LASOFOXIFENE TARTRATE

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 Search

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	C28H31NO2
Molecular Weight	413.5512
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

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

Description
Sources: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000977/WC500020092.pdf | https://www.ncbi.nlm.nih.gov/pubmed/16916275 | https://www.ncbi.nlm.nih.gov/pubmed/16368922

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 Lasofoxifene approved in the EU in 2009 is now withdrawn from use in the European Union.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

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Estrogen receptor alpha 127 Target ID: CHEMBL206 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16916275 \| http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000977/WC500020092.pdf	Modulator 822		15.0 nM [IC50]
Estrogen receptor beta 110 Target ID: CHEMBL242 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16916275 \| http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000977/WC500020092.pdf	Modulator 822

Conditions

Condition	Modality	Highest Phase	Product
Osteoporosis in postmenopausal women 6 Sources: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000977/WC500020092.pdf	Primary	Withdrawn	Fablyn Approved Use Treatment of osteoporosis in postmenopausal women at increased risk of fracture Launch Date 1.23534718E12
Advanced breast cancer 6 Sources: http://adisinsight.springer.com/trials/700282284	Primary	Phase III 663	Unknown Approved Use Unknown
Female sexual dysfunction 5 Sources: http://adisinsight.springer.com/drugs/800007522	Primary	Phase II 1144	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
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	11751385
Target specificity of selective estrogen receptor modulators within human endometrial cancer cells.	2003 Jul	12943742
Long-term treatment of lasofoxifene preserves bone mass and bone strength and does not adversely affect the uterus in ovariectomized rats.	2004 Apr	14726439
Endocrinology and hormone therapy in breast cancer: selective oestrogen receptor modulators and downregulators for breast cancer - have they lost their way?	2005	15987442
Differential effects of estrogen and raloxifene on messenger RNA and matrix metalloproteinase 2 activity in the rat uterus.	2005 Apr	15576828
Estrogen receptor ligands. Part 11: Synthesis and activity of isochromans and isothiochromans.	2005 Feb 1	15664843
[Next generation selective estrogen receptor modulators].	2006 Jan	16397365
Clinical pharmacology of multiple doses of lasofoxifene in postmenopausal women.	2006 Jan	16397284
A single-dose pharmacokinetic study of lasofoxifene in healthy volunteers and subjects with mild and moderate hepatic impairment.	2006 Jan	16397281
Not all SERMs are created equal.	2006 May-Jun	16735926
Lasofoxifene: a third-generation selective estrogen receptor modulator for the prevention and treatment of osteoporosis.	2006 Sep	16916275
Update on bazedoxifene: a novel selective estrogen receptor modulator.	2007	18044180
Effect of estrogens on skin aging and the potential role of SERMs.	2007	18044179
Effects of lasofoxifene on bone in surgically postmenopausal cynomolgus monkeys.	2007 Jan-Feb	17075430
Bazedoxifene: bazedoxifene acetate, TSE 424, TSE-424, WAY 140424.	2008	18457472
Bazedoxifene for the prevention of postmenopausal osteoporosis.	2008 Dec	19337430
Disposition of lasofoxifene, a next-generation selective estrogen receptor modulator, in healthy male subjects.	2008 Jul	18372400
Activity of three selective estrogen receptor modulators on hormone-dependent responses in the mouse uterus and mammary gland.	2008 Jun 11	18367319
Lasofoxifene for the prevention and treatment of postmenopausal osteoporosis.	2009	19898646
Docking study of triphenylphosphonium cations as estrogen receptor alpha modulators.	2009	19293997
Effects of various selective estrogen receptor modulators with or without conjugated estrogens on mouse mammary gland.	2009 Apr	19022889
Thresholds for therapies: highlights of the St Gallen International Expert Consensus on the primary therapy of early breast cancer 2009.	2009 Aug	19535820
Lasofoxifene: new drug. Osteoporosis: no better than raloxifene.	2009 Dec	20020572
A randomised, double-blinded, placebo-controlled, trial to determine the individual response in bone turnover markers to lasofoxifene therapy.	2009 Dec	19665601
New selective estrogen and androgen receptor modulators.	2009 Jul	19412100
Current and emerging pharmacologic therapies for the management of postmenopausal osteoporosis.	2009 Oct	19857095
Lasofoxifene, a new selective estrogen receptor modulator for the treatment of osteoporosis and vaginal atrophy.	2009 Sep	19640205
Modulators of androgen and estrogen receptor activity.	2010	21395502
An innovative method to classify SERMs based on the dynamics of estrogen receptor transcriptional activity in living animals.	2010 Apr	20197311
Long-term safety and efficacy of raloxifene in the prevention and treatment of postmenopausal osteoporosis: an update.	2010 Aug 9	21072271
Lasofoxifene in osteoporosis and its place in therapy.	2010 Dec	21080249
Selective estrogen receptor modulator (SERM) for the treatment of osteoporosis in postmenopausal women: focus on lasofoxifene.	2010 Feb 2	20169039
Another selective estrogen-receptor modulator for osteoporosis.	2010 Feb 25	20181977
Lasofoxifene in postmenopausal women with osteoporosis.	2010 Feb 25	20181970
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
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	20446861
Lasofoxifene for postmenopausal women with osteoporosis.	2010 Jun 10	20568310
Lasofoxifene for postmenopausal women with osteoporosis.	2010 Jun 10	20568309
Lasofoxifene for postmenopausal women with osteoporosis.	2010 Jun 10	20558377
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
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
Third-generation SERMs may face uphill battle.	2010 Nov 17	21060064
Tipping the balance for the primary prevention of breast cancer.	2010 Nov 17	21051657
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

Patents

Sample Use Guides

In Vivo Use Guide

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 `Wed Jul 05 23:15:55 UTC 2023` Edited by `admin` on `Wed Jul 05 23:15:55 UTC 2023`
Record UNII	85X09V2GSO
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

LASOFOXIFENE TARTRATE

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)