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Details

Stereochemistry ABSOLUTE
Molecular Formula C23H32Cl2NO6P.C7H17NO5
Molecular Weight 715.597
Optical Activity UNSPECIFIED
Defined Stereocenters 9 / 9
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ESTRAMUSTINE PHOSPHATE MEGLUMINE

SMILES

CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.[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=XCRFEYAXJYXVHT-HLZMRHSNSA-N
InChI=1S/C23H32Cl2NO6P.C7H17NO5/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;1-8-2-4(10)6(12)7(13)5(11)3-9/h3,5,14,18-21H,2,4,6-13H2,1H3,(H2,28,29,30);4-13H,2-3H2,1H3/t18-,19-,20+,21+,23+;4-,5+,6+,7+/m10/s1

HIDE SMILES / InChI

Molecular Formula C7H17NO5
Molecular Weight 195.2136
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 4 / 4
E/Z Centers 0
Optical Activity UNSPECIFIED

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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
4.5 µM [IC50]
Target ID: P78559
Gene ID: 4130.0
Gene Symbol: MAP1A
Target Organism: Homo sapiens (Human)
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
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
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
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
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
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%
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: Page: p.1118
unhealthy, 66
n = 4
Health Status: unhealthy
Condition: Prostate cancer
Age Group: 66
Sex: M
Population Size: 4
Sources: Page: p.1118
DLT: Malaise and fatigue, Hypotension...
Dose limiting toxicities:
Malaise and fatigue (grade 3, 75%)
Hypotension (grade 3, 25%)
Sources: 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: Page: p.1119, 1124
unhealthy, 66
n = 6
Health Status: unhealthy
Condition: Prostate cancer
Age Group: 66
Sex: M
Population Size: 6
Sources: Page: p.1119, 1124
DLT: Malaise and fatigue...
Dose limiting toxicities:
Malaise and fatigue (grade 3, 40%)
Sources: 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: Page: p.1118
unhealthy, 66
n = 4
Health Status: unhealthy
Condition: Prostate cancer
Age Group: 66
Sex: M
Population Size: 4
Sources: 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: Page: p.1118
unhealthy, 66
n = 4
Health Status: unhealthy
Condition: Prostate cancer
Age Group: 66
Sex: M
Population Size: 4
Sources: 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: Page: p.1119, 1124
unhealthy, 66
n = 6
Health Status: unhealthy
Condition: Prostate cancer
Age Group: 66
Sex: M
Population Size: 6
Sources: Page: p.1119, 1124
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer

Drug as perpetrator​

Drug as perpetrator​

PubMed

PubMed

TitleDatePubMed
Regulation of Cyp1a1 induction by dioxin as a function of cell cycle phase.
2001 Nov
Combination therapy in hormone-refractory prostate cancer.
2001 Sep
Editorial: the coming revolution in the treatment of prostate cancer patients.
2002 Aug
EMP combination chemotherapy and low-dose monotherapy in advanced prostate cancer.
2002 Feb
The flare in alkaline phosphatase activity post-orchidectomy predicts which patient may benefit from early chemotherapy in metastatic prostate cancer.
2002 Feb 1
Phase I clinical and pharmacologic trial of intravenous estramustine phosphate.
2002 Feb 15
Mechanism of action of antitumor drugs that interact with microtubules and tubulin.
2002 Jan
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 Jun 5
Docetaxel (taxotere) in the treatment of prostate cancer.
2003 Jun
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

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
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 Sat Dec 16 14:32:21 GMT 2023
Edited
by admin
on Sat Dec 16 14:32:21 GMT 2023
Record UNII
C89YOK4N2S
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ESTRAMUSTINE PHOSPHATE MEGLUMINE
Common Name English
D-GLUCITOL, 1-DEOXY-1-(METHYLAMINO)-, COMPD. WITH (17.BETA.)-ESTRA-1,3,5(10),TRIENE-3,17-DIYL 3-(BIS(2-CHLOROETHYL)CARBAMATE) 17-(DIHYDROGEN PHOSPHATE) (1:1)
Systematic Name English
Estramustine meglumine phosphate [WHO-DD]
Common Name English
ESTRAMUSTINE PHOSPHATE N-METHYLGLUCAMINE SALT
Common Name English
ESTRA-1,3,5(10)-TRIENE-3,17-DIOL (17.BETA.)-, 3-(BIS(2-CHLOROETHYL)CARBAMATE) 17-(DIHYDROGEN PHOSPHATE), COMPD. WITH 1-DEOXY-1-(METHYLAMINO)-D-GLUCITOL (1:1)
Systematic Name English
ESTRAMUSTINE MEGLUMINE PHOSPHATE
Common Name English
Code System Code Type Description
FDA UNII
C89YOK4N2S
Created by admin on Sat Dec 16 14:32:21 GMT 2023 , Edited by admin on Sat Dec 16 14:32:21 GMT 2023
PRIMARY
PUBCHEM
9961838
Created by admin on Sat Dec 16 14:32:21 GMT 2023 , Edited by admin on Sat Dec 16 14:32:21 GMT 2023
PRIMARY
CAS
325726-21-4
Created by admin on Sat Dec 16 14:32:21 GMT 2023 , Edited by admin on Sat Dec 16 14:32:21 GMT 2023
PRIMARY
SMS_ID
100000170342
Created by admin on Sat Dec 16 14:32:21 GMT 2023 , Edited by admin on Sat Dec 16 14:32:21 GMT 2023
PRIMARY
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