Steroidogenesis inhibitor

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 inhibitor
Drug class
Class identifiers
SynonymsSteroid biosynthesis inhibitor; Steroid synthesis inhibitor
UseVarious
Biological targetSteroidogenic enzymes
Chemical classSteroidal; Nonsteroidal
Legal status
In Wikidata

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

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Cholesterol synthesis inhibitors

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Cholesterol biosynthesis from acetyl-CoA.

Acetyl-CoA to lanosterol inhibitors

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Lanosterol to cholesterol inhibitors

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  • 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one of the last steps in cholesterol biosynthesis, and were formerly used to treat hypercholesterolemia, but were withdrawn from the market due to toxicity caused by accumulation of desmosterol in tissues.[12][13]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

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

Non-specific steroid hormone synthesis inhibitors

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Corticosteroid-specific synthesis inhibitors

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Sex steroid-specific synthesis inhibitors

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Other steroid synthesis inhibitors

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List of steroid metabolism modulators

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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

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References

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