Steroidogenesis inhibitor: Difference between revisions

 

==Types, examples, and uses==

 

===Cholesterol synthesis inhibitors===

* [[HMG-CoA reductase inhibitor|HMG-CoA reductase (HMGCR) inhibitor]]s, also known as statins, prevent the conversion of {{abbrlink|HMG-CoA|3-hydroxy-3-methylglutaryl-coenzyme A}} into [[mevalonic acid]], a relatively early step in the biosynthesis of cholesterol from [[acetyl coenzyme A]] (acetyl-CoA), and thereby decrease cholesterol levels.<ref name="Wolverton2012">{{cite book|author=Stephen E. Wolverton|title=Comprehensive Dermatologic Drug Therapy E-Book|url=https://books.google.com/books?id=Tqpsm5WKKlcC&pg=PA415|date=18 October 2012|publisher=Elsevier Health Sciences|isbn=1-4557-3801-8|pages=415–}}</ref> Examples of statins include [[atorvastatin]], [[lovastatin]], [[rosuvastatin]], and [[simvastatin]].<ref name="Wolverton2012" /> They are used in the treatment of [[hypercholesterolemia]] for the purpose of lowering the risk of [[atherosclerosis]]-related [[cardiovascular disease]].<ref name="Wolverton2012" />

 

* [[Farnesyl pyrophosphate synthase]] (FPPS) inhibitors prevent the conversion of [[isopentenyl pyrophosphate]] (IPP) into [[farnesyl pyrophosphate]] (FPP), a mid-range step in the biosynthesis of cholesterol from acetyl-CoA, and thereby inhibit cholesterol production.<ref name="DowdJohnson2016">{{cite book|author1=Frank J. Dowd|author2=Bart Johnson|author3=Angelo Mariotti|title=Pharmacology and Therapeutics for Dentistry - E-Book|url=https://books.google.com/books?id=6xT7DAAAQBAJ&pg=PA426|date=3 September 2016|publisher=Elsevier Health Sciences|isbn=978-0-323-44595-5|pages=426–}}</ref><ref name="Elsevier2017">{{cite book|title=Nuclear Receptors in Development and Disease|url=https://books.google.com/books?id=ZvupDQAAQBAJ&pg=PA88|date=17 May 2017|publisher=Elsevier Science|isbn=978-0-12-802196-5|pages=88–}}</ref> They notably do not significantly lower ''circulating'' levels of cholesterol however, and hence, unlike statins, are not suitable for the treatment of hypercholesterolemia.<ref name="ClementiFumagalli2015">{{cite book|author1=Francesco Clementi|author2=Guido Fumagalli|title=General and Molecular Pharmacology: Principles of Drug Action|url=https://books.google.com/books?id=GsdJCgAAQBAJ&pg=PA442|date=9 February 2015|publisher=John Wiley & Sons|isbn=978-1-118-76857-0|pages=442–}}</ref> The main examples of FPPS inhibitors are [[nitrogenous]] [[bisphosphonate]]s such as [[alendronate]], [[ibandronate]], [[pamidronate]], [[risedronate]], and [[zoledronate]], which are used in the treatment of [[osteoporosis]].<ref name="DowdJohnson2016" /><ref name="Elsevier2017" />

 

* [[7-Dehydrocholesterol reductase]] (7-DHCR) inhibitors such as [[AY-9944]] and [[BM-15766]] inhibit the production of cholesterol from [[7-dehydrocholesterol]], one of the last steps in cholesterol biosynthesis.<ref name="Gilbert-BarnessBarness2017">{{cite book|author1=E. Gilbert-Barness|author2=L.A. Barness|author3=P.M. Farrell|title=Metabolic Diseases: Foundations of Clinical Management, Genetics, and Pathology|url=https://books.google.com/books?id=YpfzDQAAQBAJ&pg=PA336|date=6 January 2017|publisher=IOS Press|isbn=978-1-61499-718-4|pages=336–337}}</ref><ref name="Bittman2013">{{cite book|author=Robert Bittman|title=Cholesterol: Its Functions and Metabolism in Biology and Medicine|url=https://books.google.com/books?id=MRfpBwAAQBAJ&pg=PA130|date=11 November 2013|publisher=Springer Science & Business Media|isbn=978-1-4615-5901-6|pages=130–}}</ref> [[Loss-of-function mutation]]s in the [[gene]] encoding 7-DHCR result in [[Smith–Lemli–Opitz syndrome]] (SLOS) and dramatic accumulation of [[7-dehydrocholesterol]].<ref name="Gilbert-BarnessBarness2017" /><ref name="Bittman2013" /> 7-DHCR inhibitors produce symptoms in animals similar to those seen SLOS, and as such, like 24-DHCR inhibitors (see below), are probably too [[toxic]] to be used clinically.<ref name="Gilbert-BarnessBarness2017" /><ref name="Bittman2013" />