Identification

Name
Estramustine
Accession Number
DB01196  (APRD00625)
Type
Small Molecule
Groups
Approved, Investigational
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][C@@]12CC[C@H](O)[C@@]1(C)CC[C@]1([H])C3=CC=C(OC(=O)N(CCCl)CCCl)C=C3CC[C@@]21[H]

Pharmacology

Indication

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

Associated Conditions
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
AMicrotubule-associated protein 2
antagonist
Human
AMicrotubule-associated protein 1A
antagonist
Human
AEstrogen receptor alpha
agonist
Human
AEstrogen receptor beta
other/unknown
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
Acetyl sulfisoxazoleThe metabolism of Estramustine can be decreased when combined with Acetyl sulfisoxazole.Approved, Vet Approved
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Estramustine.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Estramustine.Experimental
AfatinibThe serum concentration of Afatinib can be increased when it is combined with Estramustine.Approved
AmiodaroneThe metabolism of Estramustine can be decreased when combined with Amiodarone.Approved, Investigational
AncestimThe risk or severity of cytotoxicity can be increased when Ancestim is combined with Estramustine.Approved, Investigational, Withdrawn
Anthrax immune globulin humanThe risk or severity of adverse effects can be increased when Estramustine is combined with Anthrax immune globulin human.Approved
ApalutamideThe serum concentration of Estramustine can be decreased when it is combined with Apalutamide.Approved, Investigational
AprepitantThe serum concentration of Estramustine can be increased when it is combined with Aprepitant.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
Bacillus calmette-guerin substrain connaught live antigenThe risk or severity of adverse effects can be increased when Estramustine is combined with Bacillus calmette-guerin substrain connaught live antigen.Approved, Investigational
Bacillus calmette-guerin substrain tice live antigenThe risk or severity of adverse effects can be increased when Estramustine is combined with Bacillus calmette-guerin substrain tice live antigen.Approved
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Estramustine.Investigational
BevacizumabBevacizumab may increase the cardiotoxic activities of Estramustine.Approved, Investigational
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, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel 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, Investigational
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, Investigational
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, 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 levulinateCalcium levulinate can cause a decrease in the absorption of Estramustine resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved, 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
CarbamazepineThe metabolism of Estramustine can be increased when combined 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
ClarithromycinThe metabolism of Estramustine can be decreased when combined with Clarithromycin.Approved
ClemastineThe metabolism of Estramustine can be decreased when combined with Clemastine.Approved, Investigational
Clodronic AcidThe serum concentration of Estramustine can be increased when it is combined with Clodronic Acid.Approved, Investigational, Vet Approved
Clostridium tetani toxoid antigen (formaldehyde inactivated)The risk or severity of adverse effects can be increased when Estramustine is combined with Clostridium tetani toxoid antigen (formaldehyde inactivated).Approved
ClotrimazoleThe metabolism of Estramustine can be decreased when combined with Clotrimazole.Approved, Vet Approved
ColchicineThe serum concentration of Colchicine can be increased when it is combined with Estramustine.Approved
ConivaptanThe serum concentration of Conivaptan can be increased when it is combined with Estramustine.Approved, Investigational
Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated)The risk or severity of adverse effects can be increased when Estramustine is combined with Corynebacterium diphtheriae toxoid antigen (formaldehyde inactivated).Approved
CrizotinibThe metabolism of Estramustine can be decreased when combined with Crizotinib.Approved
CurcuminThe metabolism of Estramustine can be decreased when combined with Curcumin.Approved, Investigational
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, 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
DelavirdineThe metabolism of Estramustine can be decreased when combined with Delavirdine.Approved
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Estramustine.Approved
DeslanosideDeslanoside may decrease the cardiotoxic activities of Estramustine.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, Investigational
DiltiazemThe metabolism of Estramustine can be decreased when combined with Diltiazem.Approved, Investigational
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Estramustine.Approved, Investigational
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
EdoxabanThe serum concentration of Edoxaban can be increased when it is combined with Estramustine.Approved
EnzalutamideThe serum concentration of Estramustine can be decreased when it is combined with Enzalutamide.Approved
ErythromycinThe metabolism of Estramustine can be decreased when combined with Erythromycin.Approved, Investigational, Vet Approved
EverolimusThe serum concentration of Everolimus can be increased when it is combined with Estramustine.Approved
FingolimodEstramustine may increase the immunosuppressive activities of Fingolimod.Approved, Investigational
FluconazoleThe metabolism of Estramustine can be decreased when combined with Fluconazole.Approved, Investigational
FluvoxamineThe metabolism of Estramustine can be decreased when combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe metabolism of Estramustine can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Estramustine can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe metabolism of Estramustine can be increased when combined with Fosphenytoin.Approved, Investigational
Fusidic AcidThe serum concentration of Estramustine can be increased when it is combined with Fusidic Acid.Approved, Investigational
G17DTThe risk or severity of adverse effects can be increased when Estramustine is combined with G17DT.Investigational
GI-5005The risk or severity of adverse effects can be increased when Estramustine is combined with GI-5005.Investigational
GitoformateGitoformate may decrease the cardiotoxic activities of Estramustine.Experimental
Hepatitis A VaccineThe risk or severity of adverse effects can be increased when Estramustine is combined with Hepatitis A Vaccine.Approved
Hepatitis B Vaccine (Recombinant)The risk or severity of adverse effects can be increased when Estramustine is combined with Hepatitis B Vaccine (Recombinant).Approved, Withdrawn
Human rabies virus immune globulinThe risk or severity of adverse effects can be increased when Estramustine is combined with Human rabies virus immune globulin.Approved
IdelalisibThe metabolism of Estramustine can be decreased when combined with Idelalisib.Approved
ImatinibThe metabolism of Estramustine can be decreased when combined with Imatinib.Approved
IndinavirThe metabolism of Estramustine can be decreased when combined with Indinavir.Approved
INGN 201The risk or severity of adverse effects can be increased when Estramustine is combined with INGN 201.Investigational
INGN 225The risk or severity of adverse effects can be increased when Estramustine is combined with INGN 225.Investigational
IsavuconazoleThe serum concentration of Estramustine can be increased when it is combined with Isavuconazole.Approved, Investigational
IsavuconazoniumThe metabolism of Estramustine can be decreased when combined with Isavuconazonium.Approved, Investigational
IsradipineThe metabolism of Estramustine can be decreased when combined with Isradipine.Approved, Investigational
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
Japanese encephalitis virus strain sa 14-14-2 antigen (formaldehyde inactivated)The risk or severity of adverse effects can be increased when Estramustine is combined with Japanese encephalitis virus strain sa 14-14-2 antigen (formaldehyde inactivated).Approved
KetoconazoleThe metabolism of Estramustine can be decreased when combined with Ketoconazole.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
LeflunomideThe risk or severity of adverse effects can be increased when Estramustine is combined with Leflunomide.Approved, Investigational
LopinavirThe metabolism of Estramustine can be decreased when combined with Lopinavir.Approved
LorpiprazoleThe serum concentration of Estramustine can be increased when it is combined with Lorpiprazole.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
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Estramustine.Experimental
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
NaloxegolThe serum concentration of Naloxegol can be increased when it is combined with Estramustine.Approved
NatalizumabThe risk or severity of adverse effects can be increased when Estramustine is combined with Natalizumab.Approved, Investigational
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, Investigational
NevirapineThe metabolism of Estramustine can be increased when combined with Nevirapine.Approved
NilotinibThe metabolism of Estramustine can be decreased when combined with Nilotinib.Approved, Investigational
OcrelizumabOcrelizumab may increase the immunosuppressive activities of Estramustine.Approved, Investigational
OlaparibThe metabolism of Estramustine can be decreased when combined with Olaparib.Approved
OleandrinOleandrin may decrease the cardiotoxic activities of Estramustine.Experimental, Investigational
OsimertinibThe serum concentration of Estramustine can be increased when it is combined with Osimertinib.Approved
OuabainOuabain may decrease the cardiotoxic activities of Estramustine.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Estramustine.Approved, Vet Approved
PalbociclibThe serum concentration of Estramustine can be increased when it is combined with Palbociclib.Approved, Investigational
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, Investigational, Vet Approved
PeruvosidePeruvoside may decrease the cardiotoxic activities of Estramustine.Experimental
PhenobarbitalThe metabolism of Estramustine can be increased when combined with Phenobarbital.Approved, Investigational
PhenytoinThe metabolism of Estramustine can be increased when combined with Phenytoin.Approved, Vet Approved
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Estramustine.Approved, Investigational
PitolisantThe serum concentration of Estramustine can be decreased when it is combined with Pitolisant.Approved, Investigational
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
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Estramustine.Experimental
PrucaloprideThe serum concentration of Prucalopride can be increased when it is combined with Estramustine.Approved
Rabies virus inactivated antigen, AThe risk or severity of adverse effects can be increased when Estramustine is combined with Rabies virus inactivated antigen, A.Approved, Investigational
Rabies virus inactivated antigen, AThe therapeutic efficacy of Rabies virus inactivated antigen, A can be decreased when used in combination with Estramustine.Approved, Investigational
RanolazineThe serum concentration of Ranolazine can be increased when it is combined with Estramustine.Approved, Investigational
RifabutinThe metabolism of Estramustine can be increased when combined with Rifabutin.Approved, Investigational
RifampicinThe metabolism of Estramustine can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Estramustine can be increased when combined with Rifapentine.Approved, Investigational
RifaximinThe serum concentration of Rifaximin can be increased when it is combined with Estramustine.Approved, Investigational
RindopepimutThe risk or severity of adverse effects can be increased when Estramustine is combined with Rindopepimut.Investigational
RoflumilastRoflumilast may increase the immunosuppressive activities of Estramustine.Approved
Rotavirus VaccineThe risk or severity of adverse effects can be increased when Estramustine is combined with Rotavirus Vaccine.Approved
Rubella virus vaccineThe risk or severity of adverse effects can be increased when Estramustine is combined with Rubella virus vaccine.Approved, Investigational
RucaparibThe metabolism of Estramustine can be decreased when combined with Rucaparib.Approved, Investigational
Salmonella typhi ty2 vi polysaccharide antigenThe risk or severity of adverse effects can be increased when Estramustine is combined with Salmonella typhi ty2 vi polysaccharide antigen.Approved
Salmonella typhi ty21a live antigenThe risk or severity of adverse effects can be increased when Estramustine is combined with Salmonella typhi ty21a live antigen.Approved
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, Investigational
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, Investigational
SimeprevirThe serum concentration of Estramustine can be increased when it is combined with Simeprevir.Approved
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Estramustine.Approved, Investigational
SRP 299The risk or severity of adverse effects can be increased when Estramustine is combined with SRP 299.Investigational
St. John's WortThe serum concentration of Estramustine can be decreased when it is combined with St. John's Wort.Approved, 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
TacrolimusTacrolimus may increase the immunosuppressive activities of Estramustine.Approved, Investigational
TecemotideThe risk or severity of adverse effects can be increased when Estramustine is combined with Tecemotide.Investigational
TelaprevirThe metabolism of Estramustine can be decreased when combined with Telaprevir.Approved, Withdrawn
TelithromycinThe metabolism of Estramustine can be decreased when combined with Telithromycin.Approved
TG4010The risk or severity of adverse effects can be increased when Estramustine is combined with TG4010.Investigational
TiclopidineThe metabolism of Estramustine can be decreased when combined with Ticlopidine.Approved
TocilizumabThe serum concentration of Estramustine can be decreased when it is combined with Tocilizumab.Approved
TofacitinibEstramustine may increase the immunosuppressive activities of Tofacitinib.Approved, Investigational
TopotecanThe serum concentration of Topotecan can be increased when it is combined with Estramustine.Approved, Investigational
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Estramustine.Approved, Investigational
Typhoid VaccineThe risk or severity of adverse effects can be increased when Estramustine is combined with Typhoid Vaccine.Approved
Varicella Zoster Vaccine (Live/Attenuated)The risk or severity of adverse effects can be increased when Estramustine is combined with Varicella Zoster Vaccine (Live/Attenuated).Approved
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
VincristineThe excretion of Vincristine can be decreased when combined with Estramustine.Approved, Investigational
Yellow Fever VaccineThe risk or severity of adverse effects can be increased when Estramustine is combined with Yellow Fever Vaccine.Approved, Investigational
ZiprasidoneThe metabolism of Estramustine can be decreased when combined with Ziprasidone.Approved
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
HMDB0015327
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
3Active Not RecruitingTreatmentProstate Cancer1
3CompletedTreatmentProstate Cancer5
3TerminatedTreatmentProstate Cancer1
3TerminatedTreatmentProstatic Neoplasms1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Pfizer Inc.
  • Pharmaceutical Utilization Management Program VA Inc.
  • Pharmacia Inc.
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
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]
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
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]

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 July 16, 2018 21:21