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Details

Stereochemistry ABSOLUTE
Molecular Formula C28H31NO2
Molecular Weight 413.5523
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LASOFOXIFENE

SMILES

c1ccc(cc1)[C@@]2([H])CCc3cc(ccc3[C@@]2([H])c4ccc(cc4)OCCN5CCCC5)O

InChI

InChIKey=GXESHMAMLJKROZ-IAPPQJPRSA-N
InChI=1S/C28H31NO2/c30-24-11-15-27-23(20-24)10-14-26(21-6-2-1-3-7-21)28(27)22-8-12-25(13-9-22)31-19-18-29-16-4-5-17-29/h1-3,6-9,11-13,15,20,26,28,30H,4-5,10,14,16-19H2/t26-,28+/m1/s1

HIDE SMILES / InChI

Molecular Formula C28H31NO2
Molecular Weight 413.5523
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Lasofoxifene is an active component of Fablyn. Fablyn is used for the treatment of osteoporosis in postmenopausal women. Lasofoxifene is a nonsteroidal selective estrogen receptor modulator. Lasofoxifene has no effect on CYP2E1- or CYP2D6-mediated drug metabolism and should not affect drugs metabolized by other cytochrome P450 isoenzymes. Common adverse reactions considered to be related to Fablyn therapy were muscle spasms, hot flush and vaginal discharge. Lasofoxifene approved in the EU in 2009 is now withdrawn from use in the European Union.

Originator

Curator's Comment:: # Ligand Pharmaceuticals; Pfizer

Approval Year

PubMed

PubMed

TitleDatePubMed
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
In silico elucidation of the molecular mechanism defining the adverse effect of selective estrogen receptor modulators.
2007 Nov
[Status of novel bone-targeting SERMs in development].
2007 Nov 28
Bazedoxifene: bazedoxifene acetate, TSE 424, TSE-424, WAY 140424.
2008
Effects of lasofoxifene on the uterus, vagina, and breast in ovariectomized cynomolgus monkeys (Macaca fascicularis).
2008 Aug
Bazedoxifene for the prevention of postmenopausal osteoporosis.
2008 Dec
Disposition of lasofoxifene, a next-generation selective estrogen receptor modulator, in healthy male subjects.
2008 Jul
Activity of three selective estrogen receptor modulators on hormone-dependent responses in the mouse uterus and mammary gland.
2008 Jun 11
Hormone-dependent aging problems in women.
2008 Jun 30
Selective estrogen receptor modulators: an update on recent clinical findings.
2008 Mar
Effects of selective oestrogen receptor modulators on proliferation in tissue cultures of pre- and postmenopausal human endometrium.
2008 Nov
Metabolism, distribution, and excretion of a next generation selective estrogen receptor modulator, lasofoxifene, in rats and monkeys.
2008 Sep
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
Docking study of triphenylphosphonium cations as estrogen receptor alpha modulators.
2009
Treatment of osteoporosis with annual iv zoledronic acid: effects on hip fracture.
2009 Apr
Effects of various selective estrogen receptor modulators with or without conjugated estrogens on mouse mammary gland.
2009 Apr
Thresholds for therapies: highlights of the St Gallen International Expert Consensus on the primary therapy of early breast cancer 2009.
2009 Aug
Lasofoxifene: new drug. Osteoporosis: no better than raloxifene.
2009 Dec
A randomised, double-blinded, placebo-controlled, trial to determine the individual response in bone turnover markers to lasofoxifene therapy.
2009 Dec
Recent advances in managing osteoporosis.
2009 Dec 15
New selective estrogen and androgen receptor modulators.
2009 Jul
Designing the ideal selective estrogen receptor modulator--an achievable goal?
2009 May-Jun
Current and emerging pharmacologic therapies for the management of postmenopausal osteoporosis.
2009 Oct
Lasofoxifene, a new selective estrogen receptor modulator for the treatment of osteoporosis and vaginal atrophy.
2009 Sep
Modulators of androgen and estrogen receptor activity.
2010
An innovative method to classify SERMs based on the dynamics of estrogen receptor transcriptional activity in living animals.
2010 Apr
Long-term safety and efficacy of raloxifene in the prevention and treatment of postmenopausal osteoporosis: an update.
2010 Aug 9
Lasofoxifene in osteoporosis and its place in therapy.
2010 Dec
Another selective estrogen-receptor modulator for osteoporosis.
2010 Feb 25
Lasofoxifene in postmenopausal women with osteoporosis.
2010 Feb 25
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
Interest of lasofoxifene in the treatment of osteoporosis. Evaluation of "Lasofoxifene in postmenopausal women with osteoporosis". N Engl J Med 2010;362:686-96.
2010 Jul
Therapeutics. Lasofoxifene reduced vertebral fractures in postmenopausal women with osteoporosis.
2010 Jul 20
Lasofoxifene for postmenopausal women with osteoporosis.
2010 Jun 10
Lasofoxifene for postmenopausal women with osteoporosis.
2010 Jun 10
Lasofoxifene: Evidence of its therapeutic value in osteoporosis.
2010 Jun 15
Safety of bazedoxifene in a randomized, double-blind, placebo- and active-controlled Phase 3 study of postmenopausal women with osteoporosis.
2010 Jun 22
SERMs in the prevention and treatment of postmenopausal osteoporosis: an update.
2010 Mar
Endometrial safety: a key hurdle for selective estrogen receptor modulators in development.
2010 May-Jun
What is the best balance of benefits and risks among anti-resorptive therapies for postmenopausal osteoporosis?
2010 Nov
Third-generation SERMs may face uphill battle.
2010 Nov 17
Tipping the balance for the primary prevention of breast cancer.
2010 Nov 17
Breast cancer incidence in the randomized PEARL trial of lasofoxifene in postmenopausal osteoporotic women.
2010 Nov 17
Evidence-based guidelines for the pharmacological treatment of postmenopausal osteoporosis: a consensus document by the Belgian Bone Club.
2010 Oct
Lasofoxifene and cardiovascular events in postmenopausal women with osteoporosis: Five-year results from the Postmenopausal Evaluation and Risk Reduction with Lasofoxifene (PEARL) trial.
2010 Oct 26
Selective estrogen receptor modulator (SERM) lasofoxifene forms reactive quinones similar to estradiol.
2012 Jul 16
Patents

Sample Use Guides

500 ug daily. The tablet may be taken any time of day without regard to food and beverage intake.
Route of Administration: Oral
In Vitro Use Guide
Lasofoxifene was determined to be an extremely potent antagonist to the growth of estrogen-dependent MCF-7 breast cancer cell line (IC50 =0.05 nM).
Substance Class Chemical
Created
by admin
on Sat Jun 26 12:21:13 UTC 2021
Edited
by admin
on Sat Jun 26 12:21:13 UTC 2021
Record UNII
337G83N988
Record Status Validated (UNII)
Record Version
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Name Type Language
LASOFOXIFENE
EMA EPAR   INN   MART.   MI   WHO-DD  
INN  
Official Name English
LASOFOXIFENE [MI]
Common Name English
LASOFOXIFENE [MART.]
Common Name English
LASOFOXIFENE [WHO-DD]
Common Name English
LASOFOXIFENE [EMA EPAR]
Common Name English
(-)-CIS-5,6,7,8-TETRAHYDRO-6-PHENYL-5-(P-(2-(1-PYRROLIDINYL)ETHOXY)PHENYL)-2-NAPHTHOL
Common Name English
LASOFOXIFENE [INN]
Common Name English
Classification Tree Code System Code
WHO-VATC QG03XC03
Created by admin on Sat Jun 26 12:21:14 UTC 2021 , Edited by admin on Sat Jun 26 12:21:14 UTC 2021
NCI_THESAURUS C1821
Created by admin on Sat Jun 26 12:21:14 UTC 2021 , Edited by admin on Sat Jun 26 12:21:14 UTC 2021
WHO-ATC G03XC03
Created by admin on Sat Jun 26 12:21:14 UTC 2021 , Edited by admin on Sat Jun 26 12:21:14 UTC 2021
Code System Code Type Description
PUBCHEM
216416
Created by admin on Sat Jun 26 12:21:14 UTC 2021 , Edited by admin on Sat Jun 26 12:21:14 UTC 2021
PRIMARY
DRUG CENTRAL
4308
Created by admin on Sat Jun 26 12:21:14 UTC 2021 , Edited by admin on Sat Jun 26 12:21:14 UTC 2021
PRIMARY
EPA CompTox
180916-16-9
Created by admin on Sat Jun 26 12:21:14 UTC 2021 , Edited by admin on Sat Jun 26 12:21:14 UTC 2021
PRIMARY
DRUG BANK
DB06202
Created by admin on Sat Jun 26 12:21:14 UTC 2021 , Edited by admin on Sat Jun 26 12:21:14 UTC 2021
PRIMARY
CAS
180916-16-9
Created by admin on Sat Jun 26 12:21:14 UTC 2021 , Edited by admin on Sat Jun 26 12:21:14 UTC 2021
PRIMARY
NCI_THESAURUS
C80679
Created by admin on Sat Jun 26 12:21:14 UTC 2021 , Edited by admin on Sat Jun 26 12:21:14 UTC 2021
PRIMARY
FDA UNII
337G83N988
Created by admin on Sat Jun 26 12:21:14 UTC 2021 , Edited by admin on Sat Jun 26 12:21:14 UTC 2021
PRIMARY
MERCK INDEX
M6700
Created by admin on Sat Jun 26 12:21:14 UTC 2021 , Edited by admin on Sat Jun 26 12:21:14 UTC 2021
PRIMARY Merck Index
WIKIPEDIA
Lasofoxifene
Created by admin on Sat Jun 26 12:21:14 UTC 2021 , Edited by admin on Sat Jun 26 12:21:14 UTC 2021
PRIMARY
EVMPD
SUB27754
Created by admin on Sat Jun 26 12:21:14 UTC 2021 , Edited by admin on Sat Jun 26 12:21:14 UTC 2021
PRIMARY
INN
7875
Created by admin on Sat Jun 26 12:21:14 UTC 2021 , Edited by admin on Sat Jun 26 12:21:14 UTC 2021
PRIMARY
ChEMBL
CHEMBL328190
Created by admin on Sat Jun 26 12:21:14 UTC 2021 , Edited by admin on Sat Jun 26 12:21:14 UTC 2021
PRIMARY
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SALT/SOLVATE -> PARENT
METABOLIC ENZYME -> SUBSTRATE
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METABOLIC ENZYME -> SUBSTRATE
EXCRETED UNCHANGED
FECAL
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TARGET -> AGONIST
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EXCRETED UNCHANGED
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