Basic information
- Standard SMILES
C[C@]12CC[C@@H]3c4ccc(OC(=O)N(CCCl)CCCl)cc4CC[C@H]3[C@@H]1CC[C@@H]2O- InChIKey
FRPJXPJMRWBBIH-RBRWEJTLSA-N- Molecular formula
- C23H31Cl2NO3
- Average molar mass
- 440.4 g/mol
- Monoisotopic mass
- 439.16809921
Overview
Estramustine is a carbamate ester obtained by the formal condensation of the hydroxy group of 17beta-estradiol with the carboxy group of bis(2-chloroethyl)carbamic acid. It has a role as an alkylating agent, an antineoplastic agent and a radiation protective agent. It is a carbamate ester, a 17beta-hydroxy steroid and an organochlorine compound. It is functionally related to a 17beta-estradiol.
Names & identifiers
- Preferred name
- Estramustine
- IUPAC
- [(8R,9S,13S,14S,17S)-17-hydroxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-3-yl] N,N-bis(2-chloroethyl)carbamate
Names & synonyms
estramustine2998-57-4EstramustinumEstramustinaLeo-275DTXSID8046458LEO 275Leo275NSC-89201Estradiol 3-(N,N-bis(2-chloroethyl)carbamate)17beta-Estradiol 3-(bis(2-chloroethyl)carbamate)Estradiol 3-[bis(2-chloroethyl)carbamate]
Show more names
RO 21-8837Ro 22-2296/000Ro-22-2296/000[(8R,9S,13S,14S,17S)-17-hydroxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-3-yl] N,N-bis(2-chloroethyl)carbamate35LT29625AEstradiol 3-(bis(2-chloroethyl)carbamate)Ro-222296000CHEBI:4868
Database identifiers
- CAS
2998-57-4- PubChem CID
- 259331
- DTXSID
DTXSID8046458- ChEMBL
CHEMBL1575- ChEBI
CHEBI:4868- UNII
- 35LT29625A
- EC Number
- 221-076-3
- Nikkaji
- J7.659G
Properties
Computed structural properties
- XLogP
- 4
- Topological polar surface area
- 49.8 Ų
- Hydrogen bond donors
- 1
- Hydrogen bond acceptors
- 3
- Rotatable bonds
- 6
- Heavy atoms
- 29
- Formal charge
- 0
- Complexity
- 584
Experimental & physicochemical properties
DrugsPharmaceuticals -> Listed in ZINC15
LipidsLipids -> Sterol Lipids [ST] -> Steroids [ST02] -> C18 steroids (estrogens) and derivatives [ST0201]
LogP5.7
Solubility3.85e-04 g/L
Endocrine DisruptorsPotential endocrine disrupting compound
Melting Point104.5 °C
Physical DescriptionSolid
Safety & regulation
GHS classification
GHS Classification
This chemical does not meet GHS hazard criteria for 3% (1 of 33) of reports.
Danger
H351 (93.9%): Suspected of causing cancer [Warning Carcinogenicity]
P203, P280, P318, P405, and P501 (click each P-code to see the statement)
Aggregated GHS information provided per 33 reports by companies from 4 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.
Hazard information
Hazard Classes and CategoriesCarc. 2 (93.9%)
Toxicology
Drug Induced Liver Injury
Drug-Induced Liver Injury Severity and Toxicity (DILIst)
estramustine
DILI Positive
Oral
DOI:10.1016/j.drudis.2019.09.022
Chemistry & industry
Pharmacology
ATC Code
L01XX11
L - Antineoplastic and immunomodulating agents
QL - Antineoplastic and immunomodulating agents
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.
Biological Half-Life20 hours
FDA Pharmacological Classification
35LT29625A
ESTRAMUSTINE
Mechanisms of Action [MoA] - Alkylating Activity
Established Pharmacologic Class [EPC] - Alkylating Drug
Chemical Structure [CS] - Estradiol
Chemical Structure [CS] - Nitrogen Mustard Compounds
MeSH Pharmacological Classification
A class of drugs that differs from other alkylating agents used clinically in that they are monofunctional and thus unable to cross-link cellular macromolecules. Among their common properties are a requirement for metabolic activation to intermediates with antitumor efficacy and the presence in their chemical structures of N-methyl groups, that after metabolism, can covalently modify cellular DNA. The precise mechanisms by which each of these drugs acts to kill tumor cells are not completely understood. (From AMA, Drug Evaluations Annual, 1994, p2026)
Antineoplastic agents that are used to treat hormone-sensitive tumors. Hormone-sensitive tumors may be hormone-dependent, hormone-responsive, or both. A hormone-dependent tumor regresses on removal of the hormonal stimulus, by surgery or pharmacological block. Hormone-responsive tumors may regress when pharmacologic amounts of hormones are administered regardless of whether previous signs of hormone sensitivity were observed. The major hormone-responsive cancers include carcinomas of the breast, prostate, and endometrium; lymphomas; and certain leukemias. (From AMA Drug Evaluations Annual 1994, p2079)
Absorption, Distribution and ExcretionThe 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.
Cellular LocationsCytoplasm
Uses & manufacturing
UsesUse (kg; approx.) in Germany (2009): >250
Related reactions
1 records
Linked notes
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