Identification

Name
Tesmilifene
Accession Number
DB04905
Type
Small Molecule
Groups
Investigational
Description

Tesmilifene is a novel potentiator of chemotherapy which, when added to doxorubicin, achieved an unexpected and very large survival advantage over doxorubicin alone in a randomized trial in advanced breast cancer.

Structure
Thumb
Synonyms
  • Depmpe
  • DPPE
  • N,N-diethyl-2-((4-phenylmethyl)phenoxy)ethanamine
Categories
UNII
I43T3ID6G2
CAS number
98774-23-3
Weight
Average: 283.4079
Monoisotopic: 283.193614427
Chemical Formula
C19H25NO
InChI Key
NFIXBCVWIPOYCD-UHFFFAOYSA-N
InChI
InChI=1S/C19H25NO/c1-3-20(4-2)14-15-21-19-12-10-18(11-13-19)16-17-8-6-5-7-9-17/h5-13H,3-4,14-16H2,1-2H3
IUPAC Name
[2-(4-benzylphenoxy)ethyl]diethylamine
SMILES
CCN(CC)CCOC1=CC=C(CC2=CC=CC=C2)C=C1

Pharmacology

Indication

Intended for the treatment of various forms of cancer.

Structured Indications
Not Available
Pharmacodynamics
Not Available
Mechanism of action

Although the exact mechanism of action is not known, one study (PMID: 16413681) proposes that tesmilifene may be an activating p-gp substrate, which enables the p-gp pump to extrude typical p-gp substrates (such as anthracyclines or taxanes) more efficiently. This process consumes ATP, since the p-gp is absolutely, and highly dependent on ATP hydrolysis. The mechanism of cell death is likely to result not from the presence of chemotherapy inside the cell (in fact the chemotherapy is extruded) but, directly or indirectly, from the enhanced consumption of ATP. The ATP may be consumed below a threshold necessary for survival, or, (more likely) the enhanced ATP production required to maintain ATP levels may result in the generation of reactive oxygen species (ROS) to an extent that overwhelms the cell’s ability to inactivate them. The result would be additional cell death, but only in the mdr+ population. The doxorubicin would continue to act on the drug sensitive remainder of the cell population, but without the help of tesmilifene.

TargetActionsOrganism
AMultidrug resistance protein 1
inducer
Human
UHistamine H1 receptor
antagonist
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Hepatic

Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
2,5-Dimethoxy-4-ethylamphetamine2,5-Dimethoxy-4-ethylamphetamine may decrease the sedative activities of Tesmilifene.Experimental, Illicit
3,4-Methylenedioxyamphetamine3,4-Methylenedioxyamphetamine may decrease the sedative activities of Tesmilifene.Experimental, Illicit
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may decrease the sedative activities of Tesmilifene.Experimental, Illicit
AbciximabTesmilifene may increase the anticoagulant activities of Abciximab.Approved
AbirateroneThe serum concentration of Tesmilifene can be increased when it is combined with Abiraterone.Approved
AcenocoumarolTesmilifene may increase the anticoagulant activities of Acenocoumarol.Approved
Acetylsalicylic acidThe risk or severity of adverse effects can be increased when Tesmilifene is combined with Acetylsalicylic acid.Approved, Vet Approved
AfatinibThe serum concentration of Afatinib can be decreased when it is combined with Tesmilifene.Approved
AloxiprinThe risk or severity of adverse effects can be increased when Tesmilifene is combined with Aloxiprin.Experimental
AlprostadilAlprostadil may increase the antiplatelet activities of Tesmilifene.Approved, Investigational
AlteplaseTesmilifene may increase the anticoagulant activities of Alteplase.Approved
ALX-0081Tesmilifene may increase the anticoagulant activities of ALX-0081.Investigational
Aminosalicylic AcidThe risk or severity of adverse effects can be increased when Tesmilifene is combined with Aminosalicylic Acid.Approved
AmiodaroneThe metabolism of Tesmilifene can be decreased when combined with Amiodarone.Approved, Investigational
AmphetamineAmphetamine may decrease the sedative activities of Tesmilifene.Approved, Illicit
AnagrelideTesmilifene may increase the anticoagulant activities of Anagrelide.Approved
AncrodTesmilifene may increase the anticoagulant activities of Ancrod.Investigational
AndrographolideTesmilifene may increase the antiplatelet activities of Andrographolide.Investigational
AnistreplaseTesmilifene may increase the anticoagulant activities of Anistreplase.Approved
Antithrombin III humanTesmilifene may increase the anticoagulant activities of Antithrombin III human.Approved
ApixabanThe risk or severity of adverse effects can be increased when Tesmilifene is combined with Apixaban.Approved
AprepitantThe serum concentration of Tesmilifene can be increased when it is combined with Aprepitant.Approved, Investigational
ArdeparinTesmilifene may increase the anticoagulant activities of Ardeparin.Approved, Investigational, Withdrawn
ArgatrobanTesmilifene may increase the anticoagulant activities of Argatroban.Approved, Investigational
AripiprazoleThe serum concentration of Aripiprazole can be decreased when it is combined with Tesmilifene.Approved, Investigational
ArtemetherThe metabolism of Tesmilifene can be decreased when combined with Artemether.Approved
AstaxanthinTesmilifene may increase the anticoagulant activities of Astaxanthin.Investigational
AtazanavirThe metabolism of Tesmilifene can be decreased when combined with Atazanavir.Approved, Investigational
AtomoxetineThe metabolism of Tesmilifene can be decreased when combined with Atomoxetine.Approved
AtorvastatinThe risk or severity of adverse effects can be increased when Tesmilifene is combined with Atorvastatin.Approved
AzelastineAzelastine may increase the antiplatelet activities of Tesmilifene.Approved
BalsalazideThe risk or severity of adverse effects can be increased when Tesmilifene is combined with Balsalazide.Approved, Investigational
BatroxobinTesmilifene may increase the anticoagulant activities of Batroxobin.Experimental
BecaplerminTesmilifene may increase the anticoagulant activities of Becaplermin.Approved, Investigational
BemiparinTesmilifene may increase the anticoagulant activities of Bemiparin.Approved, Investigational
BenzphetamineBenzphetamine may decrease the sedative activities of Tesmilifene.Approved, Illicit
Benzylpenicilloyl PolylysineTesmilifene may decrease effectiveness of Benzylpenicilloyl Polylysine as a diagnostic agent.Approved
BeraprostTesmilifene may increase the anticoagulant activities of Beraprost.Investigational
BetahistineThe therapeutic efficacy of Betahistine can be decreased when used in combination with Tesmilifene.Approved
BetaxololThe metabolism of Tesmilifene can be decreased when combined with Betaxolol.Approved
BivalirudinTesmilifene may increase the anticoagulant activities of Bivalirudin.Approved, Investigational
BoceprevirThe metabolism of Tesmilifene can be decreased when combined with Boceprevir.Approved, Withdrawn
BortezomibThe metabolism of Tesmilifene can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Tesmilifene can be decreased when it is combined with Bosentan.Approved, Investigational
Brentuximab vedotinThe serum concentration of Brentuximab vedotin can be decreased when it is combined with Tesmilifene.Approved
BrinaseTesmilifene may increase the anticoagulant activities of Brinase.Experimental
BuflomedilTesmilifene may increase the antiplatelet activities of Buflomedil.Experimental
BupropionThe metabolism of Tesmilifene can be decreased when combined with Bupropion.Approved
ButylphthalideTesmilifene may increase the antiplatelet activities of Butylphthalide.Investigational
CabergolineThe risk or severity of adverse effects can be increased when Cabergoline is combined with Tesmilifene.Approved
CangrelorTesmilifene may increase the anticoagulant activities of Cangrelor.Approved
CarbamazepineThe metabolism of Tesmilifene can be increased when combined with Carbamazepine.Approved, Investigational
Carbaspirin calciumThe risk or severity of adverse effects can be increased when Tesmilifene is combined with Carbaspirin calcium.Experimental, Investigational
CelecoxibThe metabolism of Tesmilifene can be decreased when combined with Celecoxib.Approved, Investigational
CeritinibThe serum concentration of Tesmilifene can be increased when it is combined with Ceritinib.Approved
CertoparinTesmilifene may increase the anticoagulant activities of Certoparin.Approved, Investigational
ChloroquineThe metabolism of Tesmilifene can be decreased when combined with Chloroquine.Approved, Vet Approved
ChlorphentermineChlorphentermine may decrease the sedative activities of Tesmilifene.Illicit, Withdrawn
CholecalciferolThe metabolism of Tesmilifene can be decreased when combined with Cholecalciferol.Approved, Nutraceutical
CilostazolTesmilifene may increase the anticoagulant activities of Cilostazol.Approved
CinacalcetThe metabolism of Tesmilifene can be decreased when combined with Cinacalcet.Approved
Citric AcidTesmilifene may increase the anticoagulant activities of Citric Acid.Approved, Nutraceutical, Vet Approved
ClarithromycinThe metabolism of Tesmilifene can be decreased when combined with Clarithromycin.Approved
ClemastineThe metabolism of Tesmilifene can be decreased when combined with Clemastine.Approved
ClomipramineThe metabolism of Tesmilifene can be decreased when combined with Clomipramine.Approved, Vet Approved
CloricromenTesmilifene may increase the anticoagulant activities of Cloricromen.Experimental
ClorindioneTesmilifene may increase the anticoagulant activities of Clorindione.Experimental
ClotrimazoleThe metabolism of Tesmilifene can be decreased when combined with Clotrimazole.Approved, Vet Approved
CobicistatThe serum concentration of Tesmilifene can be increased when it is combined with Cobicistat.Approved
CocaineThe metabolism of Tesmilifene can be decreased when combined with Cocaine.Approved, Illicit
Collagenase clostridium histolyticumThe risk or severity of adverse effects can be increased when Tesmilifene is combined with Collagenase clostridium histolyticum.Approved, Investigational
ConivaptanThe serum concentration of Tesmilifene can be increased when it is combined with Conivaptan.Approved, Investigational
CrizotinibThe metabolism of Tesmilifene can be decreased when combined with Crizotinib.Approved
CyclosporineThe metabolism of Tesmilifene can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
Dabigatran etexilateTesmilifene may increase the anticoagulant activities of Dabigatran etexilate.Approved
DabrafenibThe serum concentration of Tesmilifene can be decreased when it is combined with Dabrafenib.Approved
DalteparinTesmilifene may increase the anticoagulant activities of Dalteparin.Approved
DanaparoidTesmilifene may increase the anticoagulant activities of Danaparoid.Approved, Withdrawn
DarexabanTesmilifene may increase the anticoagulant activities of Darexaban.Investigational
DarifenacinThe metabolism of Tesmilifene can be decreased when combined with Darifenacin.Approved, Investigational
DarunavirThe serum concentration of Tesmilifene can be increased when it is combined with Darunavir.Approved
DasatinibDasatinib may increase the anticoagulant activities of Tesmilifene.Approved, Investigational
DeferasiroxThe serum concentration of Tesmilifene can be decreased when it is combined with Deferasirox.Approved, Investigational
DefibrotideTesmilifene may increase the anticoagulant activities of Defibrotide.Approved, Investigational
DelavirdineThe metabolism of Tesmilifene can be decreased when combined with Delavirdine.Approved
Deoxycholic AcidThe risk or severity of adverse effects can be increased when Tesmilifene is combined with Deoxycholic Acid.Approved
dersalazineThe risk or severity of adverse effects can be increased when Tesmilifene is combined with dersalazine.Investigational
DesipramineThe metabolism of Tesmilifene can be decreased when combined with Desipramine.Approved
DesirudinTesmilifene may increase the anticoagulant activities of Desirudin.Approved
DesmoteplaseTesmilifene may increase the anticoagulant activities of Desmoteplase.Investigational
DextranTesmilifene may increase the anticoagulant activities of Dextran.Approved, Vet Approved
Dextran 40Tesmilifene may increase the anticoagulant activities of Dextran 40.Approved
Dextran 70Tesmilifene may increase the anticoagulant activities of Dextran 70.Approved
Dextran 75Tesmilifene may increase the anticoagulant activities of Dextran 75.Approved
DextroamphetamineDextroamphetamine may decrease the sedative activities of Tesmilifene.Approved, Illicit
DicoumarolTesmilifene may increase the anticoagulant activities of Dicoumarol.Approved
DiethylpropionDiethylpropion may decrease the sedative activities of Tesmilifene.Approved, Illicit
DiflunisalThe risk or severity of adverse effects can be increased when Tesmilifene is combined with Diflunisal.Approved
DihydroergocornineThe risk or severity of adverse effects can be increased when Dihydroergocornine is combined with Tesmilifene.Approved
DihydroergocristineThe risk or severity of adverse effects can be increased when Dihydroergocristine is combined with Tesmilifene.Experimental
DihydroergocryptineThe risk or severity of adverse effects can be increased when Dihydroergocryptine is combined with Tesmilifene.Experimental
DihydroergotamineThe metabolism of Tesmilifene can be decreased when combined with Dihydroergotamine.Approved
DiltiazemThe metabolism of Tesmilifene can be decreased when combined with Diltiazem.Approved
DiphenadioneTesmilifene may increase the anticoagulant activities of Diphenadione.Experimental
DiphenhydramineThe metabolism of Tesmilifene can be decreased when combined with Diphenhydramine.Approved
DitazoleTesmilifene may increase the anticoagulant activities of Ditazole.Approved, Withdrawn
DosulepinThe metabolism of Tesmilifene can be decreased when combined with Dosulepin.Approved
DoxorubicinThe serum concentration of Doxorubicin can be decreased when it is combined with Tesmilifene.Approved, Investigational
DoxycyclineThe metabolism of Tesmilifene can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe metabolism of Tesmilifene can be decreased when combined with Dronedarone.Approved
Drotrecogin alfaTesmilifene may increase the anticoagulant activities of Drotrecogin alfa.Approved, Investigational, Withdrawn
DuloxetineThe metabolism of Tesmilifene can be decreased when combined with Duloxetine.Approved
Edetic AcidTesmilifene may increase the anticoagulant activities of Edetic Acid.Approved, Vet Approved
EliglustatThe metabolism of Tesmilifene can be decreased when combined with Eliglustat.Approved
EnoxaparinTesmilifene may increase the anticoagulant activities of Enoxaparin.Approved
EnzalutamideThe serum concentration of Tesmilifene can be decreased when it is combined with Enzalutamide.Approved
EplivanserinTesmilifene may increase the anticoagulant activities of Eplivanserin.Investigational
eplivanserineTesmilifene may increase the anticoagulant activities of eplivanserine.Investigational
EpoprostenolEpoprostenol may increase the antiplatelet activities of Tesmilifene.Approved
EptifibatideTesmilifene may increase the anticoagulant activities of Eptifibatide.Approved, Investigational
ErgonovineThe risk or severity of adverse effects can be increased when Ergonovine is combined with Tesmilifene.Approved
ErgotamineThe risk or severity of adverse effects can be increased when Ergotamine is combined with Tesmilifene.Approved
ErythromycinThe metabolism of Tesmilifene can be decreased when combined with Erythromycin.Approved, Vet Approved
Ethyl biscoumacetateTesmilifene may increase the anticoagulant activities of Ethyl biscoumacetate.Withdrawn
Ferulic acidTesmilifene may increase the anticoagulant activities of Ferulic acid.Experimental
FibrinolysinTesmilifene may increase the anticoagulant activities of Fibrinolysin.Investigational
FluconazoleThe metabolism of Tesmilifene can be decreased when combined with Fluconazole.Approved
FluindioneTesmilifene may increase the anticoagulant activities of Fluindione.Investigational
FluoxetineThe metabolism of Tesmilifene can be decreased when combined with Fluoxetine.Approved, Vet Approved
FluvastatinThe serum concentration of Fluvastatin can be increased when it is combined with Tesmilifene.Approved
FluvoxamineThe metabolism of Tesmilifene can be decreased when combined with Fluvoxamine.Approved, Investigational
FondaparinuxTesmilifene may increase the anticoagulant activities of Fondaparinux.Investigational
Fondaparinux sodiumTesmilifene may increase the anticoagulant activities of Fondaparinux sodium.Approved, Investigational
FosamprenavirThe metabolism of Tesmilifene can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Tesmilifene can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe metabolism of Tesmilifene can be increased when combined with Fosphenytoin.Approved
Fusidic AcidThe serum concentration of Tesmilifene can be increased when it is combined with Fusidic Acid.Approved
GabexateTesmilifene may increase the anticoagulant activities of Gabexate.Investigational
GepefrineGepefrine may decrease the sedative activities of Tesmilifene.Experimental
GlucosamineGlucosamine may increase the antiplatelet activities of Tesmilifene.Approved
GuacetisalThe risk or severity of adverse effects can be increased when Tesmilifene is combined with Guacetisal.Experimental
Hemoglobin crosfumarilThe risk or severity of adverse effects can be increased when Tesmilifene is combined with Hemoglobin crosfumaril.Experimental
HeparinTesmilifene may increase the anticoagulant activities of Heparin.Approved, Investigational
HigenamineTesmilifene may increase the anticoagulant activities of Higenamine.Investigational
HyaluronidaseThe therapeutic efficacy of Hyaluronidase can be decreased when used in combination with Tesmilifene.Approved, Investigational
HydroxyamphetamineHydroxyamphetamine may decrease the sedative activities of Tesmilifene.Approved
HydroxytyrosolTesmilifene may increase the antiplatelet activities of Hydroxytyrosol.Investigational
Ibritumomab tiuxetanThe risk or severity of adverse effects can be increased when Tesmilifene is combined with Ibritumomab tiuxetan.Approved
IbrutinibThe risk or severity of adverse effects can be increased when Ibrutinib is combined with Tesmilifene.Approved
IbudilastTesmilifene may increase the antiplatelet activities of Ibudilast.Approved, Investigational
Icosapent ethylTesmilifene may increase the antiplatelet activities of Icosapent ethyl.Approved, Nutraceutical
IdelalisibThe serum concentration of Tesmilifene can be increased when it is combined with Idelalisib.Approved
IdraparinuxTesmilifene may increase the anticoagulant activities of Idraparinux.Investigational
IfenprodilTesmilifene may increase the antiplatelet activities of Ifenprodil.Approved, Investigational, Withdrawn
IfetrobanTesmilifene may increase the antiplatelet activities of Ifetroban.Investigational
IloprostIloprost may increase the antiplatelet activities of Tesmilifene.Approved, Investigational
ImatinibThe metabolism of Tesmilifene can be decreased when combined with Imatinib.Approved
IndinavirThe metabolism of Tesmilifene can be decreased when combined with Indinavir.Approved
IndobufenTesmilifene may increase the anticoagulant activities of Indobufen.Investigational
Iofetamine I-123Iofetamine I-123 may decrease the sedative activities of Tesmilifene.Approved
IsavuconazoniumThe metabolism of Tesmilifene can be decreased when combined with Isavuconazonium.Approved, Investigational
IsoniazidThe metabolism of Tesmilifene can be decreased when combined with Isoniazid.Approved
IsradipineThe metabolism of Tesmilifene can be decreased when combined with Isradipine.Approved
ItraconazoleThe metabolism of Tesmilifene can be decreased when combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Tesmilifene can be increased when it is combined with Ivacaftor.Approved
KetanserinTesmilifene may increase the antiplatelet activities of Ketanserin.Investigational
KetoconazoleThe metabolism of Tesmilifene can be decreased when combined with Ketoconazole.Approved, Investigational
LedipasvirThe serum concentration of Ledipasvir can be decreased when it is combined with Tesmilifene.Approved
LepirudinTesmilifene may increase the anticoagulant activities of Lepirudin.Approved
LetaxabanTesmilifene may increase the anticoagulant activities of Letaxaban.Investigational
LimaprostLimaprost may increase the antiplatelet activities of Tesmilifene.Approved, Investigational
LinagliptinThe serum concentration of Linagliptin can be decreased when it is combined with Tesmilifene.Approved
LinsidomineTesmilifene may increase the antiplatelet activities of Linsidomine.Experimental
LisdexamfetamineLisdexamfetamine may decrease the sedative activities of Tesmilifene.Approved, Investigational
LisurideThe risk or severity of adverse effects can be increased when Lisuride is combined with Tesmilifene.Approved, Investigational
LopinavirThe metabolism of Tesmilifene can be decreased when combined with Lopinavir.Approved
LorcaserinThe metabolism of Tesmilifene can be decreased when combined with Lorcaserin.Approved
LovastatinThe metabolism of Tesmilifene can be decreased when combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of Tesmilifene can be increased when it is combined with Luliconazole.Approved
LumacaftorThe metabolism of Tesmilifene can be increased when combined with Lumacaftor.Approved
LumefantrineThe metabolism of Tesmilifene can be decreased when combined with Lumefantrine.Approved
Lysergic Acid DiethylamideThe risk or severity of adverse effects can be increased when Lysergic Acid Diethylamide is combined with Tesmilifene.Illicit, Investigational, Withdrawn
ManidipineThe metabolism of Tesmilifene can be decreased when combined with Manidipine.Approved, Investigational
MelagatranTesmilifene may increase the anticoagulant activities of Melagatran.Experimental
MephedroneMephedrone may decrease the sedative activities of Tesmilifene.Investigational
MephentermineMephentermine may decrease the sedative activities of Tesmilifene.Approved
MesalazineThe risk or severity of adverse effects can be increased when Tesmilifene is combined with Mesalazine.Approved
MetergolineThe risk or severity of adverse effects can be increased when Metergoline is combined with Tesmilifene.Experimental
MethadoneThe metabolism of Tesmilifene can be decreased when combined with Methadone.Approved
MethamphetamineMethamphetamine may decrease the sedative activities of Tesmilifene.Approved, Illicit
MethotrimeprazineThe metabolism of Tesmilifene can be decreased when combined with Methotrimeprazine.Approved
MethoxyphenamineMethoxyphenamine may decrease the sedative activities of Tesmilifene.Experimental
MethylergometrineThe risk or severity of adverse effects can be increased when Methylergometrine is combined with Tesmilifene.Approved
MethysergideThe risk or severity of adverse effects can be increased when Methysergide is combined with Tesmilifene.Approved
MevastatinThe serum concentration of Mevastatin can be increased when it is combined with Tesmilifene.Experimental
Midomafetamine3,4-Methylenedioxymethamphetamine may decrease the sedative activities of Tesmilifene.Experimental, Illicit, Investigational
MidostaurinThe metabolism of Tesmilifene can be decreased when combined with Midostaurin.Approved
MifepristoneThe serum concentration of Tesmilifene can be increased when it is combined with Mifepristone.Approved, Investigational
MilrinoneMilrinone may increase the antiplatelet activities of Tesmilifene.Approved
MitotaneThe serum concentration of Tesmilifene can be decreased when it is combined with Mitotane.Approved
MMDAMMDA may decrease the sedative activities of Tesmilifene.Experimental, Illicit
NadroparinTesmilifene may increase the anticoagulant activities of Nadroparin.Approved
NafamostatTesmilifene may increase the anticoagulant activities of Nafamostat.Approved, Investigational
NaftopidilTesmilifene may increase the antiplatelet activities of Naftopidil.Investigational
NefazodoneThe metabolism of Tesmilifene can be decreased when combined with Nefazodone.Approved, Withdrawn
NelfinavirThe metabolism of Tesmilifene can be decreased when combined with Nelfinavir.Approved
NetupitantThe serum concentration of Tesmilifene can be increased when it is combined with Netupitant.Approved
NevirapineThe metabolism of Tesmilifene can be increased when combined with Nevirapine.Approved
NicergolineThe risk or severity of adverse effects can be increased when Nicergoline is combined with Tesmilifene.Approved, Investigational
NilotinibThe metabolism of Tesmilifene can be decreased when combined with Nilotinib.Approved, Investigational
NimesulideNimesulide may increase the antiplatelet activities of Tesmilifene.Approved, Investigational, Withdrawn
NintedanibThe serum concentration of Nintedanib can be decreased when it is combined with Tesmilifene.Approved
NitroaspirinThe risk or severity of adverse effects can be increased when Tesmilifene is combined with Nitroaspirin.Investigational
ObinutuzumabThe risk or severity of adverse effects can be increased when Tesmilifene is combined with Obinutuzumab.Approved
OlaparibThe metabolism of Tesmilifene can be decreased when combined with Olaparib.Approved
OlsalazineThe risk or severity of adverse effects can be increased when Tesmilifene is combined with Olsalazine.Approved
Omega-3 fatty acidsOmega-3 fatty acids may increase the antiplatelet activities of Tesmilifene.Approved, Nutraceutical
OsimertinibThe serum concentration of Tesmilifene can be increased when it is combined with Osimertinib.Approved
OtamixabanTesmilifene may increase the anticoagulant activities of Otamixaban.Investigational
OzagrelTesmilifene may increase the anticoagulant activities of Ozagrel.Investigational
PalbociclibThe serum concentration of Tesmilifene can be increased when it is combined with Palbociclib.Approved
PanobinostatThe serum concentration of Tesmilifene can be increased when it is combined with Panobinostat.Approved, Investigational
ParnaparinTesmilifene may increase the anticoagulant activities of Parnaparin.Approved, Investigational
ParoxetineThe metabolism of Tesmilifene can be decreased when combined with Paroxetine.Approved, Investigational
Peginterferon alfa-2bThe serum concentration of Tesmilifene can be decreased when it is combined with Peginterferon alfa-2b.Approved
PentobarbitalThe metabolism of Tesmilifene can be increased when combined with Pentobarbital.Approved, Vet Approved
Pentosan PolysulfateThe risk or severity of adverse effects can be increased when Pentosan Polysulfate is combined with Tesmilifene.Approved
PentoxifyllinePentoxifylline may increase the antiplatelet activities of Tesmilifene.Approved, Investigational
PergolideThe risk or severity of adverse effects can be increased when Pergolide is combined with Tesmilifene.Approved, Investigational, Vet Approved, Withdrawn
PhenindioneTesmilifene may increase the anticoagulant activities of Phenindione.Approved, Investigational
PhenobarbitalThe metabolism of Tesmilifene can be increased when combined with Phenobarbital.Approved
PhenprocoumonTesmilifene may increase the anticoagulant activities of Phenprocoumon.Approved, Investigational
PhenterminePhentermine may decrease the sedative activities of Tesmilifene.Approved, Illicit
PhenytoinThe metabolism of Tesmilifene can be increased when combined with Phenytoin.Approved, Vet Approved
PicotamideTesmilifene may increase the anticoagulant activities of Picotamide.Experimental
PosaconazoleThe metabolism of Tesmilifene can be decreased when combined with Posaconazole.Approved, Investigational, Vet Approved
PrasugrelTesmilifene may increase the anticoagulant activities of Prasugrel.Approved
PrimidoneThe metabolism of Tesmilifene can be increased when combined with Primidone.Approved, Vet Approved
PromazineThe metabolism of Tesmilifene can be decreased when combined with Promazine.Approved, Vet Approved
Protein CTesmilifene may increase the anticoagulant activities of Protein C.Approved
Protein S humanTesmilifene may increase the anticoagulant activities of Protein S human.Approved
ProtocatechualdehydeTesmilifene may increase the anticoagulant activities of Protocatechualdehyde.Approved
PseudoephedrinePseudoephedrine may decrease the sedative activities of Tesmilifene.Approved
QuinidineThe metabolism of Tesmilifene can be decreased when combined with Quinidine.Approved
RamatrobanTesmilifene may increase the antiplatelet activities of Ramatroban.Investigational
RanolazineThe metabolism of Tesmilifene can be decreased when combined with Ranolazine.Approved, Investigational
ResveratrolResveratrol may increase the antiplatelet activities of Tesmilifene.Approved, Experimental, Investigational
ReteplaseTesmilifene may increase the anticoagulant activities of Reteplase.Approved
ReviparinTesmilifene may increase the anticoagulant activities of Reviparin.Approved, Investigational
RidogrelRidogrel may increase the antiplatelet activities of Tesmilifene.Approved
RifabutinThe metabolism of Tesmilifene can be increased when combined with Rifabutin.Approved
RifampicinThe metabolism of Tesmilifene can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Tesmilifene can be increased when combined with Rifapentine.Approved
RitobegronRitobegron may decrease the sedative activities of Tesmilifene.Investigational
RitonavirThe metabolism of Tesmilifene can be decreased when combined with Ritonavir.Approved, Investigational
RivaroxabanTesmilifene may increase the anticoagulant activities of Rivaroxaban.Approved
RolapitantThe metabolism of Tesmilifene can be decreased when combined with Rolapitant.Approved
RopiniroleThe metabolism of Tesmilifene can be decreased when combined with Ropinirole.Approved, Investigational
RosiglitazoneTesmilifene may increase the anticoagulant activities of Rosiglitazone.Approved, Investigational
RosuvastatinThe serum concentration of Rosuvastatin can be increased when it is combined with Tesmilifene.Approved
Salicylic acidThe risk or severity of adverse effects can be increased when Tesmilifene is combined with Salicylic acid.Approved, Vet Approved
SaquinavirThe metabolism of Tesmilifene can be decreased when combined with Saquinavir.Approved, Investigational
SarpogrelateTesmilifene may increase the anticoagulant activities of Sarpogrelate.Investigational
SaruplaseTesmilifene may increase the anticoagulant activities of Saruplase.Experimental
SaxagliptinThe serum concentration of Saxagliptin can be decreased when it is combined with Tesmilifene.Approved
SertralineThe metabolism of Tesmilifene can be decreased when combined with Sertraline.Approved
SevofluraneSevoflurane may increase the antiplatelet activities of Tesmilifene.Approved, Vet Approved
SildenafilThe metabolism of Tesmilifene can be decreased when combined with Sildenafil.Approved, Investigational
SiltuximabThe serum concentration of Tesmilifene can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Tesmilifene can be increased when it is combined with Simeprevir.Approved
SimvastatinThe serum concentration of Simvastatin can be increased when it is combined with Tesmilifene.Approved
SofosbuvirThe serum concentration of Sofosbuvir can be decreased when it is combined with Tesmilifene.Approved
SRT501Tesmilifene may increase the antiplatelet activities of SRT501.Investigational
St. John's WortThe serum concentration of Tesmilifene can be decreased when it is combined with St. John's Wort.Investigational, Nutraceutical
StiripentolThe serum concentration of Tesmilifene can be increased when it is combined with Stiripentol.Approved
StreptokinaseTesmilifene may increase the anticoagulant activities of Streptokinase.Approved, Investigational
SulfisoxazoleThe metabolism of Tesmilifene can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
SulodexideTesmilifene may increase the anticoagulant activities of Sulodexide.Approved, Investigational
TelaprevirThe metabolism of Tesmilifene can be decreased when combined with Telaprevir.Approved, Withdrawn
TelithromycinThe metabolism of Tesmilifene can be decreased when combined with Telithromycin.Approved
TenecteplaseTesmilifene may increase the anticoagulant activities of Tenecteplase.Approved
TerbinafineThe metabolism of Tesmilifene can be decreased when combined with Terbinafine.Approved, Investigational, Vet Approved
TergurideThe risk or severity of adverse effects can be increased when Terguride is combined with Tesmilifene.Experimental
ThioridazineThe metabolism of Tesmilifene can be decreased when combined with Thioridazine.Approved, Withdrawn
TiclopidineThe metabolism of Tesmilifene can be decreased when combined with Ticlopidine.Approved
TinzaparinTesmilifene may increase the anticoagulant activities of Tinzaparin.Approved
TioclomarolTesmilifene may increase the anticoagulant activities of Tioclomarol.Experimental
TipranavirTipranavir may increase the antiplatelet activities of Tesmilifene.Approved, Investigational
TirofibanTesmilifene may increase the anticoagulant activities of Tirofiban.Approved
TocilizumabThe serum concentration of Tesmilifene can be decreased when it is combined with Tocilizumab.Approved
TositumomabThe risk or severity of adverse effects can be increased when Tesmilifene is combined with Tositumomab.Approved, Investigational
TranilastTesmilifene may increase the antiplatelet activities of Tranilast.Approved, Investigational
TranylcypromineThe metabolism of Tesmilifene can be decreased when combined with Tranylcypromine.Approved
TrapidilTesmilifene may increase the antiplatelet activities of Trapidil.Approved
TreprostinilTreprostinil may increase the antiplatelet activities of Tesmilifene.Approved, Investigational
TriflusalTesmilifene may increase the anticoagulant activities of Triflusal.Approved, Investigational
TroxerutinTesmilifene may increase the anticoagulant activities of Troxerutin.Investigational
UbidecarenoneThe serum concentration of Ubidecarenone can be increased when it is combined with Tesmilifene.Approved, Experimental
UrokinaseTesmilifene may increase the anticoagulant activities of Urokinase.Approved, Investigational, Withdrawn
VenlafaxineThe metabolism of Tesmilifene can be decreased when combined with Venlafaxine.Approved
VerapamilThe metabolism of Tesmilifene can be decreased when combined with Verapamil.Approved
VincristineThe serum concentration of Vincristine can be decreased when it is combined with Tesmilifene.Approved, Investigational
Vitamin EVitamin E may increase the antiplatelet activities of Tesmilifene.Approved, Nutraceutical, Vet Approved
VorapaxarTesmilifene may increase the anticoagulant activities of Vorapaxar.Approved
VoriconazoleThe metabolism of Tesmilifene can be decreased when combined with Voriconazole.Approved, Investigational
WarfarinTesmilifene may increase the anticoagulant activities of Warfarin.Approved
XimelagatranTesmilifene may increase the anticoagulant activities of Ximelagatran.Approved, Investigational, Withdrawn
ZiprasidoneThe metabolism of Tesmilifene can be decreased when combined with Ziprasidone.Approved
Food Interactions
Not Available

References

General References
  1. Liu J, Tu D, Dancey J, Reyno L, Pritchard KI, Pater J, Seymour LK: Quality of life analyses in a clinical trial of DPPE (tesmilifene) plus doxorubicin versus doxorubicin in patients with advanced or metastatic breast cancer: NCIC CTG Trial MA.19. Breast Cancer Res Treat. 2006 Dec;100(3):263-71. Epub 2006 Jul 6. [PubMed:16823511]
  2. Vincent M: Tesmilifene may enhance breast cancer chemotherapy by killing a clone of aggressive, multi-drug resistant cells through its action on the p-glycoprotein pump. Med Hypotheses. 2006;66(4):715-31. Epub 2006 Jan 18. [PubMed:16413681]
  3. Raghavan D, Brandes LJ, Klapp K, Snyder T, Styles E, Tsao-Wei D, Lieskovsky G, Quinn DI, Ramsey EW: Phase II trial of tesmilifene plus mitoxantrone and prednisone for hormone refractory prostate cancer: high subjective and objective response in patients with symptomatic metastases. J Urol. 2005 Nov;174(5):1808-13; discussion 1813. [PubMed:16217292]
  4. Brandes LJ, Queen GM, LaBella FS: N,N-diethyl-2-[4-(phenylmethyl)phenoxy] ethanamine (DPPE) a chemopotentiating and cytoprotective agent in clinical trials: interaction with histamine at cytochrome P450 3A4 and other isozymes that metabolize antineoplastic drugs. Cancer Chemother Pharmacol. 2000;45(4):298-304. [PubMed:10755318]
  5. Brandes LJ, Hogg GR: Study of the in-vivo antioestrogenic action of N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine HCl (DPPE), a novel intracellular histamine antagonist and antioestrogen binding site ligand. J Reprod Fertil. 1990 May;89(1):59-67. [PubMed:2374133]
External Links
PubChem Compound
108092
PubChem Substance
175426896
ChemSpider
97190
BindingDB
50085260
ChEBI
93414
ChEMBL
CHEMBL26424

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentMetastatic/Recurrent Breast Cancer1
2CompletedTreatmentMetastatic Breast Cancer (MBC)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00905 mg/mLALOGPS
logP4.65ALOGPS
logP4.64ChemAxon
logS-4.5ALOGPS
pKa (Strongest Basic)9.33ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area12.47 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity89.77 m3·mol-1ChemAxon
Polarizability33.95 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9935
Blood Brain Barrier+0.9482
Caco-2 permeable+0.8072
P-glycoprotein substrateSubstrate0.7041
P-glycoprotein inhibitor IInhibitor0.5341
P-glycoprotein inhibitor IINon-inhibitor0.885
Renal organic cation transporterInhibitor0.7133
CYP450 2C9 substrateNon-substrate0.7941
CYP450 2D6 substrateSubstrate0.6482
CYP450 3A4 substrateSubstrate0.5967
CYP450 1A2 substrateInhibitor0.9707
CYP450 2C9 inhibitorInhibitor0.5636
CYP450 2D6 inhibitorInhibitor0.9575
CYP450 2C19 inhibitorInhibitor0.6944
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8296
Ames testNon AMES toxic0.5749
CarcinogenicityNon-carcinogens0.657
BiodegradationNot ready biodegradable0.9877
Rat acute toxicity2.2808 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.7258
hERG inhibition (predictor II)Inhibitor0.8407
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 diphenylmethanes. These are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Diphenylmethanes
Direct Parent
Diphenylmethanes
Alternative Parents
Phenoxy compounds / Phenol ethers / Alkyl aryl ethers / Trialkylamines / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Diphenylmethane / Phenoxy compound / Phenol ether / Alkyl aryl ether / Tertiary aliphatic amine / Tertiary amine / Ether / Organic nitrogen compound / Organic oxygen compound / Organopnictogen compound
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inducer
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. Vincent M: Tesmilifene may enhance breast cancer chemotherapy by killing a clone of aggressive, multi-drug resistant cells through its action on the p-glycoprotein pump. Med Hypotheses. 2006;66(4):715-31. Epub 2006 Jan 18. [PubMed:16413681]
  2. Brandes LJ, Queen GM, LaBella FS: N,N-diethyl-2-[4-(phenylmethyl)phenoxy] ethanamine (DPPE) a chemopotentiating and cytoprotective agent in clinical trials: interaction with histamine at cytochrome P450 3A4 and other isozymes that metabolize antineoplastic drugs. Cancer Chemother Pharmacol. 2000;45(4):298-304. [PubMed:10755318]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Histamine receptor activity
Specific Function
In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamin...
Gene Name
HRH1
Uniprot ID
P35367
Uniprot Name
Histamine H1 receptor
Molecular Weight
55783.61 Da
References
  1. Brandes LJ, Bogdanovic RP, Cawker MD, LaBella FS: Histamine and growth: interaction of antiestrogen binding site ligands with a novel histamine site that may be associated with calcium channels. Cancer Res. 1987 Aug 1;47(15):4025-31. [PubMed:2886214]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Inducer
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. Brandes LJ, Queen GM, LaBella FS: N,N-diethyl-2-[4-(phenylmethyl)phenoxy] ethanamine (DPPE) a chemopotentiating and cytoprotective agent in clinical trials: interaction with histamine at cytochrome P450 3A4 and other isozymes that metabolize antineoplastic drugs. Cancer Chemother Pharmacol. 2000;45(4):298-304. [PubMed:10755318]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
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
References
  1. Brandes LJ, Queen GM, LaBella FS: N,N-diethyl-2-[4-(phenylmethyl)phenoxy] ethanamine (DPPE) a chemopotentiating and cytoprotective agent in clinical trials: interaction with histamine at cytochrome P450 3A4 and other isozymes that metabolize antineoplastic drugs. Cancer Chemother Pharmacol. 2000;45(4):298-304. [PubMed:10755318]
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. Brandes LJ, Queen GM, LaBella FS: N,N-diethyl-2-[4-(phenylmethyl)phenoxy] ethanamine (DPPE) a chemopotentiating and cytoprotective agent in clinical trials: interaction with histamine at cytochrome P450 3A4 and other isozymes that metabolize antineoplastic drugs. Cancer Chemother Pharmacol. 2000;45(4):298-304. [PubMed:10755318]

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