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

Details

Stereochemistry ACHIRAL
Molecular Formula C24H23ClO2
Molecular Weight 378.892
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of OSPEMIFENE

SMILES

c1ccc(cc1)/C(=C(/c2ccccc2)\c3ccc(cc3)OCCO)/CCCl

InChI

InChIKey=LUMKNAVTFCDUIE-VHXPQNKSSA-N
InChI=1S/C24H23ClO2/c25-16-15-23(19-7-3-1-4-8-19)24(20-9-5-2-6-10-20)21-11-13-22(14-12-21)27-18-17-26/h1-14,26H,15-18H2/b24-23-

HIDE SMILES / InChI

Molecular Formula C24H23ClO2
Molecular Weight 378.892
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

Ospemifene (commercial name Osphena produced by Shionogi) is anoral medication indicated for the treatment of dyspareunia – pain during sexual intercourse – encountered by some women, more often in those who are post-menopausal. Ospemifene is a selective estrogen receptor modulator (SERM) that selectively binds to estrogen receptors and either stimulates or blocks estrogen's activity in different tissue types. It has an agonistic effect on the endometrium. It’s building vaginal wall thickness which in turn reduces the pain associated with dyspareunia. Dyspareunia is most commonly caused by "vulval and vaginal atrophy”.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P03372
Gene ID: 2099
Gene Symbol: ESR1
Target Organism: Homo sapiens (Human)
827 nM [IC50]
Target ID: Q92731|||O75584
Gene ID: 2100
Gene Symbol: ESR2
Target Organism: Homo sapiens (Human)
1633 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
OSPHENA

Approved Use

Indicated for the treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause

Launch Date

1361836800000
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
533 ng/mL
60 mg single, oral
dose: 60 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
OSPEMIFENE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
4165 ng × h/mL
60 mg single, oral
dose: 60 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
OSPEMIFENE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
26 h
60 mg single, oral
dose: 60 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
OSPEMIFENE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
200 mg 1 times / day steady, oral
Highest studied dose
Dose: 200 mg, 1 times / day
Route: oral
Route: steady
Dose: 200 mg, 1 times / day
Sources:
healthy, 62 years (range: 55 - 75 years)
Health Status: healthy
Age Group: 62 years (range: 55 - 75 years)
Sex: F
Sources:
Disc. AE: Hot flushes, Dizziness...
AEs leading to
discontinuation/dose reduction:
Hot flushes (1 patient)
Dizziness (1 patient)
Chest pain
Sources:
60 mg 1 times / day multiple, oral
Recommended
Dose: 60 mg, 1 times / day
Route: oral
Route: multiple
Dose: 60 mg, 1 times / day
Sources:
unhealthy, adult (Postmenopausal)
Health Status: unhealthy
Age Group: adult (Postmenopausal)
Sex: F
Sources:
Other AEs: Thromboembolic stroke, Hemorrhagic stroke...
Other AEs:
Thromboembolic stroke
Hemorrhagic stroke
Deep vein thrombosis
Sources:
60 mg 1 times / day steady, oral
Recommended
Dose: 60 mg, 1 times / day
Route: oral
Route: steady
Dose: 60 mg, 1 times / day
Sources:
unhealthy, adult (Postmenopausal)
Health Status: unhealthy
Age Group: adult (Postmenopausal)
Sex: F
Sources:
Disc. AE: Nausea, Muscle spasms...
AEs leading to
discontinuation/dose reduction:
Nausea (1%)
Muscle spasms (0.7%)
Headache (1%)
Hyperhidrosis (0.7%)
Rash (0.7%)
Hot flush (2%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Dizziness 1 patient
Disc. AE
200 mg 1 times / day steady, oral
Highest studied dose
Dose: 200 mg, 1 times / day
Route: oral
Route: steady
Dose: 200 mg, 1 times / day
Sources:
healthy, 62 years (range: 55 - 75 years)
Health Status: healthy
Age Group: 62 years (range: 55 - 75 years)
Sex: F
Sources:
Hot flushes 1 patient
Disc. AE
200 mg 1 times / day steady, oral
Highest studied dose
Dose: 200 mg, 1 times / day
Route: oral
Route: steady
Dose: 200 mg, 1 times / day
Sources:
healthy, 62 years (range: 55 - 75 years)
Health Status: healthy
Age Group: 62 years (range: 55 - 75 years)
Sex: F
Sources:
Chest pain Disc. AE
200 mg 1 times / day steady, oral
Highest studied dose
Dose: 200 mg, 1 times / day
Route: oral
Route: steady
Dose: 200 mg, 1 times / day
Sources:
healthy, 62 years (range: 55 - 75 years)
Health Status: healthy
Age Group: 62 years (range: 55 - 75 years)
Sex: F
Sources:
Deep vein thrombosis
60 mg 1 times / day multiple, oral
Recommended
Dose: 60 mg, 1 times / day
Route: oral
Route: multiple
Dose: 60 mg, 1 times / day
Sources:
unhealthy, adult (Postmenopausal)
Health Status: unhealthy
Age Group: adult (Postmenopausal)
Sex: F
Sources:
Hemorrhagic stroke
60 mg 1 times / day multiple, oral
Recommended
Dose: 60 mg, 1 times / day
Route: oral
Route: multiple
Dose: 60 mg, 1 times / day
Sources:
unhealthy, adult (Postmenopausal)
Health Status: unhealthy
Age Group: adult (Postmenopausal)
Sex: F
Sources:
Thromboembolic stroke
60 mg 1 times / day multiple, oral
Recommended
Dose: 60 mg, 1 times / day
Route: oral
Route: multiple
Dose: 60 mg, 1 times / day
Sources:
unhealthy, adult (Postmenopausal)
Health Status: unhealthy
Age Group: adult (Postmenopausal)
Sex: F
Sources:
Hyperhidrosis 0.7%
Disc. AE
60 mg 1 times / day steady, oral
Recommended
Dose: 60 mg, 1 times / day
Route: oral
Route: steady
Dose: 60 mg, 1 times / day
Sources:
unhealthy, adult (Postmenopausal)
Health Status: unhealthy
Age Group: adult (Postmenopausal)
Sex: F
Sources:
Muscle spasms 0.7%
Disc. AE
60 mg 1 times / day steady, oral
Recommended
Dose: 60 mg, 1 times / day
Route: oral
Route: steady
Dose: 60 mg, 1 times / day
Sources:
unhealthy, adult (Postmenopausal)
Health Status: unhealthy
Age Group: adult (Postmenopausal)
Sex: F
Sources:
Rash 0.7%
Disc. AE
60 mg 1 times / day steady, oral
Recommended
Dose: 60 mg, 1 times / day
Route: oral
Route: steady
Dose: 60 mg, 1 times / day
Sources:
unhealthy, adult (Postmenopausal)
Health Status: unhealthy
Age Group: adult (Postmenopausal)
Sex: F
Sources:
Headache 1%
Disc. AE
60 mg 1 times / day steady, oral
Recommended
Dose: 60 mg, 1 times / day
Route: oral
Route: steady
Dose: 60 mg, 1 times / day
Sources:
unhealthy, adult (Postmenopausal)
Health Status: unhealthy
Age Group: adult (Postmenopausal)
Sex: F
Sources:
Nausea 1%
Disc. AE
60 mg 1 times / day steady, oral
Recommended
Dose: 60 mg, 1 times / day
Route: oral
Route: steady
Dose: 60 mg, 1 times / day
Sources:
unhealthy, adult (Postmenopausal)
Health Status: unhealthy
Age Group: adult (Postmenopausal)
Sex: F
Sources:
Hot flush 2%
Disc. AE
60 mg 1 times / day steady, oral
Recommended
Dose: 60 mg, 1 times / day
Route: oral
Route: steady
Dose: 60 mg, 1 times / day
Sources:
unhealthy, adult (Postmenopausal)
Health Status: unhealthy
Age Group: adult (Postmenopausal)
Sex: F
Sources:
Overview

OverviewOther

Other InhibitorOther SubstrateOther Inducer






Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
yes [IC50 10 uM]
yes (co-administration study)
Comment: ospemifene inhibited CYP2B6, CYP2C9, CYP2C19, CYP2C8 and CYP2D6 with IC50 values in the range of 7.8-49 μM
Page: 5, 66
yes [IC50 35 uM]
yes (co-administration study)
Comment: ospemifene inhibited CYP2B6, CYP2C9, CYP2C19, CYP2C8 and CYP2D6 with IC50 values in the range of 7.8-49 μM
Page: 5, 66
yes [IC50 7.8 uM]
yes (co-administration study)
Comment: ospemifene inhibited CYP2B6, CYP2C9, CYP2C19, CYP2C8 and CYP2D6 with IC50 values in the range of 7.8-49 μM
Page: 5, 66
yes
yes
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
yes
yes (co-administration study)
Comment: omeprazole increased Cmax 1.2-fold and AUC 1.17-fold, fluconazole increased Cmax 1.7-fold and AUC 2.7-fold; rifampin reduced Cmax by 51% and AUC by 58%
Page: 9, 11, 18
yes
yes (co-administration study)
Comment: fluconazole increased Cmax 1.7-fold and AUC 2.7-fold; rifampin reduced Cmax by 51% and AUC by 58%
Page: 9, 11, 18
yes
yes (co-administration study)
Comment: ketoconazole increased Cmax 1.5-fold and AUC by 1.4-fold, fluconazole increased Cmax 1.7-fold and AUC 2.7-fold; rifampin reduced Cmax by 51% and AUC by 58%
Page: 9, 10, 11, 18
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Effects of ospemifene, a novel SERM, on vascular markers and function in healthy, postmenopausal women.
2003 Sep-Oct
Effects of ospemifene and raloxifene on biochemical markers of bone turnover in postmenopausal women.
2006
Liver X receptors as regulators of macrophage inflammatory and metabolic pathways.
2011 Aug
Ospemifene metabolism in humans in vitro and in vivo: metabolite identification, quantitation, and CYP assignment of major hydroxylations.
2013
Patents

Sample Use Guides

One tablet (60 mg ) taken orally once daily with food
Route of Administration: Oral
In Vitro Use Guide
The growth inhibitory effects of FC-1271a and its main metabolite are investigated in MCF-7 and MDA-MB-231 human breast cancer cells at doses ranging from 0.1 to 10 uM.
Substance Class Chemical
Created
by admin
on Fri Jun 25 21:27:45 UTC 2021
Edited
by admin
on Fri Jun 25 21:27:45 UTC 2021
Record UNII
B0P231ILBK
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
OSPEMIFENE
DASH   INN   MART.   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
USAN   INN  
Official Name English
(DEAMINOHYDROXY) TOREMIFENE
Common Name English
SENSHIO
Brand Name English
TORE III
Common Name English
OSPEMIFENE [MART.]
Common Name English
OSPEMIFENE [ORANGE BOOK]
Common Name English
OSPEMIFENE [INN]
Common Name English
FC-1271
Code English
OSPEMIFENE [MI]
Common Name English
OSPEMIFENE [WHO-DD]
Common Name English
ETHANOL, 2-(4-((1Z)-4-CHLORO-1,2-DIPHENYL-1-BUTENYL)PHENOXY)-
Systematic Name English
OSPEMIFENE [USAN]
Common Name English
OSPHENA
Brand Name English
OSPEMIFENE [VANDF]
Common Name English
FC-1271A
Code English
2-(P-((Z)-4-CHLORO-1,2-DIPHENYL-1-BUTENYL)PHENOXY)ETHANOL
Common Name English
Classification Tree Code System Code
WHO-VATC QG03XC05
Created by admin on Fri Jun 25 21:27:45 UTC 2021 , Edited by admin on Fri Jun 25 21:27:45 UTC 2021
WHO-ATC G03XC05
Created by admin on Fri Jun 25 21:27:45 UTC 2021 , Edited by admin on Fri Jun 25 21:27:45 UTC 2021
NDF-RT N0000175826
Created by admin on Fri Jun 25 21:27:45 UTC 2021 , Edited by admin on Fri Jun 25 21:27:45 UTC 2021
EMA ASSESSMENT REPORTS SENSHIO (AUTHORIZED: POSTMENOPAUSE)
Created by admin on Fri Jun 25 21:27:45 UTC 2021 , Edited by admin on Fri Jun 25 21:27:45 UTC 2021
NCI_THESAURUS C1821
Created by admin on Fri Jun 25 21:27:45 UTC 2021 , Edited by admin on Fri Jun 25 21:27:45 UTC 2021
Code System Code Type Description
PUBCHEM
3036505
Created by admin on Fri Jun 25 21:27:45 UTC 2021 , Edited by admin on Fri Jun 25 21:27:45 UTC 2021
PRIMARY
NCI_THESAURUS
C76958
Created by admin on Fri Jun 25 21:27:45 UTC 2021 , Edited by admin on Fri Jun 25 21:27:45 UTC 2021
PRIMARY
DRUG BANK
DB04938
Created by admin on Fri Jun 25 21:27:45 UTC 2021 , Edited by admin on Fri Jun 25 21:27:45 UTC 2021
PRIMARY
WIKIPEDIA
Ospemifene
Created by admin on Fri Jun 25 21:27:45 UTC 2021 , Edited by admin on Fri Jun 25 21:27:45 UTC 2021
PRIMARY
MESH
C119141
Created by admin on Fri Jun 25 21:27:45 UTC 2021 , Edited by admin on Fri Jun 25 21:27:45 UTC 2021
PRIMARY
RXCUI
1370971
Created by admin on Fri Jun 25 21:27:45 UTC 2021 , Edited by admin on Fri Jun 25 21:27:45 UTC 2021
PRIMARY RxNorm
ChEMBL
CHEMBL2105395
Created by admin on Fri Jun 25 21:27:45 UTC 2021 , Edited by admin on Fri Jun 25 21:27:45 UTC 2021
PRIMARY
IUPHAR
7349
Created by admin on Fri Jun 25 21:27:45 UTC 2021 , Edited by admin on Fri Jun 25 21:27:45 UTC 2021
PRIMARY
MERCK INDEX
M8261
Created by admin on Fri Jun 25 21:27:45 UTC 2021 , Edited by admin on Fri Jun 25 21:27:45 UTC 2021
PRIMARY Merck Index
CAS
128607-22-7
Created by admin on Fri Jun 25 21:27:45 UTC 2021 , Edited by admin on Fri Jun 25 21:27:45 UTC 2021
PRIMARY
EVMPD
SUB33020
Created by admin on Fri Jun 25 21:27:45 UTC 2021 , Edited by admin on Fri Jun 25 21:27:45 UTC 2021
PRIMARY
DRUG CENTRAL
4749
Created by admin on Fri Jun 25 21:27:45 UTC 2021 , Edited by admin on Fri Jun 25 21:27:45 UTC 2021
PRIMARY
INN
7859
Created by admin on Fri Jun 25 21:27:45 UTC 2021 , Edited by admin on Fri Jun 25 21:27:45 UTC 2021
PRIMARY
FDA UNII
B0P231ILBK
Created by admin on Fri Jun 25 21:27:45 UTC 2021 , Edited by admin on Fri Jun 25 21:27:45 UTC 2021
PRIMARY
Related Record Type Details
METABOLIC ENZYME -> INHIBITOR
IC50
METABOLIC ENZYME -> SUBSTRATE
Ospemifene is primarily metabolized by CYP3A4, 2C9, and 2C19 responsible for approximately 40 to 50%, ~25%, and ~25%, respectively, of its clearance.
MAJOR
METABOLIC ENZYME -> SUBSTRATE
Ospemifene is primarily metabolized by CYP3A4, 2C9, and 2C19 responsible for approximately 40 to 50%, ~25%, and ~25%, respectively, of its clearance.
MAJOR
METABOLIC ENZYME -> SUBSTRATE
Ospemifene is primarily metabolized by CYP3A4, 2C9, and 2C19 responsible for approximately 40 to 50%, ~25%, and ~25%, respectively, of its clearance.
MAJOR
METABOLIC ENZYME -> INHIBITOR
IC50
EXCRETED UNCHANGED
Following an oral administration of ospemifene, approximately 75% and 7% of the dose was excreted in feces and urine, respectively. Less than 0.2% of the ospemifene dose was excreted unchanged in urine.
URINE
TRANSPORTER -> SUBSTRATE
The sponsor evaluated ospemifene as a potential substrate for transporters in a P-gp in vitro study. No in vivo transporter studies were conducted.
BINDER->LIGAND
BINDING
METABOLIC ENZYME -> INHIBITOR
IC50
TARGET -> INHIBITOR
Related Record Type Details
PARENT -> METABOLITE ACTIVE
MAJOR
Related Record Type Details
IMPURITY -> PARENT
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC
Tmax PHARMACOKINETIC SINGLE DOSE

Volume of Distribution PHARMACOKINETIC