Hydroxyflutamide

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Hydroxyflutamide
Hydroxyflutamide.svg
Hydroxyflutamide molecule ball.png
Clinical data
Synonyms 2-Hydroxyflutamide; HF; OHF; Flutamide-hydroxide; SCH-16423; Hydroxyniphtholide; Hydroxyniftolide; α,α,α-Trifluoro-2-methyl-4'-nitro-m-lactotoluidide
Drug class Nonsteroidal antiandrogen
Identifiers
CAS Number
  • 52806-53-8
PubChem CID
  • 91649
IUPHAR/BPS
  • 2862
ChemSpider
  • 82752
UNII
  • 31D90UKP5Y
KEGG
  • C14204
ChEBI
  • CHEBI:43064
ChEMBL
  • ChEMBL491
ECHA InfoCard 100.169.708
Chemical and physical data
Formula C11H11F3N2O4
Molar mass 292.21125 g/mol g·mol−1
3D model (JSmol)
  • Interactive image

Hydroxyflutamide (HF, OHF) (developmental code name SCH-16423), or 2-hydroxyflutamide, is a nonsteroidal antiandrogen (NSAA) and the major active metabolite of flutamide, which is considered to be a prodrug of hydroxyflutamide as the active form.[1][2] It has been reported to possess an IC50 of 700 nM for the androgen receptor (AR), which is about 4-fold less than that of bicalutamide.[3]

Affinities of selected androgen receptor ligands

Compound AR RBA (%)
Metribolone 100
Dihydrotestosterone 85
Cyproterone acetate 7.8
Bicalutamide 1.4
Nilutamide 0.9
Hydroxyflutamide 0.57
Flutamide <0.0057
Note: Human prostate tissue used for the assays. Source: [4]

Relative affinities (%) of antiandrogens at steroid-hormone receptors

Antiandrogen AR PR ER GR MR
Cyproterone acetate 8–10 60 <0.1 5 1
Chlormadinone acetate 5 175 <0.1 38 1
Megestrol acetate 5 152 <0.1 50 3
Spironolactone 7 0.4a <0.1 2a 182
Trimethyltrienolone 3.6 <1 <1 <1 <1
Inocoterone 0.8 <0.1 <0.1 <0.1 <0.1
Inocoterone acetate <0.1 <0.1 <0.1 <0.1 <0.1
Flutamide <0.1 <0.1 <0.1 <0.1 <0.1
Hydroxyflutamide 0.5–0.8 <0.1 <0.1 <0.1 <0.1
Nilutamide 0.5–0.8 <0.1 <0.1 <0.1 <0.1
Bicalutamide 1.8 <0.1 <0.1 <0.1 <0.1
Notes: (1): Reference ligands (100%) were testosterone for the AR, progesterone for the PR, estradiol for the ER, dexamethasone for the GR, and aldosterone for the MR. (2): Tissues were rat prostate (AR), rabbit uterus (PR), mouse uterus (ER), rat thymus (GR), and rat kidney (MR). (3): Incubation times (0°C) were 24 hours (AR, a), 2 hours (PR, ER), 4 hours (GR), and 1 hour (MR). (4): Assay methods were different for bicalutamide for receptors besides the AR. Sources: [5][6][7][8][9][10][11][12][13][14]

Relative affinities of first-generation nonsteroidal antiandrogens for the androgen receptor

Species IC50 (nM) RBA (ratio)
Bicalutamide 2-Hydroxyflutamide Nilutamide Bica / 2-OH-flu Bica / nilu Ref
Rat 190 700 ND 4.0 ND [15]
Rat ~400 ~900 ~900 2.3 2.3 [16]
Rat ND ND ND 3.3 ND [17]
Rata 3595 4565 18620 1.3 5.2 [18]
Human ~300 ~700 ~500 2.5 1.6 [4]
Human ~100 ~300 ND ~3.0 ND [19]
Humana 2490 2345 5300 1.0 2.1 [18]
Footnotes: a = Controversial data. Source: [20]

Relative potencies of selected antiandrogens

Antiandrogen Relative potency
Zanoterone 0.4
Cyproterone acetate 1.0
Flutamide 3.3
Hydroxyflutamide 3.5
Bicalutamide 4.3
Description: Relative potencies of orally administered antiandrogens in antagonizing 0.8 to 1.0 mg/kg s.c. testosterone propionate-induced ventral prostate weight increase in castrated immature male rats. Source: [21]

References

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