Details of the Drug

General Information of Drug (ID: DMHA18P)

Drug Name

Lasofoxifene

Synonyms

Oporia; 180916-16-9; rac-Lasofoxifene; CP 336156; Fablyn; UNII-337G83N988; (5R,6S)-6-phenyl-5-[4-(2-pyrrolidin-1-ylethoxy)phenyl]-5,6,7,8-tetrahydronaphthalen-2-ol; CHEMBL328190; 337G83N988; (-)-cis-5,6,7,8-Tetrahydro-6-phenyl-5-(p-(2-(1-pyrrolidinyl)ethoxy)phenyl)-2-naphthol; 180915-78-0; CP-336,156; LASOFOXIFENE HCL; Lasofoxifene [INN:BAN]; AC1L50OI; SCHEMBL26815; GTPL7542; CTK8F1062; BDBM20606; DTXSID50171037; GXESHMAMLJKROZ-IAPPQJPRSA-N; ZINC3918428; BCP03626; AKOS030241621; AN-3516; BCP9000842; DB06202; Oporia; Lasofoxifene [INN]; Cis-1R-(4'-pyrrolidinoethoxyphenyl)-2S-phenyl-6-hydroxy-1,2,3,4-tetrahydronaphthalene, tartrate salt; AZD9639

Indication

Disease Entry	ICD 11	Status	REF
Osteoporosis	FB83.0	Approved	[1], [2]
Virus infection	1A24-1D9Z	Discontinued in Phase 1	[3]

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 1

Molecular Weight (mw)

413.5

Topological Polar Surface Area (xlogp)

6.1

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Absorption Tmax: The time to maximum plasma concentration (Tmax) is 6.0-7.3 h [4]
Clearance: The apparent oral clearance of drug is 6.6 l L/h [5]
Half-life: The concentration or amount of drug in body reduced by one-half in 6 days [6]
Metabolism: The drug is metabolized via the hepatic CYP3A4/CYP3A5 and CYP2D6 accounts for nearly half of total metabolism of lasofoxifene [5]
Vd: The volume of distribution (Vd) of drug is 1350 L [5]

Chemical Identifiers

Formula: C28H31NO2
IUPAC Name: (5R,6S)-6-phenyl-5-[4-(2-pyrrolidin-1-ylethoxy)phenyl]-5,6,7,8-tetrahydronaphthalen-2-ol
Canonical SMILES: C1CCN(C1)CCOC2=CC=C(C=C2)[C@H]3[C@H](CCC4=C3C=CC(=C4)O)C5=CC=CC=C5
InChI: 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
InChIKey: GXESHMAMLJKROZ-IAPPQJPRSA-N

Cross-matching ID

PubChem CID: 216416
ChEBI ID: CHEBI:135938
CAS Number: 180916-16-9
DrugBank ID: DB06202
TTD ID: D09NMD

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Estrogen receptor (ESR)	TTZAYWL	ESR1_HUMAN	Modulator	[2]
Respiratory syncytial virus protein F (RSV F)	TT57ID8	FUS_HRSVA	Modulator	[7]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

References

1	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7542).
2	Pfizer. Product Development Pipeline. March 31 2009.
3	Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800026623)
4	Lewiecki EM: Lasofoxifene for the prevention and treatment of postmenopausal osteoporosis. Ther Clin Risk Manag. 2009;5:817-27. Epub 2009 Nov 2.
5	EMA Summary of product characteristics
6	Lasofoxifene: Evidence of its therapeutic value in osteoporosis. Core Evid. 2010 Jun 15;4:113-29.
7	Prospects for the development of fusion inhibitors to treat human respiratory syncytial virus infection. Curr Opin Drug Discov Devel. 2009 Jul;12(4):479-87.
8	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
9	Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800040470)
10	Motavizumab. Correction in: MAbs. 2010 Sep-Oct; 2(5): 591.
11	A potent broadly neutralizing human RSV antibody targets conserved site IV of the fusion glycoprotein. Nat Commun. 2019 Sep 12;10(1):4153.
12	Discovery of an oral respiratory syncytial virus (RSV) fusion inhibitor (GS-5806) and clinical proof of concept in a human RSV challenge study. J Med Chem. 2015 Feb 26;58(4):1630-43.
13	Discovery of Sisunatovir (RV521), an Inhibitor of Respiratory Syncytial Virus Fusion. J Med Chem. 2021 Apr 8;64(7):3658-3676.
14	Antiviral Activity of Oral JNJ-53718678 in Healthy Adult Volunteers Challenged With Respiratory Syncytial Virus: A Placebo-Controlled Study. J Infect Dis. 2018 Jul 24;218(5):748-756.
15	Respiratory Syncytial Virus Entry Inhibitors Targeting the F Protein. Viruses. 2013 January; 5(1): 211-225.
16	Modulators of vascular sex hormone receptors and their effects in estrogen-deficiency states associated with menopause. Recent Pat Cardiovasc Drug Discov. 2008 Nov;3(3):165-86.
17	Reprint of Are all estrogens the same Maturitas. 2008 Sep-Oct;61(1-2):195-201.
18	17alpha-Ethinylestradiol hinders nucleotide excision repair in zebrafish liver cells. Aquat Toxicol. 2009 Dec 13;95(4):273-8.
19	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 620).
20	Clinical pipeline report, company report or official report of Shionogi (2011).
21	Effect of selective estrogen receptor modulators on cell proliferation and estrogen receptor activities in normal human prostate stromal and epithe... Prostate Cancer Prostatic Dis. 2009;12(4):375-81.