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targets (2) transporters (1)
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Identification
Name Megestrol
Accession Number DB00351 (APRD01092)
Type small molecule
Groups approved
Description

17-Hydroxy-6-methylpregna-3,6-diene-3,20-dione. A progestational hormone used most commonly as the acetate ester. As the acetate, it is more potent than progesterone both as a progestagen and as an ovulation inhibitor. It has also been used in the palliative treatment of breast cancer. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Megestrol Acetate
  • Megestrolo [DCIT]
  • Megestrolum [INN-Latin]
  • Megestryl acetate
  • MGA
Brand names
  • Magestin
  • Maygace
  • Megace
  • Megeron
  • Megestat
  • Megestil
  • Megestin
  • Nia
  • Niagestin
  • Ovaban
  • Ovarid
  • Volidan
Brand name mixtures Not Available
Categories
  • Antineoplastic Agents, Hormonal
  • Contraceptives, Oral, Synthetic
CAS number 3562-63-8
Weight Average: 342.4718
Monoisotopic: 342.219494826
Chemical Formula C22H30O3
InChI Key InChIKey=VXIMPSPISRVBPZ-NWUMPJBXSA-N
InChI
InChI=1S/C22H30O3/c1-13-11-16-17(20(3)8-5-15(24)12-19(13)20)6-9-21(4)18(16)7-10-22(21,25)14(2)23/h11-12,16-18,25H,5-10H2,1-4H3/t16-,17+,18+,20-,21+,22+/m1/s1
Plain Text
IUPAC Name
(1S,2R,10R,11S,14R,15S)-14-acetyl-14-hydroxy-2,8,15-trimethyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-6,8-dien-5-one
SMILES
[H][C@@]12CC[C@](O)(C(C)=O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])C=C(C)C2=CC(=O)CC[C@]12C
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Bile Acids
Substructures
  • Bile Acids
  • Steroids and Steroid Derivatives
  • Hydroxy Compounds
  • Alkanes and Alkenes
  • Alcohols and Polyols
  • Isoprenes
  • Cyclohexenes and Derivatives
  • Ketones
Pharmacology
Indication For the treatment of anorexia, cachexia, or an unexplained, significant weight loss in patients with a diagnosis of acquired immunodeficiency syndrome (AIDS). Also used for the palliative management of recurrent, inoperable, or metastatic breast cancer, endometrial cancer, and prostate cancer in Canada and some other countries.
Pharmacodynamics Megestrol is a synthetic progestin and has the same physiologic effects as natural progesterone. These effects include induction of secretory changes in the endometrium, increase in basal body temperature, pituitary inhibition, and production of withdrawal bleeding in the presence of estrogen. Mestrogel has slight glucocorticoid activity and very slight mineralocorticoid activity. This drug has no estrogenic, androgenic, or anabolic activity. The precise mechanism of megestrol’s antianorexic and anticachetic effects is unknown. Initially developed as a contraceptive, it was first evaluated in breast cancer treatment in 1967.
Mechanism of action The precise mechanism by which megestrol acetate produces effects in anorexia and cachexia is unknown at the present time, but its progestin antitumour activity may involve suppression of luteinizing hormone by inhibition of pituitary function. Studies also suggest that the megestrol's weight gain effect is related to its appetite-stimulant or metabolic effects rather than its glucocorticoid-like effects or the production of edema. It has also been suggested that megestrol may alter metabolic pathyways via interferences with the production or action of mediators such as cachectin, a hormone that inhibits adipocyte lipogenic enzymes.
Absorption Variable, but well absorbed orally.
Volume of distribution Not Available
Protein binding Not Available
Metabolism

Primarily hepatic. Megestrol metabolites which were identified in urine constituted 5% to 8% of the dose administered. Respiratory excretion as labeled carbon dioxide and fat storage may have accounted for at least part of the radioactivity not found in urine and feces. No active metabolites have been identified.
Route of elimination The major route of drug elimination in humans is urine. Respiratory excretion as labeled carbon dioxide and fat storage may have accounted for at least part of the radioactivity not found in urine and feces.
Half life 34 hours
Clearance Not Available
Toxicity No serious unexpected side effects have resulted from studies involving megestrol acetate oral suspension administered in dosages as high as 1200 mg/day. Treatment with megestrol acetate, an orexigenic agent, has also resulted in iatrogenic adrenal suppression. The mechanism is presumably related to the glucocorticoid properties of megestrol acetate [PMID: 12872362].
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Bristol myers squibb
  • Par pharmaceutical inc
  • Apotex inc richmond hill
  • Roxane laboratories inc
  • Teva pharmaceuticals usa
  • Wockhardt eu operations (swiss) ag
  • Barr laboratories inc
  • Teva pharmaceuticals usa inc
  • Usl pharma inc
Packagers
Dosage forms
Form Route Strength
Suspension Oral
Tablet Oral
Prices
Unit description Cost Unit
Megestrol Acetate 40 mg/ml Suspension 480ml Bottle 297.92 USD bottle
Megestrol Acetate 40 mg/ml Suspension 240ml Bottle 149.71 USD bottle
Megestrol acetate powder 30.6 USD g
Megestrol 40 mg tablet 1.17 USD tablet
Megestrol Acetate 40 mg tablet 1.15 USD tablet
Megestrol Acetate 20 mg tablet 0.72 USD tablet
Megace 40 mg/ml oral suspension 0.71 USD ml
Megestrol 20 mg tablet 0.65 USD tablet
Patents
Country Patent Number Approved Expires
United States 7101576 2004-04-22 2024-04-22
United States 5145684 1994-01-25 2011-01-25
Properties
State solid
Melting point 218.0-220.0oC
Experimental Properties
Property Value Source
water solubility 2 µg/mL (at 37°C for the acetate salt) PhysProp
logP 3.2 PhysProp
Predicted Properties
Property Value Source
water solubility 1.04e-02 g/l ALOGPS
logP 2.70 ALOGPS
logP 3.28 ChemAxon Molconvert
logS -4.52 ALOGPS
pKa 17.61 ChemAxon Molconvert
hydrogen acceptor count 3 ChemAxon Molconvert
hydrogen donor count 1 ChemAxon Molconvert
polar surface area 54.37 ChemAxon Molconvert
rotatable bond count 1 ChemAxon Molconvert
refractivity 99.50 ChemAxon Molconvert
polarizability 39.44 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. Berenstein EG, Ortiz Z: Megestrol acetate for the treatment of anorexia-cachexia syndrome. Cochrane Database Syst Rev. 2005 Apr 18;(2):CD004310. Pubmed
  2. Pascual Lopez A, Roque i Figuls M, Urrutia Cuchi G, Berenstein EG, Almenar Pasies B, Balcells Alegre M, Herdman M: Systematic review of megestrol acetate in the treatment of anorexia-cachexia syndrome. J Pain Symptom Manage. 2004 Apr;27(4):360-9. Pubmed
  3. Rao GG, Miller DS: Hormonal therapy in epithelial ovarian cancer. Expert Rev Anticancer Ther. 2006 Jan;6(1):43-7. Pubmed
  4. Schindler AE, Campagnoli C, Druckmann R, Huber J, Pasqualini JR, Schweppe KW, Thijssen JH: Classification and pharmacology of progestins. Maturitas. 2008 Sep-Oct;61(1-2):171-80. Pubmed
  5. Orme LM, Bond JD, Humphrey MS, Zacharin MR, Downie PA, Jamsen KM, Mitchell SL, Robinson JM, Grapsas NA, Ashley DM: Megestrol acetate in pediatric oncology patients may lead to severe, symptomatic adrenal suppression. Cancer. 2003 Jul 15;98(2):397-405. Pubmed
External Links
Resource Link
KEGG Compound C07120 Link_out
PubChem Compound 19090 Link_out
PubChem Substance 46505827 Link_out
ChemSpider 18023 Link_out
ChEBI 6722 Link_out
ChEMBL 6722 Link_out
Therapeutic Targets Database DAP000861 Link_out
PharmGKB PA450350 Link_out
Drug Product Database 2223112 Link_out
RxList http://www.rxlist.com/cgi/generic4/megace_es.htm Link_out
Drugs.com http://www.drugs.com/cdi/megestrol.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Megestrol Link_out
ATC Codes
  • G03AC05
  • G03DB02
  • L02AB01
  • G03DB04
AHFS Codes
  • 10:00.00
PDB Entries Not Available
FDA label show (277.8 KB)
MSDS show (71.9 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Take with food.
Targets

1. Progesterone receptor

Pharmacological action: yes
Actions: agonist

The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues

Organism class: human
UniProt ID: P06401 Link_out
Gene: PGR Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Vadivelu S, Sharer L, Schulder M: Regression of multiple intracranial meningiomas after cessation of long-term progesterone agonist therapy. J Neurosurg. 2010 May;112(5):920-4. Pubmed
  2. Mokbel K: Focus on anastrozole and breast cancer. Curr Med Res Opin. 2003;19(8):683-8. Pubmed
  3. Wentling GK, Sevin BU, Geiger XJ, Bridges MD: Benign metastasizing leiomyoma responsive to megestrol: case report and review of the literature. Int J Gynecol Cancer. 2005 Nov-Dec;15(6):1213-7. Pubmed
  4. Gruber T, Dare AO, Balos LL, Lele S, Fenstermaker RA: Multiple meningiomas arising during long-term therapy with the progesterone agonist megestrol acetate. Case report. J Neurosurg. 2004 Feb;100(2):328-31. Pubmed
  5. Schindler AE, Campagnoli C, Druckmann R, Huber J, Pasqualini JR, Schweppe KW, Thijssen JH: Classification and pharmacology of progestins. Maturitas. 2008 Sep-Oct;61(1-2):171-80. Pubmed
  6. Wermers RA, Hurley DL, Kearns AE: Osteoporosis associated with megestrol acetate. Mayo Clin Proc. 2004 Dec;79(12):1557-61. Pubmed
  7. Wiedemann K, Hirschmann M, Knaudt K, Rupprecht R, Seier FE, Holsboer F: Sleep endocrine effects of megestrol acetate in healthy men. J Neuroendocrinol. 1998 Sep;10(9):719-27. Pubmed
  8. Lamberts SW, Uitterlinden P, Bons EG, Verleun T: Comparison of the actions of RU 38486 and megestrol acetate in the model of a transplantable adrenocorticotropin- and prolactin-secreting rat pituitary tumor. Cancer Res. 1985 Mar;45(3):1015-9. Pubmed
  9. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Glucocorticoid receptor

Pharmacological action: unknown
Actions: agonist

Receptor for glucocorticoids (GC). Has a dual mode of action:as a transcription factor that binds to glucocorticoid response elements (GRE) and as a modulator of other transcription factors. Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth

Organism class: human
UniProt ID: P04150 Link_out
Gene: NR3C1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Wermers RA, Hurley DL, Kearns AE: Osteoporosis associated with megestrol acetate. Mayo Clin Proc. 2004 Dec;79(12):1557-61. Pubmed
  2. Gonzalez Villarroel P, Fernandez Perez I, Paramo C, Gentil Gonzalez M, Carnero Lopez B, Vazquez Tunas ML, Carrasco Alvarez JA: Megestrol acetate-induced adrenal insufficiency. Clin Transl Oncol. 2008 Apr;10(4):235-7. Pubmed
  3. Wiedemann K, Hirschmann M, Knaudt K, Rupprecht R, Seier FE, Holsboer F: Sleep endocrine effects of megestrol acetate in healthy men. J Neuroendocrinol. 1998 Sep;10(9):719-27. Pubmed
  4. Chao Y, Chan WK, Wang SS, Lai KH, Chi CW, Lin CY, Chan A, Whang-Peng J, Lui WY, Lee SD: Phase II study of megestrol acetate in the treatment of hepatocellular carcinoma. J Gastroenterol Hepatol. 1997 Apr;12(4):277-81. Pubmed
  5. Lamberts SW, Uitterlinden P, Bons EG, Verleun T: Comparison of the actions of RU 38486 and megestrol acetate in the model of a transplantable adrenocorticotropin- and prolactin-secreting rat pituitary tumor. Cancer Res. 1985 Mar;45(3):1015-9. Pubmed
  6. Kontula K, Paavonen T, Luukkainen T, Andersson LC: Binding of progestins to the glucocorticoid receptor. Correlation to their glucocorticoid-like effects on in vitro functions of human mononuclear leukocytes. Biochem Pharmacol. 1983 May 1;32(9):1511-8. Pubmed
Transporters

1. Multidrug resistance protein 1

Actions: inhibitor

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Wang L, Yang CP, Horwitz SB, Trail PA, Casazza AM: Reversal of the human and murine multidrug-resistance phenotype with megestrol acetate. Cancer Chemother Pharmacol. 1994;34(2):96-102. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on October 06, 2011 16:16

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.