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Record Information
Version2.0
Creation Date2014-09-11 05:13:46 UTC
Update Date2014-12-24 20:26:56 UTC
Accession NumberT3D4730
Identification
Common NameMedroxyprogesterone Acetate
ClassSmall Molecule
DescriptionMedroxyprogesterone acetate (INN, USAN, BAN), also known as 17‘±-hydroxy-6‘±-methylprogesterone acetate, and commonly abbreviated as MPA, is a steroidal progestin, a synthetic variant of the human hormone progesterone. It is used as a contraceptive, in hormone replacement therapy and for the treatment of endometriosis as well as several other indications. MPA is a more potent derivative of its parent compound medroxyprogesterone (MP). While medroxyprogesterone is sometimes used as a synonym for medroxyprogesterone acetate, what is normally being administered is MPA and not MP.
Compound Type
  • Antineoplastic Agent, Hormonal
  • Contraceptive Agent
  • Contraceptive Agent, Female
  • Contraceptive Agent, Male
  • Drug
  • Ester
  • Ether
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
(6alpha)-17-(Acetyloxy)-6-methylpreg-4-ene-3,20-dione
17-Acetoxy-6alpha-methylprogesterone
17-Acetoxy-6α-methylprogesterone
17alpha-Hydroxy-6alpha-methylprogesterone acetate
17α-hydroxy-6α-methylprogesterone acetate
6-alpha-Methyl-17-alpha-acetoxyprogesterone
6-alpha-Methyl-17-alpha-hydroxyprogesterone acetate
6alpha-Methyl-17-acetoxy progesterone
6alpha-Methyl-17alpha-hydroxyprogesterone acetate
6alpha-Methyl-4-pregnene-3,20-dion-17alpha-ol acetate
6α-Methyl-17-acetoxy progesterone
6α-Methyl-17α-hydroxyprogesterone acetate
Depo-provera
Depo-subq provera 104
Makena
Medroxyacetate progesterone
Medroxyprogesterone 17-acetate
Medroxyprogesterone acetate
Medroxyprogesterone acetic acid
Methylacetoxyprogesterone
Metigestrona
MPA
Provera
Chemical FormulaC24H34O4
Average Molecular Mass386.524 g/mol
Monoisotopic Mass386.246 g/mol
CAS Registry Number71-58-9
IUPAC Name(1S,2R,8S,10R,11S,14R,15S)-14-acetyl-2,8,15-trimethyl-5-oxotetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadec-6-en-14-yl acetate
Traditional Nameprovera
SMILES[H][C@@]12CC[C@](OC(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
InChI IdentifierInChI=1S/C24H34O4/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/h13-14,18-20H,6-12H2,1-5H3/t14-,18+,19-,20-,22+,23-,24-/m0/s1
InChI KeyInChIKey=PSGAAPLEWMOORI-PEINSRQWSA-N
Chemical Taxonomy
Description 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.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassSteroids and steroid derivatives
Sub ClassPregnane steroids
Direct ParentGluco/mineralocorticoids, progestogins and derivatives
Alternative Parents
Substituents
  • Progestogin-skeleton
  • Steroid ester
  • 20-oxosteroid
  • 3-oxo-delta-4-steroid
  • 3-oxosteroid
  • Oxosteroid
  • Delta-4-steroid
  • Cyclohexenone
  • Alpha-acyloxy ketone
  • Carboxylic acid ester
  • Cyclic ketone
  • Ketone
  • Carboxylic acid derivative
  • Monocarboxylic acid or derivatives
  • Organic oxide
  • Hydrocarbon derivative
  • Organic oxygen compound
  • Carbonyl group
  • Organooxygen compound
  • Aliphatic homopolycyclic compound
Molecular FrameworkAliphatic homopolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point214.5°C
Boiling PointNot Available
Solubility22.2mg/L
LogP3.5
Predicted Properties
PropertyValueSource
Water Solubility0.0022 g/LALOGPS
logP3.42ALOGPS
logP4.13ChemAxon
logS-5.2ALOGPS
pKa (Strongest Acidic)17.82ChemAxon
pKa (Strongest Basic)-4.9ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area60.44 ŲChemAxon
Rotatable Bond Count3ChemAxon
Refractivity107.81 m³·mol⁻¹ChemAxon
Polarizability44.05 ųChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-00lu-0594000000-78579410f8f6799b400bJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-0a4l-3940000000-cf90a6f216d592e2ad4cJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-0udi-1339100000-e2ebb13d416a5b485ad5JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-002r-0449000000-c09cb0607e4a6118f05dJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-00dj-3940000000-2c9513d9a6a2092f5759JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-00di-3930000000-453ace561b4dc5712e85JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-009i-2947000000-2c9190ea372fd54323e9JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000i-0009000000-05f1f54a7d2de1236908JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-05p2-0049000000-ffc7818cd479acc19cabJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0uy0-0390000000-9ea2dbc66c9acf4b00baJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000l-1009000000-0f7f31209fd83cf2cddfJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0006-2019000000-f92eb379c368e053c8ffJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a6u-8049000000-31808bd6c16e7dab93e3JSpectraViewer
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
Toxicity Profile
Route of ExposureRapidly absorbed from GI tract
Mechanism of ToxicityProgestins 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.
MetabolismHepatic. 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
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)2B, possibly carcinogenic to humans. (3)
Uses/SourcesUsed 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.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsSide effects include loss of bone mineral density, BMD changes in adult women, bleeding irregularities, cancer risks, and thromboembolic disorders.
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00603
HMDB IDNot Available
PubChem Compound IDNot Available
ChEMBL IDCHEMBL717
ChemSpider IDNot Available
KEGG IDC08150
UniProt IDNot Available
OMIM ID
ChEBI ID6715
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkMedroxyprogesterone
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.

MSDST3D4730.pdf
General References
  1. 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. [19434889 ]
  2. Lenco W, Mcknight M, Macdonald AS: Effects of cortisone acetate, methylprednisolone and medroxyprogesterone on wound contracture and epithelization in rabbits. Ann Surg. 1975 Jan;181(1):67-73. [1119869 ]
  3. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

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 isoform B (PRB) is involved activation of c-SRC/MAPK signaling on hormone stimulation.Isoform A: inactive in stimulating c-Src/MAPK signaling on hormone stimulation.Isoform 4: Increases mitochondrial membrane potential and cellular respiration upon stimulation by progesterone.
Gene Name:
PGR
Uniprot ID:
P06401
Molecular Weight:
98979.96 Da
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. [16985038 ]
  2. Madauss KP, Stewart EL, Williams SP: The evolution of progesterone receptor ligands. Med Res Rev. 2007 May;27(3):374-400. [17013809 ]
  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. [17015480 ]
  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. [17109827 ]
  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. [17138644 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
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 tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3. Isoform 3 can bind to ERE and inhibit isoform 1.
Gene Name:
ESR1
Uniprot ID:
P03372
Molecular Weight:
66215.45 Da
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. [17094978 ]
  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. [17103262 ]
  3. Lessey BA, Palomino WA, Apparao KB, Young SL, Lininger RA: Estrogen receptor-alpha (ER-alpha) and defects in uterine receptivity in women. Reprod Biol Endocrinol. 2006;4 Suppl 1:S9. [17118173 ]
  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. [17203775 ]
  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. [17415709 ]