Identification
- Summary
Estramustine is an antineoplastic agent used for the management of metastatic and/or progressive prostate cancer in palliative setting.
- Brand Names
- Emcyt
- Generic Name
- Estramustine
- DrugBank Accession Number
- DB01196
- Background
A nitrogen mustard linked to estradiol, usually as phosphate; used to treat prostatic neoplasms; also has radiation protective properties.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Estramustine (DB01196)
- Weight
- Average: 440.403
Monoisotopic: 439.168099277 - Chemical Formula
- C23H31Cl2NO3
- Synonyms
- 17β-Estradiol 3-(bis(2-chloroethyl)carbamate)
- Estradiol 3-(N,N-bis(2-chloroethyl)carbamate)
- Estramustina
- Estramustine
- Estramustinum
- External IDs
- RO 22-2296/000
Pharmacology
- Indication
For the palliative treatment of patients with metastatic and/or progressive carcinoma of the prostate
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Symptomatic treatment of Metastatic prostate cancer •••••••••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- 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.
Target Actions Organism AEstrogen receptor beta other/unknownHumans AEstrogen receptor alpha agonistHumans AMicrotubule-associated protein 2 antagonistHumans AMicrotubule-associated protein 1A antagonistHumans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
The 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.
- Half-life
20 hours
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Estramustine can be increased when it is combined with Abametapir. Abatacept The risk or severity of adverse effects can be increased when Estramustine is combined with Abatacept. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Estramustine. Adenovirus type 7 vaccine live The risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Estramustine. Aldesleukin The risk or severity of adverse effects can be increased when Aldesleukin is combined with Estramustine. - Food Interactions
- Avoid milk and dairy products.
- Take on an empty stomach.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Estramustin sodium phosphate 75F375MT2N 1227300-83-5 FRPJXPJMRWBBIH-UHFFFAOYSA-N - International/Other Brands
- Estracit / Estracyt (Pfizer)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Emcyt Capsule 140 mg Oral Pfizer Canada Ulc 1995-12-31 2020-04-30 Canada 
Emcyt Capsule 140 mg/1 Oral Pfizer Laboratories Div Pfizer Inc 1992-01-01 Not applicable US 
Emcyt Cap 140mg Capsule 140 mg Oral Kabi Pharmacia Canada Inc. 1993-12-31 1996-09-10 Canada
Categories
- ATC Codes
- L01XX11 — Estramustine
- Drug Categories
- Alkylating Activity
- Alkylating Drugs
- Antineoplastic Agents
- Antineoplastic Agents, Alkylating
- Antineoplastic Agents, Hormonal
- Antineoplastic and Immunomodulating Agents
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Estradiol Congeners
- Estranes
- Estrenes
- Fused-Ring Compounds
- Hydrocarbons, Halogenated
- Immunosuppressive Agents
- Mustard Compounds
- Nitrogen Mustard Compounds
- Noxae
- P-glycoprotein inhibitors
- Steroids
- Toxic Actions
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as estrane steroids. These are steroids with a structure based on the estrane skeleton.
- Kingdom
- Organic compounds
- Super Class
- Lipids and lipid-like molecules
- Class
- Steroids and steroid derivatives
- Sub Class
- Estrane steroids
- Direct Parent
- Estrane steroids
- Alternative Parents
- 17-hydroxysteroids / Phenanthrenes and derivatives / Tetralins / Nitrogen mustard compounds / Carbamate esters / Secondary alcohols / Organic carbonic acids and derivatives / Cyclic alcohols and derivatives / Organopnictogen compounds / Organochlorides show 4 more
- Substituents
- 17-hydroxysteroid / Alcohol / Alkyl chloride / Alkyl halide / Aromatic homopolycyclic compound / Benzenoid / Carbamic acid ester / Carbonic acid derivative / Carbonyl group / Cyclic alcohol show 15 more
- Molecular Framework
- Aromatic homopolycyclic compounds
- External Descriptors
- carbamate ester, organochlorine compound, 17beta-hydroxy steroid (CHEBI:4868) / C18 steroids (estrogens) and derivatives, Estrane and derivatives (C11228) / C18 steroids (estrogens) and derivatives (LMST02010038)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 35LT29625A
- CAS number
- 2998-57-4
- InChI Key
- FRPJXPJMRWBBIH-RBRWEJTLSA-N
- InChI
- 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
- IUPAC Name
- (1S,3aS,3bR,9bS,11aS)-1-hydroxy-11a-methyl-1H,2H,3H,3aH,3bH,4H,5H,9bH,10H,11H,11aH-cyclopenta[a]phenanthren-7-yl N,N-bis(2-chloroethyl)carbamate
- SMILES
- [H][C@@]12CC[C@H](O)[C@@]1(C)CC[C@]1([H])C3=CC=C(OC(=O)N(CCCl)CCCl)C=C3CC[C@@]21[H]
References
- Synthesis Reference
Fex, H.J., Hogtierg, K.B., Konyves, I. and Kneip, P.H.0.L; U.S. Patent 3,299,104; Jan. 17, 1967; assigned to Leo AB, Sweden.
US3299104- General References
- Not Available
- External Links
- Human Metabolome Database
- HMDB0015327
- KEGG Drug
- D04066
- KEGG Compound
- C11228
- PubChem Compound
- 259331
- PubChem Substance
- 46508765
- ChemSpider
- 227635
- BindingDB
- 50333646
- 4089
- ChEBI
- 4868
- ChEMBL
- CHEMBL1575
- ZINC
- ZINC000004099032
- Therapeutic Targets Database
- DAP001307
- PharmGKB
- PA449507
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Estramustine
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 3 Completed Treatment Prostate Cancer 6 3 Terminated Treatment Neoplasms of the Prostate 1 3 Terminated Treatment Prostate Cancer 1 2 Active Not Recruiting Treatment Prostate Cancer 1 2 Completed Treatment Adenocarcinoma of Prostate 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Pfizer Inc.
- Pharmaceutical Utilization Management Program VA Inc.
- Pharmacia Inc.
- Dosage Forms
Form Route Strength Capsule Oral 140 mg/1 Injection Capsule Oral 140 mg Capsule Oral 280 MG - Prices
Unit description Cost Unit Emcyt 140 mg capsule 6.55USD capsule DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 155 Fex, H.J., Hogtierg, K.B., Konyves, I. and Kneip, P.H.0.L; U.S. Patent 3,299,104; Jan. 17, 1967; assigned to Leo AB, Sweden. logP 5.7 Not Available - Predicted Properties
Property Value Source Water Solubility 0.000385 mg/mL ALOGPS logP 4.97 ALOGPS logP 5.1 Chemaxon logS -6.1 ALOGPS pKa (Strongest Acidic) 19.38 Chemaxon pKa (Strongest Basic) -0.88 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 49.77 Å2 Chemaxon Rotatable Bond Count 6 Chemaxon Refractivity 116.21 m3·mol-1 Chemaxon Polarizability 47.96 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 1.0 Blood Brain Barrier + 0.9675 Caco-2 permeable + 0.6013 P-glycoprotein substrate Substrate 0.7382 P-glycoprotein inhibitor I Inhibitor 0.5927 P-glycoprotein inhibitor II Non-inhibitor 0.6317 Renal organic cation transporter Non-inhibitor 0.5918 CYP450 2C9 substrate Non-substrate 0.6261 CYP450 2D6 substrate Non-substrate 0.6491 CYP450 3A4 substrate Substrate 0.8003 CYP450 1A2 substrate Non-inhibitor 0.6214 CYP450 2C9 inhibitor Non-inhibitor 0.6944 CYP450 2D6 inhibitor Non-inhibitor 0.6079 CYP450 2C19 inhibitor Inhibitor 0.5464 CYP450 3A4 inhibitor Inhibitor 0.8479 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.62 Ames test Non AMES toxic 0.6062 Carcinogenicity Non-carcinogens 0.8508 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.7844 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.8235 hERG inhibition (predictor II) Non-inhibitor 0.6818
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-0006-7427900000-b87366cc1573c4f6c93a Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-059f-0062900000-7732505ed2c4ddfc2e9a Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0080-7080900000-16c7f340cca0241253a6 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-03di-2309200000-633a3f5b2db3dc295a4a Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-001i-9010000000-8a40e88acb0be9333e96 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-001i-9010000000-4d6ede9e4b51285e4b79 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-08fr-6911100000-30347cc7b68aac2dea2b Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 212.2800117 predictedDarkChem Lite v0.1.0 [M-H]- 200.82138 predictedDeepCCS 1.0 (2019) [M+H]+ 212.6263117 predictedDarkChem Lite v0.1.0 [M+H]+ 203.21696 predictedDeepCCS 1.0 (2019) [M+Na]+ 212.5248117 predictedDarkChem Lite v0.1.0 [M+Na]+ 209.12947 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Other/unknown
- General Function
- Zinc ion binding
- Specific Function
- Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent m...
- Gene Name
- ESR2
- Uniprot ID
- Q92731
- Uniprot Name
- Estrogen receptor beta
- Molecular Weight
- 59215.765 Da
References
- Ho SM: Estrogens and anti-estrogens: key mediators of prostate carcinogenesis and new therapeutic candidates. J Cell Biochem. 2004 Feb 15;91(3):491-503. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Zinc ion binding
- Specific Function
- Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissu...
- Gene Name
- ESR1
- Uniprot ID
- P03372
- Uniprot Name
- Estrogen receptor
- Molecular Weight
- 66215.45 Da
References
- Ferno M, Borg A, Ingvar C, Jonsson PE: Estrogen receptor and binding site for estramustine in metastatic malignant melanoma. Anticancer Res. 1987 Jul-Aug;7(4B):741-3. [Article]
- Yoshizumi N: [The effects of site-directed chemotherapy due to E2 as a drug carrier to the human endometrial adenocarcinoma cells in vitro]. Nihon Sanka Fujinka Gakkai Zasshi. 1985 Apr;37(4):637-45. [Article]
- von Schoultz E, Carlstrom K, Henriksson R, Lagerlof B, Hansson J: Estramustine binding protein in primary tumours and metastases of malignant melanoma. Melanoma Res. 1994 Dec;4(6):401-5. [Article]
- Tew KD: The mechanism of action of estramustine. Semin Oncol. 1983 Sep;10(3 Suppl 3):21-6. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Structural molecule activity
- Specific Function
- The exact function of MAP2 is unknown but MAPs may stabilize the microtubules against depolymerization. They also seem to have a stiffening effect on microtubules.
- Gene Name
- MAP2
- Uniprot ID
- P11137
- Uniprot Name
- Microtubule-associated protein 2
- Molecular Weight
- 199524.51 Da
References
- Moraga D, Rivas-Berrios A, Farias G, Wallin M, Maccioni RB: Estramustine-phosphate binds to a tubulin binding domain on microtubule-associated proteins MAP-2 and tau. Biochim Biophys Acta. 1992 May 22;1121(1-2):97-103. [Article]
- Stearns ME, Wang M, Sousa O: Evidence that estramustine binds MAP-1A to inhibit type IV collagenase secretion. J Cell Sci. 1991 Jan;98 ( Pt 1):55-63. [Article]
- Friden B, Rutberg M, Deinum J, Wallin M: The effect of estramustine derivatives on microtubule assembly in vitro depends on the charge of the substituent. Biochem Pharmacol. 1991 Aug 8;42(5):997-1006. [Article]
- Burns RG: Stoichiometry of estramustine phosphate binding to MAP2 measured by the disassembly of chick brain MAP2:tubulin microtubules. Cell Motil Cytoskeleton. 1990;17(3):167-73. [Article]
- Falconer MM, Vielkind U, Brown DL: Association of acetylated microtubules, vimentin intermediate filaments, and MAP 2 during early neural differentiation in EC cell culture. Biochem Cell Biol. 1989 Sep;67(9):537-44. [Article]
- Tew KD: The mechanism of action of estramustine. Semin Oncol. 1983 Sep;10(3 Suppl 3):21-6. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Structural molecule activity
- Specific Function
- Structural protein involved in the filamentous cross-bridging between microtubules and other skeletal elements.
- Gene Name
- MAP1A
- Uniprot ID
- P78559
- Uniprot Name
- Microtubule-associated protein 1A
- Molecular Weight
- 305482.26 Da
References
- Stearns ME, Wang M, Sousa O: Evidence that estramustine binds MAP-1A to inhibit type IV collagenase secretion. J Cell Sci. 1991 Jan;98 ( Pt 1):55-63. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Kelly WK, Zhu AX, Scher H, Curley T, Fallon M, Slovin S, Schwartz L, Larson S, Tong W, Hartley-Asp B, Pellizzoni C, Rocchetti M: Dose escalation study of intravenous estramustine phosphate in combination with Paclitaxel and Carboplatin in patients with advanced prostate cancer. Clin Cancer Res. 2003 Jun;9(6):2098-107. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- Multidrug resistance protein 1
- Molecular Weight
- 141477.255 Da
References
- Yang CP, Shen HJ, Horwitz SB: Modulation of the function of P-glycoprotein by estramustine. J Natl Cancer Inst. 1994 May 4;86(9):723-5. [Article]
- Tiersten AD, Nelsen C, Talbot S, Vahdat L, Fine R, Troxel A, Brafman L, Shriberg L, Antman K, Petrylak DP: A phase II trial of docetaxel and estramustine in patients with refractory metastatic breast carcinoma. Cancer. 2003 Feb 1;97(3):537-44. [Article]
- Smith CD, Zilfou JT, Zhang X, Hudes GR, Tew KD: Modulation of P-glycoprotein activity by estramustine is limited by binding to plasma proteins. Cancer. 1995 May 15;75(10):2597-604. [Article]
- Speicher LA, Barone LR, Chapman AE, Hudes GR, Laing N, Smith CD, Tew KD: P-glycoprotein binding and modulation of the multidrug-resistant phenotype by estramustine. J Natl Cancer Inst. 1994 May 4;86(9):688-94. [Article]
Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:54