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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

[H][C@@]12CC[C@H](O)[C@@]1(C)CC[C@]3([H])C4=C(CC[C@@]23[H])C=C(OC(=O)N(CCCl)CCCl)C=C4

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
138
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8297
 4.5 µM [IC50]
Modulator
828
Agonist
2678
Microtubule-associated protein 1A
5
Target ID: P78559
Gene ID: 4130.0
Gene Symbol: MAP1A
Target Organism: Homo sapiens (Human)
Antagonist
2778
Antagonist
2778
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
Approved
8429
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
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
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
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
Page: p.1118
unhealthy, 66
n = 4
Health Status: unhealthy
Condition: Prostate cancer
Age Group: 66
Sex: M
Population Size: 4
Sources:
https://pubmed.ncbi.nlm.nih.gov/11844837
Page: p.1118
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
Page: p.1118
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
Page: p.1119, 1124
unhealthy, 66
n = 6
Health Status: unhealthy
Condition: Prostate cancer
Age Group: 66
Sex: M
Population Size: 6
Sources:
https://pubmed.ncbi.nlm.nih.gov/11844837
Page: p.1119, 1124
DLT: Malaise and fatigue...
Dose limiting toxicities:
Malaise and fatigue (grade 3, 40%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/11844837
Page: p.1119, 1124
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
Page: p.1118
unhealthy, 66
n = 4
Health Status: unhealthy
Condition: Prostate cancer
Age Group: 66
Sex: M
Population Size: 4
Sources:
https://pubmed.ncbi.nlm.nih.gov/11844837
Page: p.1118
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
Page: p.1118
unhealthy, 66
n = 4
Health Status: unhealthy
Condition: Prostate cancer
Age Group: 66
Sex: M
Population Size: 4
Sources:
https://pubmed.ncbi.nlm.nih.gov/11844837
Page: p.1118
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
Page: p.1119, 1124
unhealthy, 66
n = 6
Health Status: unhealthy
Condition: Prostate cancer
Age Group: 66
Sex: M
Population Size: 6
Sources:
https://pubmed.ncbi.nlm.nih.gov/11844837
Page: p.1119, 1124
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer
P-gp
1461
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
P-gp
1650
 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
MolPort
MolPort-006-114-857
https://www.molport.com/shop/molecule-link/MolPort-006-114-857
ZINC
ZINC000004099032
http://zinc15.docking.org/substances/ZINC000004099032
eMolecules
30151822
https://www.emolecules.com/cgi-bin/more?vid=30151822
PubMed

PubMed

TitleDatePubMed
Treatment options in hormone-refractory prostate cancer: current and future approaches.
2001
Can chemotherapy alter the course of prostate cancer?
2001 Aug
Treatment of hormone refractory prostate cancer.
2001 Aug
Secondary myelodysplastic syndrome after treatment of prostate cancer with oral estramustine.
2001 Aug
Estramustine-related hypocalcemia in patients with prostate carcinoma and osteoblastic metastases.
2001 Jul
Phase I trial of weekly paclitaxel plus oral estramustine phosphate in patients with hormone-refractory prostate cancer.
2001 Jul
Paclitaxel and docetaxel in prostate cancer.
2001 Jun
Chemotherapy in patients with prostate specific antigen-only disease after primary therapy for prostate carcinoma: a phase II trial of oral estramustine and oral etoposide.
2001 Jun 1
A Phase I/II study of weekly paclitaxel and 3 days of high dose oral estramustine in patients with hormone-refractory prostate carcinoma.
2001 Jun 1
The bleb formation of the extracellular pseudopodia; early evidence of microtubule depolymerization by estramustine phosphate in glioma cell; in vitro study.
2001 Mar
Oral estramustine therapy in serum chromogranin A-positive stage D3 prostate cancer patients.
2001 Mar-Apr
The impact of docetaxel, estramustine, and low dose hydrocortisone on the quality of life of men with hormone refractory prostate cancer and their partners: a feasibility study.
2001 May
Estramustine potentiates taxane in prostate and refractory breast cancers.
2001 May
Diverging effects of 5-HT3 receptor antagonists ondansetron and granisetron on estramustine-inhibited cellular potassium transport.
2001 May
[A male case of primary bilateral breast cancers during estrogen therapy for prostate cancer].
2001 Nov
[Clinical efficacy of leuprolide acetate and combined treatment with estramustine for advanced prostate cancer].
2001 Nov
The treatment challenge of hormone-refractory prostate cancer.
2001 Nov-Dec
Modulation of endogenous beta-tubulin isotype expression as a result of human beta(III)cDNA transfection into prostate carcinoma cells.
2001 Sep 1
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
Controversies in chemotherapy of prostate cancer.
2002
Ondansetron but not granisetron affect cell volume regulation and potassium ion transport of glioma cells treated with estramustine phosphate.
2002 Aug
Editorial: the coming revolution in the treatment of prostate cancer patients.
2002 Aug
Hypertriglyceridemia and pancreatitis associated with estramustine phosphate.
2002 Aug
[Therapy for hormone-refractory prostate cancer].
2002 Dec
[Chemotherapy for prostate cancers].
2002 Dec
Fatal respiratory failure associated with treatment of prostate cancer using docetaxel and estramustine.
2002 Dec
The flare in alkaline phosphatase activity post-orchidectomy predicts which patient may benefit from early chemotherapy in metastatic prostate cancer.
2002 Feb 1
Mechanism of action of antitumor drugs that interact with microtubules and tubulin.
2002 Jan
Estramustine phosphate combined with orchidectomy as first-line therapy in patients with prostate carcinoma. Effect of age on survival.
2002 May 15
Chemotherapy for prostate cancer.
2002 Sep
Weekly epirubicin in patients with hormone-resistant prostate cancer.
2002 Sep 23
Role of chemotherapy in hormone-refractory prostate cancer. Old issues, recent advances and new perspectives.
2003
[Prostatic cancer in the young adult].
2003 Apr
Neoadjuvant docetaxel and estramustine chemotherapy in high-risk/locallyadvanced prostate cancer.
2003 Apr
A phase II trial of docetaxel and estramustine in patients with refractory metastatic breast carcinoma.
2003 Feb 1
Estimating survival benefit in castrate metastatic prostate cancer: decision making in proceeding to a definitive phase III trial.
2003 Jan
A phase I study of paclitaxel, estramustine phosphate and vinorelbine (Pacl-E-Vin) in advanced malignancies: triple tubulin targeting.
2003 Jan
Docetaxel (taxotere) in the treatment of prostate cancer.
2003 Jun
The combination of estramustine and mitoxantrone in hormone-refractory prostate cancer: a phase II feasibility study conducted by the Hellenic Cooperative Oncology Group.
2003 Jun
Dose escalation study of intravenous estramustine phosphate in combination with Paclitaxel and Carboplatin in patients with advanced prostate cancer.
2003 Jun
Current strategies in the management of hormone refractory prostate cancer.
2003 Jun
[Malignant priapism as a sign of a recurrent prostate cancer. Differential diagnosis of induratio penis plastica].
2003 Jun
Chemotherapy of prostate cancer: present and future.
2003 Jun
Randomized, multicenter, phase II trial of two multicomponent regimens in androgen-independent prostate cancer.
2003 Mar 1
Activity of docetaxel with or without estramustine phosphate versus mitoxantrone in androgen dependent and independent human prostate cancer xenografts.
2003 May
Physician attitudes toward cytotoxic chemotherapy use in patients with advanced prostate carcinoma.
2003 May 1
Characterization of the MRP4- and MRP5-mediated transport of cyclic nucleotides from intact cells.
2003 May 16
Neoadjuvant therapy before radical prostatectomy in high-risk localized prostate cancer: defining appropriate endpoints.
2003 May-Jun
High-risk localized prostate cancer: primary surgery and adjuvant therapy.
2003 May-Jun
Patents

Patents

05036062
5
JP2002511777A
414
JP2003529540A
49
JP2005519871A
28
JP2005520795A
24
JP2007538099A
18
JP2009513567A
65
JP2011522802A
30
JP2011524416A
138
JPS61189214A
6

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 Fri Dec 15 15:04:03 GMT 2023
Edited
by admin
on Fri Dec 15 15:04:03 GMT 2023
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
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
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 Fri Dec 15 15:04:03 GMT 2023 , Edited by admin on Fri Dec 15 15:04:03 GMT 2023
WHO-ATC L01XX11
Created by admin on Fri Dec 15 15:04:03 GMT 2023 , Edited by admin on Fri Dec 15 15:04:03 GMT 2023
NDF-RT N0000175558
Created by admin on Fri Dec 15 15:04:03 GMT 2023 , Edited by admin on Fri Dec 15 15:04:03 GMT 2023
LIVERTOX 373
Created by admin on Fri Dec 15 15:04:03 GMT 2023 , Edited by admin on Fri Dec 15 15:04:03 GMT 2023
NDF-RT N0000007246
Created by admin on Fri Dec 15 15:04:03 GMT 2023 , Edited by admin on Fri Dec 15 15:04:03 GMT 2023
NCI_THESAURUS C697
Created by admin on Fri Dec 15 15:04:03 GMT 2023 , Edited by admin on Fri Dec 15 15:04:03 GMT 2023
NCI_THESAURUS C25974
Created by admin on Fri Dec 15 15:04:03 GMT 2023 , Edited by admin on Fri Dec 15 15:04:03 GMT 2023
NDF-RT N0000007659
Created by admin on Fri Dec 15 15:04:03 GMT 2023 , Edited by admin on Fri Dec 15 15:04:03 GMT 2023
WHO-VATC QL01XX11
Created by admin on Fri Dec 15 15:04:03 GMT 2023 , Edited by admin on Fri Dec 15 15:04:03 GMT 2023
NDF-RT N0000000236
Created by admin on Fri Dec 15 15:04:03 GMT 2023 , Edited by admin on Fri Dec 15 15:04:03 GMT 2023
Code System Code Type Description
EVMPD
SUB07246MIG
Created by admin on Fri Dec 15 15:04:03 GMT 2023 , Edited by admin on Fri Dec 15 15:04:03 GMT 2023
PRIMARY
MESH
D004961
Created by admin on Fri Dec 15 15:04:03 GMT 2023 , Edited by admin on Fri Dec 15 15:04:03 GMT 2023
PRIMARY
MERCK INDEX
m5031
Created by admin on Fri Dec 15 15:04:03 GMT 2023 , Edited by admin on Fri Dec 15 15:04:03 GMT 2023
PRIMARY Merck Index
WIKIPEDIA
ESTRAMUSTINE
Created by admin on Fri Dec 15 15:04:03 GMT 2023 , Edited by admin on Fri Dec 15 15:04:03 GMT 2023
PRIMARY
RXCUI
4089
Created by admin on Fri Dec 15 15:04:03 GMT 2023 , Edited by admin on Fri Dec 15 15:04:03 GMT 2023
PRIMARY RxNorm
CHEBI
4868
Created by admin on Fri Dec 15 15:04:03 GMT 2023 , Edited by admin on Fri Dec 15 15:04:03 GMT 2023
PRIMARY
SMS_ID
100000082381
Created by admin on Fri Dec 15 15:04:03 GMT 2023 , Edited by admin on Fri Dec 15 15:04:03 GMT 2023
PRIMARY
DRUG BANK
DB01196
Created by admin on Fri Dec 15 15:04:03 GMT 2023 , Edited by admin on Fri Dec 15 15:04:03 GMT 2023
PRIMARY
EPA CompTox
DTXSID8046458
Created by admin on Fri Dec 15 15:04:03 GMT 2023 , Edited by admin on Fri Dec 15 15:04:03 GMT 2023
PRIMARY
NCI_THESAURUS
C479
Created by admin on Fri Dec 15 15:04:03 GMT 2023 , Edited by admin on Fri Dec 15 15:04:03 GMT 2023
PRIMARY
ChEMBL
CHEMBL1575
Created by admin on Fri Dec 15 15:04:03 GMT 2023 , Edited by admin on Fri Dec 15 15:04:03 GMT 2023
PRIMARY
PUBCHEM
259331
Created by admin on Fri Dec 15 15:04:03 GMT 2023 , Edited by admin on Fri Dec 15 15:04:03 GMT 2023
PRIMARY
FDA UNII
35LT29625A
Created by admin on Fri Dec 15 15:04:03 GMT 2023 , Edited by admin on Fri Dec 15 15:04:03 GMT 2023
PRIMARY
ECHA (EC/EINECS)
221-076-3
Created by admin on Fri Dec 15 15:04:03 GMT 2023 , Edited by admin on Fri Dec 15 15:04:03 GMT 2023
PRIMARY
CAS
2998-57-4
Created by admin on Fri Dec 15 15:04:03 GMT 2023 , Edited by admin on Fri Dec 15 15:04:03 GMT 2023
PRIMARY
DRUG CENTRAL
1065
Created by admin on Fri Dec 15 15:04:03 GMT 2023 , Edited by admin on Fri Dec 15 15:04:03 GMT 2023
PRIMARY
INN
2877
Created by admin on Fri Dec 15 15:04:03 GMT 2023 , Edited by admin on Fri Dec 15 15:04:03 GMT 2023
PRIMARY
NSC
89201
Created by admin on Fri Dec 15 15:04:03 GMT 2023 , Edited by admin on Fri Dec 15 15:04:03 GMT 2023
PRIMARY
DAILYMED
35LT29625A
Created by admin on Fri Dec 15 15:04:03 GMT 2023 , Edited by admin on Fri Dec 15 15:04:03 GMT 2023
PRIMARY
Related Record Type Details
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
PRIVACY ACT
ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
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