Identification

Name
Estramustine
Accession Number
DB01196  (APRD00625)
Type
Small Molecule
Groups
Approved
Description

A nitrogen mustard linked to estradiol, usually as phosphate; used to treat prostatic neoplasms; also has radiation protective properties. [PubChem]

Structure
Thumb
Synonyms
  • 17beta-Estradiol 3-(bis(2-chloroethyl)carbamate)
  • 17β-Estradiol 3-(bis(2-chloroethyl)carbamate)
  • Estradiol 3-(N,N-bis(2-chloroethyl)carbamate)
  • Estramustina
  • Estramustine
  • Estramustinum
External IDs
RO 22-2296/000
Product Ingredients
IngredientUNIICASInChI Key
Estramustin sodium phosphate75F375MT2N1227300-83-5FRPJXPJMRWBBIH-UHFFFAOYSA-N
Estramustine phosphateMUZ9585Y7B4891-15-0ADFOJJHRTBFFOF-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
EmcytCapsule140 mgOralPfizer1995-12-31Not applicableCanada
EmcytCapsule140 mg/1OralPharmacia & Upjohn Inc1992-01-01Not applicableUs
Emcyt Cap 140mgCapsule140 mgOralKabi Pharmacia Canada Inc.1993-12-311996-09-10Canada
International/Other Brands
Estracit / Estracyt (Pfizer)
Categories
UNII
35LT29625A
CAS number
2998-57-4
Weight
Average: 440.403
Monoisotopic: 439.168099277
Chemical Formula
C23H31Cl2NO3
InChI Key
FRPJXPJMRWBBIH-RBRWEJTLSA-N
InChI
InChI=1S/C23H31Cl2NO3/c1-23-9-8-18-17-5-3-16(29-22(28)26(12-10-24)13-11-25)14-15(17)2-4-19(18)20(23)6-7-21(23)27/h3,5,14,18-21,27H,2,4,6-13H2,1H3/t18-,19-,20+,21+,23+/m1/s1
IUPAC Name
(1S,10R,11S,14S,15S)-14-hydroxy-15-methyltetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadeca-2,4,6-trien-5-yl N,N-bis(2-chloroethyl)carbamate
SMILES
[H][[email protected]@]12CC[[email protected]](O)[[email protected]@]1(C)CC[[email protected]]1([H])C3=CC=C(OC(=O)N(CCCl)CCCl)C=C3CC[[email protected]@]21[H]

Pharmacology

Indication

For the palliative treatment of patients with metastatic and/or progressive carcinoma of the prostate

Structured Indications
Pharmacodynamics

Estramustine is an antineoplastic agent indicated in the palliative treatment of patients with metastatic and/or progressive carcinoma of the prostate. Estramustine is a combination of estradiol with nitrogen mustard. In vivo, the nitrogen-mustard moiety becomes active and participates in alkylation of DNA or other cellular components.. This causes DNA damage in rapidly dividing cancerous cells leading to cell death and ideally, tumor shrinkage.

Mechanism of action

Estramustine is a derivative of estradiol with a nitrogen mustard moiety. This gives it alkylating properties. In vivo, the nitrogen mustard component is active and can alklyate DNA and other cellular components (such as tubulin components) of rapidly dividing cells. This causes DNA strandbreaks or misscoding events. This leads to apoptosis and cell death. Also, due to the drugs estrogen component, it can bind more selectively to active estrogen receptors.

TargetActionsOrganism
AEstrogen receptor beta
other/unknown
Human
AEstrogen receptor alpha
agonist
Human
AMicrotubule-associated protein 2
antagonist
Human
AMicrotubule-associated protein 1A
antagonist
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination

The metabolic urinary patterns of the estradiol moiety of estramustine phosphate and estradiol itself are very similar, although the metabolites derived from estramustine phosphate are excreted at a slower rate.

Half life

20 hours

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
1,10-PhenanthrolineThe serum concentration of Estramustine can be decreased when it is combined with 1,10-Phenanthroline.Experimental
3,4-DichloroisocoumarinThe serum concentration of Estramustine can be decreased when it is combined with 3,4-Dichloroisocoumarin.Experimental
4-(2-Aminoethyl)Benzenesulfonyl FluorideThe serum concentration of Estramustine can be decreased when it is combined with 4-(2-Aminoethyl)Benzenesulfonyl Fluoride.Experimental
AcenocoumarolEstramustine may decrease the anticoagulant activities of Acenocoumarol.Approved
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Estramustine.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Estramustine.Experimental
AcitretinThe therapeutic efficacy of Estramustine can be decreased when used in combination with Acitretin.Approved
AdapaleneThe therapeutic efficacy of Estramustine can be decreased when used in combination with Adapalene.Approved
AfatinibThe serum concentration of Afatinib can be increased when it is combined with Estramustine.Approved
AlitretinoinThe therapeutic efficacy of Estramustine can be decreased when used in combination with Alitretinoin.Approved, Investigational
AlogliptinThe serum concentration of Estramustine can be decreased when it is combined with Alogliptin.Approved
Alpha-1-proteinase inhibitorThe serum concentration of Estramustine can be decreased when it is combined with Alpha-1-proteinase inhibitor.Approved
AmiodaroneThe metabolism of Estramustine can be decreased when combined with Amiodarone.Approved, Investigational
AmobarbitalThe therapeutic efficacy of Estramustine can be decreased when used in combination with Amobarbital.Approved, Illicit
AmprenavirThe serum concentration of Estramustine can be decreased when it is combined with Amprenavir.Approved
AncestimThe risk or severity of cytotoxicity can be increased when Ancestim is combined with Estramustine.Approved, Investigational, Withdrawn
Antithrombin III humanThe serum concentration of Estramustine can be decreased when it is combined with Antithrombin III human.Approved
ApixabanThe serum concentration of Estramustine can be decreased when it is combined with Apixaban.Approved
AprepitantThe serum concentration of Estramustine can be decreased when it is combined with Aprepitant.Approved, Investigational
AprotininThe serum concentration of Estramustine can be decreased when it is combined with Aprotinin.Approved, Withdrawn
ArgatrobanThe serum concentration of Estramustine can be decreased when it is combined with Argatroban.Approved, Investigational
ArmodafinilThe serum concentration of Estramustine can be decreased when it is combined with Armodafinil.Approved, Investigational
ArtemetherThe serum concentration of Estramustine can be decreased when it is combined with Artemether.Approved
AsunaprevirThe serum concentration of Estramustine can be decreased when it is combined with Asunaprevir.Approved, Investigational
AtazanavirThe metabolism of Estramustine can be decreased when combined with Atazanavir.Approved, Investigational
AtomoxetineThe metabolism of Estramustine can be decreased when combined with Atomoxetine.Approved
BarbexacloneThe therapeutic efficacy of Estramustine can be decreased when used in combination with Barbexaclone.Experimental
BarbitalThe therapeutic efficacy of Estramustine can be decreased when used in combination with Barbital.Illicit
BatimastatThe serum concentration of Estramustine can be decreased when it is combined with Batimastat.Experimental
BenazeprilThe serum concentration of Estramustine can be decreased when it is combined with Benazepril.Approved, Investigational
BenzamidineThe serum concentration of Estramustine can be decreased when it is combined with Benzamidine.Experimental
BevacizumabBevacizumab may increase the cardiotoxic activities of Estramustine.Approved, Investigational
BexaroteneThe serum concentration of Estramustine can be decreased when it is combined with Bexarotene.Approved, Investigational
BivalirudinThe serum concentration of Estramustine can be decreased when it is combined with Bivalirudin.Approved, Investigational
BoceprevirThe serum concentration of Estramustine can be decreased when it is combined with Boceprevir.Approved, Withdrawn
BortezomibThe metabolism of Estramustine can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Estramustine can be decreased when it is combined with Bosentan.Approved, Investigational
BosutinibThe serum concentration of Bosutinib can be increased when it is combined with Estramustine.Approved
Brentuximab vedotinThe serum concentration of Brentuximab vedotin can be increased when it is combined with Estramustine.Approved
Calcium AcetateCalcium Acetate can cause a decrease in the absorption of Estramustine resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
Calcium CarbonateCalcium Carbonate can cause a decrease in the absorption of Estramustine resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
Calcium ChlorideCalcium Chloride can cause a decrease in the absorption of Estramustine resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
Calcium CitrateCalcium Citrate can cause a decrease in the absorption of Estramustine resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
Calcium glubionateCalcium glubionate can cause a decrease in the absorption of Estramustine resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
Calcium GluceptateCalcium Gluceptate can cause a decrease in the absorption of Estramustine resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
Calcium gluconateCalcium gluconate can cause a decrease in the absorption of Estramustine resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved, Vet Approved
Calcium lactateCalcium lactate can cause a decrease in the absorption of Estramustine resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved, Experimental, Investigational, Vet Approved
Calcium lactate gluconateCalcium lactate gluconate can cause a decrease in the absorption of Estramustine resulting in a reduced serum concentration and potentially a decrease in efficacy.Experimental
Calcium laevulateCalcium laevulate can cause a decrease in the absorption of Estramustine resulting in a reduced serum concentration and potentially a decrease in efficacy.Experimental
Calcium pangamateCalcium pangamate can cause a decrease in the absorption of Estramustine resulting in a reduced serum concentration and potentially a decrease in efficacy.Experimental
Calcium PhosphateCalcium Phosphate can cause a decrease in the absorption of Estramustine resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
CamostatThe serum concentration of Estramustine can be decreased when it is combined with Camostat.Experimental
CandoxatrilThe serum concentration of Estramustine can be decreased when it is combined with Candoxatril.Experimental
CandoxatrilatThe serum concentration of Estramustine can be decreased when it is combined with Candoxatrilat.Experimental
CaptoprilThe serum concentration of Estramustine can be decreased when it is combined with Captopril.Approved
CarbamazepineThe therapeutic efficacy of Estramustine can be decreased when used in combination with Carbamazepine.Approved, Investigational
CaseinCasein can cause a decrease in the absorption of Estramustine resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
CeritinibThe serum concentration of Estramustine can be increased when it is combined with Ceritinib.Approved
CholesterolThe serum concentration of Estramustine can be decreased when it is combined with Cholesterol.Experimental, Investigational
CholestyramineThe serum concentration of Estramustine can be decreased when it is combined with Cholestyramine.Approved
ChymostatinThe serum concentration of Estramustine can be decreased when it is combined with Chymostatin.Experimental
CilastatinThe serum concentration of Estramustine can be decreased when it is combined with Cilastatin.Approved
CilazaprilThe serum concentration of Estramustine can be decreased when it is combined with Cilazapril.Approved
ClarithromycinThe metabolism of Estramustine can be decreased when combined with Clarithromycin.Approved
ClemastineThe metabolism of Estramustine can be decreased when combined with Clemastine.Approved
ClobazamThe serum concentration of Estramustine can be decreased when it is combined with Clobazam.Approved, Illicit
Clodronic AcidThe serum concentration of Estramustine can be increased when it is combined with Clodronic Acid.Approved, Investigational, Vet Approved
ClorindioneEstramustine may decrease the anticoagulant activities of Clorindione.Experimental
ClotrimazoleThe metabolism of Estramustine can be decreased when combined with Clotrimazole.Approved, Vet Approved
CobicistatThe serum concentration of Estramustine can be decreased when it is combined with Cobicistat.Approved
ColchicineThe serum concentration of Colchicine can be increased when it is combined with Estramustine.Approved
ColesevelamThe serum concentration of Estramustine can be decreased when it is combined with Colesevelam.Approved
ColestipolThe serum concentration of Estramustine can be decreased when it is combined with Colestipol.Approved
ConivaptanThe serum concentration of Conivaptan can be increased when it is combined with Estramustine.Approved, Investigational
CrizotinibThe metabolism of Estramustine can be decreased when combined with Crizotinib.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Estramustine.Approved, Investigational
CyclosporineThe metabolism of Estramustine can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
CymarinCymarin may decrease the cardiotoxic activities of Estramustine.Experimental
Dabigatran etexilateThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Estramustine.Approved
DabrafenibThe serum concentration of Estramustine can be decreased when it is combined with Dabrafenib.Approved
DarexabanThe serum concentration of Estramustine can be decreased when it is combined with Darexaban.Investigational
DarunavirThe metabolism of Estramustine can be decreased when combined with Darunavir.Approved
DasatinibThe serum concentration of Estramustine can be increased when it is combined with Dasatinib.Approved, Investigational
DeferasiroxThe serum concentration of Estramustine can be decreased when it is combined with Deferasirox.Approved, Investigational
DelanzomibThe serum concentration of Estramustine can be decreased when it is combined with Delanzomib.Investigational
DelaprilThe serum concentration of Estramustine can be decreased when it is combined with Delapril.Experimental
DelavirdineThe metabolism of Estramustine can be decreased when combined with Delavirdine.Approved
DeslanosideDeslanoside may decrease the cardiotoxic activities of Estramustine.Approved
DicoumarolEstramustine may decrease the anticoagulant activities of Dicoumarol.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Estramustine.Approved, Investigational
DigoxinDigoxin may decrease the cardiotoxic activities of Estramustine.Approved
Digoxin Immune Fab (Ovine)Digoxin Immune Fab (Ovine) may decrease the cardiotoxic activities of Estramustine.Approved
DihydroergotamineThe metabolism of Estramustine can be decreased when combined with Dihydroergotamine.Approved
DiltiazemThe metabolism of Estramustine can be decreased when combined with Diltiazem.Approved
DiphenadioneEstramustine may decrease the anticoagulant activities of Diphenadione.Experimental
DoxorubicinThe serum concentration of Doxorubicin can be increased when it is combined with Estramustine.Approved, Investigational
DoxycyclineThe metabolism of Estramustine can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe metabolism of Estramustine can be decreased when combined with Dronedarone.Approved
EcabetThe serum concentration of Estramustine can be decreased when it is combined with Ecabet.Approved, Investigational
EdoxabanThe serum concentration of Edoxaban can be increased when it is combined with Estramustine.Approved
ElafinThe serum concentration of Estramustine can be decreased when it is combined with Elafin.Investigational
ElvitegravirThe serum concentration of Estramustine can be decreased when it is combined with Elvitegravir.Approved
EnalaprilThe serum concentration of Estramustine can be decreased when it is combined with Enalapril.Approved, Vet Approved
EnalaprilatThe serum concentration of Estramustine can be decreased when it is combined with Enalaprilat.Approved
EnalkirenThe serum concentration of Estramustine can be decreased when it is combined with Enalkiren.Experimental
EnzalutamideThe serum concentration of Estramustine can be decreased when it is combined with Enzalutamide.Approved
Epigallocatechin GallateThe serum concentration of Estramustine can be decreased when it is combined with Epigallocatechin Gallate.Investigational
ErythromycinThe metabolism of Estramustine can be decreased when combined with Erythromycin.Approved, Vet Approved
Eslicarbazepine acetateThe serum concentration of Estramustine can be decreased when it is combined with Eslicarbazepine acetate.Approved
Ethyl biscoumacetateEstramustine may decrease the anticoagulant activities of Ethyl biscoumacetate.Withdrawn
EverolimusThe serum concentration of Everolimus can be increased when it is combined with Estramustine.Approved
ExenatideThe serum concentration of Estramustine can be decreased when it is combined with Exenatide.Approved, Investigational
FaldaprevirThe serum concentration of Estramustine can be decreased when it is combined with Faldaprevir.Investigational
FelbamateThe serum concentration of Estramustine can be decreased when it is combined with Felbamate.Approved
FlibanserinThe serum concentration of Flibanserin can be increased when it is combined with Estramustine.Approved
FluconazoleThe metabolism of Estramustine can be decreased when combined with Fluconazole.Approved
FluindioneEstramustine may decrease the anticoagulant activities of Fluindione.Investigational
FluvoxamineThe metabolism of Estramustine can be decreased when combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe serum concentration of Estramustine can be decreased when it is combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Estramustine can be decreased when it is combined with Fosaprepitant.Approved
FosinoprilThe serum concentration of Estramustine can be decreased when it is combined with Fosinopril.Approved
FosphenytoinThe therapeutic efficacy of Estramustine can be decreased when used in combination with Fosphenytoin.Approved
Fusidic AcidThe serum concentration of Estramustine can be increased when it is combined with Fusidic Acid.Approved
GabexateThe serum concentration of Estramustine can be decreased when it is combined with Gabexate.Investigational
GeldanamycinThe serum concentration of Estramustine can be decreased when it is combined with Geldanamycin.Experimental, Investigational
GitoformateGitoformate may decrease the cardiotoxic activities of Estramustine.Experimental
GM6001The serum concentration of Estramustine can be decreased when it is combined with GM6001.Experimental
GriseofulvinThe metabolism of Estramustine can be increased when combined with Griseofulvin.Approved, Vet Approved
HexobarbitalThe therapeutic efficacy of Estramustine can be decreased when used in combination with Hexobarbital.Approved
IdelalisibThe metabolism of Estramustine can be decreased when combined with Idelalisib.Approved
IdraparinuxThe serum concentration of Estramustine can be decreased when it is combined with Idraparinux.Investigational
ImatinibThe metabolism of Estramustine can be decreased when combined with Imatinib.Approved
ImidaprilThe serum concentration of Estramustine can be decreased when it is combined with Imidapril.Investigational
IndinavirThe metabolism of Estramustine can be decreased when combined with Indinavir.Approved
IsavuconazoniumThe metabolism of Estramustine can be decreased when combined with Isavuconazonium.Approved, Investigational
IsoflurophateThe serum concentration of Estramustine can be decreased when it is combined with Isoflurophate.Approved, Investigational, Withdrawn
IsotretinoinThe therapeutic efficacy of Estramustine can be decreased when used in combination with Isotretinoin.Approved
IsradipineThe metabolism of Estramustine can be decreased when combined with Isradipine.Approved
ItraconazoleThe metabolism of Estramustine can be decreased when combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Estramustine can be increased when it is combined with Ivacaftor.Approved
IxazomibThe serum concentration of Estramustine can be decreased when it is combined with Ixazomib.Approved
KetoconazoleThe metabolism of Estramustine can be decreased when combined with Ketoconazole.Approved, Investigational
LamotrigineThe serum concentration of Lamotrigine can be decreased when it is combined with Estramustine.Approved, Investigational
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Estramustine.Experimental
LedipasvirThe serum concentration of Ledipasvir can be increased when it is combined with Estramustine.Approved
LepirudinThe serum concentration of Estramustine can be decreased when it is combined with Lepirudin.Approved
LetaxabanThe serum concentration of Estramustine can be decreased when it is combined with Letaxaban.Investigational
LinagliptinThe serum concentration of Estramustine can be decreased when it is combined with Linagliptin.Approved
LisinoprilThe serum concentration of Estramustine can be decreased when it is combined with Lisinopril.Approved, Investigational
LopinavirThe metabolism of Estramustine can be decreased when combined with Lopinavir.Approved
LovastatinThe metabolism of Estramustine can be decreased when combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of Estramustine can be increased when it is combined with Luliconazole.Approved
LumacaftorThe serum concentration of Estramustine can be decreased when it is combined with Lumacaftor.Approved
MelagatranThe serum concentration of Estramustine can be decreased when it is combined with Melagatran.Experimental
MethohexitalThe therapeutic efficacy of Estramustine can be decreased when used in combination with Methohexital.Approved
MethylphenobarbitalThe therapeutic efficacy of Estramustine can be decreased when used in combination with Methylphenobarbital.Approved
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Estramustine.Experimental
MetreleptinThe serum concentration of Estramustine can be decreased when it is combined with Metreleptin.Approved
MifepristoneThe serum concentration of Estramustine can be increased when it is combined with Mifepristone.Approved, Investigational
MitotaneThe serum concentration of Estramustine can be decreased when it is combined with Mitotane.Approved
ModafinilThe serum concentration of Estramustine can be decreased when it is combined with Modafinil.Approved, Investigational
MoexiprilThe serum concentration of Estramustine can be decreased when it is combined with Moexipril.Approved
Mycophenolic acidThe serum concentration of Estramustine can be decreased when it is combined with Mycophenolic acid.Approved
N-(3-Propylcarbamoyloxirane-2-Carbonyl)-Isoleucyl-ProlineThe serum concentration of Estramustine can be decreased when it is combined with N-(3-Propylcarbamoyloxirane-2-Carbonyl)-Isoleucyl-Proline.Experimental
NafamostatThe serum concentration of Estramustine can be decreased when it is combined with Nafamostat.Approved, Investigational
NafcillinThe metabolism of Estramustine can be increased when combined with Nafcillin.Approved
NaloxegolThe serum concentration of Naloxegol can be increased when it is combined with Estramustine.Approved
NefazodoneThe metabolism of Estramustine can be decreased when combined with Nefazodone.Approved, Withdrawn
NelfinavirThe metabolism of Estramustine can be decreased when combined with Nelfinavir.Approved
NetupitantThe serum concentration of Estramustine can be increased when it is combined with Netupitant.Approved
NevirapineThe serum concentration of Estramustine can be decreased when it is combined with Nevirapine.Approved
NilotinibThe metabolism of Estramustine can be decreased when combined with Nilotinib.Approved, Investigational
NitroaspirinThe serum concentration of Estramustine can be decreased when it is combined with Nitroaspirin.Investigational
OlaparibThe metabolism of Estramustine can be decreased when combined with Olaparib.Approved
OleandrinOleandrin may decrease the cardiotoxic activities of Estramustine.Experimental, Investigational
OmapatrilatThe serum concentration of Estramustine can be decreased when it is combined with Omapatrilat.Investigational
OsimertinibThe serum concentration of Estramustine can be increased when it is combined with Osimertinib.Approved
OtamixabanThe serum concentration of Estramustine can be decreased when it is combined with Otamixaban.Investigational
OuabainOuabain may decrease the cardiotoxic activities of Estramustine.Approved
OxcarbazepineThe serum concentration of Estramustine can be decreased when it is combined with Oxcarbazepine.Approved
PalbociclibThe serum concentration of Estramustine can be increased when it is combined with Palbociclib.Approved
PazopanibThe serum concentration of Pazopanib can be increased when it is combined with Estramustine.Approved
PentobarbitalThe metabolism of Estramustine can be increased when combined with Pentobarbital.Approved, Vet Approved
PerindoprilThe serum concentration of Estramustine can be decreased when it is combined with Perindopril.Approved
PeruvosidePeruvoside may decrease the cardiotoxic activities of Estramustine.Experimental
PhenindioneEstramustine may decrease the anticoagulant activities of Phenindione.Approved, Investigational
PhenobarbitalThe metabolism of Estramustine can be increased when combined with Phenobarbital.Approved
PhenprocoumonEstramustine may decrease the anticoagulant activities of Phenprocoumon.Approved, Investigational
PhenytoinThe therapeutic efficacy of Estramustine can be decreased when used in combination with Phenytoin.Approved, Vet Approved
PhosphoramidonThe serum concentration of Estramustine can be decreased when it is combined with Phosphoramidon.Experimental
PosaconazoleThe metabolism of Estramustine can be decreased when combined with Posaconazole.Approved, Investigational, Vet Approved
PrimidoneThe metabolism of Estramustine can be increased when combined with Primidone.Approved, Vet Approved
PrinomastatThe serum concentration of Estramustine can be decreased when it is combined with Prinomastat.Investigational
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Estramustine.Experimental
PrucaloprideThe serum concentration of Estramustine can be decreased when it is combined with Prucalopride.Approved
QuinaprilThe serum concentration of Estramustine can be decreased when it is combined with Quinapril.Approved, Investigational
RacecadotrilThe serum concentration of Estramustine can be decreased when it is combined with Racecadotril.Investigational
RamiprilThe serum concentration of Estramustine can be decreased when it is combined with Ramipril.Approved
RanolazineThe serum concentration of Ranolazine can be increased when it is combined with Estramustine.Approved, Investigational
RemikirenThe serum concentration of Estramustine can be decreased when it is combined with Remikiren.Approved
RifabutinThe metabolism of Estramustine can be increased when combined with Rifabutin.Approved
RifampicinThe metabolism of Estramustine can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Estramustine can be increased when combined with Rifapentine.Approved
RifaximinThe serum concentration of Rifaximin can be increased when it is combined with Estramustine.Approved, Investigational
RitonavirThe serum concentration of Estramustine can be decreased when it is combined with Ritonavir.Approved, Investigational
RivaroxabanThe serum concentration of Estramustine can be decreased when it is combined with Rivaroxaban.Approved
RucaparibThe metabolism of Estramustine can be decreased when combined with Rucaparib.Approved, Investigational
S-3304The serum concentration of Estramustine can be decreased when it is combined with S-3304.Investigational
SaquinavirThe metabolism of Estramustine can be decreased when combined with Saquinavir.Approved, Investigational
SarilumabThe therapeutic efficacy of Estramustine can be decreased when used in combination with Sarilumab.Approved
SaxagliptinThe serum concentration of Estramustine can be decreased when it is combined with Saxagliptin.Approved
SecobarbitalThe therapeutic efficacy of Estramustine can be decreased when used in combination with Secobarbital.Approved, Vet Approved
SelegilineThe serum concentration of Selegiline can be increased when it is combined with Estramustine.Approved, Investigational, Vet Approved
SildenafilThe metabolism of Estramustine can be decreased when combined with Sildenafil.Approved, Investigational
SilodosinThe serum concentration of Silodosin can be increased when it is combined with Estramustine.Approved
SiltuximabThe serum concentration of Estramustine can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Estramustine can be increased when it is combined with Simeprevir.Approved
SitagliptinThe serum concentration of Estramustine can be decreased when it is combined with Sitagliptin.Approved, Investigational
SivelestatThe serum concentration of Estramustine can be decreased when it is combined with Sivelestat.Investigational
SpiraprilThe serum concentration of Estramustine can be decreased when it is combined with Spirapril.Approved
St. John's WortThe serum concentration of Estramustine can be decreased when it is combined with St. John's Wort.Investigational, Nutraceutical
StiripentolThe serum concentration of Estramustine can be increased when it is combined with Stiripentol.Approved
SulfisoxazoleThe metabolism of Estramustine can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
TelaprevirThe serum concentration of Estramustine can be decreased when it is combined with Telaprevir.Approved, Withdrawn
TelithromycinThe metabolism of Estramustine can be decreased when combined with Telithromycin.Approved
TemocaprilThe serum concentration of Estramustine can be decreased when it is combined with Temocapril.Experimental, Investigational
ThalidomideEstramustine may increase the thrombogenic activities of Thalidomide.Approved, Investigational, Withdrawn
ThiamylalThe therapeutic efficacy of Estramustine can be decreased when used in combination with Thiamylal.Approved, Vet Approved
ThiopentalThe therapeutic efficacy of Estramustine can be decreased when used in combination with Thiopental.Approved, Vet Approved
ThiorphanThe serum concentration of Estramustine can be decreased when it is combined with Thiorphan.Experimental
TiclopidineThe metabolism of Estramustine can be decreased when combined with Ticlopidine.Approved
TioclomarolEstramustine may decrease the anticoagulant activities of Tioclomarol.Experimental
TipranavirThe serum concentration of Estramustine can be decreased when it is combined with Tipranavir.Approved, Investigational
TocilizumabThe serum concentration of Estramustine can be decreased when it is combined with Tocilizumab.Approved
TopiramateThe serum concentration of Estramustine can be decreased when it is combined with Topiramate.Approved
TopotecanThe serum concentration of Topotecan can be increased when it is combined with Estramustine.Approved, Investigational
TrandolaprilThe serum concentration of Estramustine can be decreased when it is combined with Trandolapril.Approved
Tranexamic AcidEstramustine may increase the thrombogenic activities of Tranexamic Acid.Approved
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Estramustine.Approved, Investigational
TretinoinThe therapeutic efficacy of Estramustine can be decreased when used in combination with Tretinoin.Approved, Investigational, Nutraceutical
UbenimexThe serum concentration of Estramustine can be decreased when it is combined with Ubenimex.Experimental, Investigational
UlinastatinThe serum concentration of Estramustine can be decreased when it is combined with Ulinastatin.Investigational
VemurafenibThe serum concentration of Estramustine can be decreased when it is combined with Vemurafenib.Approved
VenlafaxineThe metabolism of Estramustine can be decreased when combined with Venlafaxine.Approved
VerapamilThe metabolism of Estramustine can be decreased when combined with Verapamil.Approved
VildagliptinThe serum concentration of Estramustine can be decreased when it is combined with Vildagliptin.Approved, Investigational
VincristineThe excretion of Vincristine can be decreased when combined with Estramustine.Approved, Investigational
VoriconazoleThe metabolism of Estramustine can be decreased when combined with Voriconazole.Approved, Investigational
WarfarinEstramustine may decrease the anticoagulant activities of Warfarin.Approved
XimelagatranThe serum concentration of Estramustine can be decreased when it is combined with Ximelagatran.Approved, Investigational, Withdrawn
Z-Val-Ala-Asp fluoromethyl ketoneThe serum concentration of Estramustine can be decreased when it is combined with Z-Val-Ala-Asp fluoromethyl ketone.Experimental
ZiprasidoneThe metabolism of Estramustine can be decreased when combined with Ziprasidone.Approved
ZofenoprilThe serum concentration of Estramustine can be decreased when it is combined with Zofenopril.Experimental
Food Interactions
  • Do not take with milk or milk products.
  • Take on an empty stomach.

References

Synthesis Reference

Fex, H.J., Hogtierg, K.B., Konyves, I. and Kneip, P.H.0.L; U.S. Patent 3,299,104; Jan. 17, 1967; assigned to Leo AB, Sweden.

US3299104
General References
Not Available
External Links
Human Metabolome Database
HMDB15327
KEGG Drug
D04066
KEGG Compound
C11228
PubChem Compound
259331
PubChem Substance
46508765
ChemSpider
227635
BindingDB
50333646
ChEBI
4868
ChEMBL
CHEMBL1575
Therapeutic Targets Database
DAP001307
PharmGKB
PA449507
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Estramustine
ATC Codes
L01XX11 — Estramustine
AHFS Codes
  • 10:00.00 — Antineoplastic Agents

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentProstate Cancer3
1Unknown StatusTreatmentProstate Cancer1
1, 2CompletedTreatmentLeukemias / Malignant Lymphomas / Sarcomas / Unspecified Adult Solid Tumor, Protocol Specific1
1, 2CompletedTreatmentProstate Cancer5
1, 2TerminatedTreatmentProstate Cancer1
1, 2Unknown StatusTreatmentProstate Cancer1
2Active Not RecruitingTreatmentProstate Cancer1
2CompletedTreatmentAdenocarcinoma of the Prostate / Hormone-Resistant Prostate Cancer / Recurrent Prostate Cancer / Stage IV Prostate Cancer1
2CompletedTreatmentAdenocarcinoma of the Prostate / Prostate Cancer1
2CompletedTreatmentAdenocarcinoma, Prostate1
2CompletedTreatmentHormone Resistant Prostate Cancer / Metastatic Hormone Refractory Prostate Cancer1
2CompletedTreatmentHormone-Refractory Prostate Cancer1
2CompletedTreatmentMalignant Lymphomas1
2CompletedTreatmentProstate Cancer13
2CompletedTreatmentProstate Cancer / Thromboembolism1
2CompletedTreatmentRenal Cancers1
2Not Yet RecruitingTreatmentCancer, Breast1
2RecruitingTreatmentCancer, Breast1
2TerminatedTreatmentProstate Cancer2
2TerminatedTreatmentProstatic Neoplasms1
2Unknown StatusTreatmentCancer, Breast1
2Unknown StatusTreatmentProstate Cancer2
2WithdrawnTreatmentProstate Cancer1
3CompletedTreatmentProstate Cancer5
3TerminatedTreatmentProstate Cancer1
3TerminatedTreatmentProstatic Neoplasms1
3Unknown StatusTreatmentProstate Cancer1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Dosage forms
FormRouteStrength
CapsuleOral140 mg
CapsuleOral140 mg/1
Prices
Unit descriptionCostUnit
Emcyt 140 mg capsule6.55USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)155Fex, H.J., Hogtierg, K.B., Konyves, I. and Kneip, P.H.0.L; U.S. Patent 3,299,104; Jan. 17, 1967; assigned to Leo AB, Sweden.
logP5.7Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.000385 mg/mLALOGPS
logP4.97ALOGPS
logP5.1ChemAxon
logS-6.1ALOGPS
pKa (Strongest Acidic)19.38ChemAxon
pKa (Strongest Basic)-0.88ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area49.77 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity116.21 m3·mol-1ChemAxon
Polarizability48.06 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9675
Caco-2 permeable+0.6013
P-glycoprotein substrateSubstrate0.7382
P-glycoprotein inhibitor IInhibitor0.5927
P-glycoprotein inhibitor IINon-inhibitor0.6317
Renal organic cation transporterNon-inhibitor0.5918
CYP450 2C9 substrateNon-substrate0.6261
CYP450 2D6 substrateNon-substrate0.6491
CYP450 3A4 substrateSubstrate0.8003
CYP450 1A2 substrateNon-inhibitor0.6214
CYP450 2C9 inhibitorNon-inhibitor0.6944
CYP450 2D6 inhibitorNon-inhibitor0.6079
CYP450 2C19 inhibitorInhibitor0.5464
CYP450 3A4 inhibitorInhibitor0.8479
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.62
Ames testNon AMES toxic0.6062
CarcinogenicityNon-carcinogens0.8508
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.7844 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8235
hERG inhibition (predictor II)Non-inhibitor0.6818
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

Taxonomy

Description
This compound belongs to the class of organic compounds known as estrane steroids. These are steroids with a structure based on the estrane skeleton.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Steroids and steroid derivatives
Sub Class
Estrane steroids
Direct Parent
Estrane steroids
Alternative Parents
17-hydroxysteroids / Phenanthrenes and derivatives / Tetralins / Nitrogen mustard compounds / Carbamate esters / Secondary alcohols / Organic carbonic acids and derivatives / Cyclic alcohols and derivatives / Organopnictogen compounds / Organochlorides
show 4 more
Substituents
Estrane-skeleton / Hydroxysteroid / 17-hydroxysteroid / Phenanthrene / Tetralin / Nitrogen mustard / Benzenoid / Cyclic alcohol / Carbamic acid ester / Secondary alcohol
show 15 more
Molecular Framework
Aromatic homopolycyclic compounds
External Descriptors
carbamate ester, organochlorine compound, 17beta-hydroxy steroid (CHEBI:4868) / C18 steroids (estrogens) and derivatives, Estrane and derivatives (C11228) / C18 steroids (estrogens) and derivatives (LMST02010038)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Other/unknown
General Function
Zinc ion binding
Specific Function
Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent m...
Gene Name
ESR2
Uniprot ID
Q92731
Uniprot Name
Estrogen receptor beta
Molecular Weight
59215.765 Da
References
  1. Ho SM: Estrogens and anti-estrogens: key mediators of prostate carcinogenesis and new therapeutic candidates. J Cell Biochem. 2004 Feb 15;91(3):491-503. [PubMed:14755680]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
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. Ferno M, Borg A, Ingvar C, Jonsson PE: Estrogen receptor and binding site for estramustine in metastatic malignant melanoma. Anticancer Res. 1987 Jul-Aug;7(4B):741-3. [PubMed:3314674]
  2. Yoshizumi N: [The effects of site-directed chemotherapy due to E2 as a drug carrier to the human endometrial adenocarcinoma cells in vitro]. Nihon Sanka Fujinka Gakkai Zasshi. 1985 Apr;37(4):637-45. [PubMed:3989343]
  3. von Schoultz E, Carlstrom K, Henriksson R, Lagerlof B, Hansson J: Estramustine binding protein in primary tumours and metastases of malignant melanoma. Melanoma Res. 1994 Dec;4(6):401-5. [PubMed:7703721]
  4. Tew KD: The mechanism of action of estramustine. Semin Oncol. 1983 Sep;10(3 Suppl 3):21-6. [PubMed:6364362]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Structural molecule activity
Specific Function
The exact function of MAP2 is unknown but MAPs may stabilize the microtubules against depolymerization. They also seem to have a stiffening effect on microtubules.
Gene Name
MAP2
Uniprot ID
P11137
Uniprot Name
Microtubule-associated protein 2
Molecular Weight
199524.51 Da
References
  1. Moraga D, Rivas-Berrios A, Farias G, Wallin M, Maccioni RB: Estramustine-phosphate binds to a tubulin binding domain on microtubule-associated proteins MAP-2 and tau. Biochim Biophys Acta. 1992 May 22;1121(1-2):97-103. [PubMed:1599956]
  2. Stearns ME, Wang M, Sousa O: Evidence that estramustine binds MAP-1A to inhibit type IV collagenase secretion. J Cell Sci. 1991 Jan;98 ( Pt 1):55-63. [PubMed:1647395]
  3. Friden B, Rutberg M, Deinum J, Wallin M: The effect of estramustine derivatives on microtubule assembly in vitro depends on the charge of the substituent. Biochem Pharmacol. 1991 Aug 8;42(5):997-1006. [PubMed:1908244]
  4. Burns RG: Stoichiometry of estramustine phosphate binding to MAP2 measured by the disassembly of chick brain MAP2:tubulin microtubules. Cell Motil Cytoskeleton. 1990;17(3):167-73. [PubMed:2125244]
  5. Falconer MM, Vielkind U, Brown DL: Association of acetylated microtubules, vimentin intermediate filaments, and MAP 2 during early neural differentiation in EC cell culture. Biochem Cell Biol. 1989 Sep;67(9):537-44. [PubMed:2679799]
  6. Tew KD: The mechanism of action of estramustine. Semin Oncol. 1983 Sep;10(3 Suppl 3):21-6. [PubMed:6364362]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Structural molecule activity
Specific Function
Structural protein involved in the filamentous cross-bridging between microtubules and other skeletal elements.
Gene Name
MAP1A
Uniprot ID
P78559
Uniprot Name
Microtubule-associated protein 1A
Molecular Weight
305482.26 Da
References
  1. Stearns ME, Wang M, Sousa O: Evidence that estramustine binds MAP-1A to inhibit type IV collagenase secretion. J Cell Sci. 1991 Jan;98 ( Pt 1):55-63. [PubMed:1647395]

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. 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
Inhibitor
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. Yang CP, Shen HJ, Horwitz SB: Modulation of the function of P-glycoprotein by estramustine. J Natl Cancer Inst. 1994 May 4;86(9):723-5. [PubMed:7908991]
  2. Tiersten AD, Nelsen C, Talbot S, Vahdat L, Fine R, Troxel A, Brafman L, Shriberg L, Antman K, Petrylak DP: A phase II trial of docetaxel and estramustine in patients with refractory metastatic breast carcinoma. Cancer. 2003 Feb 1;97(3):537-44. [PubMed:12548594]
  3. Smith CD, Zilfou JT, Zhang X, Hudes GR, Tew KD: Modulation of P-glycoprotein activity by estramustine is limited by binding to plasma proteins. Cancer. 1995 May 15;75(10):2597-604. [PubMed:7736407]
  4. Speicher LA, Barone LR, Chapman AE, Hudes GR, Laing N, Smith CD, Tew KD: P-glycoprotein binding and modulation of the multidrug-resistant phenotype by estramustine. J Natl Cancer Inst. 1994 May 4;86(9):688-94. [PubMed:7908988]

Drug created on June 13, 2005 07:24 / Updated on January 14, 2018 10:04