Editing Antiandrogen (section)

===Androgen receptor antagonists===
{| class="wikitable sortable floatright"
|+ Antiandrogens at steroid hormone receptors
|-
! rowspan="2" | {{No selflink|Antiandrogen}} || colspan="5" | Relative binding affinities
|-
! {{abbrlink|AR|Androgen receptor}} || {{abbrlink|PR|Progesterone receptor}} || {{abbrlink|ER|Estrogen receptor}} || {{abbrlink|GR|Glucocorticoid receptor}} || {{abbrlink|MR|Mineralocorticoid receptor}}
|-
| {{No selflink|Cyproterone acetate}} || 8–10 || 60 || <0.1 || 5 || 1
|-
| {{No selflink|Chlormadinone acetate}} || 5 || 175 || <0.1 || 38 || 1
|-
| {{No selflink|Megestrol acetate}} || 5 || 152 || <0.1 || 50 || 3
|-
| {{No selflink|Spironolactone}} || 7<!--26 for 30 min--> || 0.4<sup>a</sup> || <0.1 || 2<sup>a</sup> || 182
|-
| {{No selflink|Trimethyltrienolone}} || 3.6 || <1 || <1 || <1 || <1
|-
| {{No selflink|Inocoterone}} || 0.8 || <0.1 || <0.1 || <0.1 || <0.1
|-
| {{No selflink|Inocoterone acetate}} || <0.1 || <0.1 || <0.1 || <0.1 || <0.1
|-
| {{No selflink|Flutamide}} || <0.1 || <0.1 || <0.1 || <0.1 || <0.1
|-
| {{No selflink|Hydroxyflutamide}} || 0.5–0.8 || <0.1 || <0.1 || <0.1 || <0.1
|-
| {{No selflink|Nilutamide}} || 0.5–0.8 || <0.1 || <0.1 || <0.1 || <0.1
|-
| {{No selflink|Bicalutamide}} || 1.8 || <0.1 || <0.1 || <0.1 || <0.1
|- class="sortbottom"
| colspan="6" style="width: 1px; background-color:#eaecf0; text-align: center;" | <small>'''Notes:''' (1): Reference [[ligand (biochemistry)|ligand]]s (100%) were [[testosterone (medication)|testosterone]] for the {{abbrlink|AR|androgen receptor}}, [[progesterone (medication)|progesterone]] for the {{abbrlink|PR|progesterone receptor}}, [[estradiol (medication)|estradiol]] for the {{abbrlink|ER|estrogen receptor}}, [[dexamethasone]] for the {{abbrlink|GR|glucocorticoid receptor}}, and [[aldosterone]] for the {{abbrlink|MR|mineralocorticoid receptor}}. (2): Tissues were rat prostate (AR), rabbit uterus (PR), mouse uterus (ER), rat thymus (GR), and rat kidney (MR). (3): Incubation times (0&nbsp;°C) were 24 hours (AR, <sup>a</sup>), 2 hours (PR, ER), 4 hours (GR), and 1 hour (MR). (4): Assay methods were different for bicalutamide for receptors besides the AR. '''Sources:'''<ref name="pmid3059062">{{cite journal | vauthors = Moguilewsky M, Bouton MM | title = How the study of the biological activities of antiandrogens can be oriented towards the clinic | journal = Journal of Steroid Biochemistry | volume = 31 | issue = 4B | pages = 699–710 | date = October 1988 | pmid = 3059062 | doi = 10.1016/0022-4731(88)90021-0 }}</ref><ref name="pmid1992602">{{cite journal | vauthors = Gaillard-Moguilewsky M | title = Pharmacology of antiandrogens and value of combining androgen suppression with antiandrogen therapy | journal = Urology | volume = 37 | issue = 2 Suppl | pages = 5–12 | date = 1991 | pmid = 1992602 | doi = 10.1016/0090-4295(91)80095-O }}</ref><ref name="pmid3009970">{{cite journal | vauthors = Moguilewsky M, Fiet J, Tournemine C, Raynaud JP | title = Pharmacology of an antiandrogen, anandron, used as an adjuvant therapy in the treatment of prostate cancer | journal = Journal of Steroid Biochemistry | volume = 24 | issue = 1 | pages = 139–46 | date = January 1986 | pmid = 3009970 | doi = 10.1016/0022-4731(86)90043-9 }}</ref><ref name="pmid8136296">{{cite journal | vauthors = Teutsch G, Goubet F, Battmann T, Bonfils A, Bouchoux F, Cerede E, Gofflo D, Gaillard-Kelly M, Philibert D | title = Non-steroidal antiandrogens: synthesis and biological profile of high-affinity ligands for the androgen receptor | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 48 | issue = 1 | pages = 111–9 | date = January 1994 | pmid = 8136296 | doi = 10.1016/0960-0760(94)90257-7 | s2cid = 31404295 }}</ref><ref name="RaynaudFortin1986">{{cite book| vauthors = Raynaud JP, Fortin M, Hunt P, Ojasoo T, Doré JC, Surcouf E, Mornon JP | veditors = Gotto AM, O'Malley BW, Liliane FP |chapter=Approaches to drug development using receptors|title=The Role of Receptors in Biology and Medicine: Proceedings of the Ninth Argenteuil Symposium|url=https://books.google.com/books?id=ORFrAAAAMAAJ|year=1986|publisher=Raven Press|isbn=978-0-88167-161-2|pages=65–77}}</ref><ref name="RaynaudOjasoo1981">{{cite book| vauthors = Raynaud JP, Ojasoo T, Labrie F |title=Mechanisms of Steroid Action|chapter=Steroid hormones—agonists and antagonists|year=1981|pages=145–158|publisher=Macmillan Education UK |doi=10.1007/978-1-349-81345-2_11|isbn=978-1-349-81347-6}}</ref><ref name="pmid7421203">{{cite journal | vauthors = Raynaud JP, Bouton MM, Moguilewsky M, Ojasoo T, Philibert D, Beck G, Labrie F, Mornon JP | title = Steroid hormone receptors and pharmacology | journal = Journal of Steroid Biochemistry | volume = 12 | pages = 143–57 | date = January 1980 | pmid = 7421203 | doi = 10.1016/0022-4731(80)90264-2 }}</ref><ref name="pmid359134">{{cite journal | vauthors = Ojasoo T, Raynaud JP | title = Unique steroid congeners for receptor studies | journal = Cancer Research | volume = 38 | issue = 11 Pt 2 | pages = 4186–98 | date = November 1978 | pmid = 359134 | url = http://cancerres.aacrjournals.org/content/38/11_Part_2/4186.short | access-date = 2021-10-31 | archive-date = 2020-11-27 | archive-url = https://web.archive.org/web/20201127182040/https://cancerres.aacrjournals.org/content/38/11_Part_2/4186.short | url-status = live }}</ref><ref name="pmid171505">{{cite journal | vauthors = Raynaud JP, Bonne C, Bouton MM, Moguilewsky M, Philibert D, Azadian-Boulanger G | title = Screening for anti-hormones by receptor studies | journal = Journal of Steroid Biochemistry | volume = 6 | issue = 5 | pages = 615–22 | date = May 1975 | pmid = 171505 | doi = 10.1016/0022-4731(75)90042-4 }}</ref><ref name="pmid14600402">{{cite journal | vauthors = Hanada K, Furuya K, Yamamoto N, Nejishima H, Ichikawa K, Nakamura T, Miyakawa M, Amano S, Sumita Y, Oguro N | title = Bone anabolic effects of S-40503, a novel nonsteroidal selective androgen receptor modulator (SARM), in rat models of osteoporosis | journal = Biol. Pharm. Bull. | volume = 26 | issue = 11 | pages = 1563–9 | date = November 2003 | pmid = 14600402 | doi = 10.1248/bpb.26.1563 | doi-access = free }}</ref></small>
|}
{{Relative potencies of selected antiandrogens in rats}}

AR antagonists act by directly binding to and competitively displacing androgens like testosterone and DHT from the AR, thereby preventing them from activating the receptor and mediating their biological effects.<ref name="pmid10637363" /><ref name="ShenTaplin2010" /> AR antagonists are classified into two types, based on [[chemical structure]]: steroidal and nonsteroidal.<ref name="SchröderRadlmaier2009" /><ref name="KolvenbagFurr2009" /><ref name="pmid10637363" /><ref name="ShenTaplin2010" /><ref name="LemkeWilliams2012">{{cite book| vauthors = Lemke TL, Williams DA |title=Foye's Principles of Medicinal Chemistry|url=https://books.google.com/books?id=Sd6ot9ul-bUC&pg=PA1372|date=24 January 2012|publisher=Lippincott Williams & Wilkins|isbn=978-1-60913-345-0|pages=228–231, 1371–1372}}</ref> Steroidal AR antagonists are structurally related to [[steroid hormone]]s like testosterone and [[progesterone]], whereas nonsteroidal AR antagonists are not steroids and are structurally distinct. Steroidal AR antagonists tend to have [[off-target activity|off-target hormonal actions]] due to their structural similarity to other steroid hormones.<ref name="LemkeWilliams2012" /> In contrast, nonsteroidal AR antagonists are selective for the AR and have no off-target hormonal activity.<ref name="LemkeWilliams2012" /> For this reason, they are sometimes described as "pure" antiandrogens.<ref name="LemkeWilliams2012" />

Although they are described as antiandrogens and indeed show only such effects generally, most or all steroidal AR antagonists are actually not [[silent antagonist]]s of the AR but rather are weak [[partial agonist]]s and are able to activate the receptor in the absence of more potent AR agonists like testosterone and DHT.<ref name="pmid10637363" /><ref name="FiggChau2010" /><ref name="PoyetLabrie1985">{{cite journal | vauthors = Poyet P, Labrie F | title = Comparison of the antiandrogenic/androgenic activities of flutamide, cyproterone acetate and megestrol acetate | journal = Molecular and Cellular Endocrinology | volume = 42 | issue = 3 | pages = 283–8 | date = October 1985 | pmid = 3930312 | doi = 10.1016/0303-7207(85)90059-0 | s2cid = 24746807 }}</ref><ref name="pmid2462135">{{cite journal | vauthors = Luthy IA, Begin DJ, Labrie F | title = Androgenic activity of synthetic progestins and spironolactone in androgen-sensitive mouse mammary carcinoma (Shionogi) cells in culture | journal = Journal of Steroid Biochemistry | volume = 31 | issue = 5 | pages = 845–52 | year = 1988 | pmid = 2462135 | doi = 10.1016/0022-4731(88)90295-6}}</ref> This may have clinical implications in the specific context of prostate cancer treatment.<ref name="pmid10637363" /><ref name="PoyetLabrie1985" /> As an example, steroidal AR antagonists are able to increase prostate weight and accelerate prostate cancer cell growth in the absence of more potent AR agonists,<ref name="pmid10637363" /><ref name="PoyetLabrie1985" /> and spironolactone has been found to accelerate progression of prostate cancer in case reports.<ref name="pmid22665559">{{cite journal | vauthors = Sundar S, Dickinson PD | title = Spironolactone, a possible selective androgen receptor modulator, should be used with caution in patients with metastatic carcinoma of the prostate | journal = BMJ Case Rep | volume = 2012 | pages = bcr1120115238| year = 2012 | pmid = 22665559 | pmc = 3291010 | doi = 10.1136/bcr.11.2011.5238 }}</ref><ref name="pmid27641657">{{cite journal | vauthors = Flynn T, Guancial EA, Kilari M, Kilari D | title = Case Report: Spironolactone Withdrawal Associated With a Dramatic Response in a Patient With Metastatic Castrate-Resistant Prostate Cancer | journal = Clin Genitourin Cancer | volume = 15| issue = 1| pages = e95–e97| year = 2016 | pmid = 27641657 | doi = 10.1016/j.clgc.2016.08.006 | s2cid = 38441469 }}</ref> In addition, whereas cyproterone acetate produces ambiguous genitalia via feminization in male fetuses when administered to pregnant animals,<ref name="JamesPasqualini2013">{{cite book | vauthors = James VH, Pasqualini JR | title = Hormonal Steroids: Proceedings of the Sixth International Congress on Hormonal Steroids | url = https://books.google.com/books?id=1VMJAwAAQBAJ&pg=PA391 | date = 22 October 2013 | publisher = Elsevier Science | isbn = 978-1-4831-9067-9 | pages = 391–}}</ref> it has been found to produce masculinization of the genitalia of female fetuses of pregnant animals.<ref name="pmid10637363" /> In contrast to steroidal AR antagonists, nonsteroidal AR antagonists are silent antagonists of the AR and do not activate the receptor.<ref name="pmid9000189">{{cite journal |vauthors=Caubet JF, Tosteson TD, Dong EW, Naylon EM, Whiting GW, Ernstoff MS, Ross SD |title=Maximum androgen blockade in advanced prostate cancer: a meta-analysis of published randomized controlled trials using nonsteroidal antiandrogens |journal=Urology |volume=49 |issue=1 |pages=71–8 |year=1997 |pmid=9000189 |doi=10.1016/S0090-4295(96)00325-1 |quote=Because steroidal antiandrogens such as cyproterone acetate have intrinsic androgenic activity and lower antiandrogenic activity than the NSAAs such as flutamide and nilutamide,39–43 it is not surprising that the two classes of antiandrogens may have different efficacies.}}</ref><ref name="FiggChau2010"/><ref name=SinghGauthier2000>{{cite journal |vauthors=Singh SM, Gauthier S, Labrie F |title=Androgen receptor antagonists (antiandrogens): structure-activity relationships |journal=Current Medicinal Chemistry |volume=7 |issue=2 |pages=211–47 |date=February 2000 |pmid=10637363 |doi=10.2174/0929867003375371}}</ref><ref name="PoyetLabrie1985" /> This may be why they have greater efficacy than steroidal AR antagonists in the treatment of prostate cancer and is an important reason as to why they have largely replaced them for this indication in medicine.<ref name="pmid9000189" /><ref name="FiggChau2010" /><ref name=SinghGauthier2000 /><ref name="PoyetLabrie1985" />

Nonsteroidal antiandrogens have relatively low [[affinity (pharmacology)|affinity]] for the AR compared to steroidal AR ligands.<ref name="FiggChau2010" /><ref name="SinghGauthier2000" /><ref name="pmid2788775v">{{cite journal | vauthors = Ayub M, Levell MJ | title = The effect of ketoconazole related imidazole drugs and antiandrogens on [3H] R 1881 binding to the prostatic androgen receptor and [3H]5 alpha-dihydrotestosterone and [3H]cortisol binding to plasma proteins | journal = J. Steroid Biochem. | volume = 33 | issue = 2 | pages = 251–5 | date = August 1989 | pmid = 2788775 | doi = 10.1016/0022-4731(89)90301-4 }}</ref> For example, bicalutamide has around 2% of the affinity of DHT for the AR and around 20% of the affinity of CPA for the AR.<ref name="pmid2788775v" /> Despite their low affinity for the AR however, the lack of weak partial agonist activity of NSAAs appears to improve their potency relative to steroidal antiandrogens.<ref name="pmid2788775v" /><ref name="pmid14751673">{{cite journal | vauthors = Yamasaki K, Sawaki M, Noda S, Muroi T, Takakura S, Mitoma H, Sakamoto S, Nakai M, Yakabe Y | title = Comparison of the Hershberger assay and androgen receptor binding assay of twelve chemicals | journal = Toxicology | volume = 195 | issue = 2–3 |pages=177–86 |year = 2004 | pmid = 14751673 | doi = 10.1016/j.tox.2003.09.012| bibcode = 2004Toxgy.195..177Y }}</ref> For example, although flutamide has about 10-fold lower affinity for the AR than CPA, it shows equal or slightly greater potency to CPA as an antiandrogen in [[bioassay]]s.<ref name="pmid2788775v" /><ref name="pmid14751673" /> In addition, circulating therapeutic concentrations of nonsteroidal antiandrogens are very high, on the order of thousands of times higher than those of testosterone and DHT, and this allows them to efficaciously compete and block AR signaling.<ref name="Pratt1994">{{cite book| vauthors = Pratt WB |title= The Anticancer Drugs|url=https://books.google.com/books?id=nPR1L4K5HuEC&pg=PA220 |year=1994 |publisher=Oxford University Press |isbn=978-0-19-506739-2 |pages=220– |quote=In patients receiving flutamide at the usual dosage of 250 mg every 8 hours, the minimal plasma concentration of hydroxyflutamide is about 5 uM, which is 5,000 times the plasma concentration of testosterone (1 nM) in patients treated with an LHRH agonist.127 As hydroxyflutamide is only one percent as potent as testosterone in competing for binding to the androgen receptor,126 a plasma level of 5 uM hydroxyflutamide is required to ensure effective competition.127 [...] Both cyproterone acetate and flutamide have been demonstrated to be effective therapy (roughly equivalent to an estrogen) when used alone in the treatment of carcinoma of the prostate.123}}</ref>

AR antagonists may not bind to or block [[membrane androgen receptor]]s (mARs), which are distinct from the classical nuclear AR.<ref name="pmid19931639">{{cite journal | vauthors = Bennett NC, Gardiner RA, Hooper JD, Johnson DW, Gobe GC | title = Molecular cell biology of androgen receptor signalling | journal = Int. J. Biochem. Cell Biol. | volume = 42 | issue = 6 | pages = 813–27 | year = 2010 | pmid = 19931639 | doi = 10.1016/j.biocel.2009.11.013 }}</ref><ref name="pmid25257522">{{cite journal | vauthors = Wang C, Liu Y, Cao JM | title = G protein-coupled receptors: extranuclear mediators for the non-genomic actions of steroids | journal = Int J Mol Sci | volume = 15 | issue = 9 | pages = 15412–25 | year = 2014 | pmid = 25257522 | pmc = 4200746 | doi = 10.3390/ijms150915412 | doi-access = free }}</ref><ref name="pmid23746222">{{cite journal | vauthors = Lang F, Alevizopoulos K, Stournaras C | title = Targeting membrane androgen receptors in tumors | journal = Expert Opin. Ther. Targets | volume = 17 | issue = 8 | pages = 951–63 | year = 2013 | pmid = 23746222 | doi = 10.1517/14728222.2013.806491 | s2cid = 23918273 }}</ref> However, the mARs do not appear to be involved in [[virilization|masculinization]]. This is evidenced by the perfectly [[female]] [[phenotype]] of women with [[complete androgen insensitivity syndrome]].<ref name="PescovitzEugster2004">{{cite book| vauthors = Pescovitz OH, Eugster EA |title=Pediatric Endocrinology: Mechanisms, Manifestations, and Management|url=https://books.google.com/books?id=9gvBlktAT6YC&pg=PA248|year=2004|publisher=Lippincott Williams & Wilkins|isbn=978-0-7817-4059-3|pages=248–}}</ref><ref name="BuonocoreBracci2012">{{cite book| vauthors = Buonocore G, Bracci R, Weindling M |title=Neonatology: A Practical Approach to Neonatal Diseases|url=https://books.google.com/books?id=n_L2XpJbhLoC&pg=PA1012|date=28 January 2012|publisher=Springer Science & Business Media|isbn=978-88-470-1405-3|pages=1012–}}</ref> These women have a 46,XY [[karyotype]] (i.e., are genetically "male") and high levels of androgens but possess a defective AR and for this reason never masculinize.<ref name="PescovitzEugster2004" /><ref name="BuonocoreBracci2012" /> They are described as highly feminine, both physically as well as mentally and behaviorally.<ref name="Jordan-Young2011">{{cite book| vauthors = Jordan-Young RM |title=Brain Storm|url=https://books.google.com/books?id=2V9UuOWMXOMC&pg=PA82|date=7 January 2011|publisher=Harvard University Press|isbn=978-0-674-05879-8|pages=82–}}</ref><ref name="BlakemoreBerenbaum2013">{{cite book| vauthors = Blakemore JE, Berenbaum SA, Liben LS |title=Gender Development |url=https://books.google.com/books?id=PQ3Ylt6KnA4C&pg=PT115 |date=13 May 2013|publisher=Psychology Press|isbn=978-1-135-07932-1|pages=115–}}</ref><ref name="Maggi2012">{{cite book| vauthors = Maggi M |title= Hormonal Therapy for Male Sexual Dysfunction|url=https://books.google.com/books?id=o_A9DnMVi3cC&pg=PA6|date=30 January 2012|publisher=John Wiley & Sons|isbn=978-0-470-65760-7|pages=6–}}</ref>

====N-Terminal domain antagonists====
[[Peptide antiandrogen|N-Terminal domain AR antagonist]]s are a new type of AR antagonist that, unlike all currently marketed AR antagonists, bind to the [[N-terminal domain]] (NTD) of the AR rather than the [[ligand-binding domain]] (LBD).<ref name="ImamuraSadar2016">{{cite journal | vauthors = Imamura Y, Sadar MD | title = Androgen receptor targeted therapies in castration-resistant prostate cancer: Bench to clinic | journal = International Journal of Urology | volume = 23 | issue = 8 | pages = 654–665 | date = August 2016 | pmid = 27302572 | pmc = 6680212 | doi = 10.1111/iju.13137 }}</ref> Whereas conventional AR antagonists bind to the LBD of the AR and [[competitive antagonist|competitively]] displace androgens, thereby preventing them from [[Receptor (biochemistry)#Binding and activation|activating]] the receptor, AR NTD antagonists bind [[covalent bond|covalently]] to the NTD of the AR and prevent [[protein–protein interaction]]s subsequent to activation that are required for [[transcription (biology)|transcriptional activity]].<ref name="ImamuraSadar2016" /> As such, they are [[non-competitive antagonist|non-competitive]] and [[irreversible antagonist]]s of the AR.<ref name="De MolFenwick2016">{{cite journal | vauthors = De Mol E, Fenwick RB, Phang CT, Buzón V, Szulc E, de la Fuente A, Escobedo A, García J, Bertoncini CW, Estébanez-Perpiñá E, McEwan IJ, Riera A, Salvatella X | display-authors = 6 | title = EPI-001, A Compound Active against Castration-Resistant Prostate Cancer, Targets Transactivation Unit 5 of the Androgen Receptor | journal = ACS Chemical Biology | volume = 11 | issue = 9 | pages = 2499–2505 | date = September 2016 | pmid = 27356095 | pmc = 5027137 | doi = 10.1021/acschembio.6b00182 }}</ref> Examples of AR NTD antagonists include [[bisphenol A diglycidyl ether]] (BADGE) and its derivatives [[EPI-001]], [[ralaniten]] (EPI-002), and [[ralaniten acetate]] (EPI-506).<ref name="ImamuraSadar2016" /><ref name="pmid26389532">{{cite journal | vauthors = Martinez-Ariza G, Hulme C | title = Recent advances in allosteric androgen receptor inhibitors for the potential treatment of castration-resistant prostate cancer | journal = Pharmaceutical Patent Analyst | volume = 4 | issue = 5 | pages = 387–402 | year = 2015 | pmid = 26389532 | doi = 10.4155/ppa.15.20 }}</ref> AR NTD antagonists are under investigation for the potential treatment of prostate cancer, and it is thought that they may have greater [[efficacy]] as antiandrogens relative to conventional AR antagonists.<ref name="ImamuraSadar2016" /> In accordance with this notion, AR NTD antagonists are active against [[splice variant]]s of the AR, which conventional AR antagonists are not, and AR NTD antagonists are immune to [[gain-of-function mutation]]s in the AR LBD that convert AR antagonists into AR agonists and commonly occur in prostate cancer.<ref name="ImamuraSadar2016" />

====Androgen receptor degraders====
[[Selective androgen receptor degrader]]s (SARDs) are another new type of antiandrogen that has recently been developed.<ref name="pmid27885283">{{cite journal | vauthors = Lai AC, Crews CM | title = Induced protein degradation: an emerging drug discovery paradigm | journal = Nature Reviews. Drug Discovery | volume = 16 | issue = 2 | pages = 101–114 | date = February 2017 | pmid = 27885283 | pmc = 5684876 | doi = 10.1038/nrd.2016.211 }}</ref>  They work by enhancing the [[downregulation|degradation]] of the AR, and are analogous to [[selective estrogen receptor degrader]]s (SERDs) like [[fulvestrant]] (a drug used to treat [[hormone receptor positive breast tumor|estrogen receptor-positive]] [[breast cancer]]).<ref name="pmid27885283" /> Similarly to AR NTD antagonists, it is thought that SARDs may have greater efficacy than conventional AR antagonists, and for this reason, they are under investigation for the treatment of prostate cancer.<ref name="pmid23219429">{{cite journal | vauthors = Lai KP, Huang CK, Chang YJ, Chung CY, Yamashita S, Li L, Lee SO, Yeh S, Chang C | display-authors = 6 | title = New therapeutic approach to suppress castration-resistant prostate cancer using ASC-J9 via targeting androgen receptor in selective prostate cells | journal = The American Journal of Pathology | volume = 182 | issue = 2 | pages = 460–473 | date = February 2013 | pmid = 23219429 | pmc = 3562731 | doi = 10.1016/j.ajpath.2012.10.029 }}</ref> An example of a SARD is [[dimethylcurcumin]] (ASC-J9), which is under development as a [[topical medication]] for the potential treatment of acne.<ref name="AdisInsight-ASC-J9">{{Cite web | url = http://adisinsight.springer.com/drugs/800028542 | title = ASCJ 9 | work = AdisInsight | publisher = Springer Nature Switzerland AG | access-date = 2017-12-24 | archive-date = 2018-03-04 | archive-url = https://web.archive.org/web/20180304204526/http://adisinsight.springer.com/drugs/800028542 | url-status = live }}</ref> SARDs like dimethylcurcumin differ from conventional AR antagonists and AR NTD antagonists in that they may not necessarily bind directly to the AR.<ref name="pmid23219429" />