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

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 Lasofoxifene approved in the EU in 2009 is now withdrawn from use in the European Union.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 828		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 828

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http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000977/WC500020092.pdf	Primary	Withdrawn	Fablyn Approved Use Treatment of osteoporosis in postmenopausal women at increased risk of fracture Launch Date 2009
Advanced breast cancer 6 Sources: http://adisinsight.springer.com/trials/700282284	Primary	Phase III 656	Unknown Approved Use Unknown
Female sexual dysfunction 5 Sources: http://adisinsight.springer.com/drugs/800007522	Primary	Phase II 1132	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Developments in the pharmacotherapeutic management of osteoporosis.	2006 Aug	16872263
Lasofoxifene: a new type of selective estrogen receptor modulator for the treatment of osteoporosis.	2006 Jun	16845439
Management of age-related osteoporosis and prevention of associated fractures.	2006 Sep	18360603
The 2.0 A crystal structure of the ERalpha ligand-binding domain complexed with lasofoxifene.	2007 May	17456742
[Status of novel bone-targeting SERMs in development].	2007 Nov 28	18161145
Validation of a dissolution method with HPLC analysis for lasofoxifene tartrate low dose tablets.	2007 Sep 3	17560750
Effects of lasofoxifene on the uterus, vagina, and breast in ovariectomized cynomolgus monkeys (Macaca fascicularis).	2008 Aug	18501325
Bazedoxifene for the prevention of postmenopausal osteoporosis.	2008 Dec	19337430
Hormone-dependent aging problems in women.	2008 Jun 30	18581581
Selective estrogen receptor modulators: an update on recent clinical findings.	2008 Mar	18279543
Effects of selective oestrogen receptor modulators on proliferation in tissue cultures of pre- and postmenopausal human endometrium.	2008 Nov	18832036
Lasofoxifene for the prevention and treatment of postmenopausal osteoporosis.	2009	19898646
Progress in osteoporosis and fracture prevention: focus on postmenopausal women.	2009	19849819
Clinical issues regarding cardiovascular disease and selective estrogen receptor modulators in postmenopausal women.	2009	19811253
Docking study of triphenylphosphonium cations as estrogen receptor alpha modulators.	2009	19293997
Treatment of osteoporosis with annual iv zoledronic acid: effects on hip fracture.	2009 Apr	19536314
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
Recent advances in managing osteoporosis.	2009 Dec 15	20948681
New selective estrogen and androgen receptor modulators.	2009 Jul	19412100
Designing the ideal selective estrogen receptor modulator--an achievable goal?	2009 May-Jun	19182697
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
Therapeutics. Lasofoxifene reduced vertebral fractures in postmenopausal women with osteoporosis.	2010 Jul 20	20643977
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
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
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
Breast cancer incidence in the randomized PEARL trial of lasofoxifene in postmenopausal osteoporotic women.	2010 Nov 17	21051656
Evidence-based guidelines for the pharmacological treatment of postmenopausal osteoporosis: a consensus document by the Belgian Bone Club.	2010 Oct	20480148
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	20937977
New selective estrogen receptor modulators (SERMs) in development.	2010 Sep	20603714
Selective estrogen receptor modulator (SERM) lasofoxifene forms reactive quinones similar to estradiol.	2012 Jul 16	22642258

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).

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)