LASOFOXIFENE

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 Search

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

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 Lasofoxifene approved in the EU in 2009 is now withdrawn from use in the European Union.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 817		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 817

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http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000977/WC500020092.pdf	Primary	Withdrawn	Fablyn Approved Use Treatment of osteoporosis in postmenopausal women at increased risk of fracture Launch Date 1.23534718E12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 651	Unknown Approved Use Unknown
Female sexual dysfunction 5 Sources: http://adisinsight.springer.com/drugs/800007522	Primary	Phase II 1133	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
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	11316005
Chemical and biochemical issues related to X-ray crystallography of the ligand-binding domain of estrogen receptor alpha.	2001 May-Jun	11353539
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
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
Selective estrogen receptor modulators for postmenopausal osteoporosis: current state of development.	2007	17503894
Validation of a dissolution method with HPLC analysis for lasofoxifene tartrate low dose tablets.	2007 Sep 3	17560750
Bazedoxifene for the prevention of postmenopausal osteoporosis.	2008 Dec	19337430
Hormone-dependent aging problems in women.	2008 Jun 30	18581581
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
Clinical issues regarding cardiovascular disease and selective estrogen receptor modulators in postmenopausal women.	2009	19811253
Treatment of osteoporosis with annual iv zoledronic acid: effects on hip fracture.	2009 Apr	19536314
Thresholds for therapies: highlights of the St Gallen International Expert Consensus on the primary therapy of early breast cancer 2009.	2009 Aug	19535820
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
Selective estrogen receptor modulator (SERM) for the treatment of osteoporosis in postmenopausal women: focus on lasofoxifene.	2010 Feb 2	20169039
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
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
Tipping the balance for the primary prevention of breast cancer.	2010 Nov 17	21051657

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 `Fri Dec 16 19:07:23 UTC 2022` Edited by `admin` on `Fri Dec 16 19:07:23 UTC 2022`
Record UNII	337G83N988
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

LASOFOXIFENE

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