Chemical compound
Pharmaceutical compound
Etacstil Identifiers CAS Number PubChem CID ChemSpider UNII ChEMBL Chemical and physical data Formula C 25 H 22 O 2 Molar mass −1 3D model (JSmol ) InChI=1S/C25H22O2/c1-2-23(20-9-5-3-6-10-20)25(21-11-7-4-8-12-21)22-16-13-19(14-17-22)15-18-24(26)27/h3-18H,2H2,1H3,(H,26,27)/b18-15+,25-23-
Key:HJQQVNIORAQATK-DDJBQNAASA-N
Etacstil (developmental code namesGW-5638 ,DPC974 ) is anorally active ,nonsteroidal , combinedselective estrogen receptor modulator (SERM) andselective estrogen receptor degrader (SERD) that was developed for the treatment ofestrogen receptor -positivebreast cancer .[ 1] [ 2] [ 3] antiestrogen (tamoxifen ,aromatase inhibitor ,fulvestrant ) resistance in breast cancer by altering the shape of the estrogen receptor, thus exhibiting SERD properties.[ 4] [ 5] [ 6] [ 7] [ 8] GW-7604 ,[ 3] [ 9] [ 10] metabolite of etacstil).[ 11] tamoxifen being a prodrug ofafimoxifene (4-hydroxytamoxifen).[ 11]
Etacstil was developed in the early 1990s byDuke University ,Glaxo Wellcome , and later,Dupont .[ 12] [ 13] Bristol Myers-Squibb (BMS) acquired Dupont, and for non-scientific, corporate reasons, closed the trial and abandoned the release of etacstil and its metaboliteGW-7604 .[ 6] [ 9] [ 12]
After many dormant years, a recent resurgence of interest in SERDs has led to the development ofbrilanestrant , a structural analogue of etacstil.[ 9]
^ Kelloff GJ, Hawk ET, Sigman CC (2008-08-17).Cancer Chemoprevention: Volume 2: Strategies for Cancer Chemoprevention ISBN 9781592597680 ^ "GW 5638 Profile" .AdisInsight . Springer Nature Switzerland AG.^a b Becnel LB, Darlington YF, Orechsner S, Easton-Marks J, Watkins CA, McOwiti A, et al. "GW 5638".Nuclear Receptor Signaling Atlas .doi :10.1621/B4A9CIQ78V (inactive 15 September 2025). {{cite journal }}: CS1 maint: DOI inactive as of September 2025 (link )^ Antiestrogen GW5638 induces a unique structural change in the ER. The biological significance of this conformational change was revealed in studies that demonstrated that tamoxifen-resistant breast tumor explants are not cross-resistant to GW5638. Because of these properties, this drug is currently being developed as a potential therapeutic for tamoxifen-resistant breast cancers.Connor CE, Norris JD, Broadwater G, Willson TM, Gottardis MM,Dewhirst MW , McDonnell DP (April 2001). "Circumventing tamoxifen resistance in breast cancers using antiestrogens that induce unique conformational changes in the estrogen receptor".Cancer Research .61 (7):2917– 2922.PMID 11306468 . ^ "GW5638 uniquely alters the shape of the estrogen receptor" .The Ben May Department for Cancer Research . The University of Chicago. 2015. Archived fromthe original on 10 October 2015.^a b "Tamoxifen-like drug suggests new ways to selectively block estrogen" .The University of Chicago Medical Center . 12 May 2005. Archived fromthe original on 2018-03-27. Retrieved2016-10-25 .^ Dardes RC, O'Regan RM, Gajdos C, Robinson SP, Bentrem D, De Los Reyes A, Jordan VC (June 2002). "Effects of a new clinically relevant antiestrogen (GW5638) related to tamoxifen on breast and endometrial cancer growth in vivo".Clinical Cancer Research .8 (6):1995– 2001.PMID 12060645 . ^ Tong S, Chen Q, Shan SQ, Dewhirst MW, Yuan F (2006). "Quantitative comparison of the inhibitory effects of GW5638 and tamoxifen on angiogenesis in the cornea pocket assay".Angiogenesis .9 (2):53– 58.doi :10.1007/s10456-006-9029-x .PMID 16622786 .S2CID 35414830 . ^a b c Wardell SE, Nelson ER, Chao CA, Alley HM, McDonnell DP (October 2015)."Evaluation of the pharmacological activities of RAD1901, a selective estrogen receptor degrader" .Endocrine-Related Cancer .22 (5):713– 724.doi :10.1530/ERC-15-0287 .PMC 4545300 PMID 26162914 . ^ Bentrem D, Dardes R, Liu H, MacGregor-Schafer J, Zapf J, Jordan V (February 2001)."Molecular mechanism of action at estrogen receptor alpha of a new clinically relevant antiestrogen (GW7604) related to tamoxifen" .Endocrinology .142 (2):838– 846.doi :10.1210/endo.142.2.7932 PMID 11159857 . ^a b Bentrem D, Dardes R, Liu H, MacGregor-Schafer J, Zapf J, Jordan V (February 2001)."Molecular mechanism of action at estrogen receptor alpha of a new clinically relevant antiestrogen (GW7604) related to tamoxifen" .Endocrinology .142 (2):838– 846.doi :10.1210/endo.142.2.7932 PMID 11159857 . ^a b "Osteoporosis Drug Bazedoxifene Stops Growth Of Breast Cancer Cells" .Medical News Today . 17 June 2013. Archived fromthe original on 8 January 2014.^ Willson TM, Henke BR, Momtahen TM, Charifson PS, Batchelor KW, Lubahn DB, et al. (May 1994). "3-[4-(1,2-Diphenylbut-1-enyl)phenyl]acrylic acid: a non-steroidal estrogen with functional selectivity for bone over uterus in rats".Journal of Medicinal Chemistry .37 (11):1550– 1552.doi :10.1021/jm00037a002 .PMID 8201587 .
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
