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Identification
NameFluoxymesterone
Accession NumberDB01185  (APRD00981)
TypeSmall Molecule
GroupsApproved, Illicit
Description

An anabolic steroid that has been used in the treatment of male hypogonadism, delayed puberty in males, and in the treatment of breast neoplasms in women. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
11beta,17beta-Dihydroxy-9alpha-fluoro-17alpha-methyl-4-androster-3-oneNot AvailableNot Available
17alpha-Methyl-9alpha-fluoro-11beta-hydroxytesteroneNot AvailableNot Available
17α-Methyl-9α-fluoro-11β-hydroxytesteroneNot AvailableNot Available
9-Fluoro-11beta,17beta-dihydroxy-17-methylandrost-4-en-3-oneNot AvailableNot Available
9alpha-Fluoro-11beta-hydroxy-17-methyltestosteroneNot AvailableNot Available
FluoximesteronaSpanishINN
FluoxymesteronumLatinINN
Testosterone, 9-fluoro-11beta-hydroxy-17-methyl-Not AvailableNot Available
SaltsNot Available
Brand names
NameCompany
AndroxyNot Available
HalotestinUpjohn
Ora-TestrylBristol-Myers Squibb
TestoralMidy
U-GonoUpjohn
UItandrenCiba
Brand mixturesNot Available
Categories
CAS number76-43-7
WeightAverage: 336.4409
Monoisotopic: 336.210072999
Chemical FormulaC20H29FO3
InChI KeyYLRFCQOZQXIBAB-RBZZARIASA-N
InChI
InChI=1S/C20H29FO3/c1-17-8-6-13(22)10-12(17)4-5-15-14-7-9-19(3,24)18(14,2)11-16(23)20(15,17)21/h10,14-16,23-24H,4-9,11H2,1-3H3/t14-,15-,16-,17-,18-,19-,20-/m0/s1
IUPAC Name
(1R,2S,10S,11S,14S,15S,17S)-1-fluoro-14,17-dihydroxy-2,14,15-trimethyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-6-en-5-one
SMILES
[H][C@@]12CC[C@](C)(O)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])CCC2=CC(=O)CC[C@]12C
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassLipids
ClassSteroids and Steroid Derivatives
SubclassAndrogens and Derivatives
Direct parentAndrogens and Derivatives
Alternative parentsHydroxysteroids; Halogenated Steroids; Ketosteroids; Cyclohexanols; Tertiary Alcohols; Ketones; Cyclic Alcohols and Derivatives; Fluorohydrins; Polyamines; Organofluorides; Alkyl Fluorides
Substituentscyclohexanol; cyclic alcohol; tertiary alcohol; fluorohydrin; halohydrin; secondary alcohol; ketone; polyamine; organohalogen; organofluoride; alcohol; carbonyl group; alkyl halide; alkyl fluoride
Classification descriptionThis compound belongs to the androgens and derivatives. These are hydroxylated C19 steroid hormones. They are known to favour the development of masculine characteristics. They also show profound effects on scalp and body hair in humans.
Pharmacology
IndicationIn males, used as replacement therapy in conditions associated with symptoms of deficiency or absence of endogenous testosterone. In females, for palliation of androgenresponsive recurrent mammary cancer in women who are more than one year but less than five years postmenopausal.
PharmacodynamicsFluoxymesterone is a synthetic androgen, or male hormone, similar to testosterone. Fluoxymesterone works by attaching itself to androgen receptors; this causes it to interact with the parts of the cell involved in the making of proteins. It may cause an increase in the synthesis of some proteins or a decrease in the synthesis of others. These proteins have a variety of effects, including blocking the growth of some types of breast cancer cells, stimulating cells that cause male sexual characteristics, and stimulating the production of red blood cells.
Mechanism of actionFluoxymesterone is a synthetic androgenic anabolic steroid and is approximately 5 times as potent as natural methyltestosterone. Like testosterone and other androgenic hormones, fluoxymesterone binds to the androgen receptor. It produces retention of nitrogen, sodium, potassium, and phosphorus; increases protein anabolism; decreases amino acid catabolism and decreased urinary excretion of calcium. The antitumour activity of fluoxymesterone appears related to reduction or competitive inhibition of prolactin receptors or estrogen receptors or production.
AbsorptionOral absorption is less than 44%.
Volume of distributionNot Available
Protein bindingVery high (99%) with 80% to sex hormone binding globulin, 19% to albumin.
Metabolism

Presence of 17-alpha alkyl group reduces susceptibility to hepatic enzyme degradation, which slows metabolism and allows oral administration. Inactivation of testosterone occurs primarily in the liver

Route of eliminationNot Available
Half life9.2 hours
ClearanceNot Available
ToxicitySide effects include virilization (masculine traits in women), acne, fluid retention, and hypercalcemia.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 1.0
Blood Brain Barrier + 0.9633
Caco-2 permeable + 0.8586
P-glycoprotein substrate Substrate 0.7505
P-glycoprotein inhibitor I Non-inhibitor 0.7583
P-glycoprotein inhibitor II Non-inhibitor 0.87
Renal organic cation transporter Non-inhibitor 0.8136
CYP450 2C9 substrate Non-substrate 0.862
CYP450 2D6 substrate Non-substrate 0.8773
CYP450 3A4 substrate Substrate 0.7669
CYP450 1A2 substrate Non-inhibitor 0.9041
CYP450 2C9 substrate Non-inhibitor 0.8159
CYP450 2D6 substrate Non-inhibitor 0.9286
CYP450 2C19 substrate Non-inhibitor 0.917
CYP450 3A4 substrate Non-inhibitor 0.8354
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8585
Ames test Non AMES toxic 0.8777
Carcinogenicity Non-carcinogens 0.9242
Biodegradation Not ready biodegradable 1.0
Rat acute toxicity 2.7028 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.943
hERG inhibition (predictor II) Non-inhibitor 0.5784
Pharmacoeconomics
Manufacturers
  • Valeant pharmaceuticals international
  • Usl pharma inc
  • Watson laboratories inc
  • Pharmacia and upjohn co
  • Bristol myers squibb
Packagers
Dosage forms
FormRouteStrength
TabletOral
Prices
Unit descriptionCostUnit
Fluoxymesterone powder391.79USDg
Android 10 mg capsule11.35USDeach
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point265U.S. Patent 2,793,218 U.S. Patent 2,813,881
water solubility67.5 mg/LNot Available
logP2.38HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.0452ALOGPS
logP2.5ALOGPS
logP2.38ChemAxon
logS-3.9ALOGPS
pKa (Strongest Acidic)13.6ChemAxon
pKa (Strongest Basic)-3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area57.53 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity90.19 m3·mol-1ChemAxon
Polarizability36.63 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectra
References
Synthesis Reference

U.S. Patent 2,793,218
U.S. Patent 2,813,881

General Reference
  1. Miner JN, Chang W, Chapman MS, Finn PD, Hong MH, Lopez FJ, Marschke KB, Rosen J, Schrader W, Turner R, van Oeveren A, Viveros H, Zhi L, Negro-Vilar A: An orally active selective androgen receptor modulator is efficacious on bone, muscle, and sex function with reduced impact on prostate. Endocrinology. 2007 Jan;148(1):363-73. Epub 2006 Oct 5. Pubmed
External Links
ResourceLink
KEGG DrugD00327
PubChem Compound6446
PubChem Substance46508867
ChemSpider6205
BindingDB18189
ChEBI5120
ChEMBLCHEMBL1445
Therapeutic Targets DatabaseDAP000904
PharmGKBPA164744518
IUPHAR2861
Guide to Pharmacology2861
Drug Product Database30902
RxListhttp://www.rxlist.com/cgi/generic2/fluoxy.htm
Drugs.comhttp://www.drugs.com/cdi/fluoxymesterone.html
WikipediaFluoxymesterone
ATC CodesG03BA01
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(75.7 KB)
Interactions
Drug Interactions
Drug
AcenocoumarolThe androgen, fluoxymesterone, may increase the anticoagulant effect of acenocoumarol.
AnisindioneThe androgen, fluoxymesterone, may increase the anticoagulant effect of anisindione.
DicoumarolThe androgen, fluoxymesterone, may increase the anticoagulant effect of dicumarol.
WarfarinFluoxymesterone may increase the serum concentration and anticoagulant effect of warfarin. Monitor for changes in prothrombin time and therapeutic effects of warfarin if fluoxymesterone is initiated, discontinued or dose changed.
Food Interactions
  • Take with food.

Targets

1. Androgen receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Androgen receptor P10275 Details

References:

  1. Fernandez L, Chirino R, Boada LD, Navarro D, Cabrera N, del Rio I, Diaz-Chico BN: Stanozolol and danazol, unlike natural androgens, interact with the low affinity glucocorticoid-binding sites from male rat liver microsomes. Endocrinology. 1994 Mar;134(3):1401-8. Pubmed
  2. Kasperk CH, Wergedal JE, Farley JR, Linkhart TA, Turner RT, Baylink DJ: Androgens directly stimulate proliferation of bone cells in vitro. Endocrinology. 1989 Mar;124(3):1576-8. Pubmed
  3. Smallridge RC, Vigersky R, Glass AR, Griffin JE, White BJ, Eil C: Androgen receptor abnormalities in identical twins with oligospermia. Clinical and biochemical studies. Am J Med. 1984 Dec;77(6):1049-54. Pubmed
  4. Miner JN, Chang W, Chapman MS, Finn PD, Hong MH, Lopez FJ, Marschke KB, Rosen J, Schrader W, Turner R, van Oeveren A, Viveros H, Zhi L, Negro-Vilar A: An orally active selective androgen receptor modulator is efficacious on bone, muscle, and sex function with reduced impact on prostate. Endocrinology. 2007 Jan;148(1):363-73. Epub 2006 Oct 5. Pubmed
  5. Kemppainen JA, Langley E, Wong CI, Bobseine K, Kelce WR, Wilson EM: Distinguishing androgen receptor agonists and antagonists: distinct mechanisms of activation by medroxyprogesterone acetate and dihydrotestosterone. Mol Endocrinol. 1999 Mar;13(3):440-54. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Estrogen receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Estrogen receptor P03372 Details

References:

  1. Ingle JN, Suman VJ, Mailliard JA, Kugler JW, Krook JE, Michalak JC, Pisansky TM, Wold LE, Donohue JH, Goetz MP, Perez EA: Randomized trial of tamoxifen alone or combined with fluoxymesterone as adjuvant therapy in postmenopausal women with resected estrogen receptor positive breast cancer. North Central Cancer Treatment Group Trial 89-30-52. Breast Cancer Res Treat. 2006 Jul;98(2):217-22. Epub 2006 Mar 15. Pubmed
  2. Sledge GW Jr, Hu P, Falkson G, Tormey D, Abeloff M: Comparison of chemotherapy with chemohormonal therapy as first-line therapy for metastatic, hormone-sensitive breast cancer: An Eastern Cooperative Oncology Group study. J Clin Oncol. 2000 Jan;18(2):262-6. Pubmed
  3. Pearson OH, Manni A, Arafah BM: Antiestrogen treatment of breast cancer: an overview. Cancer Res. 1982 Aug;42(8 Suppl):3424s-3429s. Pubmed
  4. Perloff M, Norton L, Korzun AH, Wood WC, Carey RW, Gottlieb A, Aust JC, Bank A, Silver RT, Saleh F, Canellos GP, Perry MC, Weiss RB, Holland JF: Postsurgical adjuvant chemotherapy of stage II breast carcinoma with or without crossover to a non-cross-resistant regimen: a Cancer and Leukemia Group B study. J Clin Oncol. 1996 May;14(5):1589-98. Pubmed
  5. Swain SM, Steinberg SM, Bagley C, Lippman ME: Tamoxifen and fluoxymesterone versus tamoxifen and danazol in metastatic breast cancer—a randomized study. Breast Cancer Res Treat. 1988 Sep;12(1):51-7. Pubmed

3. Prolactin receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Prolactin receptor P16471 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

4. Glucocorticoid receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Glucocorticoid receptor P04150 Details

References:

  1. Mayer M, Rosen F: Interaction of anabolic steroids with glucocorticoid receptor sites in rat muscle cytosol. Am J Physiol. 1975 Nov;229(5):1381-6. Pubmed

Carriers

1. Sex hormone-binding globulin

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Sex hormone-binding globulin P04278 Details

References:

  1. Smallridge RC, Vigersky R, Glass AR, Griffin JE, White BJ, Eil C: Androgen receptor abnormalities in identical twins with oligospermia. Clinical and biochemical studies. Am J Med. 1984 Dec;77(6):1049-54. Pubmed
  2. Pugeat MM, Dunn JF, Nisula BC: Transport of steroid hormones: interaction of 70 drugs with testosterone-binding globulin and corticosteroid-binding globulin in human plasma. J Clin Endocrinol Metab. 1981 Jul;53(1):69-75. Pubmed
  3. Vigersky RA, Easley RB, Loriaux DL: Effect of fluoxymesterone on the pituitary-gonadal axis: the role of testosterone-estradiol-binding globulin. J Clin Endocrinol Metab. 1976 Jul;43(1):1-9. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on April 23, 2014 17:10