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
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 |
|
Endometrial effects of bazedoxifene acetate, a novel selective estrogen receptor modulator, in postmenopausal women. | 2005 Jun |
|
Bazedoxifene acetate: a selective estrogen receptor modulator with improved selectivity. | 2005 Sep |
|
Estrogen receptors as therapeutic targets in breast cancer. | 2006 |
|
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 |
|
[Next generation selective estrogen receptor modulators]. | 2006 Jan |
|
Estrogen receptor ligands. Part 16: 2-Aryl indoles as highly subtype selective ligands for ERalpha. | 2007 Apr 15 |
|
[Therapeutic agents for disorders of bone and calcium metabolism: Bazedoxifene]. | 2007 Jan |
|
Bazedoxifene: a third-generation selective estrogen receptor modulator for treatment of postmenopausal osteoporosis. | 2007 May |
|
Bazedoxifene for the prevention of postmenopausal osteoporosis. | 2008 Dec |
|
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 |
|
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 |
|
FRAX and its applications in health economics--cost-effectiveness and intervention thresholds using bazedoxifene in a Swedish setting as an example. | 2010 Aug |
|
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 |
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.
Name | Type | Language | ||
---|---|---|---|---|
|
Official Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Systematic Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English |
Classification Tree | Code System | Code | ||
---|---|---|---|---|
|
LIVERTOX |
NBK548475
Created by
admin on Fri Dec 15 16:03:05 GMT 2023 , Edited by admin on Fri Dec 15 16:03:05 GMT 2023
|
||
|
WHO-ATC |
G03CC07
Created by
admin on Fri Dec 15 16:03:05 GMT 2023 , Edited by admin on Fri Dec 15 16:03:05 GMT 2023
|
||
|
NDF-RT |
N0000175826
Created by
admin on Fri Dec 15 16:03:05 GMT 2023 , Edited by admin on Fri Dec 15 16:03:05 GMT 2023
|
||
|
NCI_THESAURUS |
C1821
Created by
admin on Fri Dec 15 16:03:05 GMT 2023 , Edited by admin on Fri Dec 15 16:03:05 GMT 2023
|
||
|
WHO-VATC |
QG03XC02
Created by
admin on Fri Dec 15 16:03:05 GMT 2023 , Edited by admin on Fri Dec 15 16:03:05 GMT 2023
|
||
|
WHO-ATC |
G03XC02
Created by
admin on Fri Dec 15 16:03:05 GMT 2023 , Edited by admin on Fri Dec 15 16:03:05 GMT 2023
|
Code System | Code | Type | Description | ||
---|---|---|---|---|---|
|
DTXSID70173593
Created by
admin on Fri Dec 15 16:03:05 GMT 2023 , Edited by admin on Fri Dec 15 16:03:05 GMT 2023
|
PRIMARY | |||
|
C447119
Created by
admin on Fri Dec 15 16:03:05 GMT 2023 , Edited by admin on Fri Dec 15 16:03:05 GMT 2023
|
PRIMARY | |||
|
8168
Created by
admin on Fri Dec 15 16:03:05 GMT 2023 , Edited by admin on Fri Dec 15 16:03:05 GMT 2023
|
PRIMARY | |||
|
DB06401
Created by
admin on Fri Dec 15 16:03:05 GMT 2023 , Edited by admin on Fri Dec 15 16:03:05 GMT 2023
|
PRIMARY | |||
|
Q16TT9C5BK
Created by
admin on Fri Dec 15 16:03:05 GMT 2023 , Edited by admin on Fri Dec 15 16:03:05 GMT 2023
|
PRIMARY | |||
|
BAZEDOXIFENE
Created by
admin on Fri Dec 15 16:03:05 GMT 2023 , Edited by admin on Fri Dec 15 16:03:05 GMT 2023
|
PRIMARY | |||
|
154257
Created by
admin on Fri Dec 15 16:03:05 GMT 2023 , Edited by admin on Fri Dec 15 16:03:05 GMT 2023
|
PRIMARY | |||
|
100000089657
Created by
admin on Fri Dec 15 16:03:05 GMT 2023 , Edited by admin on Fri Dec 15 16:03:05 GMT 2023
|
PRIMARY | |||
|
Q16TT9C5BK
Created by
admin on Fri Dec 15 16:03:05 GMT 2023 , Edited by admin on Fri Dec 15 16:03:05 GMT 2023
|
PRIMARY | |||
|
C73598
Created by
admin on Fri Dec 15 16:03:05 GMT 2023 , Edited by admin on Fri Dec 15 16:03:05 GMT 2023
|
PRIMARY | |||
|
198481-32-2
Created by
admin on Fri Dec 15 16:03:05 GMT 2023 , Edited by admin on Fri Dec 15 16:03:05 GMT 2023
|
PRIMARY | |||
|
SUB26694
Created by
admin on Fri Dec 15 16:03:05 GMT 2023 , Edited by admin on Fri Dec 15 16:03:05 GMT 2023
|
PRIMARY | |||
|
4334
Created by
admin on Fri Dec 15 16:03:05 GMT 2023 , Edited by admin on Fri Dec 15 16:03:05 GMT 2023
|
PRIMARY | |||
|
CHEMBL46740
Created by
admin on Fri Dec 15 16:03:05 GMT 2023 , Edited by admin on Fri Dec 15 16:03:05 GMT 2023
|
PRIMARY | |||
|
1441386
Created by
admin on Fri Dec 15 16:03:05 GMT 2023 , Edited by admin on Fri Dec 15 16:03:05 GMT 2023
|
PRIMARY |
ACTIVE MOIETY
METABOLITE (PARENT)
METABOLITE (PARENT)
METABOLITE (PARENT)
METABOLITE (PARENT)
SALT/SOLVATE (PARENT)