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Details

Stereochemistry ABSOLUTE
Molecular Formula C23H31Cl2NO3
Molecular Weight 440.403
Optical Activity UNSPECIFIED
Defined Stereocenters 5 / 5
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ESTRAMUSTINE

SMILES

C[C@]12CC[C@H]3[C@@H](CCC4=CC(OC(=O)N(CCCl)CCCl)=CC=C34)[C@@H]1CC[C@@H]2O

InChI

InChIKey=FRPJXPJMRWBBIH-RBRWEJTLSA-N
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

HIDE SMILES / InChI
Molecular Formula C23H31Cl2NO3
Molecular Weight 440.403
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 5 / 5
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/018045s023lbl.pdf

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. Also, due to the drugs estrogen component, it can bind more selectively to active estrogen receptors. Used for the palliative treatment of patients with metastatic and/or progressive carcinoma of the prostate.

CNS Activity

Originator

Approval Year

1981
142
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8504
 4.5 µM [IC50]
Modulator
846
Agonist
2752
Microtubule-associated protein 1A
6
Target ID: P78559
Gene ID: 4130.0
Gene Symbol: MAP1A
Target Organism: Homo sapiens (Human)
Antagonist
2849
Antagonist
2849
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
Approved
8583
Emcyt

Approved Use

EMCYT Capsules are indicated in the palliative treatment of patients with metastatic and/or progressive carcinoma of the prostate.

Launch Date

1991
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
362 ng/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/6714283
140 mg single, oral
dose: 140 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ESTRAMUSTINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: FED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
972 ng × h/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/16568471
280 mg 3 times / day multiple, oral
dose: 280 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
ESTRAMUSTINE blood
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
2.88 μg × h/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/6714283
140 mg single, oral
dose: 140 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ESTRAMUSTINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: FED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
13.6 h
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/6714283
140 mg single, oral
dose: 140 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ESTRAMUSTINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: FED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
50%
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/7736407
ESTRAMUSTINE plasma
Homo sapiens
population: HEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
3000 mg/m2 1 times / week multiple, intravenous
Highest studied dose
Dose: 3000 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 3000 mg/m2, 1 times / week
Sources:
https://pubmed.ncbi.nlm.nih.gov/11844837
unhealthy, 66
Health Status: unhealthy
Age Group: 66
Sex: M
Sources:
https://pubmed.ncbi.nlm.nih.gov/11844837
DLT: Malaise and fatigue, Hypotension...
Dose limiting toxicities:
Malaise and fatigue (grade 3, 75%)
Hypotension (grade 3, 25%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/11844837
2500 mg/m2 1 times / week multiple, intravenous
MTD
Dose: 2500 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 2500 mg/m2, 1 times / week
Sources:
https://pubmed.ncbi.nlm.nih.gov/11844837
unhealthy, 66
Health Status: unhealthy
Age Group: 66
Sex: M
Sources:
https://pubmed.ncbi.nlm.nih.gov/11844837
DLT: Malaise and fatigue...
Dose limiting toxicities:
Malaise and fatigue (grade 3, 40%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/11844837
AEs

AEs

AESignificanceDosePopulation
Hypotension grade 3, 25%
DLT
3000 mg/m2 1 times / week multiple, intravenous
Highest studied dose
Dose: 3000 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 3000 mg/m2, 1 times / week
Sources:
https://pubmed.ncbi.nlm.nih.gov/11844837
unhealthy, 66
Health Status: unhealthy
Age Group: 66
Sex: M
Sources:
https://pubmed.ncbi.nlm.nih.gov/11844837
Malaise and fatigue grade 3, 75%
DLT
3000 mg/m2 1 times / week multiple, intravenous
Highest studied dose
Dose: 3000 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 3000 mg/m2, 1 times / week
Sources:
https://pubmed.ncbi.nlm.nih.gov/11844837
unhealthy, 66
Health Status: unhealthy
Age Group: 66
Sex: M
Sources:
https://pubmed.ncbi.nlm.nih.gov/11844837
Malaise and fatigue grade 3, 40%
DLT
2500 mg/m2 1 times / week multiple, intravenous
MTD
Dose: 2500 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 2500 mg/m2, 1 times / week
Sources:
https://pubmed.ncbi.nlm.nih.gov/11844837
unhealthy, 66
Health Status: unhealthy
Age Group: 66
Sex: M
Sources:
https://pubmed.ncbi.nlm.nih.gov/11844837
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer
P-gp
1741
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
P-gp
1932
 yes
Sourcing

Sourcing

Vendor/AggregatorIDURL
ChEBI
CHEBI:4868
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:4868
ChemicalBook
CB9127416
https://www.chemicalbook.com/ChemicalProductProperty_EN_CB9127416
eMolecules
30151822
https://www.emolecules.com/cgi-bin/more?vid=30151822
MolPort
MolPort-006-114-857
https://www.molport.com/shop/molecule-link/MolPort-006-114-857
ZINC
ZINC000004099032
http://zinc15.docking.org/substances/ZINC000004099032
PubMed

PubMed

TitleDatePubMed
Neoadjuvant therapy before radical prostatectomy in high-risk localized prostate cancer: defining appropriate endpoints.
2003-06-18
High-risk localized prostate cancer: primary surgery and adjuvant therapy.
2003-06-18
Docetaxel (taxotere) in the treatment of prostate cancer.
2003-06
The combination of estramustine and mitoxantrone in hormone-refractory prostate cancer: a phase II feasibility study conducted by the Hellenic Cooperative Oncology Group.
2003-06
Dose escalation study of intravenous estramustine phosphate in combination with Paclitaxel and Carboplatin in patients with advanced prostate cancer.
2003-06
Current strategies in the management of hormone refractory prostate cancer.
2003-06
[Malignant priapism as a sign of a recurrent prostate cancer. Differential diagnosis of induratio penis plastica].
2003-06
Chemotherapy of prostate cancer: present and future.
2003-06
Characterization of the MRP4- and MRP5-mediated transport of cyclic nucleotides from intact cells.
2003-05-16
Physician attitudes toward cytotoxic chemotherapy use in patients with advanced prostate carcinoma.
2003-05-01
Activity of docetaxel with or without estramustine phosphate versus mitoxantrone in androgen dependent and independent human prostate cancer xenografts.
2003-05
[Prostatic cancer in the young adult].
2003-04
Neoadjuvant docetaxel and estramustine chemotherapy in high-risk/locallyadvanced prostate cancer.
2003-04
Randomized, multicenter, phase II trial of two multicomponent regimens in androgen-independent prostate cancer.
2003-03-01
A phase II trial of docetaxel and estramustine in patients with refractory metastatic breast carcinoma.
2003-02-01
Estimating survival benefit in castrate metastatic prostate cancer: decision making in proceeding to a definitive phase III trial.
2003-01
A phase I study of paclitaxel, estramustine phosphate and vinorelbine (Pacl-E-Vin) in advanced malignancies: triple tubulin targeting.
2003-01
Bisphosphonate therapy for hormone refractory prostate cancer with bone metastasis.
2003-01
Role of chemotherapy in hormone-refractory prostate cancer. Old issues, recent advances and new perspectives.
2003
[Therapy for hormone-refractory prostate cancer].
2002-12
[Chemotherapy for prostate cancers].
2002-12
Fatal respiratory failure associated with treatment of prostate cancer using docetaxel and estramustine.
2002-12
An active regimen of weekly paclitaxel and estramustine in metastatic androgen-independent prostate cancer.
2002-12
Editorial: States and state transitions are all that really matter.
2002-12
Combination chemotherapy with paclitaxel, estramustine and carboplatin for hormone refractory prostate cancer.
2002-12
[Hormonal chemotherapy for hormone-refractory prostate cancer].
2002-11
Pattern of somatic androgen receptor gene mutations in patients with hormone-refractory prostate cancer.
2002-11
Penile metastasis of prostatic adenocarcinoma.
2002-10
Drug resistance in prostate cancer cell lines is influenced by androgen dependence and p53 status.
2002-10
Combined anti-microtubule therapy: a phase II study of weekly docetaxel plus estramustine in patients with metastatic breast cancer.
2002-10
Weekly epirubicin in patients with hormone-resistant prostate cancer.
2002-09-23
Chemotherapy for prostate cancer.
2002-09
[Second cancer after starting treatment for prostate cancer].
2002-08
Ondansetron but not granisetron affect cell volume regulation and potassium ion transport of glioma cells treated with estramustine phosphate.
2002-08
Chemotherapy for androgen-independent prostate cancer.
2002-08
Editorial: the coming revolution in the treatment of prostate cancer patients.
2002-08
Hypertriglyceridemia and pancreatitis associated with estramustine phosphate.
2002-08
High activity Rhenium-186 HEDP with autologous peripheral blood stem cell rescue: a phase I study in progressive hormone refractory prostate cancer metastatic to bone.
2002-06-05
Acute estramustine-induced hypocalcemia unmasking severe vitamin D deficiency.
2002-06-01
The role of chemotherapy in advanced prostate cancer.
2002-06
Docetaxel in the integrated management of prostate cancer. Current applications and future promise.
2002-06
Effects of docetaxel on pain due to metastatic androgen-independent prostate cancer.
2002-06
Estramustine phosphate combined with orchidectomy as first-line therapy in patients with prostate carcinoma. Effect of age on survival.
2002-05-15
Estramustine phosphate enhances the effects of hyperthermia and induces the small heat shock protein HSP27 in the human prostate carcinoma cell line PC-3.
2002-05
A phase II Hoosier Oncology Group study of vinorelbine and estramustine phosphate in hormone-refractory prostate cancer.
2002-03
EMP combination chemotherapy and low-dose monotherapy in advanced prostate cancer.
2002-02
Mechanism of action of antitumor drugs that interact with microtubules and tubulin.
2002-01
The antimicrotubule drug estramustine but not irradiation induces apoptosis in malignant glioma involving AKT and caspase pathways.
2002-01
Estramustine plus a taxane for advanced prostate cancer: the new standard therapy?
2002
Phase I trial of oral estramustine and 3-hr infusional paclitaxel for the treatment of hormone refractory prostate cancer.
2002
Patents

Patents

05036062
6
20050222431
14
20070037988
12
20070116729
163
20070244331
14
JP2002511777A
420
JP2003529540A
50
JP2005519871A
30
JP2005520795A
26
JP2007538099A
19
JP2009513567A
66
JP2011522802A
31
JP2011524416A
146
JPS61189214A
7

Sample Use Guides

In Vivo Use Guide
The recommended daily dose is 14 mg per kg of body weight (ie, one 140 mg capsule for each 10 kg or 22 lb of body weight), given in 3 or 4 divided doses. Most patients in studies in the United States have been treated at a dosage range of 10 to 16 mg per kg per day.
Route of Administration: Oral
In Vitro Use Guide
Estramustine inhibited human endothelial cell proliferation with an IC50 of 4.5 uM and was active at 10-33% of the maximum tolerated dose (MTD) from clinical schedules
Substance Class Chemical
Created
by admin
on Mon Mar 31 17:45:13 GMT 2025
Edited
by admin
on Mon Mar 31 17:45:13 GMT 2025
Record UNII
35LT29625A
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ESTRAMUSTINE
INN   MI   USAN   VANDF   WHO-DD  
USAN   INN  
Official Name English
LEO-275
Preferred Name English
RO-22-2296/000
Code English
RO 22-2296/000
Code English
NSC-89201
Code English
Estramustine [WHO-DD]
Common Name English
estramustine [INN]
Common Name English
RO-222296000
Code English
RO-22-2296000
Code English
LEO275
Code English
ESTRA-1,3,5(10)-TRIENE-3,17-DIOL, 3-(BIS(2-CHLOROETHYL)CARBAMATE), (17B)-
Common Name English
ESTRAMUSTINE [USAN]
Common Name English
ESTRAMUSTINE [MI]
Common Name English
ESTRAMUSTINE [VANDF]
Common Name English
Estradiol 3-[bis(2-chloroethyl)carbamate]
Common Name English
Classification Tree Code System Code
NDF-RT N0000007246
Created by admin on Mon Mar 31 17:45:13 GMT 2025 , Edited by admin on Mon Mar 31 17:45:13 GMT 2025
WHO-ATC L01XX11
Created by admin on Mon Mar 31 17:45:13 GMT 2025 , Edited by admin on Mon Mar 31 17:45:13 GMT 2025
NDF-RT N0000175558
Created by admin on Mon Mar 31 17:45:13 GMT 2025 , Edited by admin on Mon Mar 31 17:45:13 GMT 2025
LIVERTOX 373
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NDF-RT N0000007246
Created by admin on Mon Mar 31 17:45:13 GMT 2025 , Edited by admin on Mon Mar 31 17:45:13 GMT 2025
NCI_THESAURUS C697
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NCI_THESAURUS C25974
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NDF-RT N0000007659
Created by admin on Mon Mar 31 17:45:13 GMT 2025 , Edited by admin on Mon Mar 31 17:45:13 GMT 2025
WHO-VATC QL01XX11
Created by admin on Mon Mar 31 17:45:13 GMT 2025 , Edited by admin on Mon Mar 31 17:45:13 GMT 2025
NDF-RT N0000000236
Created by admin on Mon Mar 31 17:45:13 GMT 2025 , Edited by admin on Mon Mar 31 17:45:13 GMT 2025
Code System Code Type Description
EVMPD
SUB07246MIG
Created by admin on Mon Mar 31 17:45:13 GMT 2025 , Edited by admin on Mon Mar 31 17:45:13 GMT 2025
PRIMARY
MESH
D004961
Created by admin on Mon Mar 31 17:45:13 GMT 2025 , Edited by admin on Mon Mar 31 17:45:13 GMT 2025
PRIMARY
MERCK INDEX
m5031
Created by admin on Mon Mar 31 17:45:13 GMT 2025 , Edited by admin on Mon Mar 31 17:45:13 GMT 2025
PRIMARY Merck Index
WIKIPEDIA
ESTRAMUSTINE
Created by admin on Mon Mar 31 17:45:13 GMT 2025 , Edited by admin on Mon Mar 31 17:45:13 GMT 2025
PRIMARY
RXCUI
4089
Created by admin on Mon Mar 31 17:45:13 GMT 2025 , Edited by admin on Mon Mar 31 17:45:13 GMT 2025
PRIMARY RxNorm
CHEBI
4868
Created by admin on Mon Mar 31 17:45:13 GMT 2025 , Edited by admin on Mon Mar 31 17:45:13 GMT 2025
PRIMARY
SMS_ID
100000082381
Created by admin on Mon Mar 31 17:45:13 GMT 2025 , Edited by admin on Mon Mar 31 17:45:13 GMT 2025
PRIMARY
DRUG BANK
DB01196
Created by admin on Mon Mar 31 17:45:13 GMT 2025 , Edited by admin on Mon Mar 31 17:45:13 GMT 2025
PRIMARY
EPA CompTox
DTXSID8046458
Created by admin on Mon Mar 31 17:45:13 GMT 2025 , Edited by admin on Mon Mar 31 17:45:13 GMT 2025
PRIMARY
NCI_THESAURUS
C479
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PRIMARY
ChEMBL
CHEMBL1575
Created by admin on Mon Mar 31 17:45:13 GMT 2025 , Edited by admin on Mon Mar 31 17:45:13 GMT 2025
PRIMARY
PUBCHEM
259331
Created by admin on Mon Mar 31 17:45:13 GMT 2025 , Edited by admin on Mon Mar 31 17:45:13 GMT 2025
PRIMARY
FDA UNII
35LT29625A
Created by admin on Mon Mar 31 17:45:13 GMT 2025 , Edited by admin on Mon Mar 31 17:45:13 GMT 2025
PRIMARY
ECHA (EC/EINECS)
221-076-3
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PRIMARY
CAS
2998-57-4
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PRIMARY
DRUG CENTRAL
1065
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PRIMARY
INN
2877
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PRIMARY
NSC
89201
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PRIMARY
DAILYMED
35LT29625A
Created by admin on Mon Mar 31 17:45:13 GMT 2025 , Edited by admin on Mon Mar 31 17:45:13 GMT 2025
PRIMARY
Related Record Type Details
TUBULIN BETA CHAIN
TARGET->LIGAND
Related Record Type Details
Structure of ALESTRAMUSTINE
PRODRUG -> METABOLITE ACTIVE
Structure of ESTRADIOL
METABOLITE -> PARENT
Metabolite produced by hydrolysis. Estramustine,s primary mechanism of antineoplastic action is inhibition of mitosis.
PLASMA
Structure of ESTRAMUSTINE PHOSPHATE
PRODRUG -> METABOLITE ACTIVE
Related Record Type Details
Structure of ESTRAMUSTINE
ACTIVE MOIETY
NIH
NCATS
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ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
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