jun 26 02:37:45 UTC 2021
Code System Code Type Description
EPA CompTox
198481-32-2
Created by admin on Sat Jun 26 02:37:45 UTC 2021 , Edited by admin on Sat Jun 26 02:37:45 UTC 2021
PRIMARY
MESH
C447119
Created by admin on Sat Jun 26 02:37:45 UTC 2021 , Edited by admin on Sat Jun 26 02:37:45 UTC 2021
PRIMARY
INN
8168
Created by admin on Sat Jun 26 02:37:45 UTC 2021 , Edited by admin on Sat Jun 26 02:37:45 UTC 2021
PRIMARY
DRUG BANK
DB06401
Created by admin on Sat Jun 26 02:37:45 UTC 2021 , Edited by admin on Sat Jun 26 02:37:45 UTC 2021
PRIMARY
WIKIPEDIA
BAZEDOXIFENE
Created by admin on Sat Jun 26 02:37:45 UTC 2021 , Edited by admin on Sat Jun 26 02:37:45 UTC 2021
PRIMARY
PUBCHEM
154257
Created by admin on Sat Jun 26 02:37:45 UTC 2021 , Edited by admin on Sat Jun 26 02:37:45 UTC 2021
PRIMARY
FDA UNII
Q16TT9C5BK
Created by admin on Sat Jun 26 02:37:45 UTC 2021 , Edited by admin on Sat Jun 26 02:37:45 UTC 2021
PRIMARY
NCI_THESAURUS
C73598
Created by admin on Sat Jun 26 02:37:45 UTC 2021 , Edited by admin on Sat Jun 26 02:37:45 UTC 2021
PRIMARY
CAS
198481-32-2
Created by admin on Sat Jun 26 02:37:45 UTC 2021 , Edited by admin on Sat Jun 26 02:37:45 UTC 2021
PRIMARY
EVMPD
SUB26694
Created by admin on Sat Jun 26 02:37:45 UTC 2021 , Edited by admin on Sat Jun 26 02:37:45 UTC 2021
PRIMARY
DRUG CENTRAL
4334
Created by admin on Sat Jun 26 02:37:45 UTC 2021 , Edited by admin on Sat Jun 26 02:37:45 UTC 2021
PRIMARY
ChEMBL
CHEMBL46740
Created by admin on Sat Jun 26 02:37:45 UTC 2021 , Edited by admin on Sat Jun 26 02:37:45 UTC 2021
PRIMARY
RXCUI
1441386
Created by admin on Sat Jun 26 02:37:45 UTC 2021 , Edited by admin on Sat Jun 26 02:37:45 UTC 2021
PRIMARY