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.

Structure

Similar Structures

Synonyms

11β,17β-Dihydroxy-9α-fluoro-17α-methyl-4-androster-3-one
17α-Methyl-9α-fluoro-11β-hydroxytesterone
9-Fluoro-11β,17β-dihydroxy-17-methylandrost-4-en-3-one
9α-Fluoro-11β-hydroxy-17-methyltestosterone
Fluoximesterona
Fluoxymesterone
Fluoxymestérone
Fluoxymesteronum

External IDs

NSC-12165

Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Halotestin	Tablet	5 mg	Oral	Pfizer	1962-12-31	2006-08-02
Halotestin	Tablet	10 mg/1	Oral	UNSPECIFIED	2006-02-06	Not applicable
Halotestin	Tablet	5 mg/1	Oral	UNSPECIFIED	2006-02-06	Not applicable
Halotestin	Tablet	2 mg/1	Oral	UNSPECIFIED	2006-02-06	Not applicable

Generic Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Androxy	Tablet	10 mg/1	Oral	Upsher-Smith Laboratories, LLC	1983-10-21	Not applicable

International/Other Brands

Ora-Testryl (Bristol-Myers Squibb) / Testoral (Midy) / U-Gono (Upjohn) / UItandren (Ciba)

Categories

UNII

9JU12S4YFY

CAS number

76-43-7

Weight

Average: 336.4409
Monoisotopic: 336.210072999

Chemical Formula

C₂₀H₂₉FO₃

InChI Key

YLRFCQOZQXIBAB-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[8.7.0.0²,⁷.0¹¹,¹⁵]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

Pharmacology

Indication

In 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.

Associated Conditions

Pharmacodynamics

Fluoxymesterone 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 action

Fluoxymesterone 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.

Target	Actions	Organism
AAndrogen receptor	agonist	Humans
AEstrogen receptor alpha	antagonist	Humans
AProlactin receptor	antagonist	Humans
UGlucocorticoid receptor	antagonist	Humans
UCorticosteroid 11-beta-dehydrogenase isozyme 2	inhibitor	Humans

Absorption

Oral absorption is less than 44%.

Volume of distribution

Not Available

Protein binding

Very 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 elimination

Not Available

Half life

9.2 hours

Clearance

Not Available

Toxicity

Side effects include virilization (masculine traits in women), acne, fluid retention, and hypercalcemia.

Affected organisms

Humans and other mammals

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

Drug	Interaction
(R)-warfarin	Fluoxymesterone may increase the anticoagulant activities of (R)-warfarin.
(S)-Warfarin	Fluoxymesterone may increase the anticoagulant activities of (S)-Warfarin.
2,4-thiazolidinedione	Fluoxymesterone may increase the hypoglycemic activities of 2,4-thiazolidinedione.
4-hydroxycoumarin	Fluoxymesterone may increase the anticoagulant activities of 4-hydroxycoumarin.
Acarbose	Fluoxymesterone may increase the hypoglycemic activities of Acarbose.
Acenocoumarol	Fluoxymesterone may increase the anticoagulant activities of Acenocoumarol.
Acetohexamide	Fluoxymesterone may increase the hypoglycemic activities of Acetohexamide.
AICA ribonucleotide	Fluoxymesterone may increase the hypoglycemic activities of AICA ribonucleotide.
Albiglutide	Fluoxymesterone may increase the hypoglycemic activities of Albiglutide.
Aldosterone	The risk or severity of fluid retention can be increased when Aldosterone is combined with Fluoxymesterone.

Food Interactions

Take with food.

References

Synthesis Reference

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

General References

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:17023534]

External Links

Human Metabolome Database: HMDB0015316
KEGG Drug: D00327
PubChem Compound: 6446
PubChem Substance: 46508867
ChemSpider: 6205
BindingDB: 18189
ChEBI: 5120
ChEMBL: CHEMBL1445
Therapeutic Targets Database: DAP000904
PharmGKB: PA164744518
IUPHAR: 2861
Guide to Pharmacology: GtP Drug Page
RxList: RxList Drug Page
Drugs.com: Drugs.com Drug Page
Wikipedia: Fluoxymesterone

ATC Codes

G03BA01 — Fluoxymesterone

MSDS

Download (75.7 KB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
2	Terminated	Treatment	Metastatic Breast Cancer (MBC)	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Major Pharmaceuticals
Qualitest
Spectrum Pharmaceuticals
USL Pharma Inc.
Valeant Ltd.

Dosage forms

Form	Route	Strength
Tablet	Oral	10 mg/1
Tablet	Oral	2 mg/1
Tablet	Oral	5 mg
Tablet	Oral	5 mg/1

Prices

Unit description	Cost	Unit
Fluoxymesterone powder	391.79USD	g
Android 10 mg capsule	11.35USD	each

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Not Available

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	265	U.S. Patent 2,793,218 U.S. Patent 2,813,881
water solubility	67.5 mg/L	Not Available
logP	2.38	HANSCH,C ET AL. (1995)

Predicted Properties

Property	Value	Source
Water Solubility	0.0452 mg/mL	ALOGPS
logP	2.5	ALOGPS
logP	2.38	ChemAxon
logS	-3.9	ALOGPS
pKa (Strongest Acidic)	13.6	ChemAxon
pKa (Strongest Basic)	-3	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	3	ChemAxon
Hydrogen Donor Count	2	ChemAxon
Polar Surface Area	57.53 Å²	ChemAxon
Rotatable Bond Count	0	ChemAxon
Refractivity	90.19 m³·mol^-1	ChemAxon
Polarizability	36.63 Å³	ChemAxon
Number of Rings	4	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

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 inhibitor	Non-inhibitor	0.8159
CYP450 2D6 inhibitor	Non-inhibitor	0.9286
CYP450 2C19 inhibitor	Non-inhibitor	0.917
CYP450 3A4 inhibitor	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

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	Not Available
Mass Spectrum (Electron Ionization)	MS	splash10-006x-5951000000-4c37d94fe4ed0b343941
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not Available

Taxonomy

Description: This compound belongs to the class of organic compounds known as androgens and derivatives. These are 3-hydroxylated C19 steroid hormones. They are known to favor the development of masculine characteristics. They also show profound effects on scalp and body hair in humans.
Kingdom: Organic compounds
Super Class: Lipids and lipid-like molecules
Class: Steroids and steroid derivatives
Sub Class: Androstane steroids
Direct Parent: Androgens and derivatives
Alternative Parents: Halogenated steroids / 3-oxo delta-4-steroids / 17-hydroxysteroids / 11-beta-hydroxysteroids / Delta-4-steroids / Cyclohexenones / Tertiary alcohols / Secondary alcohols / Fluorohydrins / Cyclic alcohols and derivatives
show 4 more
Substituents: Androgen-skeleton / 3-oxo-delta-4-steroid / 3-oxosteroid / 17-hydroxysteroid / 11-hydroxysteroid / 11-beta-hydroxysteroid / Oxosteroid / 9-halo-steroid / Halo-steroid / Hydroxysteroid
show 20 more
Molecular Framework: Aliphatic homopolycyclic compounds
External Descriptors: 11beta-hydroxy steroid, 3-oxo Delta(4)-steroid, 17beta-hydroxy steroid, fluorinated steroid, anabolic androgenic steroid (CHEBI:5120) / C19 steroids (androgens) and derivatives (LMST02020025)

Targets

Property	Measurement	pH	Temperature (°C)	References
EC 50 (nM)	0.3	7.4	37	17439112
Ki (nM)	5.7	7.4	37	17439112

Details1. Androgen receptor

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Agonist

General Function: Zinc ion binding
Specific Function: Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription ...
Gene Name: AR
Uniprot ID: P10275
Uniprot Name: Androgen receptor
Molecular Weight: 98987.9 Da

References

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:8119180]
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:2521824]
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:6439037]
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:17023534]
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:10077001]
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Details2. Estrogen receptor alpha

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Antagonist

General Function: Zinc ion binding
Specific Function: Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissu...
Gene Name: ESR1
Uniprot ID: P03372
Uniprot Name: Estrogen receptor
Molecular Weight: 66215.45 Da

References

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:16538529]
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:10637238]
Pearson OH, Manni A, Arafah BM: Antiestrogen treatment of breast cancer: an overview. Cancer Res. 1982 Aug;42(8 Suppl):3424s-3429s. [PubMed:7044524]
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:8622076]
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:3058238]

Details3. Prolactin receptor

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Antagonist

General Function: Protein homodimerization activity
Specific Function: This is a receptor for the anterior pituitary hormone prolactin (PRL). Acts as a prosurvival factor for spermatozoa by inhibiting sperm capacitation through suppression of SRC kinase activation and...
Gene Name: PRLR
Uniprot ID: P16471
Uniprot Name: Prolactin receptor
Molecular Weight: 69505.045 Da

References

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
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:17016423]

Details4. Glucocorticoid receptor

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Antagonist

General Function: Zinc ion binding
Specific Function: Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modula...
Gene Name: NR3C1
Uniprot ID: P04150
Uniprot Name: Glucocorticoid receptor
Molecular Weight: 85658.57 Da

References

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:173192]

Details5. Corticosteroid 11-beta-dehydrogenase isozyme 2

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Steroid binding
Specific Function: Catalyzes the conversion of cortisol to the inactive metabolite cortisone. Modulates intracellular glucocorticoid levels, thus protecting the nonselective mineralocorticoid receptor from occupation...
Gene Name: HSD11B2
Uniprot ID: P80365
Uniprot Name: Corticosteroid 11-beta-dehydrogenase isozyme 2
Molecular Weight: 44126.06 Da

References

Furstenberger C, Vuorinen A, Da Cunha T, Kratschmar DV, Saugy M, Schuster D, Odermatt A: The anabolic androgenic steroid fluoxymesterone inhibits 11beta-hydroxysteroid dehydrogenase 2-dependent glucocorticoid inactivation. Toxicol Sci. 2012 Apr;126(2):353-61. doi: 10.1093/toxsci/kfs022. Epub 2012 Jan 23. [PubMed:22273746]

Carriers

Details1. Sex hormone-binding globulin

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Antagonist

General Function: Androgen binding
Specific Function: Functions as an androgen transport protein, but may also be involved in receptor mediated processes. Each dimer binds one molecule of steroid. Specific for 5-alpha-dihydrotestosterone, testosterone...
Gene Name: SHBG
Uniprot ID: P04278
Uniprot Name: Sex hormone-binding globulin
Molecular Weight: 43778.755 Da

References

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:6439037]
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:7195405]
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:947929]

Drug created on June 13, 2005 07:24 / Updated on March 08, 2019 19:22

Fluoxymesterone

Identification

Structure for Fluoxymesterone (DB01185)

Pharmacology

Interactions

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Taxonomy

Targets

References

References

References

References

References

Carriers

References