BAZEDOXIFENE

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

Structure Search

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

HIDE SMILES / InChI

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

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022247s002lbl.pdf
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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Estrogen receptor 75 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	Modulator 828		23.0 nM [IC50]
Estrogen receptor beta 110 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/	Modulator 828		89.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hot flashes 3 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022247s002lbl.pdf	Palliative		Approved 8429	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 2013
Postmenopausal osteoporosis 59 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022247s002lbl.pdf	Preventing		Approved 8429	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 2013

C_max

Value	Dose	Co-administered	Analyte	Population
6.9 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/022247Orig1s001lbl.pdf	20 mg 1 times / day steady-state, oral dose: 20 mg route of administration: Oral experiment type: STEADY-STATE co-administered: ESTROGENS, CONJUGATED	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/022247Orig1s001lbl.pdf	20 mg 1 times / day steady-state, oral dose: 20 mg route of administration: Oral experiment type: STEADY-STATE co-administered: ESTROGENS, CONJUGATED	ESTROGENS, CONJUGATED	BAZEDOXIFENE unknown	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
30 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/022247Orig1s001lbl.pdf	20 mg 1 times / day steady-state, oral dose: 20 mg route of administration: Oral experiment type: STEADY-STATE co-administered: ESTROGENS, CONJUGATED	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: https://pubmed.ncbi.nlm.nih.gov/27128831	healthy, 45 - 70 years n = 11 Health Status: healthy Age Group: 45 - 70 years Sex: F Population Size: 11 Sources: https://pubmed.ncbi.nlm.nih.gov/27128831	Sources: https://pubmed.ncbi.nlm.nih.gov/27128831
120 mg single, oral Highest studied dose Dose: 120 mg Route: oral Route: single Dose: 120 mg Sources: https://pubmed.ncbi.nlm.nih.gov/28756067	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: https://pubmed.ncbi.nlm.nih.gov/28756067	Sources: https://pubmed.ncbi.nlm.nih.gov/28756067

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
			inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP 111	CYP 270 UGT 192 UGT1A1 418 UGT1A10 291	CYP 76

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP 147	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/022247Orig1s000ClinPharmR.pdf Page: 5.0	no
CYP 147	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/022247Orig1s000ClinPharmR.pdf Page: 5.0	no

Drug as victim

Target	Modality	Activity
CYP 270	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/022247Orig1s000PharmR.pdf Page: 39.0	minor
UGT 192	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/022247Orig1s000ClinPharmR.pdf Page: 5.0	yes
UGT1A1 418	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/022247Orig1s000PharmR.pdf Page: 39.0	yes
UGT1A10 291	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/022247Orig1s000PharmR.pdf Page: 39.0	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/022247Orig1s000PharmR.pdf Page: 38.0

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY428267	https://www.001chemical.com/chem/198481-32-2
AA Blocks	AA002BGW	https://www.aablocks.com/goods/Goods/detail?id=AA002BGW
AK Scientific, Inc. (AKSCI)	3473AH	http://www.aksci.com/item_detail.php?cat=3473AH
Achemtek	0102-022126	http://www.achemtek.com/198481-32-2
Acorn PharmaTech	ACN-030060	http://www.acornpharmatech.com/
Adooq BioScience	A15019	https://www.adooq.com/bazedoxifene.html
AlchemyPharm	AP10432	https://www.alchemypharm.com/pharm/198481-32-2.html
Ambeed	A696565	https://www.ambeed.com/products/198481-32-2.html
Ambinter	Amb22057409	http://www.ambinter.com/reference/22057409
Angene	AGN-PC-0509EJ	http://www.angenechemical.com/productshow/AGN-PC-0509EJ.html
ApexBio Technology	A3232	http://www.apexbt.com/bazedoxifene.html
Ark Pharma Scientific Limited	A-0608	http://www.arkpharmtech.com/product/32559.html
Aurum Pharmatech LLC	W-5320	http://www.Aurumpharmatech.com/Product/ProductDetails/W_5320
BLD Pharm	BD160016	http://www.bldpharm.com/products/198481-32-2.html
BioCrick	BCC1411	http://www.biocrick.com/Bazedoxifene-BCC1411.html
BioSynth	J-012822	https://www.biosynth.com/en/products/all-products/products/J-012822.html
CSNpharm	CSN12297	https://www.csnpharm.com/products/bazedoxifene.html
Chem Scene	CS-0932	http://www.chemscene.com/198481-32-2.html
Chemspace	CSSB00020668792	https://chem-space.com/CSSB00020668792
Clearsynth	CS-L-00024	https://www.clearsynth.com/en/CSL00024.html
DC Chemicals	DC8922	http://www.dcchemicals.com//product_show-Bazedoxifene.html
Lab Network	LN01341877	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01341877
MedChem Express	HY-A0031	https://www.medchemexpress.com/bazedoxifene.html
MolPort	MolPort-009-198-833	https://www.molport.com/shop/molecule-link/MolPort-009-198-833
Molcore	MC428267	https://www.molcore.com/product/198481-32-2
MuseChem	I002519	https://www.musechem.com/product/I002519.html
Parchem	28305	http://www.parchem.com/chemical-supplier-distributor/Bazedoxifene-018305.aspx
Smolecule	S548678	http://www.smolecule.com/products/s548678
Smolecule	S751004	https://www.smolecule.com/products/s751004
Synblock Inc	SB19326	http://www.synblock.com/product/198481-32-2.html
THE BioTek	bt-288085	https://www.thebiotek.com/product/inhibitors/bt-288085
THE BioTek	bt-302203	https://www.thebiotek.com/product/others/bt-302203
Tenova Pharmaceuticals Inc	T31190	https://www.tenovapharma.com/Bazedoxifene
eNovation Chemicals	D320200	http://www.enovationchem.com/productDetails.asp?productID=D320200

PubMed

Title	Date	PubMed
Design, synthesis, and preclinical characterization of novel, highly selective indole estrogens.	2001 May 24	11356100
Endometrial effects of bazedoxifene acetate, a novel selective estrogen receptor modulator, in postmenopausal women.	2005 Jun	15932835
Estrogen receptors as therapeutic targets in breast cancer.	2006	16515478
[Next generation selective estrogen receptor modulators].	2006 Jan	16397365
The future of the new selective estrogen receptor modulators.	2007 Mar	17448265
Bazedoxifene: bazedoxifene acetate, TSE 424, TSE-424, WAY 140424.	2008	18457472
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	18072873
Progress in osteoporosis and fracture prevention: focus on postmenopausal women.	2009	19849819
Vitamin D status, parathyroid function, bone turnover, and BMD in postmenopausal women with osteoporosis: global perspective.	2009 Apr	19049341
Metabolic disposition of [14C]bazedoxifene in healthy postmenopausal women.	2009 Jun	19273530
Bazedoxifene effects on the reproductive tract in postmenopausal women at risk for osteoporosis.	2009 Nov-Dec	19546825
New therapies for osteoporosis: zoledronic acid, bazedoxifene, and denosumab.	2009 Sep	19723467
Modulators of androgen and estrogen receptor activity.	2010	21395502
FRAX and its applications in health economics--cost-effectiveness and intervention thresholds using bazedoxifene in a Swedish setting as an example.	2010 Aug	20493983
Treating postmenopausal osteoporosis in women at increased risk of fracture - critical appraisal of bazedoxifene: a review.	2010 Aug 9	21072279
Long-term safety and efficacy of raloxifene in the prevention and treatment of postmenopausal osteoporosis: an update.	2010 Aug 9	21072271
Bazedoxifene when paired with conjugated estrogens is a new paradigm for treatment of postmenopausal women.	2010 Dec	21073353
Management of osteoporosis in patients hospitalized for hip fractures.	2010 Dec	21058000
The utility and limitations of FRAX: A US perspective.	2010 Dec	20811963
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	19914376
Acute administration of non-classical estrogen receptor agonists attenuates ischemia-induced hippocampal neuron loss in middle-aged female rats.	2010 Jan 8	20062809
Lasofoxifene: Evidence of its therapeutic value in osteoporosis.	2010 Jun 15	20694069
SERMs in the prevention and treatment of postmenopausal osteoporosis: an update.	2010 Mar	20485909
Endometrial safety: a key hurdle for selective estrogen receptor modulators in development.	2010 May-Jun	20107426
Tissue-selective agents: selective estrogen receptor modulators and the tissue-selective estrogen complex.	2010 Sep	20956688
New selective estrogen receptor modulators (SERMs) in development.	2010 Sep	20603714
In vitro metabolism, permeability, and efflux of bazedoxifene in humans.	2010 Sep	20516255

Patents

Sample Use Guides

In Vivo Use Guide

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

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 `Fri Dec 15 16:03:05 GMT 2023` Edited by `admin` on `Fri Dec 15 16:03:05 GMT 2023`
Record UNII	Q16TT9C5BK
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

BAZEDOXIFENE

Official Name

English

BAZEDOXIFENE [MI]

Common Name

English

AK-R215 COMPONENT BAZEDOXIFENE

Common Name

English

AK R215 COMPONENT BAZEDOXIFENE

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 [WHO-DD]

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