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Details

Stereochemistry ABSOLUTE
Molecular Formula C28H31NO2
Molecular Weight 413.5512
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LASOFOXIFENE

SMILES

OC1=CC=C2[C@H]([C@H](CCC2=C1)C3=CC=CC=C3)C4=CC=C(OCCN5CCCC5)C=C4

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 413.5512
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 Lasofoxifene approved in the EU in 2009 is now withdrawn from use in the European Union.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
Lasofoxifene (CP-336,156) protects against the age-related changes in bone mass, bone strength, and total serum cholesterol in intact aged male rats.
2001 Apr
LAS, a novel selective estrogen receptor modulator with chemopreventive and therapeutic activity in the N-nitroso-N-methylurea-induced rat mammary tumor model.
2001 Dec 15
Embryo/fetal toxicity assessment of lasofoxifene, a selective estrogen receptor modulator (SERM), in rats and rabbits.
2004 Jun
Reproductive toxicity assessment of lasofoxifene, a selective estrogen receptor modulator (SERM), in female rats.
2004 Jun
Selective estrogen receptor modulators protect hippocampal neurons from kainic acid excitotoxicity: differences with the effect of estradiol.
2004 Nov
[Lasofoxifene, a next generation estrogen receptor modulator: preclinical studies].
2004 Oct
Differential effects of estrogen and raloxifene on messenger RNA and matrix metalloproteinase 2 activity in the rat uterus.
2005 Apr
Estrogen receptor ligands. Part 11: Synthesis and activity of isochromans and isothiochromans.
2005 Feb 1
Selective estrogen receptor modulators with conformationally restricted side chains. Synthesis and structure-activity relationship of ERalpha-selective tetrahydroisoquinoline ligands.
2005 Jan 27
Lasofoxifene (Pfizer).
2005 Oct
Urogenital effects of selective estrogen receptor modulators: a systematic review.
2005 Sep
Prevention of breast cancer using selective oestrogen receptor modulators (SERMs).
2006
Developments in the pharmacotherapeutic management of osteoporosis.
2006 Aug
A single-dose pharmacokinetic study of lasofoxifene in healthy volunteers and subjects with mild and moderate hepatic impairment.
2006 Jan
Lasofoxifene enhances vaginal mucus formation without causing hypertrophy and increases estrogen receptor beta and androgen receptor in rats.
2006 Jul-Aug
Effects of lasofoxifene on the pharmacokinetics and pharmacodynamics of single-dose warfarin.
2006 Jun
Prevention of bone loss in postmenopausal women treated with lasofoxifene compared with raloxifene.
2006 May-Jun
Not all SERMs are created equal.
2006 May-Jun
Update on bazedoxifene: a novel selective estrogen receptor modulator.
2007
Effects of three cytochrome P450 inhibitors, ketoconazole, fluconazole, and paroxetine, on the pharmacokinetics of lasofoxifene.
2007 Jan
Effects of lasofoxifene on bone in surgically postmenopausal cynomolgus monkeys.
2007 Jan-Feb
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
Activity of three selective estrogen receptor modulators on hormone-dependent responses in the mouse uterus and mammary gland.
2008 Jun 11
Metabolism, distribution, and excretion of a next generation selective estrogen receptor modulator, lasofoxifene, in rats and monkeys.
2008 Sep
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
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
Designing the ideal selective estrogen receptor modulator--an achievable goal?
2009 May-Jun
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
Lasofoxifene in osteoporosis and its place in therapy.
2010 Dec
Selective estrogen receptor modulator (SERM) for the treatment of osteoporosis in postmenopausal women: focus on lasofoxifene.
2010 Feb 2
Another selective estrogen-receptor modulator for osteoporosis.
2010 Feb 25
Lasofoxifene in postmenopausal women with osteoporosis.
2010 Feb 25
Therapeutics. Lasofoxifene reduced vertebral fractures in postmenopausal women with osteoporosis.
2010 Jul 20
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
Third-generation SERMs may face uphill battle.
2010 Nov 17
Tipping the balance for the primary prevention of breast cancer.
2010 Nov 17
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
New selective estrogen receptor modulators (SERMs) in development.
2010 Sep
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 Fri Dec 15 16:03:54 GMT 2023
Edited
by admin
on Fri Dec 15 16:03:54 GMT 2023
Record UNII
337G83N988
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
LASOFOXIFENE
EMA EPAR   INN   MART.   MI   WHO-DD  
INN  
Official Name English
Lasofoxifene [WHO-DD]
Common Name English
LASOFOXIFENE [MI]
Common Name English
LASOFOXIFENE [MART.]
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 Fri Dec 15 16:03:55 GMT 2023 , Edited by admin on Fri Dec 15 16:03:55 GMT 2023
NCI_THESAURUS C1821
Created by admin on Fri Dec 15 16:03:55 GMT 2023 , Edited by admin on Fri Dec 15 16:03:55 GMT 2023
WHO-ATC G03XC03
Created by admin on Fri Dec 15 16:03:55 GMT 2023 , Edited by admin on Fri Dec 15 16:03:55 GMT 2023
Code System Code Type Description
CHEBI
135938
Created by admin on Fri Dec 15 16:03:55 GMT 2023 , Edited by admin on Fri Dec 15 16:03:55 GMT 2023
PRIMARY
SMS_ID
100000092767
Created by admin on Fri Dec 15 16:03:55 GMT 2023 , Edited by admin on Fri Dec 15 16:03:55 GMT 2023
PRIMARY
PUBCHEM
216416
Created by admin on Fri Dec 15 16:03:55 GMT 2023 , Edited by admin on Fri Dec 15 16:03:55 GMT 2023
PRIMARY
DRUG CENTRAL
4308
Created by admin on Fri Dec 15 16:03:55 GMT 2023 , Edited by admin on Fri Dec 15 16:03:55 GMT 2023
PRIMARY
EPA CompTox
DTXSID50171037
Created by admin on Fri Dec 15 16:03:55 GMT 2023 , Edited by admin on Fri Dec 15 16:03:55 GMT 2023
PRIMARY
DRUG BANK
DB06202
Created by admin on Fri Dec 15 16:03:55 GMT 2023 , Edited by admin on Fri Dec 15 16:03:55 GMT 2023
PRIMARY
CAS
180916-16-9
Created by admin on Fri Dec 15 16:03:55 GMT 2023 , Edited by admin on Fri Dec 15 16:03:55 GMT 2023
PRIMARY
NCI_THESAURUS
C80679
Created by admin on Fri Dec 15 16:03:55 GMT 2023 , Edited by admin on Fri Dec 15 16:03:55 GMT 2023
PRIMARY
FDA UNII
337G83N988
Created by admin on Fri Dec 15 16:03:55 GMT 2023 , Edited by admin on Fri Dec 15 16:03:55 GMT 2023
PRIMARY
MERCK INDEX
m6700
Created by admin on Fri Dec 15 16:03:55 GMT 2023 , Edited by admin on Fri Dec 15 16:03:55 GMT 2023
PRIMARY Merck Index
WIKIPEDIA
Lasofoxifene
Created by admin on Fri Dec 15 16:03:55 GMT 2023 , Edited by admin on Fri Dec 15 16:03:55 GMT 2023
PRIMARY
EVMPD
SUB27754
Created by admin on Fri Dec 15 16:03:55 GMT 2023 , Edited by admin on Fri Dec 15 16:03:55 GMT 2023
PRIMARY
INN
7875
Created by admin on Fri Dec 15 16:03:55 GMT 2023 , Edited by admin on Fri Dec 15 16:03:55 GMT 2023
PRIMARY
ChEMBL
CHEMBL328190
Created by admin on Fri Dec 15 16:03:55 GMT 2023 , Edited by admin on Fri Dec 15 16:03:55 GMT 2023
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
EXCRETED UNCHANGED
FECAL
METABOLIC ENZYME -> SUBSTRATE
TARGET -> AGONIST
METABOLIC ENZYME -> SUBSTRATE
EXCRETED UNCHANGED
URINE
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
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ACTIVE MOIETY