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Details

Stereochemistry ABSOLUTE
Molecular Formula C23H32Cl2NO6P
Molecular Weight 520.383
Optical Activity UNSPECIFIED
Defined Stereocenters 5 / 5
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ESTRAMUSTINE PHOSPHATE

SMILES

[H][C@@]12CC[C@H](OP(O)(O)=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=ADFOJJHRTBFFOF-RBRWEJTLSA-N
InChI=1S/C23H32Cl2NO6P/c1-23-9-8-18-17-5-3-16(31-22(27)26(12-10-24)13-11-25)14-15(17)2-4-19(18)20(23)6-7-21(23)32-33(28,29)30/h3,5,14,18-21H,2,4,6-13H2,1H3,(H2,28,29,30)/t18-,19-,20+,21+,23+/m1/s1

HIDE SMILES / InChI
Molecular Formula C23H32Cl2NO6P
Molecular Weight 520.383
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
Progressing prostate carcinoma.
2001
Neoadjuvant docetaxel followed by radical prostatectomy in patients with high-risk localized prostate cancer: a preliminary report.
2001 Aug
Secondary myelodysplastic syndrome after treatment of prostate cancer with oral estramustine.
2001 Aug
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
Phase I trial of oral estramustine and 3-hr infusional paclitaxel for the treatment of hormone refractory prostate cancer.
2002
Phase II evaluation of docetaxel plus one-day oral estramustine phosphate in the treatment of patients with androgen independent prostate carcinoma.
2002 Mar 1
[Prostatic cancer in the young adult].
2003 Apr
A phase II trial of docetaxel and estramustine in patients with refractory metastatic breast carcinoma.
2003 Feb 1
Current strategies in the management of hormone refractory prostate cancer.
2003 Jun
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 15:54:42 GMT 2023
Edited
by admin
on Fri Dec 15 15:54:42 GMT 2023
Record UNII
MUZ9585Y7B
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ESTRAMUSTINE PHOSPHATE
WHO-DD  
Common Name English
ESTRAMUSTINE 17-(DIHYDROGEN PHOSPHATE) [MI]
Common Name English
LS 299
Common Name English
ESTRAMUSTINE 17-(DIHYDROGEN PHOSPHATE)
MI  
Common Name English
LS-299
Common Name English
ESTRADIOL, 3-(BIS(2-CHLOROETHYL)CARBAMATE) DIHYDROGEN PHOSPHATE
Common Name English
ESTRACYT
Brand Name English
NSC-89199
Code English
Estramustine phosphate [WHO-DD]
Common Name English
Code System Code Type Description
EPA CompTox
DTXSID7048667
Created by admin on Fri Dec 15 15:54:43 GMT 2023 , Edited by admin on Fri Dec 15 15:54:43 GMT 2023
PRIMARY
CHEBI
31562
Created by admin on Fri Dec 15 15:54:43 GMT 2023 , Edited by admin on Fri Dec 15 15:54:43 GMT 2023
PRIMARY
ECHA (EC/EINECS)
225-512-3
Created by admin on Fri Dec 15 15:54:43 GMT 2023 , Edited by admin on Fri Dec 15 15:54:43 GMT 2023
PRIMARY
FDA UNII
MUZ9585Y7B
Created by admin on Fri Dec 15 15:54:43 GMT 2023 , Edited by admin on Fri Dec 15 15:54:43 GMT 2023
PRIMARY
SMS_ID
100000092342
Created by admin on Fri Dec 15 15:54:43 GMT 2023 , Edited by admin on Fri Dec 15 15:54:43 GMT 2023
PRIMARY
CAS
4891-15-0
Created by admin on Fri Dec 15 15:54:43 GMT 2023 , Edited by admin on Fri Dec 15 15:54:43 GMT 2023
PRIMARY
DRUG BANK
DB14674
Created by admin on Fri Dec 15 15:54:43 GMT 2023 , Edited by admin on Fri Dec 15 15:54:43 GMT 2023
PRIMARY
NSC
89199
Created by admin on Fri Dec 15 15:54:43 GMT 2023 , Edited by admin on Fri Dec 15 15:54:43 GMT 2023
PRIMARY
PUBCHEM
259329
Created by admin on Fri Dec 15 15:54:43 GMT 2023 , Edited by admin on Fri Dec 15 15:54:43 GMT 2023
PRIMARY
RXCUI
105556
Created by admin on Fri Dec 15 15:54:43 GMT 2023 , Edited by admin on Fri Dec 15 15:54:43 GMT 2023
PRIMARY RxNorm
MERCK INDEX
m5031
Created by admin on Fri Dec 15 15:54:43 GMT 2023 , Edited by admin on Fri Dec 15 15:54:43 GMT 2023
PRIMARY Merck Index
DRUG CENTRAL
1066
Created by admin on Fri Dec 15 15:54:43 GMT 2023 , Edited by admin on Fri Dec 15 15:54:43 GMT 2023
PRIMARY
WIKIPEDIA
Estramustine phosphate
Created by admin on Fri Dec 15 15:54:43 GMT 2023 , Edited by admin on Fri Dec 15 15:54:43 GMT 2023
PRIMARY
CHEBI
68643
Created by admin on Fri Dec 15 15:54:43 GMT 2023 , Edited by admin on Fri Dec 15 15:54:43 GMT 2023
PRIMARY
EVMPD
SUB01969MIG
Created by admin on Fri Dec 15 15:54:43 GMT 2023 , Edited by admin on Fri Dec 15 15:54:43 GMT 2023
PRIMARY
Related Record Type Details
Structure of ESTRAMUSTINE PHOSPHATE MEGLUMINE
SALT/SOLVATE -> PARENT
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SALT/SOLVATE -> PARENT
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METABOLITE ACTIVE -> PRODRUG
Structure of ESTROMUSTINE
METABOLITE ACTIVE -> PRODRUG
Structure of ESTRAMUSTINE
METABOLITE ACTIVE -> PRODRUG
Related Record Type Details
Structure of ESTRAMUSTINE
ACTIVE MOIETY
NIH
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