U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C28H31NO2.C4H6O6
Molecular Weight 563.6381
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LASOFOXIFENE TARTRATE

SMILES

O[C@@H]([C@H](O)C(O)=O)C(O)=O.OC1=CC2=C(C=C1)[C@H]([C@H](CC2)C3=CC=CC=C3)C4=CC=C(OCCN5CCCC5)C=C4

InChI

InChIKey=INEHJXCWEVNEDZ-LUDNRVPPSA-N
InChI=1S/C28H31NO2.C4H6O6/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;5-1(3(7)8)2(6)4(9)10/h1-3,6-9,11-13,15,20,26,28,30H,4-5,10,14,16-19H2;1-2,5-6H,(H,7,8)(H,9,10)/t26-,28+;1-,2-/m10/s1

HIDE SMILES / InChI

Molecular Formula C4H6O6
Molecular Weight 150.0868
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

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 Lasofoxifene approved in the EU in 2009 is now withdrawn from use in the European Union.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
Target specificity of selective estrogen receptor modulators within human endometrial cancer cells.
2003 Jul
Selective estrogen receptor modulators protect hippocampal neurons from kainic acid excitotoxicity: differences with the effect of estradiol.
2004 Nov
Differential effects of estrogen and raloxifene on messenger RNA and matrix metalloproteinase 2 activity in the rat uterus.
2005 Apr
Lasofoxifene (Pfizer).
2005 Oct
[Next generation selective estrogen receptor modulators].
2006 Jan
Clinical pharmacology of multiple doses of lasofoxifene in postmenopausal women.
2006 Jan
A single-dose pharmacokinetic study of lasofoxifene in healthy volunteers and subjects with mild and moderate hepatic impairment.
2006 Jan
Effects of lasofoxifene on the pharmacokinetics and pharmacodynamics of single-dose warfarin.
2006 Jun
Management of age-related osteoporosis and prevention of associated fractures.
2006 Sep
Lasofoxifene: a third-generation selective estrogen receptor modulator for the prevention and treatment of osteoporosis.
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
Selective estrogen receptor modulators for postmenopausal osteoporosis: current state of development.
2007
The future of the new selective estrogen receptor modulators.
2007 Mar
The 2.0 A crystal structure of the ERalpha ligand-binding domain complexed with lasofoxifene.
2007 May
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
Validation of a dissolution method with HPLC analysis for lasofoxifene tartrate low dose tablets.
2007 Sep 3
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
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
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
Docking study of triphenylphosphonium cations as estrogen receptor alpha modulators.
2009
Thresholds for therapies: highlights of the St Gallen International Expert Consensus on the primary therapy of early breast cancer 2009.
2009 Aug
A randomised, double-blinded, placebo-controlled, trial to determine the individual response in bone turnover markers to lasofoxifene therapy.
2009 Dec
New selective estrogen and androgen receptor modulators.
2009 Jul
Designing the ideal selective estrogen receptor modulator--an achievable goal?
2009 May-Jun
Modulators of androgen and estrogen receptor activity.
2010
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
Selective estrogen receptor modulator (SERM) for the treatment of osteoporosis in postmenopausal women: focus on lasofoxifene.
2010 Feb 2
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
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 for postmenopausal women with osteoporosis.
2010 Jun 10
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
Breast cancer incidence in the randomized PEARL trial of lasofoxifene in postmenopausal osteoporotic women.
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 15:47:27 GMT 2023
Edited
by admin
on Fri Dec 15 15:47:27 GMT 2023
Record UNII
85X09V2GSO
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
LASOFOXIFENE TARTRATE
DASH   JAN   MART.   MI   USAN  
USAN  
Official Name English
LASOFOXIFENE D-TARTRATE
Common Name English
CP-336156-CB
Code English
CP-336156
Code English
CB-336156EB
Code English
2-Naphthalenol, 5,6,7,8-tetrahydro-6-phenyl-5-[4-[2-(1-pyrrolidinyl)ethoxy]phenyl]-, (5R,6S)-, (2S,3S)-2,3-dihydroxybutanedioate (1:1)
Systematic Name English
LASOFOXIFENE TARTRATE [JAN]
Common Name English
CP-336,156-CB
Code English
FABLYN
Brand Name English
(-)-CIS-5,6,7,8-TETRAHYDRO-6-PHENYL-5-(P-(2-(1-PYRROLIDINYL)ETHOXY)PHENYL))-2-NAPHTHOL D-TARTRATE (1:1)
Common Name English
LASOFOXIFENE TARTRATE [USAN]
Common Name English
Lasofoxifene tartrate [WHO-DD]
Common Name English
OPORIA
Brand Name English
LASOFOXIFENE TARTRATE [MI]
Common Name English
LASOFOXIFENE TARTRATE [MART.]
Common Name English
Classification Tree Code System Code
EMA ASSESSMENT REPORTS FABLYN (WITHDRAWN: OSTEOPOROSIS, POSTMENOPAUSAL)
Created by admin on Fri Dec 15 15:47:27 GMT 2023 , Edited by admin on Fri Dec 15 15:47:27 GMT 2023
NCI_THESAURUS C1821
Created by admin on Fri Dec 15 15:47:27 GMT 2023 , Edited by admin on Fri Dec 15 15:47:27 GMT 2023
Code System Code Type Description
FDA UNII
85X09V2GSO
Created by admin on Fri Dec 15 15:47:27 GMT 2023 , Edited by admin on Fri Dec 15 15:47:27 GMT 2023
PRIMARY
DRUG BANK
DBSALT001953
Created by admin on Fri Dec 15 15:47:27 GMT 2023 , Edited by admin on Fri Dec 15 15:47:27 GMT 2023
PRIMARY
PUBCHEM
3081919
Created by admin on Fri Dec 15 15:47:27 GMT 2023 , Edited by admin on Fri Dec 15 15:47:27 GMT 2023
PRIMARY
CAS
190791-29-8
Created by admin on Fri Dec 15 15:47:27 GMT 2023 , Edited by admin on Fri Dec 15 15:47:27 GMT 2023
PRIMARY
SMS_ID
100000092749
Created by admin on Fri Dec 15 15:47:27 GMT 2023 , Edited by admin on Fri Dec 15 15:47:27 GMT 2023
PRIMARY
USAN
KK-66
Created by admin on Fri Dec 15 15:47:27 GMT 2023 , Edited by admin on Fri Dec 15 15:47:27 GMT 2023
PRIMARY
EVMPD
SUB30307
Created by admin on Fri Dec 15 15:47:27 GMT 2023 , Edited by admin on Fri Dec 15 15:47:27 GMT 2023
PRIMARY
NCI_THESAURUS
C80680
Created by admin on Fri Dec 15 15:47:27 GMT 2023 , Edited by admin on Fri Dec 15 15:47:27 GMT 2023
PRIMARY
EPA CompTox
DTXSID60940655
Created by admin on Fri Dec 15 15:47:27 GMT 2023 , Edited by admin on Fri Dec 15 15:47:27 GMT 2023
PRIMARY
MERCK INDEX
m6700
Created by admin on Fri Dec 15 15:47:27 GMT 2023 , Edited by admin on Fri Dec 15 15:47:27 GMT 2023
PRIMARY Merck Index
CHEBI
135938
Created by admin on Fri Dec 15 15:47:27 GMT 2023 , Edited by admin on Fri Dec 15 15:47:27 GMT 2023
PRIMARY
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PARENT -> SALT/SOLVATE
PARENT -> SALT/SOLVATE
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ACTIVE MOIETY