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targets (2) enzymes (4)
for drugs
Identification
Name Medroxyprogesterone
Accession Number DB00603 (APRD00627)
Type small molecule
Groups approved
Description

(6 alpha)-17-Hydroxy-6-methylpregn-4-ene-3,20-dione. A synthetic progestational hormone used in veterinary practice as an estrus regulator. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • CBP-1011
  • Hydroxymethylprogesterone
  • MAP
  • Medroprogesterone Acetate
  • Medrossiprogesterone [Dcit]
  • Medroxiprogesterona [INN-Spanish]
  • Medroxiprogesteronum
  • Medroxyprogesteron
  • Medroxyprogesteron acetate
  • Medroxyprogesteronum [INN-Latin]
Brand names
  • Aragest
  • Aragest 5
  • Asconale
  • Clinofem
  • Clinovir
  • Colirest
  • Depo-Clinovir
  • Depo-Prodasone
  • Depo-Progestin
  • Depo-Promone
  • Depot-Medroxyprogesterone acetate
  • DMPA
  • Farlutal
  • Farlutin
  • G-Farlutal
  • Gestapuran
  • Hematrol
  • Hysron
  • Indivina
  • Lunelle
  • Lutopolar
  • Lutoral
  • Med-Pro
  • Meprate
  • Metigestrona
  • MPA Gyn 5
  • Nadigest
  • Nidaxin
  • Novo-Medrone
  • Oragest
  • Perlutex
  • Perlutex Leo
  • Prodasone
  • Progestalfa
  • Progevera
  • Provera
  • Proverone
  • Ralovera
  • Repromap
  • Repromix
  • Sirprogen
  • Sodelut G
  • Veramix
Brand name mixtures
  • Lunelle (Medroxyprogesterone + Estradiol)
Categories
  • Contraceptives
  • Contraceptives, Oral, Synthetic
  • Progestins
CAS number 520-85-4
Weight Average: 344.4877
Monoisotopic: 344.235144890
Chemical Formula C22H32O3
InChI Key InChIKey=FRQMUZJSZHZSGN-HBNHAYAOSA-N
InChI
InChI=1S/C22H32O3/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/h12-13,16-18,25H,5-11H2,1-4H3/t13-,16+,17-,18-,20+,21-,22-/m0/s1
Plain Text
IUPAC Name
(1S,2R,8S,10R,11S,14R,15S)-14-acetyl-14-hydroxy-2,8,15-trimethyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-6-en-5-one
SMILES
[H][C@@]12CC[C@](O)(C(C)=O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])C[C@H](C)C2=CC(=O)CC[C@]12C
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Steroids and Steroid Derivatives
Substructures
  • Steroids and Steroid Derivatives
  • Hydroxy Compounds
  • Alkanes and Alkenes
  • Alcohols and Polyols
  • Cyclohexenes and Derivatives
  • Ketones
Pharmacology
Indication Used as a contraceptive and to treat secondary amenorrhea, abnormal uterine bleeding, pain associated with endometriosis, endometrial and renal cell carcinomas, paraphilia in males, GnRH-dependent forms of precocious puberty, as well as to prevent endometrial changes associated with estrogens.
Pharmacodynamics Medroxyprogesterone is a synthetic progestin more potent than progesterone.
Mechanism of action Progestins diffuse freely into target cells in the female reproductive tract, mammary gland, hypothalamus, and the pituitary and bind to the progesterone receptor. Once bound to the receptor, progestins slow the frequency of release of gonadotropin releasing hormone (GnRH) from the hypothalamus and blunt the pre-ovulatory LH surge.
Absorption Rapidly absorbed from GI tract
Volume of distribution Not Available
Protein binding 90%
Metabolism

Hepatic

Enzyme Metabolite Reaction Km Vmax
Cytochrome P450 3A4 6-beta-hydroxymedroxyprogesterone hydroxylation 39.2 11.2
Cytochrome P450 3A4 2-beta-hydroxymedroxyprogesterone hydroxylation 25.5 10.0
Cytochrome P450 3A4 1-beta-hydroxymedroxyprogesterone hydroxylation 19.2 10.1
Route of elimination Following oral dosing, MPA is extensively metabolized in the liver via hydroxylation, with subsequent conjugation and elimination in the urine. Most MPA metabolites are excreted in the urine as glucuronide conjugates with only minor amounts excreted as sulfates.
Half life 50 days
Clearance
  • 64110 +/- 42662 mL/min [postmenopausal women under fasting conditions with a single Dose of 2 × 10 mg]
  • 74123 +/- 35126 mL/min [postmenopausal women under fasting conditions with a single Dose of 8 × 2.5 mg]
  • 41963 +/- 38402 mL/min [postmenopausal women following daily administration of one PROVERA 10 mg tablet for 7 days]
Toxicity Side effects include loss of bone mineral density, BMD changes in adult women, bleeding irregularities, cancer risks, and thromboembolic disorders.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Sandoz canada inc
  • Teva parenteral medicines inc
  • Barr laboratories inc
  • Duramed pharmaceuticals inc sub barr laboratories inc
  • Usl pharma inc
  • Pharmacia and upjohn co
Packagers
Dosage forms
Form Route Strength
Suspension Intramuscular
Tablet Oral
Prices
Unit description Cost Unit
Depo-Provera 400 mg/ml Suspension 2.5ml Vial 201.13 USD vial
Depo-subq provera 104 syringe 108.17 USD syringe
Depo-provera 400 mg/ml vial 96.7 USD ml
Depo-Provera 150 mg/ml Suspension 1ml Syringe 94.58 USD syringe
MedroxyPROGESTERone Acetate 150 mg/ml Suspension 1ml Syringe 60.56 USD syringe
MedroxyPROGESTERone Acetate 150 mg/ml Suspension 1ml Vial 55.17 USD vial
Depo-Provera 150 mg/ml 31.02 USD ml
Medroxyprogesterone Acetate 150 mg/ml 23.05 USD ml
Medroxyprogesterone ace powder 18.97 USD g
Depo-Provera 50 mg/ml 6.01 USD ml
Provera 10 mg tablet 2.03 USD tablet
Provera 5 mg tablet 1.57 USD tablet
Provera 100 mg Tablet 1.41 USD tablet
Provera 2.5 mg tablet 1.15 USD tablet
Apo-Medroxy 100 mg Tablet 0.96 USD tablet
Provera 10 mg Tablet 0.73 USD tablet
MedroxyPROGESTERone Acetate 10 mg tablet 0.51 USD tablet
MedroxyPROGESTERone Acetate 5 mg tablet 0.48 USD tablet
MedroxyPROGESTERone Acetate 2.5 mg tablet 0.43 USD tablet
Medroxyprogesterone 10 mg tablet 0.4 USD tablet
Provera 5 mg Tablet 0.36 USD tablet
Medroxyprogesterone 5 mg tablet 0.33 USD tablet
Apo-Medroxy 10 mg Tablet 0.33 USD tablet
Novo-Medrone 10 mg Tablet 0.33 USD tablet
Medroxyprogesterone 2.5 mg tablet 0.32 USD tablet
Provera 2.5 mg Tablet 0.18 USD tablet
Apo-Medroxy 5 mg Tablet 0.16 USD tablet
Novo-Medrone 5 mg Tablet 0.16 USD tablet
Apo-Medroxy 2.5 mg Tablet 0.08 USD tablet
Novo-Medrone 2.5 mg Tablet 0.08 USD tablet
Patents
Country Patent Number Approved Expires
Canada 2409059 2006-04-18 2021-04-25
Properties
State solid
Melting point 220 - 223.5 oC
Experimental Properties
Property Value Source
water solubility 22.2mg/L PhysProp
logP 3.5 PhysProp
Predicted Properties
Property Value Source
water solubility 1.54e-02 g/l ALOGPS
logP 3.52 ALOGPS
logP 3.69 ChemAxon Molconvert
logS -4.35 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 98.65 ChemAxon Molconvert
polarizability 39.91 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Compound C07119 Link_out
PubChem Compound 10631 Link_out
PubChem Substance 46508895 Link_out
ChemSpider 10185 Link_out
ChEBI 6715 Link_out
ChEMBL 6715 Link_out
Therapeutic Targets Database DAP001211 Link_out
Drug Product Database 2247583 Link_out
RxList http://www.rxlist.com/cgi/generic/medrox.htm Link_out
Drugs.com http://www.drugs.com/medroxyprogesterone.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Medroxyprogesterone Link_out
ATC Codes
  • G03AC06
  • G03DA02
  • L02AB02
AHFS Codes
  • 68:32.00
PDB Entries Not Available
FDA label show (1.2 MB)
MSDS Not Available
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. Risch HA, Bale AE, Beck PA, Zheng W: PGR +331 A/G and increased risk of epithelial ovarian cancer. Cancer Epidemiol Biomarkers Prev. 2006 Sep;15(9):1738-41. Pubmed
  2. Madauss KP, Stewart EL, Williams SP: The evolution of progesterone receptor ligands. Med Res Rev. 2007 May;27(3):374-400. Pubmed
  3. Gizard F, Robillard R, Gross B, Barbier O, Revillion F, Peyrat JP, Torpier G, Hum DW, Staels B: TReP-132 is a novel progesterone receptor coactivator required for the inhibition of breast cancer cell growth and enhancement of differentiation by progesterone. Mol Cell Biol. 2006 Oct;26(20):7632-44. Pubmed
  4. Wu HB, Fabian S, Jenab S, Quinones-Jenab V: Progesterone receptors activation after acute cocaine administration. Brain Res. 2006 Dec 18;1126(1):188-92. Epub 2006 Nov 15. Pubmed
  5. Boonyaratanakornkit V, McGowan E, Sherman L, Mancini MA, Cheskis BJ, Edwards DP: The role of extranuclear signaling actions of progesterone receptor in mediating progesterone regulation of gene expression and the cell cycle. Mol Endocrinol. 2007 Feb;21(2):359-75. Epub 2006 Nov 30. 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

Pharmacological action: yes
Actions: agonist

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 tissues

Organism class: human
UniProt ID: P03372 Link_out
Gene: ESR1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Jain JK, Li A, Yang W, Minoo P, Felix JC: Mifepristone alters expression of endometrial steroid receptors and their cofactors in new users of medroxyprogesterone acetate. Fertil Steril. 2007 Jan;87(1):8-23. Epub 2006 Nov 7. Pubmed
  2. Kumar AS, Cureton E, Shim V, Sakata T, Moore DH, Benz CC, Esserman LJ, Hwang ES: Type and duration of exogenous hormone use affects breast cancer histology. Ann Surg Oncol. 2007 Feb;14(2):695-703. Epub 2006 Nov 14. Pubmed
  3. Lessey BA, Palomino WA, Apparao K, Young SL, Lininger RA: Estrogen receptor-alpha (ER-alpha) and defects in uterine receptivity in women. Reprod Biol Endocrinol. 2006 Oct 9;4 Suppl 1:S9. Pubmed
  4. Yuri T, Tsukamoto R, Uehara N, Matsuoka Y, Tsubura A: Effects of different durations of estrogen and progesterone treatment on development of N-methyl-N-nitrosourea-induced mammary carcinomas in female Lewis rats. In Vivo. 2006 Nov-Dec;20(6B):829-36. Pubmed
  5. Ghebeh H, Tulbah A, Mohammed S, Elkum N, Bin Amer SM, Al-Tweigeri T, Dermime S: Expression of B7-H1 in breast cancer patients is strongly associated with high proliferative Ki-67-expressing tumor cells. Int J Cancer. 2007 Aug 15;121(4):751-8. Pubmed
Enzymes

1. Cytochrome P450 3A4

Actions: substrate, inducer

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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Zhang JW, Liu Y, Zhao JY, Wang LM, Ge GB, Gao Y, Li W, Liu HT, Liu HX, Zhang YY, Sun J, Yang L: Metabolic profiling and cytochrome P450 reaction phenotyping of medroxyprogesterone acetate. Drug Metab Dispos. 2008 Nov;36(11):2292-8. Epub 2008 Aug 25. Pubmed
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 2C8

Actions: inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti- cancer drug paclitaxel (taxol)

UniProt ID: P10632 Link_out
Gene: CYP2C8
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Walsky RL, Gaman EA, Obach RS: Examination of 209 drugs for inhibition of cytochrome P450 2C8. J Clin Pharmacol. 2005 Jan;45(1):68-78. Pubmed
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

3. 3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type II

Actions: inhibitor

3beta-HSD is a bifunctional enzyme, that catalyzes the oxidative conversion of delta(5)-ene-3-beta-hydroxy steroid, and the oxidative conversion of ketosteroids. The 3beta-HSD enzymatic system plays a crucial role in the biosynthesis of all classes of hormonal steroids

UniProt ID: P26439 Link_out
Gene: HSD3B2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Lee TC, Miller WL, Auchus RJ: Medroxyprogesterone acetate and dexamethasone are competitive inhibitors of different human steroidogenic enzymes. J Clin Endocrinol Metab. 1999 Jun;84(6):2104-10. Pubmed

4. Cytochrome P450 2C9

Actions: inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:05

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.