Identification

Name
Ospemifene
Accession Number
DB04938
Type
Small Molecule
Groups
Approved
Description

Ospemifene is a new selective non-hormonal estrogen receptor modulator (SERM) that is used for the treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause. FDA approved on February 26, 2013.

Structure
Thumb
Synonyms
  • 2-(4-(4-Chloro-1,2-diphenyl-but-1-enyl)phenoxy)ethanol
  • 2-(P-((Z)-4-Chloro-1,2-diphenyl-1-butenyl)phenoxy)ethanol
  • Deamino-hydroxytoremifene
External IDs
FC-1271 / FC-1271A
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
OsphenaTablet, film coated60 mg/1OralShionogi2013-02-26Not applicableUs
International/Other Brands
Osphena
Categories
UNII
B0P231ILBK
CAS number
128607-22-7
Weight
Average: 378.891
Monoisotopic: 378.138657687
Chemical Formula
C24H23ClO2
InChI Key
LUMKNAVTFCDUIE-VHXPQNKSSA-N
InChI
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-
IUPAC Name
2-{4-[(1Z)-4-chloro-1,2-diphenylbut-1-en-1-yl]phenoxy}ethan-1-ol
SMILES
OCCOC1=CC=C(C=C1)C(=C(\CCCl)C1=CC=CC=C1)\C1=CC=CC=C1

Pharmacology

Indication

Ospemifene is used for the treatment of moderate to dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause.

Structured Indications
Pharmacodynamics

The half maximal inhibitory concentration (IC50) for estrogen receptor (ER) alpha and beta are 0.8 μM and 1.7 μM, respectively. Ospemifene has potential uses in the management of osteoporosis in postmenopausal women. It interacts with osteoblasts and osteoclasts in such a way that it reduces bone turnover. It also has potential uses in the prevention of breast cancer. Studies suggest that ospemifene, in a dose-dependent manner, reduces the incidence of tumours.

Mechanism of action

Ospemifene is a next generation SERM (selective estrogen receptor modulator) 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.

TargetActionsOrganism
AEstrogen receptor alpha
antagonist
agonist
Human
Absorption

When a single oral dose of ospemifene 60 mg is given to postmenopausal women under fasted conditions, the pharmacokinetic parameters are as follows: Tmax = 2 hours (range of 1 - 8 hours); Cmax = 533 ng/mL; AUC (0-inf) = 4165 ng•hr/mL. When the same aforementioned dose is given to postmenopausal women under fed conditions, the pharmacokinetic parameters are as follows: Tmax = 2.5 hours (1 - 6 hours); Cmax = 1198 ng/mL; AUC (0-inf) = 7521 ng•hr/mL. Accumulation occurs following repeated doses. Time to steady state = 9 days.
Although the bioavailability of ospemifene has not been formally evaluated, it is expected to have a low bioavailability because of its lipophilic nature.

Volume of distribution

448 L

Protein binding

>99% bound to serum proteins

Metabolism

Ospemifene is hepatically metabolized via CYP3A4, CYP2C9, CYP2C19, and CYP2B6. The major metabolite was 4-hydroxyospemifene, 25% of the parent compound will undergo this biotransformation. Other metabolites include 4'-hydroxy-ospemifene, <7% of the parent compound will undergo this biotransformation. In order of decreasing potency, ospemifene was suggested to be a weak inhibitor for CYP2B6, CYP2C9, CYP2C19, CYP2C8, CYP2D6 and CYP3A4.

Route of elimination

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.

Half life

Terminal half-life = 26 hours .

Clearance

Total body clearance = 9.16 L/hr.

Toxicity

Adverse reactions (≥1 percent) include: hot flush, vaginal discharge, muscle spasms, genital discharge, hyperhidrosis.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AbirateroneThe metabolism of Ospemifene can be decreased when combined with Abiraterone.Approved
AfimoxifeneThe risk or severity of adverse effects can be increased when Afimoxifene is combined with Ospemifene.Investigational
AmiodaroneThe serum concentration of Ospemifene can be increased when it is combined with Amiodarone.Approved, Investigational
AprepitantThe serum concentration of Ospemifene can be increased when it is combined with Aprepitant.Approved, Investigational
ArmodafinilThe metabolism of Ospemifene can be decreased when combined with Armodafinil.Approved, Investigational
AtazanavirThe serum concentration of Ospemifene can be increased when it is combined with Atazanavir.Approved, Investigational
AtomoxetineThe metabolism of Ospemifene can be decreased when combined with Atomoxetine.Approved
BazedoxifeneThe risk or severity of adverse effects can be increased when Bazedoxifene is combined with Ospemifene.Approved, Investigational
BoceprevirThe serum concentration of Ospemifene can be increased when it is combined with Boceprevir.Approved, Withdrawn
BortezomibThe metabolism of Ospemifene can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Ospemifene can be decreased when it is combined with Bosentan.Approved, Investigational
CapecitabineThe serum concentration of Ospemifene can be increased when it is combined with Capecitabine.Approved, Investigational
CarbamazepineThe metabolism of Ospemifene can be increased when combined with Carbamazepine.Approved, Investigational
CeritinibThe serum concentration of Ospemifene can be increased when it is combined with Ceritinib.Approved
ChloramphenicolThe metabolism of Ospemifene can be decreased when combined with Chloramphenicol.Approved, Vet Approved
ChlorotrianiseneThe risk or severity of adverse effects can be increased when Chlorotrianisene is combined with Ospemifene.Investigational, Withdrawn
CholecalciferolThe metabolism of Ospemifene can be decreased when combined with Cholecalciferol.Approved, Nutraceutical
CimetidineThe metabolism of Ospemifene can be decreased when combined with Cimetidine.Approved
CitalopramThe metabolism of Ospemifene can be decreased when combined with Citalopram.Approved
ClarithromycinThe serum concentration of Ospemifene can be increased when it is combined with Clarithromycin.Approved
ClemastineThe metabolism of Ospemifene can be decreased when combined with Clemastine.Approved
ClomifeneThe risk or severity of adverse effects can be increased when Clomifene is combined with Ospemifene.Approved, Investigational
ClopidogrelThe metabolism of Ospemifene can be decreased when combined with Clopidogrel.Approved, Nutraceutical
ClotrimazoleThe metabolism of Ospemifene can be decreased when combined with Clotrimazole.Approved, Vet Approved
CobicistatThe serum concentration of Ospemifene can be increased when it is combined with Cobicistat.Approved
ConivaptanThe serum concentration of Ospemifene can be increased when it is combined with Conivaptan.Approved, Investigational
Conjugated estrogensThe risk or severity of adverse effects can be increased when Conjugated estrogens is combined with Ospemifene.Approved
CrisaboroleThe metabolism of Ospemifene can be decreased when combined with Crisaborole.Approved
CrizotinibThe metabolism of Ospemifene can be decreased when combined with Crizotinib.Approved
CyclosporineThe metabolism of Ospemifene can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
DabrafenibThe serum concentration of Ospemifene can be decreased when it is combined with Dabrafenib.Approved
DaidzeinThe risk or severity of adverse effects can be increased when Daidzein is combined with Ospemifene.Experimental
DarunavirThe serum concentration of Ospemifene can be increased when it is combined with Darunavir.Approved
DasatinibThe serum concentration of Ospemifene can be increased when it is combined with Dasatinib.Approved, Investigational
DeferasiroxThe serum concentration of Ospemifene can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe serum concentration of Ospemifene can be increased when it is combined with Delavirdine.Approved
DesipramineThe metabolism of Ospemifene can be decreased when combined with Desipramine.Approved
DienestrolThe risk or severity of adverse effects can be increased when Dienestrol is combined with Ospemifene.Approved, Investigational
DiethylstilbestrolThe risk or severity of adverse effects can be increased when Diethylstilbestrol is combined with Ospemifene.Approved, Investigational
DihydroergotamineThe metabolism of Ospemifene can be decreased when combined with Dihydroergotamine.Approved
DiltiazemThe metabolism of Ospemifene can be decreased when combined with Diltiazem.Approved
DosulepinThe serum concentration of Ospemifene can be increased when it is combined with Dosulepin.Approved
DoxorubicinThe metabolism of Ospemifene can be decreased when combined with Doxorubicin.Approved, Investigational
DoxycyclineThe metabolism of Ospemifene can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe metabolism of Ospemifene can be decreased when combined with Dronedarone.Approved
EfavirenzThe metabolism of Ospemifene can be decreased when combined with Efavirenz.Approved, Investigational
EnclomipheneThe risk or severity of adverse effects can be increased when Enclomiphene is combined with Ospemifene.Investigational
EnzalutamideThe serum concentration of Ospemifene can be decreased when it is combined with Enzalutamide.Approved
EpimestrolThe risk or severity of adverse effects can be increased when Epimestrol is combined with Ospemifene.Experimental
EquolThe risk or severity of adverse effects can be increased when Equol is combined with Ospemifene.Investigational
ErythromycinThe metabolism of Ospemifene can be decreased when combined with Erythromycin.Approved, Vet Approved
Eslicarbazepine acetateThe metabolism of Ospemifene can be decreased when combined with Eslicarbazepine acetate.Approved
EsomeprazoleThe metabolism of Ospemifene can be decreased when combined with Esomeprazole.Approved, Investigational
EstradiolThe risk or severity of adverse effects can be increased when Estradiol is combined with Ospemifene.Approved, Investigational, Vet Approved
EstriolThe risk or severity of adverse effects can be increased when Estriol is combined with Ospemifene.Approved, Investigational, Vet Approved
EstroneThe risk or severity of adverse effects can be increased when Estrone is combined with Ospemifene.Approved
Ethinyl EstradiolThe risk or severity of adverse effects can be increased when Ethinyl Estradiol is combined with Ospemifene.Approved
EtravirineThe metabolism of Ospemifene can be decreased when combined with Etravirine.Approved
FesoterodineThe serum concentration of the active metabolites of Fesoterodine can be increased when Fesoterodine is used in combination with Ospemifene.Approved
FloxuridineThe serum concentration of Ospemifene can be increased when it is combined with Floxuridine.Approved
FluconazoleThe serum concentration of Ospemifene can be increased when it is combined with Fluconazole.Approved
FluorouracilThe serum concentration of Ospemifene can be increased when it is combined with Fluorouracil.Approved
FluoxetineThe metabolism of Ospemifene can be decreased when combined with Fluoxetine.Approved, Vet Approved
FluvastatinThe metabolism of Ospemifene can be decreased when combined with Fluvastatin.Approved
FluvoxamineThe metabolism of Ospemifene can be decreased when combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe metabolism of Ospemifene can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Ospemifene can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe metabolism of Ospemifene can be increased when combined with Fosphenytoin.Approved
Fusidic AcidThe serum concentration of Ospemifene can be increased when it is combined with Fusidic Acid.Approved
GemfibrozilThe serum concentration of Ospemifene can be increased when it is combined with Gemfibrozil.Approved
GenisteinThe risk or severity of adverse effects can be increased when Genistein is combined with Ospemifene.Investigational
HexestrolThe risk or severity of adverse effects can be increased when Hexestrol is combined with Ospemifene.Withdrawn
ImatinibThe metabolism of Ospemifene can be decreased when combined with Imatinib.Approved
IndinavirThe serum concentration of Ospemifene can be increased when it is combined with Indinavir.Approved
IrbesartanThe metabolism of Ospemifene can be decreased when combined with Irbesartan.Approved, Investigational
IsavuconazoniumThe metabolism of Ospemifene can be decreased when combined with Isavuconazonium.Approved, Investigational
IsoniazidThe metabolism of Ospemifene can be decreased when combined with Isoniazid.Approved
IsradipineThe metabolism of Ospemifene can be decreased when combined with Isradipine.Approved
ItraconazoleThe serum concentration of Ospemifene can be increased when it is combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Ospemifene can be increased when it is combined with Ivacaftor.Approved
KetoconazoleThe serum concentration of Ospemifene can be increased when it is combined with Ketoconazole.Approved, Investigational
LasofoxifeneThe risk or severity of adverse effects can be increased when Lasofoxifene is combined with Ospemifene.Approved, Investigational
LeflunomideThe metabolism of Ospemifene can be decreased when combined with Leflunomide.Approved, Investigational
LobeglitazoneThe metabolism of Ospemifene can be decreased when combined with Lobeglitazone.Approved, Investigational
LopinavirThe serum concentration of Ospemifene can be increased when it is combined with Lopinavir.Approved
LosartanThe metabolism of Ospemifene can be decreased when combined with Losartan.Approved
LovastatinThe metabolism of Ospemifene can be decreased when combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of Ospemifene can be increased when it is combined with Luliconazole.Approved
LumacaftorThe serum concentration of Ospemifene can be decreased when it is combined with Lumacaftor.Approved
ManidipineThe metabolism of Ospemifene can be decreased when combined with Manidipine.Approved, Investigational
MestranolThe risk or severity of adverse effects can be increased when Mestranol is combined with Ospemifene.Approved
MethallenestrilThe risk or severity of adverse effects can be increased when Methallenestril is combined with Ospemifene.Experimental
MetoprololThe serum concentration of Metoprolol can be increased when it is combined with Ospemifene.Approved, Investigational
MidostaurinThe serum concentration of Ospemifene can be increased when it is combined with Midostaurin.Approved
MifepristoneThe serum concentration of Ospemifene can be increased when it is combined with Mifepristone.Approved, Investigational
MitotaneThe serum concentration of Ospemifene can be decreased when it is combined with Mitotane.Approved
MoclobemideThe metabolism of Ospemifene can be decreased when combined with Moclobemide.Approved
ModafinilThe metabolism of Ospemifene can be decreased when combined with Modafinil.Approved, Investigational
MoxestrolThe risk or severity of adverse effects can be increased when Moxestrol is combined with Ospemifene.Experimental
NefazodoneThe serum concentration of Ospemifene can be increased when it is combined with Nefazodone.Approved, Withdrawn
NelfinavirThe serum concentration of Ospemifene can be increased when it is combined with Nelfinavir.Approved
NetupitantThe serum concentration of Ospemifene can be increased when it is combined with Netupitant.Approved
NevirapineThe metabolism of Ospemifene can be increased when combined with Nevirapine.Approved
NicardipineThe serum concentration of Ospemifene can be increased when it is combined with Nicardipine.Approved
NilotinibThe metabolism of Ospemifene can be decreased when combined with Nilotinib.Approved, Investigational
OlaparibThe metabolism of Ospemifene can be decreased when combined with Olaparib.Approved
OmeprazoleThe metabolism of Ospemifene can be decreased when combined with Omeprazole.Approved, Investigational, Vet Approved
OrmeloxifeneThe risk or severity of adverse effects can be increased when Ormeloxifene is combined with Ospemifene.Experimental
OsimertinibThe serum concentration of Ospemifene can be increased when it is combined with Osimertinib.Approved
PalbociclibThe serum concentration of Ospemifene can be increased when it is combined with Palbociclib.Approved
PantoprazoleThe metabolism of Ospemifene can be decreased when combined with Pantoprazole.Approved
ParoxetineThe metabolism of Ospemifene can be decreased when combined with Paroxetine.Approved, Investigational
PentobarbitalThe metabolism of Ospemifene can be increased when combined with Pentobarbital.Approved, Vet Approved
PhenobarbitalThe metabolism of Ospemifene can be increased when combined with Phenobarbital.Approved
PhenytoinThe metabolism of Ospemifene can be increased when combined with Phenytoin.Approved, Vet Approved
Polyestradiol phosphateThe risk or severity of adverse effects can be increased when Polyestradiol phosphate is combined with Ospemifene.Approved
PosaconazoleThe serum concentration of Ospemifene can be increased when it is combined with Posaconazole.Approved, Investigational, Vet Approved
PrimidoneThe metabolism of Ospemifene can be increased when combined with Primidone.Approved, Vet Approved
PromestrieneThe risk or severity of adverse effects can be increased when Promestriene is combined with Ospemifene.Investigational
PyrimethamineThe metabolism of Ospemifene can be decreased when combined with Pyrimethamine.Approved, Vet Approved
QuazepamThe serum concentration of Ospemifene can be increased when it is combined with Quazepam.Approved, Illicit
QuinestrolThe risk or severity of adverse effects can be increased when Quinestrol is combined with Ospemifene.Approved
QuinineThe metabolism of Ospemifene can be decreased when combined with Quinine.Approved
RaloxifeneThe risk or severity of adverse effects can be increased when Raloxifene is combined with Ospemifene.Approved, Investigational
RanolazineThe metabolism of Ospemifene can be decreased when combined with Ranolazine.Approved, Investigational
RifabutinThe metabolism of Ospemifene can be increased when combined with Rifabutin.Approved
RifampicinThe metabolism of Ospemifene can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Ospemifene can be increased when combined with Rifapentine.Approved
RitonavirThe serum concentration of Ospemifene can be increased when it is combined with Ritonavir.Approved, Investigational
SaquinavirThe serum concentration of Ospemifene can be increased when it is combined with Saquinavir.Approved, Investigational
SecobarbitalThe metabolism of Ospemifene can be increased when combined with Secobarbital.Approved, Vet Approved
SecoisolariciresinolThe risk or severity of adverse effects can be increased when Secoisolariciresinol is combined with Ospemifene.Investigational
SertralineThe metabolism of Ospemifene can be decreased when combined with Sertraline.Approved
SildenafilThe metabolism of Ospemifene can be decreased when combined with Sildenafil.Approved, Investigational
SiltuximabThe serum concentration of Ospemifene can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Ospemifene can be increased when it is combined with Simeprevir.Approved
SorafenibThe metabolism of Ospemifene can be decreased when combined with Sorafenib.Approved, Investigational
St. John's WortThe serum concentration of Ospemifene can be decreased when it is combined with St. John&#39;s Wort.Investigational, Nutraceutical
StiripentolThe serum concentration of Ospemifene can be increased when it is combined with Stiripentol.Approved
SulfadiazineThe serum concentration of Ospemifene can be increased when it is combined with Sulfadiazine.Approved, Vet Approved
SulfamethoxazoleThe metabolism of Ospemifene can be decreased when combined with Sulfamethoxazole.Approved
SulfisoxazoleThe serum concentration of Ospemifene can be increased when it is combined with Sulfisoxazole.Approved, Vet Approved
Synthetic Conjugated Estrogens, AThe risk or severity of adverse effects can be increased when Synthetic Conjugated Estrogens, A is combined with Ospemifene.Approved
Synthetic Conjugated Estrogens, BThe risk or severity of adverse effects can be increased when Synthetic Conjugated Estrogens, B is combined with Ospemifene.Approved
TamoxifenThe risk or severity of adverse effects can be increased when Tamoxifen is combined with Ospemifene.Approved
TelaprevirThe serum concentration of Ospemifene can be increased when it is combined with Telaprevir.Approved, Withdrawn
TelithromycinThe serum concentration of Ospemifene can be increased when it is combined with Telithromycin.Approved
ThioridazineThe serum concentration of Thioridazine can be increased when it is combined with Ospemifene.Approved, Withdrawn
ThiotepaThe metabolism of Ospemifene can be decreased when combined with Thiotepa.Approved
TiboloneThe risk or severity of adverse effects can be increased when Tibolone is combined with Ospemifene.Approved, Investigational
TicagrelorThe metabolism of Ospemifene can be decreased when combined with Ticagrelor.Approved
TiclopidineThe metabolism of Ospemifene can be decreased when combined with Ticlopidine.Approved
TocilizumabThe serum concentration of Ospemifene can be decreased when it is combined with Tocilizumab.Approved
TolbutamideThe serum concentration of Ospemifene can be increased when it is combined with Tolbutamide.Approved
TopiramateThe metabolism of Ospemifene can be decreased when combined with Topiramate.Approved
TopiroxostatThe metabolism of Ospemifene can be decreased when combined with Topiroxostat.Approved, Investigational
ToremifeneThe risk or severity of adverse effects can be increased when Toremifene is combined with Ospemifene.Approved, Investigational
TranylcypromineThe metabolism of Ospemifene can be decreased when combined with Tranylcypromine.Approved
TrimethoprimThe metabolism of Ospemifene can be decreased when combined with Trimethoprim.Approved, Vet Approved
Valproic AcidThe metabolism of Ospemifene can be decreased when combined with Valproic Acid.Approved, Investigational
ValsartanThe metabolism of Ospemifene can be decreased when combined with Valsartan.Approved, Investigational
VenlafaxineThe metabolism of Ospemifene can be decreased when combined with Venlafaxine.Approved
VerapamilThe metabolism of Ospemifene can be decreased when combined with Verapamil.Approved
VoriconazoleThe serum concentration of Ospemifene can be increased when it is combined with Voriconazole.Approved, Investigational
ZafirlukastThe metabolism of Ospemifene can be decreased when combined with Zafirlukast.Approved, Investigational
ZeranolThe risk or severity of adverse effects can be increased when Zeranol is combined with Ospemifene.Vet Approved
ZiprasidoneThe metabolism of Ospemifene can be decreased when combined with Ziprasidone.Approved
ZucapsaicinThe metabolism of Ospemifene can be decreased when combined with Zucapsaicin.Approved
Food Interactions
  • In general, food increased the bioavailability of ospemifene by approximately 2-3 fold.

References

Synthesis Reference

Marja Sodervall, Maire Eloranta, Arja Kalapudas, Brian Kearton, Michael McKenzie, "METHODS FOR THE PREPARATION OF FISPEMIFENE FROM OSPEMIFENE." U.S. Patent US20080214860, issued September 04, 2008.

US20080214860
General References
  1. Taras TL, Wurz GT, DeGregorio MW: In vitro and in vivo biologic effects of Ospemifene (FC-1271a) in breast cancer. J Steroid Biochem Mol Biol. 2001 Jun;77(4-5):271-9. [PubMed:11457665]
  2. Voipio SK, Komi J, Kangas L, Halonen K, DeGregorio MW, Erkkola RU: Effects of ospemifene (FC-1271a) on uterine endometrium, vaginal maturation index, and hormonal status in healthy postmenopausal women. Maturitas. 2002 Nov 20;43(3):207-14. [PubMed:12443837]
  3. Rutanen EM, Heikkinen J, Halonen K, Komi J, Lammintausta R, Ylikorkala O: Effects of ospemifene, a novel SERM, on hormones, genital tract, climacteric symptoms, and quality of life in postmenopausal women: a double-blind, randomized trial. Menopause. 2003 Sep-Oct;10(5):433-9. [PubMed:14501605]
  4. Ylikorkala O, Cacciatore B, Halonen K, Lassila R, Lammintausta R, Rutanen EM, Heikkinen J, Komi J: Effects of ospemifene, a novel SERM, on vascular markers and function in healthy, postmenopausal women. Menopause. 2003 Sep-Oct;10(5):440-7. [PubMed:14501606]
  5. Tolonen A, Koskimies P, Turpeinen M, Uusitalo J, Lammintausta R, Pelkonen O: Ospemifene metabolism in humans in vitro and in vivo: metabolite identification, quantitation, and CYP assignment of major hydroxylations. Drug Metabol Drug Interact. 2013;28(3):153-61. doi: 10.1515/dmdi-2013-0016. [PubMed:23729558]
  6. McCall JL, DeGregorio MW: Pharmacologic evaluation of ospemifene. Expert Opin Drug Metab Toxicol. 2010 Jun;6(6):773-9. doi: 10.1517/17425255.2010.487483. [PubMed:20429673]
External Links
KEGG Drug
D08958
PubChem Compound
3036505
PubChem Substance
175426911
ChemSpider
2300501
ChEBI
73275
ChEMBL
CHEMBL2105395
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Ospemifene
ATC Codes
G03XC05 — Ospemifene
FDA label
Download (350 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentAtrophy / Vaginal Diseases1
3CompletedTreatmentAtrophy / Vaginal Diseases5
3CompletedTreatmentVaginal Dryness1
4CompletedTreatmentPainful Intercourse / Vulvovaginal Atrophy1
4RecruitingTreatmentSexual Dysfunction, Physiological1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Tablet, film coatedOral60 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US8470890No2004-02-132024-02-13Us
US6245819No2000-07-212020-07-21Us
US8236861No2006-08-112026-08-11Us
US8772353No2004-02-132024-02-13Us
US9241915No2004-02-132024-02-13Us
US8642079No2008-07-092028-07-09Us
US9566252No2000-07-212020-07-21Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityInsoluble FDA label
Predicted Properties
PropertyValueSource
Water Solubility0.000526 mg/mLALOGPS
logP5.7ALOGPS
logP5.56ChemAxon
logS-5.9ALOGPS
pKa (Strongest Acidic)15.1ChemAxon
pKa (Strongest Basic)-2.8ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area29.46 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity121.68 m3·mol-1ChemAxon
Polarizability41.97 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9972
Blood Brain Barrier+0.7095
Caco-2 permeable+0.6894
P-glycoprotein substrateNon-substrate0.587
P-glycoprotein inhibitor IInhibitor0.7541
P-glycoprotein inhibitor IIInhibitor0.5935
Renal organic cation transporterNon-inhibitor0.6587
CYP450 2C9 substrateNon-substrate0.7712
CYP450 2D6 substrateNon-substrate0.8459
CYP450 3A4 substrateNon-substrate0.5552
CYP450 1A2 substrateNon-inhibitor0.5168
CYP450 2C9 inhibitorNon-inhibitor0.7604
CYP450 2D6 inhibitorNon-inhibitor0.8754
CYP450 2C19 inhibitorInhibitor0.5512
CYP450 3A4 inhibitorNon-inhibitor0.7578
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6072
Ames testNon AMES toxic0.597
CarcinogenicityNon-carcinogens0.767
BiodegradationNot ready biodegradable0.5073
Rat acute toxicity2.3083 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.5657
hERG inhibition (predictor II)Non-inhibitor0.6556
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as stilbenes. These are organic compounds containing a 1,2-diphenylethylene moiety. Stilbenes (C6-C2-C6 ) are derived from the common phenylpropene (C6-C3) skeleton building block. The introduction of one or more hydroxyl groups to a phenyl ring lead to stilbenoids.
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Stilbenes
Sub Class
Not Available
Direct Parent
Stilbenes
Alternative Parents
Diphenylmethanes / Phenoxy compounds / Phenol ethers / Alkyl aryl ethers / Primary alcohols / Organochlorides / Hydrocarbon derivatives / Alkyl chlorides
Substituents
Stilbene / Diphenylmethane / Phenoxy compound / Phenol ether / Alkyl aryl ether / Monocyclic benzene moiety / Benzenoid / Ether / Alcohol / Organochloride
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
aromatic ether, organochlorine compound, primary alcohol (CHEBI:73275)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
Agonist
General Function
Zinc ion binding
Specific Function
Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissu...
Gene Name
ESR1
Uniprot ID
P03372
Uniprot Name
Estrogen receptor
Molecular Weight
66215.45 Da
References
  1. Komi J, Heikkinen J, Rutanen EM, Halonen K, Lammintausta R, Ylikorkala O: Effects of ospemifene, a novel SERM, on biochemical markers of bone turnover in healthy postmenopausal women. Gynecol Endocrinol. 2004 Mar;18(3):152-8. [PubMed:15255284]
  2. Wurz GT, Read KC, Marchisano-Karpman C, Gregg JP, Beckett LA, Yu Q, Degregorio MW: Ospemifene inhibits the growth of dimethylbenzanthracene-induced mammary tumors in Sencar mice. J Steroid Biochem Mol Biol. 2005 Nov;97(3):230-40. Epub 2005 Sep 8. [PubMed:16153821]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Tolonen A, Koskimies P, Turpeinen M, Uusitalo J, Lammintausta R, Pelkonen O: Ospemifene metabolism in humans in vitro and in vivo: metabolite identification, quantitation, and CYP assignment of major hydroxylations. Drug Metabol Drug Interact. 2013;28(3):153-61. doi: 10.1515/dmdi-2013-0016. [PubMed:23729558]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Tolonen A, Koskimies P, Turpeinen M, Uusitalo J, Lammintausta R, Pelkonen O: Ospemifene metabolism in humans in vitro and in vivo: metabolite identification, quantitation, and CYP assignment of major hydroxylations. Drug Metabol Drug Interact. 2013;28(3):153-61. doi: 10.1515/dmdi-2013-0016. [PubMed:23729558]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Tolonen A, Koskimies P, Turpeinen M, Uusitalo J, Lammintausta R, Pelkonen O: Ospemifene metabolism in humans in vitro and in vivo: metabolite identification, quantitation, and CYP assignment of major hydroxylations. Drug Metabol Drug Interact. 2013;28(3):153-61. doi: 10.1515/dmdi-2013-0016. [PubMed:23729558]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. Tolonen A, Koskimies P, Turpeinen M, Uusitalo J, Lammintausta R, Pelkonen O: Ospemifene metabolism in humans in vitro and in vivo: metabolite identification, quantitation, and CYP assignment of major hydroxylations. Drug Metabol Drug Interact. 2013;28(3):153-61. doi: 10.1515/dmdi-2013-0016. [PubMed:23729558]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da

Drug created on October 21, 2007 16:23 / Updated on November 09, 2017 03:49