BAZEDOXIFENE

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 Search

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

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

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 67 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 780		23.0 nM [IC50]
Estrogen receptor beta 106 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 780		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 8043	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
Postmenopausal osteoporosis 59 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022247s002lbl.pdf	Preventing		Approved 8043	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

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 1475

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP 98	CYP 236 UGT 173 UGT1A1 393 UGT1A10 273	CYP 70

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP 132	inducer 1440 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/022247Orig1s000ClinPharmR.pdf Page: 5.0	no
CYP 132	inhibitor 3045 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/022247Orig1s000ClinPharmR.pdf Page: 5.0	no

Drug as victim

Target	Modality	Activity
CYP 236	substrate 3113 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/022247Orig1s000PharmR.pdf Page: 39.0	minor
UGT 173	substrate 3113 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/022247Orig1s000ClinPharmR.pdf Page: 5.0	yes
UGT1A1 393	substrate 3113 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/022247Orig1s000PharmR.pdf Page: 39.0	yes
UGT1A10 273	substrate 3113 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 1507	inhibitor 1489 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
Novel therapies for osteoporosis.	2003 Apr	12665416
Lasofoxifene: CP 336156, CP-336156.	2005	15801869
Endometrial effects of bazedoxifene acetate, a novel selective estrogen receptor modulator, in postmenopausal women.	2005 Jun	15932835
Emerging selective estrogen receptor modulators: special focus on effects on coronary heart disease in postmenopausal women.	2006	16451093
Management of age-related osteoporosis and prevention of associated fractures.	2006 Sep	18360603
Effect of estrogens on skin aging and the potential role of SERMs.	2007	18044179
[Therapeutic agents for disorders of bone and calcium metabolism: Bazedoxifene].	2007 Jan	17211091
Bazedoxifene: a third-generation selective estrogen receptor modulator for treatment of postmenopausal osteoporosis.	2007 May	17426077
Bazedoxifene and bazedoxifene combined with conjugated estrogens for the management of postmenopausal osteoporosis.	2007 Oct	17922629
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
Bazedoxifene for the prevention of postmenopausal osteoporosis.	2008 Dec	19337430
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	18703623
[Newly developed drugs for osteoporosis in overseas and their future roles for the therapy].	2008 Oct	18830046
Clinical issues regarding cardiovascular disease and selective estrogen receptor modulators in postmenopausal women.	2009	19811253
Differential biochemical and cellular actions of Premarin estrogens: distinct pharmacology of bazedoxifene-conjugated estrogens combination.	2009 Jan	19036900
Advances in the treatment of menopausal symptoms.	2009 Jul	19586429
Bazedoxifene: a new selective estrogen receptor modulator for the treatment of postmenopausal osteoporosis.	2009 Jun	19445558
Emerging drugs for postmenopausal osteoporosis.	2009 Mar	19249985
The effects of bazedoxifene on mammographic breast density in postmenopausal women with osteoporosis.	2009 Nov-Dec	19503006
Modulators of androgen and estrogen receptor activity.	2010	21395502
Aprela, a single tablet formulation of bazedoxifene and conjugated equine estrogens (Premarin) for the potential treatment of menopausal symptoms.	2010 Apr	20336595
Effects of bazedoxifene/conjugated estrogens on quality of life in postmenopausal women with symptoms of vulvar/vaginal atrophy.	2010 Apr	19863455
Disposition of bazedoxifene in rats.	2010 Aug	20528166
FRAX and its applications in health economics--cost-effectiveness and intervention thresholds using bazedoxifene in a Swedish setting as an example.	2010 Aug	20493983
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
Selective estrogen receptor modulator (SERM) for the treatment of osteoporosis in postmenopausal women: focus on lasofoxifene.	2010 Feb 2	20169039
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
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	19533603
Acute administration of non-classical estrogen receptor agonists attenuates ischemia-induced hippocampal neuron loss in middle-aged female rats.	2010 Jan 8	20062809
Efficacy and safety of bazedoxifene, a novel selective estrogen receptor modulator for the prevention and treatment of postmenopausal osteoporosis.	2010 Jul	20429824
Bazedoxifene: a novel selective estrogen receptor modulator for postmenopausal osteoporosis.	2010 Jun	20184423
Lasofoxifene: Evidence of its therapeutic value in osteoporosis.	2010 Jun 15	20694069
Safety of bazedoxifene in a randomized, double-blind, placebo- and active-controlled Phase 3 study of postmenopausal women with osteoporosis.	2010 Jun 22	20569451
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
What is the best balance of benefits and risks among anti-resorptive therapies for postmenopausal osteoporosis?	2010 Nov	20309524
Evidence-based guidelines for the pharmacological treatment of postmenopausal osteoporosis: a consensus document by the Belgian Bone Club.	2010 Oct	20480148
New selective estrogen receptor modulators (SERMs) in development.	2010 Sep	20603714
Assessment of individual fracture risk: FRAX and beyond.	2010 Sep	20563901
In vitro metabolism, permeability, and efflux of bazedoxifene in humans.	2010 Sep	20516255
New treatment modalities in osteoporosis.	2010 Sep-Oct	20350910

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 `Sat Jun 26 02:37:45 UTC 2021` Edited by `admin` on `Sat Jun 26 02:37:45 UTC 2021`
Record UNII	Q16TT9C5BK
Record Status	`Validated (UNII)`
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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

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