Estramustine: Difference between revisions

Estramustine
INN
Drug class	Chemotherapeutic agent; Estrogen; Estrogen ester
Routes of administration
Pregnancy category
Bioavailability
Metabolism
Elimination half-life
Excretion
Legal status
CAS Number	2998-57-4
PubChem	259331
DrugBank
ChemSpider	227635
KEGG	D04066

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Revision as of 04:53, 1 July 2024

Chemical compound

Estramustine (INN

, USAN

, BAN

) is an estrogen and cytostatic antineoplastic agent which was never marketed.<ref name="Elks2014">,

 The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. online version, 
  
 Springer, 
  
  
  
 ISBN 978-1-4757-2085-3, 
  
  
  
 Pages: 502–,</ref><ref name="IndexNominum2000">, 
  
 Index Nominum 2000: International Drug Directory. online version, 
  
 Taylor & Francis, 
  
  
  
 ISBN 978-3-88763-075-1, 
  
  
  
 Pages: 406–,</ref> It is a carbamate derivative of estradiol and acts in part as a prodrug of estradiol in the body.<ref name="Elks2014" /><ref name="IndexNominum2000" /> Estramustine phosphate, the C17β phosphate ester of estramustine and a prodrug of estramustine, estromustine, estradiol, and estrone, is marketed and used in the treatment of prostate cancer.<ref name="Elks2014" /><ref name="IndexNominum2000" />

Synthesis

Estramustine is a carbamate derivative of the natural hormone, estradiol. The amine (ClCH₂CH₂)₂NH

is treated with phosgene to give the acid chloride of normustine. This reacts with the phenolic hydroxyl group of estradiol in the presence of a base to give estramustine.<ref>, 
 Potential anticancer agents. II. Urethan-type nitrogen mustards of some natural sex hormones, 
 Journal of Medicinal Chemistry, 
 
 Vol. 10(Issue: 2),
 pp. 172–174,
 DOI: 10.1021/jm00314a009,
 PMID: 6034059,</ref><ref>, 
 Comparative study of microtubule inhibitors--estramustine and natural podophyllotoxin conjugated PAMAM dendrimer on glioma cell proliferation, 
 European Journal of Medicinal Chemistry, 
 
 Vol. 68,
 pp. 47–57,
 DOI: 10.1016/j.ejmech.2013.07.007,
 PMID: 23954240,</ref>

References

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Most recent articles Ongoing trials	Wikipedia

@@ Line 1: / Line 1: @@
-== Estramustine: A Comprehensive Overview of its Development and Clinical Significance ==
+{{Short description|Chemical compound}}
+{{About|a non-clinically used compound|the pharmaceutical drug|Estramustine phosphate}}
+{{cs1 config|name-list-style=vanc|display-authors=6}}
+{{Drugbox
+| Verifiedfields = verified
+| Watchedfields = verified
+| verifiedrevid =
+| IUPAC_name = [(8''R'',9''S'',13''S'',14''S'',17''S'')-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
+| image = Estramustine.svg
+| alt = Skeletal formula of estramustine
+| width = 250px
+| image2 = Estramustine 3D ball.png
+| alt2 = Ball-and-stick model of the estramustine molecule
+| width2 = 250px
-'''Estramustine''' (INN, USAN, BAN) is an intriguing compound that amalgamates the therapeutic traits of an [[estrogen]] with those of a cytostatic [[antineoplastic agent]]. Its journey, albeit not leading to a commercial launch, provides crucial learnings about the nuances of prodrugs, estrogens, and drug commercialization strategy.
+<!--Clinical data-->
+| tradename = Emcyt, Estracyt
+| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
+| pregnancy_US = <!-- A / B / C / D / X -->
+| pregnancy_category =
+| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
+| legal_CA =
+| legal_UK =
+| legal_US =
+| legal_status =
+| routes_of_administration =
+| class = [[Chemotherapeutic agent]]; [[Estrogen (medication)|Estrogen]]; [[Estrogen ester]]
-=== Chemical and Pharmacological Properties ===
+<!--Pharmacokinetic data-->
+| bioavailability =
+| protein_bound =
+| metabolism =
+| elimination_half-life =
+| excretion =
-Chemically, estramustine falls under the category of [[estrogen ester]]. Specifically, it's the C3 normustine ester of [[estradiol]], a principal female sex hormone. This molecular architecture bestows it with the ability to act as a [[prodrug]] of estradiol when introduced into the human system.
+<!-- Identifiers -->
+| CAS_number_Ref = {{cascite|correct|??}}
+| CAS_number = 2998-57-4
+| CAS_supplemental =
+| ATC_prefix = L01
+| ATC_suffix = XX11
+| ATC_supplemental =
+| PubChem = 259331
+| IUPHAR_ligand =
+| DrugBank_Ref = {{drugbankcite|changed|drugbank}}
+| DrugBank =
+| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
+| ChemSpiderID = 227635
+| UNII_Ref = {{fdacite|correct|FDA}}
+| UNII = 35LT29625A
+| KEGG_Ref = {{keggcite|correct|kegg}}
+| KEGG = D04066
+| ChEBI_Ref = {{ebicite|correct|EBI}}
+| ChEBI = 4868
+| ChEMBL_Ref = {{ebicite|correct|EBI}}
+| ChEMBL = 1575
+| synonyms = EM; EaM; Leo 275; Ro 21-8837; Estradiol 3-(bis(2-chloroethyl)carbamate) ester; Estra-1,3,5(10)-triene-3,17β-diol 3-(bis(2-chloroethyl)carbamate) ester
-A prodrug is ingeniously designed such that, post-administration, it undergoes metabolic conversion to yield a pharmacologically active entity. In the scenario of estramustine, enzymatic hydrolysis cleaves its ester bond, setting estradiol free to play its physiological and therapeutic role<ref>Cassidy J, Misset JL. (2002). Oxford textbook of palliative medicine. Oxford University Press.</ref>.
+<!--Chemical data-->
+| C=23 | H=31 | Cl=2 | N=1 | O=3
+| SMILES = C[C@]12CC[C@H]3[C@H]([C@@H]1CC[C@@H]2O)CCC4=C3C=CC(=C4)OC(=O)N(CCCl)CCCl
+| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
+| StdInChI = 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
+| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
+| StdInChIKey = FRPJXPJMRWBBIH-RBRWEJTLSA-N
+}}
-=== Estramustine Phosphate: A Therapeutic Derivative ===
+'''Estramustine''' ({{abbrlink|INN|International Nonproprietary Name}}, {{abbrlink|USAN|United States Adopted Name}}, {{abbrlink|BAN|British Approved Name}}) is an [[estrogen (medication)|estrogen]] and [[cytostatic]] [[antineoplastic agent]] which was never marketed.<ref name="Elks2014">{{cite book| vauthors = Elks J |title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA502|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=502–}}</ref><ref name="IndexNominum2000">{{cite book|title=Index Nominum 2000: International Drug Directory|url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA406|date=January 2000|publisher=Taylor & Francis|isbn=978-3-88763-075-1|pages=406–}}</ref> It is a [[carbamate]] derivative of [[estradiol]] and acts in part as a [[prodrug]] of estradiol in the body.<ref name="Elks2014" /><ref name="IndexNominum2000" /> [[Estramustine phosphate]], the C17β [[phosphate]] [[ester]] of estramustine and a prodrug of estramustine, [[estromustine]], estradiol, and [[estrone (medication)|estrone]], is marketed and used in the treatment of [[prostate cancer]].<ref name="Elks2014" /><ref name="IndexNominum2000" />
+==Synthesis==
+Estramustine is a [[carbamate]] derivative of the natural hormone, [[estradiol]]. The [[amine]] {{chem2|(ClCH2CH2)2NH}} is treated with [[phosgene]] to give the [[acid chloride]] of [[normustine]]. This reacts with the [[phenol|phenolic hydroxyl group]] of estradiol in the presence of a [[base (chemistry)|base]] to give estramustine.<ref>{{cite journal | vauthors = Niculescu-Duvăz I, Cambanis A, Tărnăuceanu E | title = Potential anticancer agents. II. Urethan-type nitrogen mustards of some natural sex hormones | journal = Journal of Medicinal Chemistry | volume = 10 | issue = 2 | pages = 172–174 | date = March 1967 | pmid = 6034059 | doi = 10.1021/jm00314a009 }}</ref><ref>{{cite journal | vauthors = Sk UH, Dixit D, Sen E | title = Comparative study of microtubule inhibitors--estramustine and natural podophyllotoxin conjugated PAMAM dendrimer on glioma cell proliferation | journal = European Journal of Medicinal Chemistry | volume = 68 | pages = 47–57 | date = October 2013 | pmid = 23954240 | doi = 10.1016/j.ejmech.2013.07.007 }}</ref>
-Clinical parlance often revolves around '''estramustine phosphate''', a derivative of estramustine. Chemically, it's the C17β phosphate ester iteration of estramustine. Upon dosing, this compound metamorphoses into a prodrug for not just estramustine, but a cascade of related entities including:
+== See also ==
-* [[Estromustine]]
+* [[Estradiol mustard]]
-* [[Estradiol]]
+* [[List of hormonal cytostatic antineoplastic agents]]
-* [[Estrone]]
+* [[List of estrogen esters#Estradiol esters|List of estrogen esters § Estradiol esters]]
-Of these, while estradiol stands as a primary female sex hormone, estrone takes a backseat as a secondary one.
+== References ==
+{{Reflist}}
-In the realm of therapeutic oncology, estramustine phosphate carved a niche for itself, especially in tackling [[prostate cancer]], a malignancy that's pervasive among males. This molecule's dual-faceted estrogenic and antineoplastic armory makes it adept at multi-pronged prostate cancer cell targeting<ref>Crawford ED, Eisenberger MA, McLeod DG, et al. (1989). A controlled trial of leuprolide with and without flutamide in prostatic carcinoma. N Engl J Med; 321:419-424.</ref>.
-=== Market Dynamics and Clinical Decision-Making ===
-Although estramustine never saw a market shelf, its phosphate offshoot did become a staple in prostate cancer therapeutics. Opting for one version of a drug over another is seldom arbitrary. Such determinations hinge on a spectrum of variables:
-* Therapeutic prowess
-* Augmented pharmacokinetics
-* Fiscal feasibility in drug creation
-* Intellectual property tactics
-* The balance between efficacy and adverse effects
-These choices offer a window into the interplay of scientific investigation, patient outcomes, and the commercial pulse of the drug industry<ref>Grabowski H. (2004). Are the economics of pharmaceutical research and development changing? Productivity, patents and political pressures. Pharmacoeconomics. 22(Suppl 2):15-24.</ref>.
-=== Conclusion ===
-The narrative of estramustine and its phosphate derivative underlines the innovative spirit and strategic dexterity essential in drug R&D. Through a profound grasp of the chemistry and dynamics of compounds like these, the medical and scientific community can finetune therapeutic regimens for ailments such as prostate cancer, amplifying patient benefits.
+{{Chemotherapeutic agents}}
-== References ==
-<references />
 {{Estrogen receptor modulators}}
 {{Androgen receptor modulators}}
 [[Category:Abandoned drugs]]
 [[Category:Antiandrogens]]
@@ Line 45: / Line 88: @@
 [[Category:Carbamates]]
 [[Category:Chloroethyl compounds]]
-[[Category:Diols]]
+[[Category:Secondary alcohols]]
 [[Category:Estradiol esters]]
 [[Category:Estranes]]
@@ Line 54: / Line 97: @@
 [[Category:Nitrogen mustards]]
 [[Category:Organochlorides]]
+[[Category:Drugs developed by Pfizer]]
 {{Steroid-stub}}
 {{Antineoplastic-drug-stub}}
-{{nt}}