Jump to content

Steroidogenesis inhibitor

From Wikipedia, the free encyclopedia
(Redirected from Steroidogenesis modulator)
Steroidogenesis inhibitor
Drug class
Class identifiers
SynonymsSteroid biosynthesis inhibitor; Steroid synthesis inhibitor
UseVarious
Biological targetSteroidogenic enzymes
Chemical classSteroidal; Nonsteroidal
Legal status
In Wikidata

A steroidogenesis inhibitor, also known as a steroid biosynthesis inhibitor, is a type of drug which inhibits one or more of the enzymes that are involved in the process of steroidogenesis, the biosynthesis of endogenous steroids and steroid hormones.[1] They may inhibit the production of cholesterol and other sterols, sex steroids such as androgens, estrogens, and progestogens, corticosteroids such as glucocorticoids and mineralocorticoids, and neurosteroids.[1][2] They are used in the treatment of a variety of medical conditions that depend on endogenous steroids.[1]

Steroidogenesis inhibitors are analogous in effect and use to antigonadotropins (which specifically inhibit gonadal sex steroid production), but work via a different mechanism of action; whereas antigonadotropins suppress gonadal production of sex steroids by effecting negative feedback on and thereby suppressing the hypothalamic–pituitary–gonadal axis, steroidogenesis inhibitors directly inhibit the enzymatic biosynthesis of steroids.[1]

Types, examples, and uses

[edit]

Cholesterol synthesis inhibitors

[edit]
Cholesterol biosynthesis from acetyl-CoA.

Acetyl-CoA to lanosterol inhibitors

[edit]

Lanosterol to cholesterol inhibitors

[edit]
  • 24-Dehydrocholesterol reductase (24-DHCR) inhibitors such as azacosterol and triparanol inhibit the production of cholesterol from desmosterol, one of the last steps in cholesterol biosynthesis, and were formerly used to treat hypercholesterolemia, but were withdrawn from the market due to toxicity caused by accumulation of desmosterol in tissues.[12][13]

Steroid hormone synthesis inhibitors

[edit]
Steroidogenesis, biosynthesis of steroid hormones from cholesterol.[14]

Non-specific steroid hormone synthesis inhibitors

[edit]

Corticosteroid-specific synthesis inhibitors

[edit]

Sex steroid-specific synthesis inhibitors

[edit]

Other steroid synthesis inhibitors

[edit]

List of steroid metabolism modulators

[edit]
Enzyme SubstratesProducts Inhibitors Inducers
HMG-CoA reductase
(HMGCR)
HMG-CoAMevalonic acid AtorvastatinCerivastatinColestoloneFluvastatinLovastatinMevastatinPitavastatinPravastatinRosuvastatinSimvastatin
FPPSTooltip Farnesyl pyrophosphate synthetase Dimethylallyl pyrophosphate (isoprenyl pyrophosphate)Farnesyl pyrophosphateIsopentenyl pyrophosphateFarnesyl pyrophosphate Alendronic acidIbandronic acidIncadronic acidPamidronic acidRisedronic acidZoledronic acid
7-DHCRTooltip 7-Dehydrocholesterol reductase 7-DehydrocholesterolCholesterol AY-9944BM-15766Triparanol
24-DHCRTooltip 24-Dehydrocholesterol reductase DesmosterolCholesterol AzacosterolClomifeneTriparanolWY-3457
P450sccTooltip Cholesterol side-chain cleavage enzyme
(CYP11A1)
Cholesterol22R-Hydroxycholesterol22R-Hydroxycholesterol20α,22R-Dihydroxycholesterol20α,22R-DihydroxycholesterolPregnenolone 22-ABC3,3′-Dimethoxybenzidine3-MethoxybenzidineAminoglutethimideAmphenone BCanrenoneCyanoketoneDanazolEtomidateKetoconazoleLevoketoconazoleMitotaneSpironolactoneTrilostane
3β-HSDTooltip 3β-Hydroxysteroid dehydrogenase
(HSD3B)
PregnenoloneProgesterone17α-Hydroxypregnenolone17α-HydroxyprogesteroneDehydroepiandrosteroneAndrostenedione5-AndrostenediolTestosteroneAndrostadienolAndrostadienone 4-MAΔ4-AbirateroneAbirateroneAbiraterone acetateAmphenone BAzasteneCyanoketoneCyproterone acetateDanazolEpostaneGenisteinGestrinoneMedrogestoneMedroxyprogesterone acetateMetriboloneMetyraponeNorethisteroneOxymetholonePioglitazoneRosiglitazoneTrilostaneTroglitazone
17α-Hydroxylase,
17,20-lyase
(CYP17A1)
Pregnenolone17α-HydroxypregnenoloneProgesterone17α-Hydroxyprogesterone17α-HydroxypregnenoloneDehydroepiandrosterone17α-HydroxyprogesteroneAndrostenedione 22-ABC22-OximeΔ4-AbirateroneAbirateroneAbiraterone acetateAmphenone BBifluranolBifonazoleCanrenoneCFG-920ClotrimazoleCyanoketoneCyproterone acetateDanazolEconazoleEtomidateFlutamideGaleteroneGestrinoneIsoconazoleKetoconazoleL-39LevoketoconazoleLiarozoleLY-207,320MDL-27,302MiconazoleMifepristoneNilutamideOrteronelPioglitazoneProchlorazRosiglitazoneSeviteronelSpironolactoneStanozololSU-9055SU-10603TGF-βTioconazoleTroglitazoneVN/87-1YM116
11β-HSDTooltip 11β-Hydroxysteroid dehydrogenase
(HSD11B)
CortisolCortisone 11-Ketoprogesterone11α-Hydroxyprogesterone11β-Hydroxyprogesterone18α-Glycyrrhizic acidABT-384AcetoxoloneAmphenone BCarbenoxoloneEnoxolone (glycyrrhetinic acid)Epigallocatechin gallateGlycyrrhizin (glycyrrhizic acid) (licorice) • Progesterone
21-Hydroxylase
(CYP21A2)
Progesterone11-Deoxycorticosterone17α-Hydroxyprogesterone11-Deoxycortisol AminoglutethimideAmphenone BBifonazoleCanrenoneClotrimazoleDiazepamEconazoleGenisteinIsoconazoleKetoconazoleLevoketoconazoleMetyraponeMiconazoleMidazolamSpironolactoneAbirateroneAbiraterone acetateTioconazole
11β-Hydroxylase
(CYP11B1)
11-DeoxycorticosteroneCorticosterone11-DeoxycortisolCortisol Δ4-AbirateroneAbirateroneAbiraterone acetateAminoglutethimideCanrenoneEtomidateFadrozoleFETOKetoconazoleLevoketoconazoleMetomidateMetyrapolMetyraponeMitotanePotassium canrenoateSpironolactoneTrilostaneOsilodrostat
Aldosterone
synthase
(CYP11B2)
CorticosteroneAldosterone 18-Ethynylprogesterone (18-ethinylprogesterone)18-VinylprogesteroneAminoglutethimideAzelnidipineBenidipineCanrenoneCilnidipineEfonidipineFAD286FadrozoleKetoconazoleMetyraponeMespirenoneOsilodrostatPotassium canrenoateSpironolactone
17β-HSDTooltip 17β-Hydroxysteroid dehydrogenase
(HSD17B)
Dehydroepiandrosterone5-AndrostenediolAndrostenedioneTestosteroneEstroneEstradiol DanazolEthanolFisetinRM-532-105SimvastatinSTX-2171STX-2622STX-2624
5α-Reductase
(SRD5A)
Cholestenone5α-CholestanoneProgesterone5α-Dihydroprogesterone3α-DihydroprogesteroneAllopregnanolone3β-DihydroprogesteroneIsopregnanoloneDeoxycorticosterone5α-DihydrodeoxycorticosteroneCorticosterone5α-DihydrocorticosteroneCortisol5α-DihydrocortisolAldosterone5α-DihydroaldosteroneAndrostenedione5α-AndrostanedioneTestosterone5α-DihydrotestosteroneAndrostadienoneAndrostenone 22-OximeΔ4-AbirateroneAbirateroneAbiraterone acetateAlfatradiolAzelaic acidβ-SitosterolBexlosterideChlormadinone acetateCl-4AS-1DutasterideEpitestosteroneEpristerideFatty acids (α-linolenic acid, linoleic acid, γ-linolenic acid, monolinolein, oleic acid) • FinasterideGanoderic acidGestodeneIzonsterideL-39LapisterideOxendoloneSaw palmetto extractTFM-4AS-1TurosterideVitamin B6Zinc
3α-HSDTooltip 3α-Hydroxysteroid dehydrogenase
(AKR1C4)
5α-DihydroprogesteroneAllopregnanoloneDHDOCTHDOCDihydrotestosterone3α-Androstanediol CoumestrolDaidzeinGenisteinIndometacinMedroxyprogesterone acetate FluoxetineFluvoxamineMirtazapineParoxetineSertralineVenlafaxine
Aromatase
(CYP19A1)
16α-Hydroxyandrostenedione16α-HydroxyestroneAndrostenedioneEstroneNandroloneEstradiolMetandienoneMethylestradiolMethyltestosteroneMethylestradiolTestosteroneEstradiol 4-AT4-Cyclohexylaniline4'-Hydroxynorendoxifen4-Hydroxytestosterone5α-DHNET20α-DihydroprogesteroneAbyssinone IIalpha-NaphthoflavoneAminoglutethimideAnastrozoleAscorbic acid (vitamin C) • AtamestaneATDBifonazoleCGP-45,688CGS-47,645Chalconoids (e.g., isoliquiritigenin) • ClotrimazoleCorynesidone ACoumestrolDHTDifeconazoleEconazoleEllagitanninsEndosulfanExemestaneFadrozoleFatty acids (e.g., conjugated linoleic acid, linoleic acid, linolenic acid, palmitic acid) • FenarimolFinrozoleFlavonoids (e.g., 7-hydroxyflavone, 7-hydroxyflavanone, 7,8-DHF, acacetin, apigenin, baicalein, biochanin A, chrysin, EGCG, gossypetin, hesperetin, liquiritigenin, myricetin, naringenin, pinocembrin, rotenone, quercetin, sakuranetin, tectochrysin) • FormestaneImazalilIsoconazoleKetoconazoleLeflutrozoleLetrozoleLiarozoleMelatoninMEN-11066MiconazoleMinamestaneNimorazoleNKS01NorendoxifenORG-33,201PenconazolePhenytoinPGE2 (dinoprostone)PlomestaneProchlorazPropiconazoleQuinolinoids (e.g., berberine, casimiroin, triptoquinone A, XHN22, XHN26, XHN27) • Resorcylic acid lactones (e.g., zearalenone) • Rogletimide (pyridoglutethimide)Stilbenoids (e.g., resveratrol) • Terpenoids (e.g., dehydroabietic acid, (–)-dehydrololiolide, retinol (vitamin A), Δ9-THC, tretinoin) • TestolactoneTioconazoleTriadimefonTriadimenolTroglitazoneValproic acidVorozoleXanthones (e.g., garcinone D, garcinone E, α-mangostin, γ-mangostin, monodictyochrome A, monodictyochrome B) • YM-511Zinc AtrazineFlavonoids (e.g., genistein, quercetin)
SSTTooltip Steroid sulfotransferase/ESTTooltip Estrogen sulfotransferase DehydroepiandrosteroneDehydroepiandrosterone sulfateEstroneEstrone sulfate 4′OH-CB796-Hydroxyflavone2,6-Dichloro-4-nitrophenol (DCNP)7,8-DihydroxyflavoneEquolGalanginGenisteinParabens (e.g., butylparaben) • Pentachlorophenol (PCP)Triclosan
STSTooltip Steroid sulfatase Cholesterol sulfateCholesterolDehydroepiandrosterone sulfateDehydroepiandrosteroneEstrone sulfateEstronePregnenolone sulfatePregnenolone AHBSDanazolEstradiol sulfamate (E2MATE)Estrone sulfamate (EMATE)Irosustat (STX64, 667 Coumate, BN-83495)KW-2581SR-16157STX213STX681STX1938
Sterol
27-hydroxylase

(CYP27A1)
Cholesterol27-Hydroxycholesterol AnastrozoleBicalutamideDexmedetomidineFadrozolePosaconazoleRavuconazole
Cholesterol
7α-hydroxylase
(CYP7A1)
Cholesterol7α-Hydroxycholesterol (intermediate to bile acids) KetoconazoleLevoketoconazole
Lanosterol
14α-demethylase
(CYP51A1)
Lanosterol4,4-Dimethylcholesta-8(9),14,24-trien-3β-ol (intermediate to ergosterol) AlbaconazoleAliconazoleAlteconazoleArasertaconazoleAzaconazoleAzalanstatBecliconazoleBifonazoleBrolaconazoleButoconazoleChlormidazoleCisconazoleClotrimazoleCroconazoleCyproconazoleDemoconazoleDiniconazoleDoconazoleEberconazoleEconazoleEconazole/triamcinoloneEfinaconazoleEmbeconazoleEnilconazoleEtaconazoleFenticonazoleFluconazoleFlutrimazoleFosfluconazoleFurconazoleHexaconazoleIsavuconazoleIsavuconazonium chlorideIsavuconazonium sulfateIsoconazoleItraconazoleKetoconazoleLanoconazoleLevoketoconazoleLuliconazoleMiconazoleNeticonazoleOmoconazoleOrconazoleOxiconazoleParconazolePenconazolePosaconazolePropiconazolePramiconazoleQuilseconazoleRavuconazoleSaperconazoleSertaconazoleSulconazoleTebuconazoleTerconazole (triaconazole)TioconazoleUniconazoleValconazoleVoriconazoleZinoconazoleZoficonazole


See also

[edit]

References

[edit]
  1. ^ a b c d Vanden Bossche H (1992). "Inhibitors of P450-dependent steroid biosynthesis: from research to medical treatment". J. Steroid Biochem. Mol. Biol. 43 (8): 1003–21. doi:10.1016/0960-0760(92)90328-G. PMID 22217845. S2CID 5876596.
  2. ^ a b Tvrdeić, Ante; Poljak, Ljiljana (2016). "Neurosteroids, GABAA receptors and neurosteroid based drugs: are we witnessing the dawn of the new psychiatric drugs?". Endocrine Oncology and Metabolism. 2 (1): 60–71. doi:10.21040/eom/2016.2.7. ISSN 1849-8922.
  3. ^ a b c Stephen E. Wolverton (18 October 2012). Comprehensive Dermatologic Drug Therapy E-Book. Elsevier Health Sciences. pp. 415–. ISBN 978-1-4557-3801-4.
  4. ^ a b Frank J. Dowd; Bart Johnson; Angelo Mariotti (3 September 2016). Pharmacology and Therapeutics for Dentistry - E-Book. Elsevier Health Sciences. pp. 426–. ISBN 978-0-323-44595-5.
  5. ^ a b Nuclear Receptors in Development and Disease. Elsevier Science. 17 May 2017. pp. 88–. ISBN 978-0-12-802196-5.
  6. ^ Francesco Clementi; Guido Fumagalli (9 February 2015). General and Molecular Pharmacology: Principles of Drug Action. John Wiley & Sons. pp. 442–. ISBN 978-1-118-76857-0.
  7. ^ "9α-hydroxy-3-oxo-4,24(25)-stigmastadien-26-oic acid derivatives, a process for preparing same and pharmaceutical compositions containing same".
  8. ^ Schroepfer GJ, Chu AJ, Needleman DH, Izumi A, Nguyen PT, Wang KS, Little JM, Sherrill BC, Kisic A (1988). "Inhibitors of sterol synthesis. Metabolism of 5 alpha-cholest-8(14)-en-3 beta-ol-15-one after intravenous administration to bile duct-cannulated rats". J. Biol. Chem. 263 (9): 4110–23. doi:10.1016/S0021-9258(18)68897-0. PMID 3346239.
  9. ^ Schroepfer GJ, Parish EJ, Kisic A, Jackson EM, Farley CM, Mott GE (1982). "5 alpha-Cholest-8(14)-en-3 beta-ol-15-one, a potent inhibitor of sterol biosynthesis, lowers serum cholesterol and alters distributions of cholesterol in lipoproteins in baboons". Proc. Natl. Acad. Sci. U.S.A. 79 (9): 3042–6. Bibcode:1982PNAS...79.3042S. doi:10.1073/pnas.79.9.3042. PMC 346345. PMID 6953447.
  10. ^ a b c E. Gilbert-Barness; L.A. Barness; P.M. Farrell (6 January 2017). Metabolic Diseases: Foundations of Clinical Management, Genetics, and Pathology. IOS Press. pp. 336–337. ISBN 978-1-61499-718-4.
  11. ^ a b c Robert Bittman (11 November 2013). Cholesterol: Its Functions and Metabolism in Biology and Medicine. Springer Science & Business Media. pp. 130–. ISBN 978-1-4615-5901-6.
  12. ^ Peter M. Elias (21 January 2016). Advances in Lipid Research: Skin Lipids. Elsevier. pp. 218–. ISBN 978-1-4832-1545-7.
  13. ^ Carl A. Burtis; Edward R. Ashwood; David E. Bruns (14 October 2012). Tietz Textbook of Clinical Chemistry and Molecular Diagnostics - E-Book. Elsevier Health Sciences. pp. 733–. ISBN 978-1-4557-5942-2.
  14. ^ Häggström M, Richfield D (2014). "Diagram of the pathways of human steroidogenesis". WikiJournal of Medicine. 1 (1). doi:10.15347/wjm/2014.005. ISSN 2002-4436.
  15. ^ a b c Kenneth L. Becker (2001). Principles and Practice of Endocrinology and Metabolism. Lippincott Williams & Wilkins. pp. 735–. ISBN 978-0-7817-1750-2.
  16. ^ a b c d e f g h i j J. Larry Jameson; Leslie J. De Groot (18 May 2010). Endocrinology - E-Book: Adult and Pediatric. Elsevier Health Sciences. pp. 301–302. ISBN 978-1-4557-1126-0.
  17. ^ a b c d e f Paul R. Ortiz de Montellano (13 March 2015). Cytochrome P450: Structure, Mechanism, and Biochemistry. Springer. pp. 851–879. ISBN 978-3-319-12108-6.
  18. ^ Dimitrios A. Linos; Jon A. van Heerden (5 December 2005). Adrenal Glands: Diagnostic Aspects and Surgical Therapy. Springer Science & Business Media. pp. 171–. ISBN 978-3-540-26861-1.
  19. ^ Waun Ki Hong; American Association for Cancer Research (2010). Holland-Frei Cancer Medicine 8. PMPH-USA. pp. 756–. ISBN 978-1-60795-014-1.
  20. ^ a b L Martini (2 December 2012). Hormonal Steroids Biochemistry, Pharmacology, and Therapeutics: Proceedings of the First International Congress on Hormonal Steroids. Elsevier. pp. 383–. ISBN 978-0-323-14465-0.
  21. ^ a b Ray S, Sharma I (1987). "Development of progesterone antagonists as fertility regulating agents". Pharmazie. 42 (10): 656–61. PMID 3325988.
  22. ^ Marcello D. Bronstein (1 October 2010). Cushing's Syndrome: Pathophysiology, Diagnosis and Treatment. Springer Science & Business Media. pp. 157–. ISBN 978-1-60327-449-4.
  23. ^ William D. Figg; Cindy H. Chau; Eric J. Small (14 September 2010). Drug Management of Prostate Cancer. Springer Science & Business Media. pp. 96–98. ISBN 978-1-60327-829-4.
  24. ^ Stephen Neidle (30 September 2013). Cancer Drug Design and Discovery. Academic Press. pp. 341–. ISBN 978-0-12-397228-6.
  25. ^ a b c Fleseriu M, Castinetti F (2016). "Updates on the role of adrenal steroidogenesis inhibitors in Cushing's syndrome: a focus on novel therapies". Pituitary. 19 (6): 643–653. doi:10.1007/s11102-016-0742-1. PMC 5080363. PMID 27600150.
  26. ^ Jürg Müller (6 December 2012). Regulation of Aldosterone Biosynthesis. Springer Science & Business Media. pp. 39–. ISBN 978-3-642-96062-8.
  27. ^ Jerome F. Strauss; Robert L. Barbieri (28 August 2013). Yen & Jaffe's Reproductive Endocrinology E-Book: Physiology, Pathophysiology, and Clinical Management. Elsevier Health Sciences. pp. 81–82. ISBN 978-1-4557-5972-9.
  28. ^ Ralph M. Trüeb (26 February 2013). Female Alopecia: Guide to Successful Management. Springer Science & Business Media. pp. 79–. ISBN 978-3-642-35503-5.
  29. ^ Rob Bradbury (30 January 2007). Cancer. Springer Science & Business Media. pp. 46–50. ISBN 978-3-540-33120-9.
  30. ^ Aman U. Buzdar (8 November 2007). Endocrine Therapies in Breast Cancer. OUP Oxford. pp. 37–40. ISBN 978-0-19-921814-1.
  31. ^ Mueller JW, Gilligan LC, Idkowiak J, Arlt W, Foster PA (2015). "The Regulation of Steroid Action by Sulfation and Desulfation". Endocr. Rev. 36 (5): 526–63. doi:10.1210/er.2015-1036. PMC 4591525. PMID 26213785.
  32. ^ Gibbs TT, Russek SJ, Farb DH (2006). "Sulfated steroids as endogenous neuromodulators". Pharmacol. Biochem. Behav. 84 (4): 555–67. doi:10.1016/j.pbb.2006.07.031. PMID 17023038. S2CID 33659983.
  33. ^ Prough RA, Clark BJ, Klinge CM (2016). "Novel mechanisms for DHEA action". J. Mol. Endocrinol. 56 (3): R139–55. doi:10.1530/JME-16-0013. PMID 26908835.
  34. ^ Carlström K, Döberl A, Pousette A, Rannevik G, Wilking N (1984). "Inhibition of steroid sulfatase activity by danazol". Acta Obstet Gynecol Scand Suppl. 123: 107–11. doi:10.3109/00016348409156994. PMID 6238495. S2CID 45817485.
  35. ^ a b Sadozai H (2013). "Steroid sulfatase inhibitors: promising new therapy for breast cancer". J Pak Med Assoc. 63 (4): 509–15. PMID 23905452.
  36. ^ a b Thomas MP, Potter BV (2015). "Estrogen O-sulfamates and their analogues: Clinical steroid sulfatase inhibitors with broad potential". J. Steroid Biochem. Mol. Biol. 153: 160–9. doi:10.1016/j.jsbmb.2015.03.012. PMID 25843211. S2CID 24116740.
  37. ^ a b Tekoa L. King; Mary C. Brucker (25 October 2010). Pharmacology for Women's Health. Jones & Bartlett Publishers. pp. 292–. ISBN 978-1-4496-5800-7.
[edit]