Tamoxifen , a triphenylethylene derivative and the most well-known and widely used SERM.This is a list ofselective estrogen receptor modulators (SERMs).
SERMs that have been approved for medical use includeanordrin (+mifepristone (Zi Yun)),bazedoxifene (+conjugated estrogens (Duavee)),broparestrol (Acnestrol),clomifene (Clomid),cyclofenil (Sexovid),lasofoxifene (Fablyn),ormeloxifene (Centron, Novex, Novex-DS, Sevista),ospemifene (Osphena; deaminohydroxytoremifene),raloxifene (Evista),tamoxifen (Nolvadex), andtoremifene (Fareston; 4-chlorotamoxifen).[ 1]
SERMs that are currently under development and in clinical trials includeacolbifene ,afimoxifene (4-hydroxytamoxifen; metabolite of tamoxifen),elacestrant ,enclomifene ((E )-clomifene),endoxifen (4-hydroxy-N -desmethyltamoxifen; metabolite of tamoxifen), andzuclomifene ((Z )-clomifene).[ 2]
SERMs that have not been approved for medical use includearzoxifene ,brilanestrant ,clomifenoxide (clomiphene N-oxide; metabolite of clomifene),[ 3] droloxifene (3-hydroxytamoxifen),etacstil ,fispemifene ,GW-7604 (4-hydroxyetacstil; metabolite of etacstil),idoxifene (pyrrolidino-4-iodotamoxifen),levormeloxifene ((L )-ormeloxifene),miproxifene ,nafoxidine ,nitromifene (CI-628),NNC 45-0095 ,panomifene ,pipendoxifene (ERA-923),trioxifene , andzindoxifene (D-16726).[ 4] [ 1] [ 5] [ 6] [ 7]
Sivifene (A-007) was initially thought to be a SERM due to its structural similarity to tamoxifen but it was subsequently found not to bind to theestrogen receptor (ER).[ 8] Tesmilifene (DPPE; YMB-1002, BMS-217380-01) is also structurally related to tamoxifen but similarly does not bind to the ER and is not a SERM.[ 9] [ 10]
SERMs can be variously classifiedstructurally astriphenylethylenes (tamoxifen, clomifene, toremifene, droloxifene, idoxifene, ospemifene, fispemifene, afimoxifene, others),benzothiophenes (raloxifene, arzoxifene),indoles (bazedoxifene, zindoxifene, pipendoxifene),tetrahydronaphthalenes (lasofoxifene, nafoxidine), andbenzopyrans (acolbifene, ormeloxifene, levormeloxifene).[ 11] [ 12] [ 13]
^a b Pinkerton, JoAnn V.; Thomas, Semara (2014). "Use of SERMs for treatment in postmenopausal women".The Journal of Steroid Biochemistry and Molecular Biology .142 :142– 154.doi :10.1016/j.jsbmb.2013.12.011 .ISSN 0960-0760 .PMID 24373794 .S2CID 24196362 . ^ "Home - AdisInsight" .adisinsight.springer.com .^ Analytical Profiles of Drug Substances and Excipients 112– 113.ISBN 978-0-08-086120-3 ^ World Health Organization (2013),The use of stems in the selection of International Nonproprietary Names (INN)for pharmaceutical substances (PDF) ^ J. Elks (14 November 2014).The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies ISBN 978-1-4757-2085-3 ^ I.K. Morton; Judith M. Hall (6 December 2012).Concise Dictionary of Pharmacological Agents: Properties and Synonyms ISBN 978-94-011-4439-1 ^ Taylor, Hugh S. (2009)."Designing the ideal selective estrogen receptor modulator-an achievable goal?" .Menopause .16 (3):609– 615.doi :10.1097/gme.0b013e3181906fa3 .ISSN 1072-3714 .PMC 3107842 PMID 19182697 . ^ Eilender, David; LoRusso, Patricia; Thomas, Leonard; McCormick, Catherine; Rodgers, Andrew H.; Hooper, Catherine L.; Tornyos, Karl; Krementz, Edward T.; Parker, Steven; Morgan, Lee Roy (2005). "4,4′-Dihydroxybenzophenone-2,4-dinitrophenylhydrazone (A-007): a topical treatment for cutaneous metastases from malignant cancers".Cancer Chemotherapy and Pharmacology .57 (6):719– 726.doi :10.1007/s00280-005-0124-2 .ISSN 0344-5704 .PMID 16184382 .S2CID 10830366 . ^ Brandes LJ (2008)."N,N-diethyl-2-[4-(phenylmethyl) phenoxy] ethanamine (DPPE; tesmilifene), a chemopotentiating agent with hormetic effects on DNA synthesis in vitro, may improve survival in patients with metastatic breast cancer" .Hum Exp Toxicol .27 (2):143– 7.doi :10.1177/0960327108090751 PMID 18480139 .S2CID 20966915 . ^ Brandes LJ, Hermonat MW (1984). "A diphenylmethane derivative specific for the antiestrogen binding site found in rat liver microsomes".Biochem. Biophys. Res. Commun .123 (2):724– 8.doi :10.1016/0006-291x(84)90289-4 .PMID 6548377 . ^ John P. Bilezikian; Lawrence G. Raisz; T. John Martin (29 September 2008).Principles of Bone Biology ISBN 978-0-08-056875-1 ^ Stuart Silverman; Bo Abrahamsen (29 December 2015).The Duration and Safety of Osteoporosis Treatment: Anabolic and Antiresorptive Therapy ISBN 978-3-319-23639-1 ^ Atta-ur Rahman; Khurshid Zaman (28 November 2014).Topics in Anti-Cancer Research 559– 565.ISBN 978-1-60805-908-9
Estrogens
ER Tooltip Estrogen receptor agonistsSteroidal: Alfatradiol Certainandrogens /anabolic steroids (e.g.,testosterone ,testosterone esters ,methyltestosterone ,metandienone ,nandrolone esters ) (via estrogenic metabolites) Certainprogestins (e.g.,norethisterone ,noretynodrel ,etynodiol diacetate ,tibolone ) Clomestrone Cloxestradiol acetate Conjugated estriol Conjugated estrogens Epiestriol Epimestrol Esterified estrogens Estetrol † Estradiol Estradiol esters (e.g.,estradiol acetate ,estradiol benzoate ,estradiol cypionate ,estradiol enanthate ,estradiol undecylate ,estradiol valerate ,polyestradiol phosphate ,estradiol ester mixtures (Climacteron ))Estramustine phosphate Estriol Estriol esters (e.g.,estriol succinate ,polyestriol phosphate )Estrogenic substances Estrone Estrone esters Ethinylestradiol # Hydroxyestrone diacetate Mestranol Methylestradiol Moxestrol Nilestriol Prasterone (dehydroepiandrosterone; DHEA) Promestriene Quinestradol Quinestrol Progonadotropins
Antiestrogens
ER Tooltip Estrogen receptor antagonistsSERMs Tooltip selective estrogen receptor modulators /SERDs Tooltip selective estrogen receptor downregulators )Aromatase inhibitors Antigonadotropins Androgens /anabolic steroids (e.g.,testosterone ,testosterone esters ,nandrolone esters ,oxandrolone ,fluoxymesterone )D2 receptor antagonists (prolactin releasers) (e.g.,domperidone ,metoclopramide ,risperidone ,haloperidol ,chlorpromazine ,sulpiride )GnRH agonists (e.g.,leuprorelin ,goserelin )GnRH antagonists (e.g.,cetrorelix ,elagolix )Progestogens (e.g.,chlormadinone acetate ,cyproterone acetate ,gestonorone caproate ,hydroxyprogesterone caproate ,medroxyprogesterone acetate ,megestrol acetate )Others
ER Tooltip Estrogen receptor
Agonists Steroidal: 2-Hydroxyestradiol 2-Hydroxyestrone 3-Methyl-19-methyleneandrosta-3,5-dien-17β-ol 3α-Androstanediol 3α,5α-Dihydrolevonorgestrel 3β,5α-Dihydrolevonorgestrel 3α-Hydroxytibolone 3β-Hydroxytibolone 3β-Androstanediol 4-Androstenediol 4-Androstenedione 4-Fluoroestradiol 4-Hydroxyestradiol 4-Hydroxyestrone 4-Methoxyestradiol 4-Methoxyestrone 5-Androstenediol 7-Oxo-DHEA 7α-Hydroxy-DHEA 7α-Methylestradiol 7β-Hydroxyepiandrosterone 8,9-Dehydroestradiol 8,9-Dehydroestrone 8β-VE2 10β,17β-Dihydroxyestra-1,4-dien-3-one (DHED) 11β-Chloromethylestradiol 11β-Methoxyestradiol 15α-Hydroxyestradiol 16-Ketoestradiol 16-Ketoestrone 16α-Fluoroestradiol 16α-Hydroxy-DHEA 16α-Hydroxyestrone 16α-Iodoestradiol 16α-LE2 16β-Hydroxyestrone 16β,17α-Epiestriol (16β-hydroxy-17α-estradiol) 17α-Estradiol (alfatradiol )17α-Dihydroequilenin 17α-Dihydroequilin 17α-Epiestriol (16α-hydroxy-17α-estradiol) 17α-Ethynyl-3α-androstanediol 17α-Ethynyl-3β-androstanediol 17β-Dihydroequilenin 17β-Dihydroequilin 17β-Methyl-17α-dihydroequilenin Abiraterone Abiraterone acetate Alestramustine Almestrone Anabolic steroids (e.g.,testosterone andesters ,methyltestosterone ,metandienone (methandrostenolone) ,nandrolone andesters , many others; via estrogenic metabolites)Atrimustine Bolandiol Bolandiol dipropionate Butolame Clomestrone Cloxestradiol Conjugated estriol Conjugated estrogens Cyclodiol Cyclotriol DHEA DHEA-S ent -EstradiolEpiestriol (16β-epiestriol, 16β-hydroxy-17β-estradiol) Epimestrol Equilenin Equilin ERA-63 (ORG-37663) Esterified estrogens Estetrol Estradiol Estramustine Estramustine phosphate Estrapronicate Estrazinol Estriol Estrofurate Estrogenic substances Estromustine Estrone Etamestrol (eptamestrol) Ethinylandrostenediol Ethinylestradiol Ethinylestriol Ethylestradiol Etynodiol Etynodiol diacetate Hexolame Hippulin Hydroxyestrone diacetate Lynestrenol Lynestrenol phenylpropionate Mestranol Methylestradiol Moxestrol Mytatrienediol Nilestriol Norethisterone Noretynodrel Orestrate Pentolame Prodiame Prolame Promestriene RU-16117 Quinestradol Quinestrol Tibolone Xenoestrogens: Anise -related (e.g.,anethole ,anol ,dianethole ,dianol ,photoanethole )Chalconoids (e.g.,isoliquiritigenin ,phloretin ,phlorizin (phloridzin) ,wedelolactone )Coumestans (e.g.,coumestrol ,psoralidin )Flavonoids (incl.7,8-DHF ,8-prenylnaringenin ,apigenin ,baicalein ,baicalin ,biochanin A ,calycosin ,catechin ,daidzein ,daidzin ,ECG ,EGCG ,epicatechin ,equol ,formononetin ,glabrene ,glabridin ,genistein ,genistin ,glycitein ,kaempferol ,liquiritigenin ,mirificin ,myricetin ,naringenin ,penduletin ,pinocembrin ,prunetin ,puerarin ,quercetin ,tectoridin ,tectorigenin )Lavender oil Lignans (e.g.,enterodiol ,enterolactone ,nyasol (cis -hinokiresinol) )Metalloestrogens (e.g.,cadmium )Pesticides (e.g.,alternariol ,dieldrin ,endosulfan ,fenarimol ,HPTE ,methiocarb ,methoxychlor ,triclocarban ,triclosan )Phytosteroids (e.g.,digitoxin (digitalis ),diosgenin ,guggulsterone )Phytosterols (e.g.,β-sitosterol ,campesterol ,stigmasterol )Resorcylic acid lactones (e.g.,zearalanone ,α-zearalenol ,β-zearalenol ,zearalenone ,zeranol (α-zearalanol) ,taleranol (teranol, β-zearalanol) )Steroid -like (e.g.,deoxymiroestrol ,miroestrol )Stilbenoids (e.g.,resveratrol ,rhaponticin )Synthetic xenoestrogens (e.g.,alkylphenols ,bisphenols (e.g.,BPA ,BPF ,BPS ),DDT ,parabens ,PBBs ,PHBA ,phthalates ,PCBs )Others (e.g.,agnuside ,rotundifuran ) MixedSERMs Tooltip Selective estrogen receptor modulators ) Antagonists Coregulator-binding modulators: ERX-11
GPER Tooltip G protein-coupled estrogen receptor
Agonists Antagonists Unknown
