Identification

Name
Megestrol acetate
Accession Number
DB00351  (APRD01092)
Type
Small Molecule
Groups
Approved, Investigational, Vet 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.

Structure
Thumb
Synonyms
  • 17-Acetoxy-6-methylpregna-4,6-diene-3,20-dione
  • 17-Hydroxy-6-methylpregna-4,6-diene-3,20-dione 17-acetate
  • 17alpha-Acetoxy-6-dehydro-6-methylprogesterone
  • 17alpha-Hydroxy-6-methylpregna-4,6-diene-3,20-dione acetate
  • 17α-Acetoxy-6-dehydro-6-methylprogesterone
  • 17α-Hydroxy-6-methylpregna-4,6-diene-3,20-dione acetate
  • 6-Dehydro-6-methyl-17alpha-acetoxyprogesterone
  • 6-Dehydro-6-methyl-17α-acetoxyprogesterone
  • 6-Methyl-17alpha-acetoxypregna-4,6-diene-3,20-dione
  • 6-Methyl-17alpha-hydroxy-delta(sup 6)-progesterone acetate
  • 6-Methyl-17α-acetoxypregna-4,6-diene-3,20-dione
  • 6-Methyl-17α-hydroxy-delta(sup 6)-progesterone acetate
  • 6-Methyl-6-dehydro-17alpha-acetoxyprogesterone
  • 6-Methyl-6-dehydro-17α-acetoxyprogesterone
  • 6-Methyl-delta(sup 4,6)-pregnadien-17alpha-ol-3,20-dione acetate
  • 6-Methyl-delta(sup 4,6)-pregnadien-17α-ol-3,20-dione acetate
  • 6-Methyl-delta(sup 6)-dehydro-17alpha-acetoxyprogesterone
  • 6-Methyl-delta(sup 6)-dehydro-17α-acetoxyprogesterone
  • MGA
External IDs
BDH 1298 / BDH-1298 / NSC-71423 / SC 10363 / SC-10363
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Linmegestrol - Tab 160mgTablet160 mgOralLinson Pharma Co.1995-12-312006-05-29Canada
Linmegestrol - Tab 40mgTablet40 mgOralLinson Pharma Co.1995-12-312004-08-05Canada
MegaceSuspension40 mg/1mLOralE.R. Squibb & Sons, L.L.C.2009-06-012019-03-31Us
MegaceTablet40 mg/1OralE.R. Squibb & Sons, L.L.C.2005-01-012006-08-31Us
MegaceTablet20 mg/1OralE.R. Squibb & Sons, L.L.C.2005-01-012005-05-31Us
MegaceTablet160 mgOralBristol Myers Squibb1987-12-312009-03-09Canada
MegaceTablet40 mgOralBristol Myers Squibb1977-12-312006-05-29Canada
MegaceSuspension40 mg/1mLOralPhysicians Total Care, Inc.1994-03-232011-03-31Us
Megace EsSuspension125 mg/1mLOralPhysicians Total Care, Inc.2006-04-13Not applicableUs
Megace ESSuspension125 mg/1mLOralPar Pharmaceutical2005-07-02Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-megestrolTablet160 mgOralApotex CorporationNot applicableNot applicableCanada
Apo-megestrolTablet40 mgOralApotex CorporationNot applicableNot applicableCanada
MegestolSuspension40 mg/1mLOralStat Rx USA2002-02-15Not applicableUs
Megestrol AcetateSuspension40 mg/1mLOralCardinal Health2006-07-07Not applicableUs
Megestrol AcetateSuspension125 mg/1mLOralT Wi Pharmaceuticals, Inc.2015-03-01Not applicableUs
Megestrol AcetateTablet20 mg/1OralCardinal Health2011-05-13Not applicableUs
Megestrol AcetateTablet40 mg/1OralWest-Ward Pharmaceuticals Corp.1995-09-292020-01-31Us
Megestrol AcetateSuspension400 mg/10mLOralCardinal Health2004-02-252015-08-31Us
Megestrol AcetateSuspension40 mg/1mLOralApotex Corporation2006-02-162011-03-11Us
Megestrol AcetateSuspension40 mg/1mLOralPrecision Dose Inc.2014-10-08Not applicableUs
International/Other Brands
Magestin / Maygace / Megeron / Megestat / Megestil / Megestin / Niagestin / Ovaban / Ovarid / Volidan
Categories
UNII
TJ2M0FR8ES
CAS number
595-33-5
Weight
Average: 384.516
Monoisotopic: 384.23005951
Chemical Formula
C24H32O4
InChI Key
RQZAXGRLVPAYTJ-GQFGMJRRSA-N
InChI
InChI=1S/C24H32O4/c1-14-12-18-19(22(4)9-6-17(27)13-21(14)22)7-10-23(5)20(18)8-11-24(23,15(2)25)28-16(3)26/h12-13,18-20H,6-11H2,1-5H3/t18-,19+,20+,22-,23+,24+/m1/s1
IUPAC Name
(1S,2R,10R,11S,14R,15S)-14-acetyl-2,8,15-trimethyl-5-oxotetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadeca-6,8-dien-14-yl acetate
SMILES
[H][C@@]12CC[C@](OC(C)=O)(C(C)=O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])C=C(C)C2=CC(=O)CC[C@]12C

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.

Associated Conditions
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.

TargetActionsOrganism
AProgesterone receptor
agonist
Human
UGlucocorticoid receptor
agonist
Human
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
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe therapeutic efficacy of (R)-warfarin can be increased when used in combination with Megestrol acetate.
(S)-WarfarinThe therapeutic efficacy of (S)-Warfarin can be increased when used in combination with Megestrol acetate.
16-BromoepiandrosteroneThe metabolism of Megestrol acetate can be decreased when combined with 16-Bromoepiandrosterone.
2,4-thiazolidinedioneThe therapeutic efficacy of 2,4-thiazolidinedione can be decreased when used in combination with Megestrol acetate.
3,5-diiodothyropropionic acidThe metabolism of Megestrol acetate can be decreased when combined with 3,5-diiodothyropropionic acid.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Megestrol acetate.
5-androstenedioneThe metabolism of Megestrol acetate can be decreased when combined with 5-androstenedione.
6-Deoxyerythronolide BThe metabolism of Megestrol acetate can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Megestrol acetate.
AbacavirMegestrol acetate may decrease the excretion rate of Abacavir which could result in a higher serum level.
Food Interactions
  • Take with food.

References

Synthesis Reference

Klaus ANNEN, Thomas Linz, Karl-Heinz Neff, Rolf Bohlmann, Henry Laurent, "PROCESS FOR PREPARING 17ALPHA-ACETOXY-6-METHYLENEPREGN-4-ENE-3,20-DIONE, MEDROXYPROGESTERONE ACETATE AND MEGESTROL ACETATE." U.S. Patent US20090012321, issued January 08, 2009.

US20090012321
General References
  1. Berenstein EG, Ortiz Z: Megestrol acetate for the treatment of anorexia-cachexia syndrome. Cochrane Database Syst Rev. 2005 Apr 18;(2):CD004310. [PubMed:15846706]
  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:15050664]
  3. Rao GG, Miller DS: Hormonal therapy in epithelial ovarian cancer. Expert Rev Anticancer Ther. 2006 Jan;6(1):43-7. [PubMed:16375643]
  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:19434889]
  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:12872362]
External Links
KEGG Drug
D00952
KEGG Compound
C08151
PubChem Compound
11683
PubChem Substance
46505827
ChemSpider
11192
ChEBI
6723
ChEMBL
CHEMBL1201139
Therapeutic Targets Database
DAP000861
PharmGKB
PA450351
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Megestrol
ATC Codes
G03DB02 — MegestrolL02AB01 — MegestrolG03AA04 — Megestrol and ethinylestradiolG03AC05 — MegestrolG03FA08 — Megestrol and estrogenG03FB04 — Megestrol and estrogenG03AB01 — Megestrol and ethinylestradiol
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
FDA label
Download (278 KB)
MSDS
Download (71.9 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedPreventionCognitive Impairments1
1CompletedNot AvailableAbsorption / Bioavailability / Pharmacokinetics1
1CompletedSupportive CareHealthy Volunteers2
1CompletedTreatmentAnorexic / Cachexia1
1CompletedTreatmentCachexia / HIV Wasting Syndrome / Human Immunodeficiency Virus (HIV) Infections1
1TerminatedNot AvailableHealthy Volunteers1
1Unknown StatusNot AvailableHealthy Volunteers1
1, 2Active Not RecruitingTreatmentClaudication / PAD1
1, 2Unknown StatusTreatmentCancer, Breast / Endometrial Cancers / Mesothelioma, Malignant1
2Active Not RecruitingTreatmentEndometrial Cancers1
2Active Not RecruitingTreatmentEstrogen Receptor-Positive Breast Cancer / HER2-Negative Breast Cancer / Progesterone Receptor-positive Breast Cancer / Recurrent Breast Cancer / Stage IIIA Breast Cancer / Stage IIIB Breast Cancer / Stage IIIC Breast Cancer / Stage IV Breast Cancer1
2CompletedSupportive CareCachexia / Leukemias / Malignant Lymphomas / Myelodysplastic Syndromes / Myelodysplastic/Myeloproliferative Diseases / Neoplasms, Brain / Tumors, Central Nervous System / Unspecified Childhood Solid Tumor, Protocol Specific1
2CompletedSupportive CareCachexia / Tiredness / Unspecified Adult Solid Tumor, Protocol Specific1
2CompletedTreatmentAIDS Wasting Syndrome / Anorexic / Cachexia / HIV Wasting Syndrome / Human Immunodeficiency Virus (HIV) Infections / Involuntary Weight Loss1
2CompletedTreatmentAnorexic / Cachexia / Human Immunodeficiency Virus (HIV) Infections1
2CompletedTreatmentAtypical Endometrial Hyperplasia / Endometrial Carcinoma1
2CompletedTreatmentCancer, Breast1
2CompletedTreatmentCancers1
2CompletedTreatmentChronic Obstructive Pulmonary Disease (COPD)1
2CompletedTreatmentChronic Oral Food Refusal1
2CompletedTreatmentEndometrial Adenocarcinomas / Endometrial Atypical Hyperplasia1
2CompletedTreatmentEndometrial Cancers1
2CompletedTreatmentEndometrial Carcinoma / Recurrent Uterine Corpus Carcinoma / Stage IIIA Uterine Corpus Cancer / Stage IIIB Uterine Corpus Cancer / Stage IIIC1 Uterine Corpus Cancer / Stage IIIC2 Uterine Corpus Cancer / Stage IVA Uterine Corpus Cancer / Stage IVB Uterine Corpus Cancer1
2CompletedTreatmentHIV Wasting Syndrome / Human Immunodeficiency Virus (HIV) Infections1
2Not Yet RecruitingTreatmentEndometrial Carcinoma1
2RecruitingSupportive CareHead and Neck Carcinoma1
2RecruitingTreatmentCancer, Breast1
2RecruitingTreatmentNeoplasms, Breast1
2TerminatedSupportive CareAnorexic / Weight Changes1
2TerminatedTreatmentHigh Grade Squamous Intraepithelial Neoplasia / Stage 0 Uterine Corpus Cancer1
2WithdrawnSupportive CareAnorexic1
2WithdrawnTreatmentAtypical Endometrial Hyperplasia / Endometrial Adenocarcinomas / Recurrent Endometrial Carcinoma / Stage IA Endometrial Carcinoma / Stage IB Endometrial Carcinoma / Stage II Endometrial Carcinoma / Stage IIIA Endometrial Carcinoma / Stage IIIB Endometrial Carcinoma / Stage IIIC Endometrial Carcinoma / Stage IVA Endometrial Carcinoma / Stage IVB Endometrial Carcinoma1
2, 3RecruitingTreatmentAnorexic / Cancer Cachexia1
2, 3RecruitingTreatmentAtypical Endometrial Hyperplasia1
2, 3RecruitingTreatmentEndometrial Neoplasm Malignant Stage I1
2, 3TerminatedTreatmentDementias1
3CompletedSupportive CareAnorexic / Cachexia1
3CompletedSupportive CareAnorexic / Cachexia / Head and Neck Carcinoma / Quality of Life1
3CompletedSupportive CareAnorexic / Cachexia / Lung Cancers1
3CompletedSupportive CareCancer, Breast / Menopausal Hot Flushes1
3CompletedSupportive CareUnspecified Adult Solid Tumor, Protocol Specific / Weight Changes1
3CompletedTreatmentAnorexic / Cachexia / Human Immunodeficiency Virus (HIV) Infections1
3CompletedTreatmentLiver Cancer1
3CompletedTreatmentMetastatic Breast Cancer (MBC)1
3Not Yet RecruitingTreatmentAnorexic / Cachexia; Cancer1
3TerminatedTreatmentAnorexic / Cachexia / Obese experiencing rapid weight loss2
3TerminatedTreatmentEndometrial Cancers1
4CompletedTreatmentAnorexic / Cachexia / Human Immunodeficiency Virus (HIV) Infections1
4WithdrawnTreatmentCachexia1
Not AvailableCompletedHealth Services ResearchAdrenal Insufficiency1
Not AvailableCompletedTreatmentAcquired Immune Deficiency Syndrome (AIDS) / HIV Wasting Syndrome / Human Immunodeficiency Virus (HIV) Infections1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1

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
  • Advanced Pharmaceutical Services Inc.
  • Apotex Inc.
  • A-S Medication Solutions LLC
  • Atlantic Biologicals Corporation
  • Barr Pharmaceuticals
  • Bristol-Myers Squibb Co.
  • Cardinal Health
  • Carlisle Laboratories Inc.
  • Dept Health Central Pharmacy
  • Goldline Laboratories Inc.
  • Major Pharmaceuticals
  • Martec USA LLC
  • Mckesson Corp.
  • Mead Johnson and Co.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mylan
  • Nucare Pharmaceuticals Inc.
  • Par Pharmaceuticals
  • Pharmaceutical Association
  • Pharmaceutical Utilization Management Program VA Inc.
  • Pharmachemie BV
  • Physicians Total Care Inc.
  • Precision Dose Inc.
  • Prepak Systems Inc.
  • Professional Co.
  • Qualitest
  • Resource Optimization and Innovation LLC
  • Roxane Labs
  • Sandhills Packaging Inc.
  • Southwood Pharmaceuticals
  • Stat Rx Usa
  • Teva Pharmaceutical Industries Ltd.
  • Tya Pharmaceuticals
  • UDL Laboratories
  • United Research Laboratories Inc.
  • Vangard Labs Inc.
  • Vistapharm Inc.
  • Wockhardt Ltd.
Dosage forms
FormRouteStrength
TabletOral20 mg/1
TabletOral40 mg/1
SuspensionOral125 mg/1mL
SuspensionOral40 mg
SuspensionOral40 mg/1mL
TabletOral160 mg
TabletOral40 mg
SuspensionOral400 mg/10mL
SuspensionOral800 mg/20mL
Prices
Unit descriptionCostUnit
Megestrol Acetate 40 mg/ml Suspension 480ml Bottle297.92USD bottle
Megestrol Acetate 40 mg/ml Suspension 240ml Bottle149.71USD bottle
Megestrol acetate powder30.6USD g
Megestrol 40 mg tablet1.17USD tablet
Megestrol Acetate 40 mg tablet1.15USD tablet
Megestrol Acetate 20 mg tablet0.72USD tablet
Megace 40 mg/ml oral suspension0.71USD ml
Megestrol 20 mg tablet0.65USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5145684No1994-01-252011-01-25Us
US7101576No2004-04-222024-04-22Us
US9101540No2004-04-222024-04-22Us
US9101549No2004-04-222024-04-22Us
US9107827No2004-04-222024-04-22Us
US9040088No2004-04-222024-04-22Us
US6592903No2000-09-212020-09-21Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)218.0-220.0 °CNot Available
water solubility2 µg/mL (at 37 °C for the acetate salt)Not Available
logP3.2Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00336 mg/mLALOGPS
logP3.71ALOGPS
logP3.72ChemAxon
logS-5.1ALOGPS
pKa (Strongest Acidic)17.83ChemAxon
pKa (Strongest Basic)-4.9ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area60.44 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity108.66 m3·mol-1ChemAxon
Polarizability43.51 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9959
Blood Brain Barrier+0.9617
Caco-2 permeable+0.651
P-glycoprotein substrateSubstrate0.6107
P-glycoprotein inhibitor IInhibitor0.9149
P-glycoprotein inhibitor IIInhibitor0.7016
Renal organic cation transporterNon-inhibitor0.7753
CYP450 2C9 substrateNon-substrate0.8642
CYP450 2D6 substrateNon-substrate0.908
CYP450 3A4 substrateSubstrate0.7744
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.8907
CYP450 2D6 inhibitorNon-inhibitor0.9532
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8095
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.899
Ames testNon AMES toxic0.9775
CarcinogenicityNon-carcinogens0.9273
BiodegradationNot ready biodegradable0.9354
Rat acute toxicity1.8121 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9429
hERG inhibition (predictor II)Non-inhibitor0.7761
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-002r-0379000000-6d73cd082b939b89d5ce
MS/MS Spectrum - , positiveLC-MS/MSsplash10-060r-2890000000-fa2ec02a8c51a731cc7b
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00n0-0497000000-046272fbcad7d1d41298

Taxonomy

Description
This compound belongs to the class of organic compounds known as gluco/mineralocorticoids, progestogins and derivatives. These are steroids with a structure based on a hydroxylated prostane moiety.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Steroids and steroid derivatives
Sub Class
Pregnane steroids
Direct Parent
Gluco/mineralocorticoids, progestogins and derivatives
Alternative Parents
Steroid esters / 20-oxosteroids / 3-oxosteroids / Cyclohexenones / Alpha-acyloxy ketones / Carboxylic acid esters / Monocarboxylic acids and derivatives / Organic oxides / Hydrocarbon derivatives
Substituents
Progestogin-skeleton / 20-oxosteroid / Steroid ester / 3-oxosteroid / Oxosteroid / Cyclohexenone / Alpha-acyloxy ketone / Ketone / Carboxylic acid ester / Cyclic ketone
Molecular Framework
Aliphatic homopolycyclic compounds
External Descriptors
C21 steroids (gluco/mineralocorticoids, progestogens) and derivatives (C08151) / C21 steroids (gluco/mineralocorticoids, progestogins) and derivatives (LMST02030118)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
Specific Function
The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Progesterone receptor ...
Gene Name
PGR
Uniprot ID
P06401
Uniprot Name
Progesterone receptor
Molecular Weight
98979.96 Da
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. doi: 10.3171/2009.8.JNS09201. [PubMed:19731987]
  2. Mokbel K: Focus on anastrozole and breast cancer. Curr Med Res Opin. 2003;19(8):683-8. [PubMed:14687437]
  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:16343217]
  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:15086241]
  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:19434889]
  6. Wermers RA, Hurley DL, Kearns AE: Osteoporosis associated with megestrol acetate. Mayo Clin Proc. 2004 Dec;79(12):1557-61. [PubMed:15595341]
  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:9744490]
  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:2982481]
  9. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
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
  1. Wermers RA, Hurley DL, Kearns AE: Osteoporosis associated with megestrol acetate. Mayo Clin Proc. 2004 Dec;79(12):1557-61. [PubMed:15595341]
  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:18411198]
  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:9744490]
  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:9195366]
  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:2982481]
  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:6222739]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. House L, Seminerio MJ, Mirkov S, Ramirez J, Skor M, Sachleben JR, Isikbay M, Singhal H, Greene GL, Vander Griend D, Conzen SD, Ratain MJ: Metabolism of megestrol acetate in vitro and the role of oxidative metabolites. Xenobiotica. 2018 Oct;48(10):973-983. doi: 10.1080/00498254.2017.1386335. Epub 2017 Nov 10. [PubMed:29050522]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
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:8194172]

Drug created on June 13, 2005 07:24 / Updated on October 16, 2018 08:25