Hydroxyflutamide
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]
Compound | AR RBA (%) | |
---|---|---|
Metribolone | 100 | |
Dihydrotestosterone | 85 | |
Cyproterone acetate | 7.8 | |
Bicalutamide | 1.4 | |
Nilutamide | 0.9 | |
Hydroxyflutamide | 0.57 | |
Flutamide | <0.0057 | |
Notes: Human prostate tissue used for the assays. Sources: See template. |
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: See template. |
Species | IC50 (nM) | RBA (ratio) | ||||
---|---|---|---|---|---|---|
Bicalutamide | 2-Hydroxyflutamide | Nilutamide | Bica / 2-OH-flu | Bica / nilu | Ref | |
Rat | 190 | 700 | ND | 4.0 | ND | [4] |
Rat | ~400 | ~900 | ~900 | 2.3 | 2.3 | [5] |
Rat | ND | ND | ND | 3.3 | ND | [6] |
Rata | 3595 | 4565 | 18620 | 1.3 | 5.2 | [7] |
Human | ~300 | ~700 | ~500 | 2.5 | 1.6 | [8] |
Human | ~100 | ~300 | ND | ~3.0 | ND | [9] |
Humana | 2490 | 2345 | 5300 | 1.0 | 2.1 | [7] |
Footnotes: a = Controversial data. Sources: See template. |
Antiandrogen | Relative potency |
---|---|
Bicalutamide | 4.3 |
Hydroxyflutamide | 3.5 |
Flutamide | 3.3 |
Cyproterone acetate | 1.0 |
Zanoterone | 0.4 |
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. Sources: See template. |
Clinical data | |
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Other names | 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 | |
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CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.169.708 |
Chemical and physical data | |
Formula | C11H11F3N2O4 |
Molar mass | 292.214 g·mol−1 |
3D model (JSmol) | |
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References
- Serra, C; Sandor, NL; Jang, H; Lee, D; Toraldo, G; Guarneri, T; Wong, S; Zhang, A; Guo, W; Jasuja, R; Bhasin, S (2013). "The effects of testosterone deprivation and supplementation on proteasomal and autophagy activity in the skeletal muscle of the male mouse: Differential effects on high-androgen responder and low-androgen responder muscle groups". Endocrinology. 154 (12): 4594–606. doi:10.1210/en.2013-1004. PMC 3836062. PMID 24105483.
- Singh, Shankar; Gauthier, Sylvain; Labrie, Fernand (2000). "Androgen Receptor Antagonists (Antiandrogens) Structure-Activity Relationships". Current Medicinal Chemistry. 7 (2): 211–247. doi:10.2174/0929867003375371. ISSN 0929-8673. PMID 10637363.
- Furr BJ (1995). "Casodex: preclinical studies and controversies". Annals of the New York Academy of Sciences. 761: 79–96. doi:10.1111/j.1749-6632.1995.tb31371.x. PMID 7625752.
- Furr BJ, Valcaccia B, Curry B, Woodburn JR, Chesterson G, Tucker H (June 1987). "ICI 176,334: a novel non-steroidal, peripherally selective antiandrogen". J. Endocrinol. 113 (3): R7–9. doi:10.1677/joe.0.113R007. PMID 3625091.
- Teutsch G, Goubet F, Battmann T, Bonfils A, Bouchoux F, Cerede E, Gofflo D, Gaillard-Kelly M, Philibert D (January 1994). "Non-steroidal antiandrogens: synthesis and biological profile of high-affinity ligands for the androgen receptor". J. Steroid Biochem. Mol. Biol. 48 (1): 111–9. doi:10.1016/0960-0760(94)90257-7. PMID 8136296.
- Winneker RC, Wagner MM, Batzold FH (December 1989). "Studies on the mechanism of action of Win 49596: a steroidal androgen receptor antagonist". J. Steroid Biochem. 33 (6): 1133–8. doi:10.1016/0022-4731(89)90420-2. PMID 2615358.
- Luo, S; Martel, C; LeBlanc, G; Candas, B; Singh, S M; Labrie, C; Simard, J; Belanger, A; Labrie, F (1996). "Relative potencies of Flutamide and Casodex: preclinical studies". Endocrine Related Cancer. 3 (3): 229–241. doi:10.1677/erc.0.0030229. ISSN 1351-0088.
- Ayub M, Levell MJ (August 1989). "The effect of ketoconazole related imidazole drugs and antiandrogens on [3H] R 1881 binding to the prostatic androgen receptor and [3H]5 alpha-dihydrotestosterone and [3H]cortisol binding to plasma proteins". J. Steroid Biochem. 33 (2): 251–5. doi:10.1016/0022-4731(89)90301-4. PMID 2788775.
- Kemppainen JA, Wilson EM (July 1996). "Agonist and antagonist activities of hydroxyflutamide and Casodex relate to androgen receptor stabilization". Urology. 48 (1): 157–63. doi:10.1016/S0090-4295(96)00117-3. PMID 8693644.
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