Steroidogenesis inhibitor

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Steroidogenesis inhibitor
Drug class
Class identifiers
Synonyms Steroid biosynthesis inhibitor; Steroid synthesis inhibitor
Use Various
Biological target Steroidogenic enzymes
Chemical class Steroidal; Nonsteroidal
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 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

Cholesterol synthesis inhibitors

Acetyl-CoA to lanosterol inhibitors

Lanosterol to cholesterol inhibitors

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one of the last steps in cholesterol biosynthesis, and were formerly used to treat hypercholesterolemia, but were withdrawn from the market due to toxicity caused by accumulation of desmosterol in tissues.[12][13]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

Non-specific steroid hormone synthesis inhibitors

Corticosteroid-specific synthesis inhibitors

Sex steroid-specific synthesis inhibitors

Other steroid synthesis inhibitors

List of steroid metabolism modulators

Enzyme SubstratesProducts Inhibitors Inducers
HMG-CoA reductase
(HMGCR)
HMG-CoAMevalonic acid AtorvastatinCerivastatinColestoloneFluvastatinLovastatinMevastatinPitavastatinPravastatinRosuvastatinSimvastatin
FPPS Dimethylallyl pyrophosphate (isoprenyl pyrophosphate)Farnesyl pyrophosphateIsopentenyl pyrophosphateFarnesyl pyrophosphate Alendronic acidIbandronic acidIncadronic acidPamidronic acidRisedronic acidZoledronic acid
7-DHCR 7-DehydrocholesterolCholesterol AY-9944BM-15766Triparanol
24-DHCR DesmosterolCholesterol AzacosterolClomifeneTriparanolWY-3457
P450scc
(CYP11A1)
Cholesterol22R-Hydroxycholesterol22R-Hydroxycholesterol20α,22R-Dihydroxycholesterol20α,22R-DihydroxycholesterolPregnenolone 22-ABC3,3′-Dimethoxybenzidine3-MethoxybenzidineAminoglutethimideAmphenone BCanrenoneCyanoketoneDanazolEtomidateKetoconazoleLevoketoconazoleMitotaneSpironolactoneTrilostane
3β-HSD
(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-HSD
(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 canrenoateSpironolactoneTrilostane
Aldosterone
synthase
(CYP11B2)
CorticosteroneAldosterone 18-Ethynylprogesterone (18-ethinylprogesterone)18-VinylprogesteroneAminoglutethimideAzelnidipineBenidipineCanrenoneCilnidipineEfonidipineFAD286FadrozoleKetoconazoleMetyraponeMespirenoneOsilodrostatPotassium canrenoateSpironolactone
17β-HSD
(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-HSD
(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)
SST/EST DehydroepiandrosteroneDehydroepiandrosterone sulfateEstroneEstrone sulfate 4′OH-CB796-Hydroxyflavone2,6-Dichloro-4-nitrophenol (DCNP)7,8-DihydroxyflavoneEquolGalanginGenisteinParabens (e.g., butylparaben) • Pentachlorophenol (PCP)Triclosan
STS 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

References

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External links

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