DT-Web

DB01185 - Fluoxymesterone


Identification
Name Fluoxymesterone
Accession Number DB01185 (APRD00981)
Type small molecule
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
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 336.4409
Groups illicit
Monoisotopic Weight 336.210072999
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.
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.
Absorption Oral absorption is less than 44%.
Protein binding Very high (99%) with 80% to sex hormone binding globulin, 19% to albumin.
Biotransformation 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
Toxicity Side effects include virilization (masculine traits in women), acne, fluid retention, and hypercalcemia.
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Acenocoumarol The androgen, fluoxymesterone, may increase the anticoagulant effect of acenocoumarol.
Anisindione The androgen, fluoxymesterone, may increase the anticoagulant effect of anisindione.
Dicumarol The androgen, fluoxymesterone, may increase the anticoagulant effect of dicumarol.
Warfarin Fluoxymesterone 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


Androgen receptor
Name Androgen receptor
Gene Name AR
Pharmacological action yes
Actions agonist
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
  • 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
  • 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
  • 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
  • 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
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
DTHybrid score 1.2175
Estrogen receptor
Name Estrogen receptor
Gene Name ESR1
Pharmacological action yes
Actions antagonist
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
  • 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
  • Pearson OH, Manni A, Arafah BM: Antiestrogen treatment of breast cancer: an overview. Cancer Res. 1982 Aug;42(8 Suppl):3424s-3429s. - Pubmed
  • 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
  • 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
DTHybrid score 0.8101
Prolactin receptor
Name Prolactin receptor
Gene Name PRLR
Pharmacological action yes
Actions antagonist
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
  • 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
DTHybrid score 0.7712
Glucocorticoid receptor
Name Glucocorticoid receptor
Gene Name NR3C1
Pharmacological action unknown
Actions antagonist
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
DTHybrid score 0.9057

Carriers


Predictions


Id Partner name Gene Name Score
85 Growth hormone receptor GHR 0.4259
232 Corticosteroid-binding globulin SERPINA6 0.2638
6241 Nuclear receptor coactivator 2 NCOA2 0.2436
4512 Cytochrome P450 3A4 CYP3A4 0.1569
3811 Cytochrome P450 19A1 CYP19A1 0.1523
614 Progesterone receptor PGR 0.1387
869 Estrogen receptor beta ESR2 0.1357
1588 Multidrug resistance protein 1 ABCB1 0.079
469 Annexin A1 ANXA1 0.0497
737 Mineralocorticoid receptor NR3C2 0.0478
6139 Solute carrier organic anion transporter family member 1A2 SLCO1A2 0.047
4924 Cytochrome P450 2C8 CYP2C8 0.0407
587 Serum albumin ALB 0.0384
4757 Cytochrome P450 2C9 CYP2C9 0.0378
4118 Cytochrome P450 3A5 CYP3A5 0.0368
805 Cytochrome P450 11B1, mitochondrial CYP11B1 0.0361
269 Adrenodoxin, mitochondrial FDX1 0.0348
6016 Cytochrome P450 2C19 CYP2C19 0.0312
1649 Small inducible cytokine A2 CCL2 0.0275
4200 Cytochrome P450 1A2 CYP1A2 0.0274
6107 Cytochrome P450 3A7 CYP3A7 0.0259
6024 Cytochrome P450 1A1 CYP1A1 0.0257
6017 Cholesterol side-chain cleavage enzyme, mitochondrial CYP11A1 0.0257
380 Cytochrome P450 17A1 CYP17A1 0.0246
226 Gonadotropin-releasing hormone receptor GNRHR 0.0231
6030 Cytochrome P450 2B6 CYP2B6 0.0229
217 Estradiol 17-beta-dehydrogenase 1 HSD17B1 0.0229
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0193
6142 Solute carrier family 22 member 8 SLC22A8 0.0182
723 Cytosolic phospholipase A2 PLA2G4A 0.0179
6145 Solute carrier family 22 member 1 SLC22A1 0.0166
1898 Cytochrome P450 1B1 CYP1B1 0.0159
3810 Catechol O-methyltransferase COMT 0.015
66 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type II HSD3B2 0.0149
1735 Canalicular multispecific organic anion transporter 1 ABCC2 0.014
290 Prostaglandin G/H synthase 2 PTGS2 0.014
596 3-oxo-5-alpha-steroid 4-dehydrogenase 1 SRD5A1 0.014
4119 Cytochrome P450 2D6 CYP2D6 0.013
6022 UDP-glucuronosyltransferase 1-1 UGT1A1 0.0127
6228 Nuclear receptor coactivator 1 NCOA1 0.0122
6023 Cytochrome P450 11B2, mitochondrial CYP11B2 0.0121
687 Tyrosine-protein phosphatase non-receptor type 1 PTPN1 0.0118
3941 Amine oxidase [flavin-containing] A MAOA 0.0111
2751 Holliday junction ATP-dependent DNA helicase ruvB ruvB 0.0105
4755 Holliday junction ATP-dependent DNA helicase ruvB ruvB 0.0105
6141 Sodium/bile acid cotransporter SLC10A1 0.0105
3923 Cholinesterase BCHE 0.0101
5718 Cytochrome P450 2A6 CYP2A6 0.0098
373 Transthyretin TTR 0.0094
4615 Chain A, Red Copper Protein Nitrosocyanin NE0143 0.0093
57 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type I HSD3B1 0.0083
6147 Solute carrier family 22 member 3 SLC22A3 0.008
3939 Amine oxidase [flavin-containing] B MAOB 0.0078
1284 Nuclear receptor subfamily 1 group I member 2 NR1I2 0.0077
2107 Microtubule-associated protein 1A MAP1A 0.0075
4120 NADPH--cytochrome P450 reductase POR 0.0074
4604 Liver carboxylesterase 1 CES1 0.0071
650 Aldo-keto reductase family 1 member C3 AKR1C3 0.0071
1758 GTPase HRas HRAS 0.0068
862 Multidrug resistance-associated protein 1 ABCC1 0.0065
6014 Cytochrome P450 2A13 CYP2A13 0.0064
6031 Cytochrome P450 3A43 CYP3A43 0.0063
6500 Phospholipase A2 PLA2G1B 0.006
1852 Microtubule-associated protein 2 MAP2 0.0056
776 Bile salt export pump ABCB11 0.0055
1632 Solute carrier organic anion transporter family member 2B1 SLCO2B1 0.0055
6013 Cytochrome P450 2E1 CYP2E1 0.0055
6220 Aryl hydrocarbon receptor AHR 0.0053
6153 Solute carrier organic anion transporter family member 4A1 SLCO4A1 0.0051
364 Corticosteroid 11-beta-dehydrogenase isozyme 1 HSD11B1 0.0048
1490 Solute carrier organic anion transporter family member 1B1 SLCO1B1 0.0048
6085 Fatty acid-binding protein, intestinal FABP2 0.0047
2300 Lysozyme E 0.0047
3633 Lysozyme R 0.0047
5597 Lysozyme 17 0.0047
6158 Solute carrier organic anion transporter family member 1C1 SLCO1C1 0.0046
1729 Solute carrier family 22 member 6 SLC22A6 0.0043
6157 Solute carrier organic anion transporter family member 1B3 SLCO1B3 0.0042
20 Prostaglandin G/H synthase 1 PTGS1 0.0039
833 Organic cation/carnitine transporter 1 SLC22A4 0.0039
1024 Solute carrier family 22 member 11 SLC22A11 0.0038
6143 Solute carrier family 22 member 7 SLC22A7 0.0036
4210 Toll-like receptor 4 TLR4 0.0036
6144 Solute carrier family 22 member 2 SLC22A2 0.0035
6148 Multidrug resistance-associated protein 7 ABCC10 0.0035
6020 Aldehyde oxidase AOX1 0.0035
992 Protein tyrosine kinase 2 beta PTK2B 0.0033
1291 cAMP response element-binding protein CREB1 0.0033
468 Cytochrome P450 4A11 CYP4A11 0.003
3809 Estrogen-related receptor gamma ESRRG 0.0027
3830 Calreticulin CALR 0.0025
6035 Nuclear receptor ROR-beta RORB 0.0024
6034 Hydroxyindole O-methyltransferase ASMT 0.0024
6036 Eosinophil peroxidase EPX 0.0024
84 Nuclear receptor 0B1 NR0B1 0.0023
571 Melatonin receptor type 1A MTNR1A 0.0021
362 Melatonin receptor type 1B MTNR1B 0.0021
765 Indoleamine 2,3-dioxygenase IDO1 0.002
817 DNA topoisomerase 2-alpha TOP2A 0.002
696 Kappa-type opioid receptor OPRK1 0.002
467 Delta-type opioid receptor OPRD1 0.002
847 Mu-type opioid receptor OPRM1 0.0019
243 Ribosyldihydronicotinamide dehydrogenase [quinone] NQO2 0.0016
1192 Sulfotransferase 1A1 SULT1A1 0.0015
6149 Solute carrier family 22 member 10 SLC22A10 0.0014
6167 Organic solute transporter subunit beta OSTB 0.0014
6166 Organic solute transporter subunit alpha OSTA 0.0014
465 Calmodulin CALM1 0.0013
1757 Myeloperoxidase MPO 0.0013
6104 Dimethylaniline monooxygenase [N-oxide-forming] 1 FMO1 0.0013
6155 ATP-binding cassette transporter sub-family C member 11 ABCC11 0.0012
6025 UDP-glucuronosyltransferase 1-4 UGT1A4 0.0011
6160 Solute carrier organic anion transporter family member 3A1 SLCO3A1 0.0011
6101 Dimethylaniline monooxygenase [N-oxide-forming] 3 FMO3 0.0011
7 Nitric oxide synthase, inducible NOS2 0.0011
1709 Canalicular multispecific organic anion transporter 2 ABCC3 0.0009
2164 Multidrug resistance-associated protein 4 ABCC4 0.0008
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