Identification

Name
Toremifene
Accession Number
DB00539  (APRD00391)
Type
Small Molecule
Groups
Approved, Investigational
Description

A first generation nonsteroidal selective estrogen receptor modulator (SERM) that is structurally related to tamoxifen. Like tamoxifen, it is an estrogen agonist for bone tissue and cholesterol metabolism but is antagonistic on mammary and uterine tissue. [PubChem]

Structure
Thumb
Synonyms
  • Toremifeno
  • Toremifenum
External IDs
GTX-006 / J33.157K
Product Ingredients
IngredientUNIICASInChI Key
Toremifene citrate2498Y783QT89778-27-8IWEQQRMGNVVKQW-OQKDUQJOSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
FarestonTablet60 mg/1OralG Tx1997-06-302017-08-15Us
FarestonTablet60 mg/1OralKyowa Kirin Limited1997-06-30Not applicableUs
FarestonTablet60 mgOralOrion Corporation1996-02-14Not applicableEu
FarestonTablet60 mgOralOrion Corporation1996-02-14Not applicableEu
International/Other Brands
Acapodene
Categories
UNII
7NFE54O27T
CAS number
89778-26-7
Weight
Average: 405.96
Monoisotopic: 405.18594223
Chemical Formula
C26H28ClNO
InChI Key
XFCLJVABOIYOMF-QPLCGJKRSA-N
InChI
InChI=1S/C26H28ClNO/c1-28(2)19-20-29-24-15-13-23(14-16-24)26(22-11-7-4-8-12-22)25(17-18-27)21-9-5-3-6-10-21/h3-16H,17-20H2,1-2H3/b26-25-
IUPAC Name
(2-{4-[(1Z)-4-chloro-1,2-diphenylbut-1-en-1-yl]phenoxy}ethyl)dimethylamine
SMILES
CN(C)CCOC1=CC=C(C=C1)C(=C(\CCCl)C1=CC=CC=C1)\C1=CC=CC=C1

Pharmacology

Indication

For the treatment of metastatic breast cancer in postmenopausal women with estrogen receptor-positive or receptor-unknown tumors. Toremifene is currently under investigation as a preventative agent for prostate cancer in men with high-grade prostatic intraepithelial neoplasia and no evidence of prostate cancer.

Structured Indications
Pharmacodynamics

Toremifene is an antineoplastic hormonal agent primarily used in the treatment of advanced breast cancer. Toremifene is a nonsteroidal agent that has demonstrated potent antiestrogenic properties in animal test systems. The antiestrogenic effects may be related to its ability to compete with estrogen for binding sites in target tissues such as breast. Toremifene inhibits the induction of rat mammary carcinoma induced by dimethylbenzanthracene (DMBA) and causes the regression of already established DMBA-induced tumors. In this rat model, Toremifene appears to exert its antitumor effects by binding the estrogen receptors. In cytosols derived from human breast adenocarcinomas, Toremifene competes with estradiol for estrogen receptor protein.

Mechanism of action

Toremifene is a nonsteroidal triphenylethylene derivative. Toremifene binds to estrogen receptors and may exert estrogenic, antiestrogenic, or both activities, depending upon the duration of treatment, animal species, gender, target organ, or endpoint selected. The antitumor effect of toremifene in breast cancer is believed to be mainly due to its antiestrogenic effects, in other words, its ability to compete with estrogen for binding sites in the cancer, blocking the growth-stimulating effects of estrogen in the tumor. Toremifene may also inhibit tumor growth through other mechanisms, such as induction of apoptosis, regulation of oncogene expression, and growth factors.

TargetActionsOrganism
AEstrogen receptor alpha
modulator
Human
USex hormone-binding globulinNot AvailableHuman
Absorption

Well absorbed

Volume of distribution
  • 580 L
Protein binding

Toremifen is primarily bound to albumin (92%), 2% bound to α1-acid glycoprotein, and 6% bound to β1-globulin in the serum.

Metabolism

Hepatic. Mainly by CYP3A4 to N-demethyltoremifene, which exhibits antiestrogenic effects but has weak antitumor potency in vivo.

Route of elimination

Toremifene is extensively metabolized, principally by CYP3A4 to N-demethyltoremifene, which is also antiestrogenic but with weak in vivo antitumor potency.

Half life

5 days

Clearance
  • 5 L/h
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AbirateroneThe serum concentration of Toremifene can be increased when it is combined with Abiraterone.Approved
AcenocoumarolToremifene may increase the anticoagulant activities of Acenocoumarol.Approved
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Toremifene.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Toremifene.Experimental
AlfuzosinAlfuzosin may increase the QTc-prolonging activities of Toremifene.Approved, Investigational
AmantadineAmantadine may increase the QTc-prolonging activities of Toremifene.Approved
AmiodaroneThe risk or severity of adverse effects can be increased when Amiodarone is combined with Toremifene.Approved, Investigational
AmitriptylineAmitriptyline may increase the QTc-prolonging activities of Toremifene.Approved
AmoxapineAmoxapine may increase the QTc-prolonging activities of Toremifene.Approved
AnagrelideThe risk or severity of QTc prolongation can be increased when Anagrelide is combined with Toremifene.Approved
ApomorphineApomorphine may increase the QTc-prolonging activities of Toremifene.Approved, Investigational
AprepitantThe serum concentration of Toremifene can be increased when it is combined with Aprepitant.Approved, Investigational
ArformoterolArformoterol may increase the QTc-prolonging activities of Toremifene.Approved, Investigational
AripiprazoleAripiprazole may increase the QTc-prolonging activities of Toremifene.Approved, Investigational
Arsenic trioxideThe risk or severity of QTc prolongation can be increased when Toremifene is combined with Arsenic trioxide.Approved, Investigational
ArtemetherThe risk or severity of QTc prolongation can be increased when Toremifene is combined with Artemether.Approved
AsenapineThe risk or severity of QTc prolongation can be increased when Toremifene is combined with Asenapine.Approved
AtazanavirThe risk or severity of adverse effects can be increased when Atazanavir is combined with Toremifene.Approved, Investigational
AtomoxetineAtomoxetine may increase the QTc-prolonging activities of Toremifene.Approved
AzithromycinThe metabolism of Toremifene can be decreased when combined with Azithromycin.Approved
BedaquilineBedaquiline may increase the QTc-prolonging activities of Toremifene.Approved
BendroflumethiazideBendroflumethiazide may increase the hypercalcemic activities of Toremifene.Approved
BevacizumabBevacizumab may increase the cardiotoxic activities of Toremifene.Approved, Investigational
BoceprevirThe risk or severity of adverse effects can be increased when Boceprevir is combined with Toremifene.Approved, Withdrawn
BortezomibBortezomib may increase the QTc-prolonging activities of Toremifene.Approved, Investigational
BosentanThe serum concentration of Toremifene can be decreased when it is combined with Bosentan.Approved, Investigational
BuserelinBuserelin may increase the QTc-prolonging activities of Toremifene.Approved
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Toremifene.Approved
CaffeineThe metabolism of Toremifene can be decreased when combined with Caffeine.Approved
CarbamazepineThe serum concentration of Toremifene can be decreased when it is combined with Carbamazepine.Approved, Investigational
CeritinibThe serum concentration of Toremifene can be increased when it is combined with Ceritinib.Approved
ChloroquineChloroquine may increase the QTc-prolonging activities of Toremifene.Approved, Vet Approved
ChlorothiazideChlorothiazide may increase the hypercalcemic activities of Toremifene.Approved, Vet Approved
ChlorpromazineChlorpromazine may increase the QTc-prolonging activities of Toremifene.Approved, Vet Approved
ChlorthalidoneChlorthalidone may increase the hypercalcemic activities of Toremifene.Approved
CiprofloxacinCiprofloxacin may increase the QTc-prolonging activities of Toremifene.Approved, Investigational
CisaprideThe risk or severity of QTc prolongation can be increased when Toremifene is combined with Cisapride.Approved, Investigational, Withdrawn
CitalopramThe metabolism of Toremifene can be decreased when combined with Citalopram.Approved
ClarithromycinThe risk or severity of adverse effects can be increased when Clarithromycin is combined with Toremifene.Approved
ClemastineThe metabolism of Toremifene can be decreased when combined with Clemastine.Approved
ClomipramineClomipramine may increase the QTc-prolonging activities of Toremifene.Approved, Vet Approved
ClorindioneToremifene may increase the anticoagulant activities of Clorindione.Experimental
ClotrimazoleThe metabolism of Toremifene can be decreased when combined with Clotrimazole.Approved, Vet Approved
ClozapineClozapine may increase the QTc-prolonging activities of Toremifene.Approved
CobicistatThe risk or severity of adverse effects can be increased when Cobicistat is combined with Toremifene.Approved
ConivaptanThe serum concentration of Toremifene can be increased when it is combined with Conivaptan.Approved, Investigational
CrizotinibThe metabolism of Toremifene can be decreased when combined with Crizotinib.Approved
CyclopenthiazideCyclopenthiazide may increase the hypercalcemic activities of Toremifene.Experimental
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Toremifene.Approved, Investigational
CyclosporineThe metabolism of Toremifene can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
CymarinCymarin may decrease the cardiotoxic activities of Toremifene.Experimental
Cyproterone acetateThe serum concentration of Toremifene can be decreased when it is combined with Cyproterone acetate.Approved, Investigational
DabrafenibThe serum concentration of Toremifene can be decreased when it is combined with Dabrafenib.Approved
DarunavirThe risk or severity of adverse effects can be increased when Darunavir is combined with Toremifene.Approved
DasatinibThe serum concentration of Toremifene can be increased when it is combined with Dasatinib.Approved, Investigational
DeferasiroxThe serum concentration of Toremifene can be decreased when it is combined with Deferasirox.Approved, Investigational
DegarelixDegarelix may increase the QTc-prolonging activities of Toremifene.Approved
DelavirdineThe metabolism of Toremifene can be decreased when combined with Delavirdine.Approved
DesfluraneDesflurane may increase the QTc-prolonging activities of Toremifene.Approved
DesipramineDesipramine may increase the QTc-prolonging activities of Toremifene.Approved
DeslanosideDeslanoside may decrease the cardiotoxic activities of Toremifene.Approved
DicoumarolToremifene may increase the anticoagulant activities of Dicoumarol.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Toremifene.Approved, Investigational
DigoxinDigoxin may decrease the cardiotoxic activities of Toremifene.Approved
Digoxin Immune Fab (Ovine)Digoxin Immune Fab (Ovine) may decrease the cardiotoxic activities of Toremifene.Approved
DihydroergotamineThe metabolism of Toremifene can be decreased when combined with Dihydroergotamine.Approved
DiltiazemThe metabolism of Toremifene can be decreased when combined with Diltiazem.Approved
DiphenadioneToremifene may increase the anticoagulant activities of Diphenadione.Experimental
DiphenhydramineDiphenhydramine may increase the QTc-prolonging activities of Toremifene.Approved
DisopyramideThe risk or severity of QTc prolongation can be increased when Disopyramide is combined with Toremifene.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Toremifene.Approved, Investigational
DofetilideThe risk or severity of QTc prolongation can be increased when Dofetilide is combined with Toremifene.Approved
DolasetronDolasetron may increase the QTc-prolonging activities of Toremifene.Approved
DomperidoneThe risk or severity of QTc prolongation can be increased when Toremifene is combined with Domperidone.Approved, Investigational, Vet Approved
DosulepinThe metabolism of Toremifene can be decreased when combined with Dosulepin.Approved
DoxepinDoxepin may increase the QTc-prolonging activities of Toremifene.Approved
DoxycyclineThe metabolism of Toremifene can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe metabolism of Toremifene can be decreased when combined with Dronedarone.Approved
DroperidolDroperidol may increase the QTc-prolonging activities of Toremifene.Approved, Vet Approved
EliglustatThe risk or severity of QTc prolongation can be increased when Toremifene is combined with Eliglustat.Approved
EnzalutamideThe serum concentration of Toremifene can be decreased when it is combined with Enzalutamide.Approved
EribulinEribulin may increase the QTc-prolonging activities of Toremifene.Approved, Investigational
ErythromycinThe metabolism of Toremifene can be decreased when combined with Erythromycin.Approved, Vet Approved
EscitalopramThe risk or severity of QTc prolongation can be increased when Toremifene is combined with Escitalopram.Approved, Investigational
Ethyl biscoumacetateToremifene may increase the anticoagulant activities of Ethyl biscoumacetate.Withdrawn
EzogabineEzogabine may increase the QTc-prolonging activities of Toremifene.Approved
FamotidineFamotidine may increase the QTc-prolonging activities of Toremifene.Approved
FelbamateFelbamate may increase the QTc-prolonging activities of Toremifene.Approved
FingolimodFingolimod may increase the QTc-prolonging activities of Toremifene.Approved, Investigational
FlecainideFlecainide may increase the QTc-prolonging activities of Toremifene.Approved, Withdrawn
FluconazoleFluconazole may increase the QTc-prolonging activities of Toremifene.Approved
FluindioneToremifene may increase the anticoagulant activities of Fluindione.Investigational
FluoxetineThe risk or severity of QTc prolongation can be increased when Fluoxetine is combined with Toremifene.Approved, Vet Approved
FlupentixolThe risk or severity of QTc prolongation can be increased when Toremifene is combined with Flupentixol.Approved, Withdrawn
FluvoxamineThe metabolism of Toremifene can be decreased when combined with Fluvoxamine.Approved, Investigational
FormoterolFormoterol may increase the QTc-prolonging activities of Toremifene.Approved, Investigational
FosamprenavirThe metabolism of Toremifene can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Toremifene can be increased when it is combined with Fosaprepitant.Approved
FoscarnetFoscarnet may increase the QTc-prolonging activities of Toremifene.Approved
FosphenytoinThe serum concentration of Toremifene can be decreased when it is combined with Fosphenytoin.Approved
Fusidic AcidThe serum concentration of Toremifene can be increased when it is combined with Fusidic Acid.Approved
Gadobenic acidGadobenic acid may increase the QTc-prolonging activities of Toremifene.Approved
GalantamineGalantamine may increase the QTc-prolonging activities of Toremifene.Approved
GemifloxacinGemifloxacin may increase the QTc-prolonging activities of Toremifene.Approved, Investigational
GitoformateGitoformate may decrease the cardiotoxic activities of Toremifene.Experimental
GoserelinGoserelin may increase the QTc-prolonging activities of Toremifene.Approved
GranisetronGranisetron may increase the QTc-prolonging activities of Toremifene.Approved, Investigational
HaloperidolHaloperidol may increase the QTc-prolonging activities of Toremifene.Approved
HistrelinHistrelin may increase the QTc-prolonging activities of Toremifene.Approved
HydrochlorothiazideHydrochlorothiazide may increase the hypercalcemic activities of Toremifene.Approved, Vet Approved
HydroflumethiazideHydroflumethiazide may increase the hypercalcemic activities of Toremifene.Approved, Investigational
HydroxyzineHydroxyzine may increase the QTc-prolonging activities of Toremifene.Approved
IbandronateIbandronate may increase the QTc-prolonging activities of Toremifene.Approved, Investigational
IbutilideThe risk or severity of QTc prolongation can be increased when Ibutilide is combined with Toremifene.Approved
IdelalisibThe serum concentration of Toremifene can be increased when it is combined with Idelalisib.Approved
IloperidoneThe risk or severity of QTc prolongation can be increased when Toremifene is combined with Iloperidone.Approved
ImatinibThe metabolism of Toremifene can be decreased when combined with Imatinib.Approved
ImipramineImipramine may increase the QTc-prolonging activities of Toremifene.Approved
IndacaterolIndacaterol may increase the QTc-prolonging activities of Toremifene.Approved
IndapamideIndapamide may increase the hypercalcemic activities of Toremifene.Approved
IndinavirThe risk or severity of adverse effects can be increased when Indinavir is combined with Toremifene.Approved
IsavuconazoniumThe metabolism of Toremifene can be decreased when combined with Isavuconazonium.Approved, Investigational
IsofluraneIsoflurane may increase the QTc-prolonging activities of Toremifene.Approved, Vet Approved
IsradipineIsradipine may increase the QTc-prolonging activities of Toremifene.Approved
ItraconazoleThe risk or severity of adverse effects can be increased when Itraconazole is combined with Toremifene.Approved, Investigational
IvabradineIvabradine may increase the QTc-prolonging activities of Toremifene.Approved
IvacaftorThe serum concentration of Toremifene can be increased when it is combined with Ivacaftor.Approved
KetoconazoleThe risk or severity of adverse effects can be increased when Ketoconazole is combined with Toremifene.Approved, Investigational
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Toremifene.Experimental
LapatinibLapatinib may increase the QTc-prolonging activities of Toremifene.Approved, Investigational
LenvatinibLenvatinib may increase the QTc-prolonging activities of Toremifene.Approved
LeuprolideLeuprolide may increase the QTc-prolonging activities of Toremifene.Approved, Investigational
LevofloxacinLevofloxacin may increase the QTc-prolonging activities of Toremifene.Approved, Investigational
LidocaineThe metabolism of Toremifene can be decreased when combined with Lidocaine.Approved, Vet Approved
LithiumLithium may increase the QTc-prolonging activities of Toremifene.Approved
LobeglitazoneThe metabolism of Toremifene can be decreased when combined with Lobeglitazone.Approved, Investigational
LopinavirThe risk or severity of adverse effects can be increased when Lopinavir is combined with Toremifene.Approved
LovastatinThe metabolism of Toremifene can be decreased when combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of Toremifene can be increased when it is combined with Luliconazole.Approved
LumacaftorThe serum concentration of Toremifene can be decreased when it is combined with Lumacaftor.Approved
LumefantrineThe risk or severity of QTc prolongation can be increased when Toremifene is combined with Lumefantrine.Approved
MaprotilineMaprotiline may increase the QTc-prolonging activities of Toremifene.Approved
MefloquineMefloquine may increase the QTc-prolonging activities of Toremifene.Approved
MethadoneMethadone may increase the QTc-prolonging activities of Toremifene.Approved
MethotrimeprazineMethotrimeprazine may increase the QTc-prolonging activities of Toremifene.Approved
MethyclothiazideMethyclothiazide may increase the hypercalcemic activities of Toremifene.Approved
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Toremifene.Experimental
MetoclopramideMetoclopramide may increase the QTc-prolonging activities of Toremifene.Approved, Investigational
MetolazoneMetolazone may increase the hypercalcemic activities of Toremifene.Approved
MetronidazoleMetronidazole may increase the QTc-prolonging activities of Toremifene.Approved
MexiletineThe metabolism of Toremifene can be decreased when combined with Mexiletine.Approved
MidostaurinThe metabolism of Toremifene can be decreased when combined with Midostaurin.Approved
MifepristoneThe serum concentration of Toremifene can be increased when it is combined with Mifepristone.Approved, Investigational
MirabegronMirabegron may increase the QTc-prolonging activities of Toremifene.Approved
MirtazapineMirtazapine may increase the QTc-prolonging activities of Toremifene.Approved
MitotaneThe serum concentration of Toremifene can be decreased when it is combined with Mitotane.Approved
MoexiprilMoexipril may increase the QTc-prolonging activities of Toremifene.Approved
MoxifloxacinMoxifloxacin may increase the QTc-prolonging activities of Toremifene.Approved, Investigational
NefazodoneThe risk or severity of adverse effects can be increased when Nefazodone is combined with Toremifene.Approved, Withdrawn
NelfinavirThe risk or severity of adverse effects can be increased when Nelfinavir is combined with Toremifene.Approved
NetupitantThe serum concentration of Toremifene can be increased when it is combined with Netupitant.Approved
NevirapineThe serum concentration of Toremifene can be decreased when it is combined with Nevirapine.Approved
NicardipineNicardipine may increase the QTc-prolonging activities of Toremifene.Approved
NilotinibThe metabolism of Toremifene can be decreased when combined with Nilotinib.Approved, Investigational
NorfloxacinNorfloxacin may increase the QTc-prolonging activities of Toremifene.Approved
NortriptylineNortriptyline may increase the QTc-prolonging activities of Toremifene.Approved
OctreotideOctreotide may increase the QTc-prolonging activities of Toremifene.Approved, Investigational
OfloxacinOfloxacin may increase the QTc-prolonging activities of Toremifene.Approved
OlanzapineOlanzapine may increase the QTc-prolonging activities of Toremifene.Approved, Investigational
OlaparibThe metabolism of Toremifene can be decreased when combined with Olaparib.Approved
OleandrinOleandrin may decrease the cardiotoxic activities of Toremifene.Experimental, Investigational
OlodaterolOlodaterol may increase the QTc-prolonging activities of Toremifene.Approved
OndansetronOndansetron may increase the QTc-prolonging activities of Toremifene.Approved
OsimertinibThe serum concentration of Toremifene can be increased when it is combined with Osimertinib.Approved
OspemifeneThe risk or severity of adverse effects can be increased when Toremifene is combined with Ospemifene.Approved
OuabainOuabain may decrease the cardiotoxic activities of Toremifene.Approved
OxytocinOxytocin may increase the QTc-prolonging activities of Toremifene.Approved, Vet Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Toremifene.Approved, Vet Approved
PalbociclibThe serum concentration of Toremifene can be increased when it is combined with Palbociclib.Approved
PaliperidoneThe risk or severity of QTc prolongation can be increased when Toremifene is combined with Paliperidone.Approved
PanobinostatPanobinostat may increase the QTc-prolonging activities of Toremifene.Approved, Investigational
ParoxetineParoxetine may increase the QTc-prolonging activities of Toremifene.Approved, Investigational
PasireotidePasireotide may increase the QTc-prolonging activities of Toremifene.Approved
PazopanibPazopanib may increase the QTc-prolonging activities of Toremifene.Approved
Peginterferon alfa-2bThe serum concentration of Toremifene can be increased when it is combined with Peginterferon alfa-2b.Approved
PentamidinePentamidine may increase the QTc-prolonging activities of Toremifene.Approved
PentobarbitalThe serum concentration of Toremifene can be decreased when it is combined with Pentobarbital.Approved, Vet Approved
PerflutrenPerflutren may increase the QTc-prolonging activities of Toremifene.Approved
PeruvosidePeruvoside may decrease the cardiotoxic activities of Toremifene.Experimental
PhenindioneToremifene may increase the anticoagulant activities of Phenindione.Approved, Investigational
PhenobarbitalThe serum concentration of Toremifene can be decreased when it is combined with Phenobarbital.Approved
PhenprocoumonToremifene may increase the anticoagulant activities of Phenprocoumon.Approved, Investigational
PhenytoinThe serum concentration of Toremifene can be decreased when it is combined with Phenytoin.Approved, Vet Approved
PimozideThe risk or severity of QTc prolongation can be increased when Toremifene is combined with Pimozide.Approved
PolythiazidePolythiazide may increase the hypercalcemic activities of Toremifene.Approved
PosaconazoleThe risk or severity of adverse effects can be increased when Posaconazole is combined with Toremifene.Approved, Investigational, Vet Approved
PrimaquinePrimaquine may increase the QTc-prolonging activities of Toremifene.Approved
PrimidoneThe serum concentration of Toremifene can be decreased when it is combined with Primidone.Approved, Vet Approved
ProcainamideThe risk or severity of QTc prolongation can be increased when Toremifene is combined with Procainamide.Approved
PromazinePromazine may increase the QTc-prolonging activities of Toremifene.Approved, Vet Approved
PromethazinePromethazine may increase the QTc-prolonging activities of Toremifene.Approved
PropafenonePropafenone may increase the QTc-prolonging activities of Toremifene.Approved
PropofolPropofol may increase the QTc-prolonging activities of Toremifene.Approved, Investigational, Vet Approved
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Toremifene.Experimental
ProtriptylineProtriptyline may increase the QTc-prolonging activities of Toremifene.Approved
QuetiapineThe risk or severity of QTc prolongation can be increased when Toremifene is combined with Quetiapine.Approved
QuinethazoneQuinethazone may increase the hypercalcemic activities of Toremifene.Approved
QuinidineThe risk or severity of QTc prolongation can be increased when Toremifene is combined with Quinidine.Approved
QuinineThe risk or severity of QTc prolongation can be increased when Quinine is combined with Toremifene.Approved
RanolazineThe serum concentration of Toremifene can be increased when it is combined with Ranolazine.Approved, Investigational
RifabutinThe serum concentration of Toremifene can be decreased when it is combined with Rifabutin.Approved
RifampicinThe serum concentration of Toremifene can be decreased when it is combined with Rifampicin.Approved
RifapentineThe serum concentration of Toremifene can be decreased when it is combined with Rifapentine.Approved
RilpivirineRilpivirine may increase the QTc-prolonging activities of Toremifene.Approved
RisperidoneRisperidone may increase the QTc-prolonging activities of Toremifene.Approved, Investigational
RitonavirRitonavir may increase the QTc-prolonging activities of Toremifene.Approved, Investigational
RopiniroleThe metabolism of Toremifene can be decreased when combined with Ropinirole.Approved, Investigational
SalbutamolSalbutamol may increase the QTc-prolonging activities of Toremifene.Approved, Vet Approved
SalmeterolSalmeterol may increase the QTc-prolonging activities of Toremifene.Approved
SaquinavirThe risk or severity of adverse effects can be increased when Saquinavir is combined with Toremifene.Approved, Investigational
SertralineSertraline may increase the QTc-prolonging activities of Toremifene.Approved
SevofluraneSevoflurane may increase the QTc-prolonging activities of Toremifene.Approved, Vet Approved
SildenafilThe metabolism of Toremifene can be decreased when combined with Sildenafil.Approved, Investigational
SiltuximabThe serum concentration of Toremifene can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Toremifene can be increased when it is combined with Simeprevir.Approved
SolifenacinSolifenacin may increase the QTc-prolonging activities of Toremifene.Approved
SorafenibSorafenib may increase the QTc-prolonging activities of Toremifene.Approved, Investigational
SotalolThe risk or severity of QTc prolongation can be increased when Sotalol is combined with Toremifene.Approved
St. John's WortThe serum concentration of Toremifene can be decreased when it is combined with St. John's Wort.Investigational, Nutraceutical
StiripentolThe serum concentration of Toremifene can be increased when it is combined with Stiripentol.Approved
SugammadexThe therapeutic efficacy of Sugammadex can be decreased when used in combination with Toremifene.Approved
SulfamethoxazoleSulfamethoxazole may increase the QTc-prolonging activities of Toremifene.Approved
SulfisoxazoleThe metabolism of Toremifene can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
SunitinibSunitinib may increase the QTc-prolonging activities of Toremifene.Approved, Investigational
TamoxifenTamoxifen may increase the QTc-prolonging activities of Toremifene.Approved
TelaprevirThe risk or severity of adverse effects can be increased when Telaprevir is combined with Toremifene.Approved, Withdrawn
TelavancinTelavancin may increase the QTc-prolonging activities of Toremifene.Approved
TelithromycinThe risk or severity of adverse effects can be increased when Telithromycin is combined with Toremifene.Approved
Tenofovir disoproxilThe metabolism of Toremifene can be decreased when combined with Tenofovir disoproxil.Approved, Investigational
TerbutalineTerbutaline may increase the QTc-prolonging activities of Toremifene.Approved
TeriflunomideThe serum concentration of Toremifene can be decreased when it is combined with Teriflunomide.Approved
TetrabenazineThe risk or severity of QTc prolongation can be increased when Toremifene is combined with Tetrabenazine.Approved
TheophyllineThe metabolism of Toremifene can be decreased when combined with Theophylline.Approved
ThioridazineThe risk or severity of QTc prolongation can be increased when Toremifene is combined with Thioridazine.Approved, Withdrawn
ThiothixeneThiothixene may increase the QTc-prolonging activities of Toremifene.Approved
TiclopidineThe metabolism of Toremifene can be decreased when combined with Ticlopidine.Approved
TioclomarolToremifene may increase the anticoagulant activities of Tioclomarol.Experimental
TizanidineTizanidine may increase the QTc-prolonging activities of Toremifene.Approved
TocilizumabThe serum concentration of Toremifene can be decreased when it is combined with Tocilizumab.Approved
TolterodineTolterodine may increase the QTc-prolonging activities of Toremifene.Approved, Investigational
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Toremifene.Approved, Investigational
TrazodoneTrazodone may increase the QTc-prolonging activities of Toremifene.Approved, Investigational
TreprostinilTreprostinil may increase the QTc-prolonging activities of Toremifene.Approved, Investigational
TrichlormethiazideTrichlormethiazide may increase the hypercalcemic activities of Toremifene.Approved, Vet Approved
TrimethoprimTrimethoprim may increase the QTc-prolonging activities of Toremifene.Approved, Vet Approved
TrimipramineTrimipramine may increase the QTc-prolonging activities of Toremifene.Approved
TriptorelinTriptorelin may increase the QTc-prolonging activities of Toremifene.Approved, Vet Approved
VandetanibThe risk or severity of QTc prolongation can be increased when Toremifene is combined with Vandetanib.Approved
VardenafilVardenafil may increase the QTc-prolonging activities of Toremifene.Approved
VemurafenibThe serum concentration of Toremifene can be increased when it is combined with Vemurafenib.Approved
VenlafaxineVenlafaxine may increase the QTc-prolonging activities of Toremifene.Approved
VerapamilThe metabolism of Toremifene can be decreased when combined with Verapamil.Approved
VilanterolVilanterol may increase the QTc-prolonging activities of Toremifene.Approved
VoriconazoleThe risk or severity of adverse effects can be increased when Voriconazole is combined with Toremifene.Approved, Investigational
VorinostatVorinostat may increase the QTc-prolonging activities of Toremifene.Approved, Investigational
WarfarinToremifene may increase the anticoagulant activities of Warfarin.Approved
ZiprasidoneThe metabolism of Toremifene can be decreased when combined with Ziprasidone.Approved
ZucapsaicinThe metabolism of Toremifene can be decreased when combined with Zucapsaicin.Approved
ZuclopenthixolThe risk or severity of QTc prolongation can be increased when Toremifene is combined with Zuclopenthixol.Approved, Investigational
Food Interactions
Not Available

References

Synthesis Reference

Reijo Toivola, Tuomas Huuhtanen, "Toremifene crystallization method." U.S. Patent US20070093556, issued April 26, 2007.

US20070093556
General References
  1. Price N, Sartor O, Hutson T, Mariani S: Role of 5a-reductase inhibitors and selective estrogen receptor modulators as potential chemopreventive agents for prostate cancer. Clin Prostate Cancer. 2005 Mar;3(4):211-4. [PubMed:15882476]
  2. Taneja SS, Smith MR, Dalton JT, Raghow S, Barnette G, Steiner M, Veverka KA: Toremifene--a promising therapy for the prevention of prostate cancer and complications of androgen deprivation therapy. Expert Opin Investig Drugs. 2006 Mar;15(3):293-305. [PubMed:16503765]
  3. Thompson IM: Chemoprevention of prostate cancer: agents and study designs. J Urol. 2007 Sep;178(3 Pt 2):S9-S13. Epub 2007 Jul 20. [PubMed:17644117]
  4. Ariazi EA, Ariazi JL, Cordera F, Jordan VC: Estrogen receptors as therapeutic targets in breast cancer. Curr Top Med Chem. 2006;6(3):181-202. [PubMed:16515478]
  5. Musa MA, Khan MO, Cooperwood JS: Medicinal chemistry and emerging strategies applied to the development of selective estrogen receptor modulators (SERMs). Curr Med Chem. 2007;14(11):1249-61. [PubMed:17504144]
External Links
Human Metabolome Database
HMDB14679
KEGG Compound
C08166
PubChem Compound
3005573
PubChem Substance
46506087
ChemSpider
2275722
BindingDB
58492
ChEBI
9635
ChEMBL
CHEMBL1655
Therapeutic Targets Database
DAP000793
PharmGKB
PA451731
HET
T0R
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Toremifene
ATC Codes
L02BA02 — Toremifene
PDB Entries
5jq7

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceNormal Healthy Volunteers1
2CompletedPreventionProstate Cancer1
2CompletedPreventionProstatic Intraepithelial Neoplasia1
2CompletedTreatmentDesmoid Tumors1
2RecruitingTreatmentCancer, Breast1
2TerminatedTreatmentNeoplasms, Breast1
2Unknown StatusTreatmentDesmoid Type-fibromatosis1
2WithdrawnTreatmentCancer, Ovarian1
3CompletedDiagnosticCirculatory; Change1
3CompletedPreventionBone destruction / Fracture Bone / Prostate Cancer1
3CompletedPreventionPreneoplastic Conditions / Prostatic Intraepithelial Neoplasia1
3CompletedTreatmentBreast Pain1
3CompletedTreatmentCancer, Breast1
3CompletedTreatmentNeoplasms, Breast / Neoplasms, Hormone-Dependent1
3Not Yet RecruitingTreatmentCancer, Breast / Chemotherapy Induced Amenorrhea / Ovarian Function Suppression1
3RecruitingTreatmentCancer, Breast1
3TerminatedTreatmentCancer, Breast1
3TerminatedTreatmentNeoplasms, Breast / Neoplasms, Hormone-Dependent2
3WithdrawnPreventionRisk of Bone Fracture Occurrences1
4Not Yet RecruitingTreatmentHER2/Neu Negative / Invasive Breast Carcinoma / One to five years postmenopausal / Stage 0 Breast Cancer / Stage IA Breast Cancer1
4RecruitingTreatmentCancer, Breast1
4RecruitingTreatmentFemale Breast Cancer1

Pharmacoeconomics

Manufacturers
  • Gtx inc
Packagers
Dosage forms
FormRouteStrength
TabletOral60 mg/1
TabletOral60 mg
Prices
Unit descriptionCostUnit
Fareston 60 mg tablet11.84USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US4696949No1992-09-292009-09-29Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)108-110 °CNot Available
logP6.8Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.000409 mg/mLALOGPS
logP5.65ALOGPS
logP6.27ChemAxon
logS-6ALOGPS
pKa (Strongest Basic)8.76ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area12.47 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity133.41 m3·mol-1ChemAxon
Polarizability46.49 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.7488
Caco-2 permeable+0.8266
P-glycoprotein substrateSubstrate0.7067
P-glycoprotein inhibitor IInhibitor0.79
P-glycoprotein inhibitor IINon-inhibitor0.5917
Renal organic cation transporterInhibitor0.7552
CYP450 2C9 substrateNon-substrate0.7502
CYP450 2D6 substrateNon-substrate0.759
CYP450 3A4 substrateSubstrate0.7574
CYP450 1A2 substrateInhibitor0.8683
CYP450 2C9 inhibitorNon-inhibitor0.882
CYP450 2D6 inhibitorInhibitor0.7217
CYP450 2C19 inhibitorNon-inhibitor0.7443
CYP450 3A4 inhibitorNon-inhibitor0.8824
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5128
Ames testNon AMES toxic0.7545
CarcinogenicityNon-carcinogens0.616
BiodegradationNot ready biodegradable0.9601
Rat acute toxicity2.3467 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.7708
hERG inhibition (predictor II)Inhibitor0.5086
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 GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0a4i-0010900000-f55f03796d8b627e24e1

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 / Trialkylamines / Organopnictogen compounds / Organochlorides / Hydrocarbon derivatives / Alkyl chlorides
Substituents
Stilbene / Diphenylmethane / Phenoxy compound / Phenol ether / Alkyl aryl ether / Monocyclic benzene moiety / Benzenoid / Tertiary amine / Tertiary aliphatic amine / Ether
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
aromatic ether, tertiary amine, organochlorine compound (CHEBI:9635)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Modulator
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. Locci P, Bellocchio S, Lilli C, Marinucci L, Cagini L, Baroni T, Giustozzi G, Balducci C, Becchetti E: Synthesis and secretion of transforming growth factor-beta1 by human desmoid fibroblast cell line and its modulation by toremifene. J Interferon Cytokine Res. 2001 Nov;21(11):961-70. [PubMed:11747628]
  2. Liu X, Pisha E, Tonetti DA, Yao D, Li Y, Yao J, Burdette JE, Bolton JL: Antiestrogenic and DNA damaging effects induced by tamoxifen and toremifene metabolites. Chem Res Toxicol. 2003 Jul;16(7):832-7. [PubMed:12870885]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  4. Jones KL, Buzdar AU: A review of adjuvant hormonal therapy in breast cancer. Endocr Relat Cancer. 2004 Sep;11(3):391-406. [PubMed:15369444]
  5. Shelly W, Draper MW, Krishnan V, Wong M, Jaffe RB: Selective estrogen receptor modulators: an update on recent clinical findings. Obstet Gynecol Surv. 2008 Mar;63(3):163-81. doi: 10.1097/OGX.0b013e31816400d7. [PubMed:18279543]
  6. Gennari L, Merlotti D, Valleggi F, Martini G, Nuti R: Selective estrogen receptor modulators for postmenopausal osteoporosis: current state of development. Drugs Aging. 2007;24(5):361-79. [PubMed:17503894]
  7. Lewis-Wambi JS, Jordan VC: Treatment of Postmenopausal Breast Cancer with Selective Estrogen Receptor Modulators (SERMs). Breast Dis. 2005-2006;24:93-105. [PubMed:16917142]
  8. Ariazi EA, Ariazi JL, Cordera F, Jordan VC: Estrogen receptors as therapeutic targets in breast cancer. Curr Top Med Chem. 2006;6(3):181-202. [PubMed:16515478]
  9. Taneja SS, Smith MR, Dalton JT, Raghow S, Barnette G, Steiner M, Veverka KA: Toremifene--a promising therapy for the prevention of prostate cancer and complications of androgen deprivation therapy. Expert Opin Investig Drugs. 2006 Mar;15(3):293-305. [PubMed:16503765]
  10. Goldstein LJ: Controversies in adjuvant endocrine treatment of premenopausal women. Clin Breast Cancer. 2006 Feb;6 Suppl 2:S36-40. [PubMed:16595024]
  11. Smith MR: Treatment-related osteoporosis in men with prostate cancer. Clin Cancer Res. 2006 Oct 15;12(20 Pt 2):6315s-6319s. [PubMed:17062721]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Androgen binding
Specific Function
Functions as an androgen transport protein, but may also be involved in receptor mediated processes. Each dimer binds one molecule of steroid. Specific for 5-alpha-dihydrotestosterone, testosterone...
Gene Name
SHBG
Uniprot ID
P04278
Uniprot Name
Sex hormone-binding globulin
Molecular Weight
43778.755 Da
References
  1. Hong H, Branham WS, Ng HW, Moland CL, Dial SL, Fang H, Perkins R, Sheehan D, Tong W: Human sex hormone-binding globulin binding affinities of 125 structurally diverse chemicals and comparison with their binding to androgen receptor, estrogen receptor, and alpha-fetoprotein. Toxicol Sci. 2015 Feb;143(2):333-48. doi: 10.1093/toxsci/kfu231. Epub 2014 Oct 27. [PubMed:25349334]

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. Taneja SS, Smith MR, Dalton JT, Raghow S, Barnette G, Steiner M, Veverka KA: Toremifene--a promising therapy for the prevention of prostate cancer and complications of androgen deprivation therapy. Expert Opin Investig Drugs. 2006 Mar;15(3):293-305. [PubMed:16503765]
  2. Kivisto KT, Villikka K, Nyman L, Anttila M, Neuvonen PJ: Tamoxifen and toremifene concentrations in plasma are greatly decreased by rifampin. Clin Pharmacol Ther. 1998 Dec;64(6):648-54. [PubMed:9871429]
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d 24-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
CYP1A1
Uniprot ID
P04798
Uniprot Name
Cytochrome P450 1A1
Molecular Weight
58164.815 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
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
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Rao US, Fine RL, Scarborough GA: Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92. [PubMed:7914405]

Drug created on June 13, 2005 07:24 / Updated on November 07, 2017 01:39