# Seviteronel

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> Markdown URL: https://mediated.wiki/source/Seviteronel.md
> Source: https://en.wikipedia.org/wiki/Seviteronel
> Source revision: 1329008466
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{{Short description|Chemical compound}}
__NOTOC__
{{Drugbox
| Verifiedfields =
| Watchedfields =
| verifiedrevid =
| IUPAC_name = (1''S'')-1-[6,7-Bis(difluoromethoxy)naphthalen-2-yl]-2-methyl-1-(2''H''-triazol-4-yl)propan-1-ol
| image = VT-464.svg
| image_class = skin-invert-image
| width = 250px

<!--Clinical data-->
| tradename =
| 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 = [By mouth](/source/Oral_administration)
| class = [Androgen biosynthesis inhibitor](/source/Androgen_biosynthesis_inhibitor); [Nonsteroidal antiandrogen](/source/Nonsteroidal_antiandrogen)

<!--Pharmacokinetic data-->
| bioavailability =
| protein_bound =
| metabolism =
| elimination_half-life =
| excretion =

<!--Identifiers-->
| CAS_number_Ref =
| CAS_number = 1610537-15-9
| CAS_supplemental =
| ATC_prefix = None
| ATC_suffix =
| PubChem = 78357816
| DrugBank_Ref =
| DrugBank =
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 8S5OIN36X4
| ChemSpiderID_Ref =
| ChemSpiderID = 32738723
| synonyms = VT-464; INO-464

<!--Chemical data-->
| C=18 | H=17 | F=4 | N=3 | O=3
| SMILES = CC(C)C(C1=CC2=CC(=C(C=C2C=C1)OC(F)F)OC(F)F)(C3=NNN=C3)O
| StdInChI = 1S/C18H17F4N3O3/c1-9(2)18(26,15-8-23-25-24-15)12-4-3-10-6-13(27-16(19)20)14(28-17(21)22)7-11(10)5-12/h3-9,16-17,26H,1-2H3,(H,23,24,25)/t18-/m0/s1
| StdInChIKey = ZBRAJOQFSNYJMF-SFHVURJKSA-N
}}

'''Seviteronel''' (developmental codes '''VT-464''' and, formerly, '''INO-464''') is an [experimental cancer medication](/source/experimental_cancer_treatment) which is under development by Viamet Pharmaceuticals and Innocrin Pharmaceuticals for the treatment of [prostate cancer](/source/prostate_cancer) and [breast cancer](/source/breast_cancer).<ref name="AdisInsight">{{Cite web | url = http://adisinsight.springer.com/drugs/800035241 | title = Seviteronel - Innocrin Pharmaceuticals | work = AdisInsight | publisher = Springer Nature Switzerland AG | access-date = 2015-07-20 | archive-date = 2015-07-22 | archive-url = https://web.archive.org/web/20150722081355/http://adisinsight.springer.com/drugs/800035241 | url-status = live }}</ref> It is a [nonsteroidal](/source/nonsteroidal) [CYP17A1 inhibitor](/source/CYP17A1_inhibitor) and works by [inhibiting](/source/enzyme_inhibitor) the [production](/source/biosynthesis) of [androgen](/source/androgen)s and [estrogen](/source/estrogen)s in the body.<ref name="AdisInsight" /> As of July 2017, seviteronel is in [phase II](/source/Phases_of_clinical_research) [clinical trial](/source/clinical_trial)s for both prostate cancer and breast cancer.<ref name="AdisInsight" /> In January 2016, it was designated [fast-track](/source/Fast_track_(FDA)) status by the [United States](/source/United_States) [Food and Drug Administration](/source/Food_and_Drug_Administration) for prostate cancer.<ref name="AdisInsight" /><ref name="PharmTech">{{Cite web|url=http://www.pharmaceutical-technology.com/news/newsfda-grants-fast-track-status-innocrins-seviteronel-treat-metastatic-crpc-4770025|title=FDA grants fast-track status for Innocrin's seviteronel to treat metastatic CRPC|date=6 January 2016|work=PharmaceuticalTechnology|access-date=2 May 2016|archive-date=3 June 2016|archive-url=https://web.archive.org/web/20160603094805/http://www.pharmaceutical-technology.com/news/newsfda-grants-fast-track-status-innocrins-seviteronel-treat-metastatic-crpc-4770025|url-status=live}}</ref> In April 2017, seviteronel received fast-track designation for breast cancer as well.<ref name="AdisInsight" />
__TOC__

==Pharmacology==

===Pharmacodynamics===
Seviteronel is a [nonsteroidal antiandrogen](/source/nonsteroidal_antiandrogen), acting specifically as an [androgen](/source/androgen) [synthesis](/source/biosynthesis) [inhibitor](/source/enzyme_inhibitor) via inhibition of the [enzyme](/source/enzyme) [CYP17A1](/source/CYP17A1), for the treatment of [castration-resistant prostate cancer](/source/castration-resistant_prostate_cancer).<ref name="pmid23880851">{{cite journal | vauthors = Yin L, Hu Q, Hartmann RW | title = Recent progress in pharmaceutical therapies for castration-resistant prostate cancer | journal = International Journal of Molecular Sciences | volume = 14 | issue = 7 | pages = 13958–13978 | date = July 2013 | pmid = 23880851 | pmc = 3742227 | doi = 10.3390/ijms140713958 | doi-access = free }}</ref><ref name="pmid24759590">{{cite journal | vauthors = Stein MN, Patel N, Bershadskiy A, Sokoloff A, Singer EA | title = Androgen synthesis inhibitors in the treatment of castration-resistant prostate cancer | journal = Asian Journal of Andrology | volume = 16 | issue = 3 | pages = 387–400 | year = 2014 | pmid = 24759590 | pmc = 4023364 | doi = 10.4103/1008-682X.129133 | doi-access = free }}</ref><ref name="pmid24775307">{{cite journal | vauthors = Rafferty SW, Eisner JR, Moore WR, Schotzinger RJ, Hoekstra WJ | title = Highly-selective 4-(1,2,3-triazole)-based P450c17a 17,20-lyase inhibitors | journal = Bioorganic & Medicinal Chemistry Letters | volume = 24 | issue = 11 | pages = 2444–2447 | date = June 2014 | pmid = 24775307 | doi = 10.1016/j.bmcl.2014.04.024 | url = https://zenodo.org/record/896321 }}</ref><ref name="pmid25351916">{{cite journal | vauthors = Toren PJ, Kim S, Pham S, Mangalji A, Adomat H, Guns ES, Zoubeidi A, Moore W, Gleave ME | display-authors = 6 | title = Anticancer activity of a novel selective CYP17A1 inhibitor in preclinical models of castrate-resistant prostate cancer | journal = Molecular Cancer Therapeutics | volume = 14 | issue = 1 | pages = 59–69 | date = January 2015 | pmid = 25351916 | doi = 10.1158/1535-7163.MCT-14-0521 | doi-access = free }}</ref><ref name="Neidle2013">{{cite book | vauthors = Hu Q, Hartmann RW | chapter = The Renaissance of CYP17 Inhibitors for the Treatment of Prostate Cancer| veditors = Neidle S |title=Cancer Drug Design and Discovery| chapter-url = https://books.google.com/books?id=HS6IAAAAQBAJ&pg=PA342|date=30 September 2013|publisher=Academic Press|isbn=978-0-12-397228-6|pages=341–342}}</ref><ref name="KellyMD2014">{{cite book|vauthors=Poole A, Alva A, Batten J, Agarwal N|chapter=Metastatic Castrate-Resistant Prostate Inhibitors: Role of Androgen Signaling Inhibitors|veditors=Kelly WK, Trabulsi EJ, Zaorsky NG|title=Prostate Cancer: A Multidisciplinary Approach to Diagnosis and Management|chapter-url=https://books.google.com/books?id=UzTtBQAAQBAJ&pg=PA342|date=17 December 2014|publisher=Demos Medical Publishing|isbn=978-1-936287-59-8|pages=342–|access-date=19 October 2016|archive-date=10 January 2023|archive-url=https://web.archive.org/web/20230110003510/https://books.google.com/books?id=UzTtBQAAQBAJ&pg=PA342|url-status=live}}</ref> It has approximately 10-fold [selectivity](/source/binding_selectivity) for the inhibition of [17,20-lyase](/source/17%2C20-lyase) ({{abbrlink|IC<sub>50</sub>|half-maximal inhibitory concentration}} = 69&nbsp;nM) over [17α-hydroxylase](/source/17%CE%B1-hydroxylase) ({{abbr|IC<sub>50</sub>|half-maximal inhibitory concentration}} = 670&nbsp;nM), which results in less interference with [corticosteroid](/source/corticosteroid) production relative to the approved CYP17A1 inhibitor [abiraterone acetate](/source/abiraterone_acetate) (which must be administered in combination with [prednisone](/source/prednisone) to avoid [glucocorticoid deficiency](/source/adrenal_insufficiency) and [mineralocorticoid excess](/source/mineralocorticoid_excess) due to 17α-hydroxylase inhibition) and hence may be administerable without a concomitant [exogenous](/source/exogenous) [glucocorticoid](/source/glucocorticoid).<ref name="pmid27154414">{{cite journal | vauthors = Bird IM, Abbott DH | title = The hunt for a selective 17,20 lyase inhibitor; learning lessons from nature | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 163 | pages = 136–146 | date = October 2016 | pmid = 27154414 | pmc = 5046225 | doi = 10.1016/j.jsbmb.2016.04.021 | quote = VT464 is another recently developed compound proposed to act as a selective lyase inhibitor, and more complete data is available in the public domain to support this claim. A review of preliminary data released suggest the IC50 for Human CYP17 lyase activity is ten times lower than for hydroxylase 15 and in nonhuman primates VT464 was able to suppress circulating testosterone as effectively as abiraterone, but with minimally depressed cortisol (remaining at 82% control compared to only 9% with aberaterone), and without associated increases in pregnenolone, progesterone and mineralocorticoids otherwise observed with abiraterone. Like Galaterone, VT464 is also in use in clinical trials without co-administration of prednisone. Together with the clear lack of suppression of circulating cortisol in nonhuman primates, these data argue that VT464 may indeed be a selective 17,20 lyase inhibitor. }}</ref> Seviteronel is 58-fold more selective for inhibition of 17,20-lyase than [abiraterone](/source/abiraterone) (the [active metabolite](/source/active_metabolite) of abiraterone acetate), which has {{abbr|IC<sub>50</sub>|half-maximal inhibitory concentration}} values for inhibition of 17,20-lyase and 17α-hydroxylase of 15&nbsp;nM and 2.5&nbsp;nM, respectively.<ref name="Neidle2013" /> In addition, in ''[in vitro](/source/in_vitro)'' models, seviteronel appears to possess greater efficacy as an antiandrogen relative to abiraterone.<ref name="pmid25351916" /> Similarly to abiraterone acetate, seviteronel has also been found to act to some extent as an [antagonist](/source/receptor_antagonist) of the [androgen receptor](/source/androgen_receptor).<ref name="pmid25351916" />

==Society and culture==

===Generic names===
''Seviteronel'' is the [generic name](/source/generic_term) of the drug and its {{abbrlink|INN|International Nonproprietary Name}}.<ref name="WHO2016">{{Cite journal |url=https://www.who.int/medicines/publications/druginformation/innlists/RL76.pdf |title=International Nonproprietary Names for Pharmaceutical Substances (INN) | journal = WHO Drug Information | volume = 30 | issue = 3 | date = 2016 | page = 533 |publisher=[World Health Organization](/source/World_Health_Organization) |archive-url=https://web.archive.org/web/20220216082642/https://www.who.int/medicines/publications/druginformation/innlists/RL76.pdf |archive-date=2022-02-16 }}</ref>

== See also ==
* [List of investigational sex-hormonal agents § Androgenics](/source/List_of_investigational_sex-hormonal_agents)

== References ==
{{Reflist}}

== Further reading ==
{{refbegin}}
* {{cite journal | vauthors = Gomez L, Kovac JR, Lamb DJ | title = CYP17A1 inhibitors in castration-resistant prostate cancer | journal = Steroids | volume = 95 | pages = 80–87 | date = March 2015 | pmid = 25560485 | pmc = 4323677 | doi = 10.1016/j.steroids.2014.12.021 }}
* {{cite journal | vauthors = Bambury RM, Rathkopf DE | title = Novel and next-generation androgen receptor-directed therapies for prostate cancer: Beyond abiraterone and enzalutamide | journal = Urologic Oncology | volume = 34 | issue = 8 | pages = 348–355 | date = August 2016 | pmid = 26162486 | doi = 10.1016/j.urolonc.2015.05.025 }}
{{refend}}

== External links ==
* [http://adisinsight.springer.com/drugs/800035241 Seviteronel - AdisInsight]

{{Androgens and antiandrogens}}
{{Androgen receptor modulators}}

Category:Tertiary alcohols
Category:CYP17A1 inhibitors
Category:Experimental cancer drugs
Category:Naphthalenes
Category:Nonsteroidal antiandrogens
Category:Organofluorides
Category:Prostate cancer
Category:Triazoles
Category:Phenol ethers

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Adapted from the Wikipedia article [Seviteronel](https://en.wikipedia.org/wiki/Seviteronel) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Seviteronel?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.