Medroxyprogesterone Acetate (CED0002784)

Record Information
Version1.0
Creation Date2014-09-11 05:13:46 UTC
Update Date2026-08-22 04:03:52 UTC
Accession NumberCHEM003687
Identification
Common NameMedroxyprogesterone Acetate
ClassSmall Molecule
Description
Medroxyprogesterone Acetate (C24H34O4) is an exogenous compound with an average molecular weight of 386.52 g/mol. It exists as a solid at room temperature. Medroxyprogesterone Acetate belongs to the pregnane steroids, a subclass of steroids and steroid derivatives within the organic compounds. This compound is classified under the superclass of lipids and lipid-like molecules. The compound interacts with two recorded protein targets: the progesterone receptor (PGR) and the estrogen receptor (ESR1). Medroxyprogesterone Acetate has been identified in or released from 57 recorded sources. These include electrical and electronic equipment such as antennas, amplifiers, coils, auxiliary devices, and adjustable resistors. Within household cleaning and consumer products, it is found in bleaching agents, perfumes within detergents and soaps, cigar cigarettes, ash trays, and non electric simulated smoking devices. In building and construction, it is associated with roofs, floors, ceilings, fencing, and ladders. It is also found in household items such as watch chains and rosaries. Additionally, the compound is present in food, food processing, and cookware, specifically in food preservation, fermentation processes for beer, the preparation of malt, the preparation of wort, and the preparation of wine or sparkling wine.
Contaminant Type
  • Antineoplastic Agent, Hormonal
  • Contraceptive Agent
  • Contraceptive Agent, Female
  • Contraceptive Agent, Male
  • Drug
  • Ester
  • Ether
  • Human Neurotoxin
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Synonyms
ValueSource
(6alpha)-17-(Acetyloxy)-6-methylpreg-4-ene-3,20-dioneChEBI
17-Acetoxy-6alpha-methylprogesteroneChEBI
17alpha-Hydroxy-6alpha-methylprogesterone acetateChEBI
6-alpha-Methyl-17-alpha-acetoxyprogesteroneChEBI
6-alpha-Methyl-17-alpha-hydroxyprogesterone acetateChEBI
6alpha-Methyl-17-acetoxy progesteroneChEBI
6alpha-Methyl-17alpha-hydroxyprogesterone acetateChEBI
6alpha-Methyl-4-pregnene-3,20-dion-17alpha-ol acetateChEBI
CBP-1011ChEBI
Depo-proveraChEBI
Depot medroxyprogesterone acetateChEBI
DMPAChEBI
MAPChEBI
Medroxyacetate progesteroneChEBI
Medroxyprogesterone 17-acetateChEBI
MethylacetoxyprogesteroneChEBI
MetigestronaChEBI
MPAChEBI
Depo-subq provera 104Kegg
ProveraKegg
(6a)-17-(Acetyloxy)-6-methylpreg-4-ene-3,20-dioneGenerator
(6Α)-17-(acetyloxy)-6-methylpreg-4-ene-3,20-dioneGenerator
17-Acetoxy-6a-methylprogesteroneGenerator
17-Acetoxy-6α-methylprogesteroneGenerator
17a-Hydroxy-6a-methylprogesterone acetateGenerator
17a-Hydroxy-6a-methylprogesterone acetic acidGenerator
17alpha-Hydroxy-6alpha-methylprogesterone acetic acidGenerator
17Α-hydroxy-6α-methylprogesterone acetateGenerator
17Α-hydroxy-6α-methylprogesterone acetic acidGenerator
6-a-Methyl-17-a-acetoxyprogesteroneGenerator
6-Α-methyl-17-α-acetoxyprogesteroneGenerator
6-a-Methyl-17-a-hydroxyprogesterone acetateGenerator
6-a-Methyl-17-a-hydroxyprogesterone acetic acidGenerator
6-alpha-Methyl-17-alpha-hydroxyprogesterone acetic acidGenerator
6-Α-methyl-17-α-hydroxyprogesterone acetateGenerator
6-Α-methyl-17-α-hydroxyprogesterone acetic acidGenerator
6a-Methyl-17-acetoxy progesteroneGenerator
6Α-methyl-17-acetoxy progesteroneGenerator
6a-Methyl-17a-hydroxyprogesterone acetateGenerator
6a-Methyl-17a-hydroxyprogesterone acetic acidGenerator
6alpha-Methyl-17alpha-hydroxyprogesterone acetic acidGenerator
6Α-methyl-17α-hydroxyprogesterone acetateGenerator
6Α-methyl-17α-hydroxyprogesterone acetic acidGenerator
6a-Methyl-4-pregnene-3,20-dion-17a-ol acetateGenerator
6a-Methyl-4-pregnene-3,20-dion-17a-ol acetic acidGenerator
6alpha-Methyl-4-pregnene-3,20-dion-17alpha-ol acetic acidGenerator
6Α-methyl-4-pregnene-3,20-dion-17α-ol acetateGenerator
6Α-methyl-4-pregnene-3,20-dion-17α-ol acetic acidGenerator
Depot medroxyprogesterone acetic acidGenerator
Medroxyacetic acid progesteroneGenerator
Medroxyprogesterone 17-acetic acidGenerator
Medroxyprogesterone acetic acidGenerator
6-alpha-Methyl-17alpha-hydroxyprogesterone acetateMeSH
(6 alpha)-17-(Acetoxy)-6-methylpregn-4-ene-3,20-dioneMeSH
depo Medroxyprogesterone acetateMeSH
depo-Medroxyprogesterone acetateMeSH
GestapuranMeSH
6 alpha Methyl 17alpha hydroxyprogesterone acetateMeSH
CurretabMeSH
CycrinMeSH
depo ProveraMeSH
Medroxyprogesterone 17 acetateMeSH
Medroxyprogesterone 17-acetate, (6 alpha,17 alpha)-isomerMeSH
VeramixMeSH
DepoProveraMeSH
FarlutalMeSH
Medroxyprogesterone 17-acetate, (6 beta)-isomerMeSH
PerlutexMeSH
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 KeyPSGAAPLEWMOORI-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
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Organoleptic EffectsNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point214.5°C
Boiling PointNot Available
Solubility22.2mg/L
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
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
LC-MS/MSLC-MS/MS Spectrumsplash10-00lu-0594000000-78579410f8f6799b400bNot AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-0a4l-3940000000-cf90a6f216d592e2ad4cNot AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-0udi-1339100000-e2ebb13d416a5b485ad5Not AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-002r-0449000000-c09cb0607e4a6118f05dNot AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-00dj-3940000000-2c9513d9a6a2092f5759Not AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-00di-3930000000-453ace561b4dc5712e85Not AvailableView Spectrum
LC-MS/MSLC-MS/MS Spectrumsplash10-009i-2947000000-2c9190ea372fd54323e9Not AvailableView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrumsplash10-000i-0009000000-05f1f54a7d2de1236908Not AvailableView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrumsplash10-05p2-0049000000-ffc7818cd479acc19cabNot AvailableView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrumsplash10-0uy0-0390000000-9ea2dbc66c9acf4b00baNot AvailableView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrumsplash10-000l-1009000000-0f7f31209fd83cf2cddfNot AvailableView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrumsplash10-0006-2019000000-f92eb379c368e053c8ffNot AvailableView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrumsplash10-0a6u-8049000000-31808bd6c16e7dab93e3Not AvailableView Spectrum
Toxicity Profile
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.
Carcinogenicity (IARC Classification)2B, possibly carcinogenic to humans. (3)
Minimum Risk LevelNot Available
SymptomsSide effects include loss of bone mineral density, BMD changes in adult women, bleeding irregularities, cancer risks, and thromboembolic disorders.
TreatmentNot Available
Toxicity Values
Toxicity ValueUnitValue RangeOrganismDose DescriptorRoute of ExposurePredicted or ExperimentalReference
8652.0Log mg/kg[4900:15000]RatLD50oralpredictedNot Available
Health Effects
Health EffectRelationshipDirectionReference
Exposure Sources
Source IDSourceSectorReference
10InsecticidesAgriculture & land managementNot Available
233BrushesPersonal care & cosmeticsNot Available
495CeilingsBuilding & ConstructionNot Available
496FencingBuilding & ConstructionNot Available
497FloorsBuilding & ConstructionNot Available
498LaddersBuilding & ConstructionNot Available
499RoofsBuilding & ConstructionNot Available
500Stairs And RampsBuilding & ConstructionNot Available
501Sunshades Awnings Or Outside ScreensBuilding & ConstructionNot Available
502Sunshades Awnings Or Outside ScreensBuilding & ConstructionNot Available
503Tents Or CanopiesBuilding & ConstructionNot Available
504Adjustable ResistorsElectrical & Electronic EquipmentNot Available
505AmplifiersElectrical & Electronic EquipmentNot Available
506AntennasElectrical & Electronic EquipmentNot Available
507Auxiliary DevicesElectrical & Electronic EquipmentNot Available
508CoilsElectrical & Electronic EquipmentNot Available
509Colour Television SystemsElectrical & Electronic EquipmentNot Available
510Communication Cables Or ConductorsElectrical & Electronic EquipmentNot Available
511Conductors Or Conductive Bodies Characterised By The Conductive MaterialsElectrical & Electronic EquipmentNot Available
513Cores Yokes Or ArmaturesElectrical & Electronic EquipmentNot Available
514Discharge LampsElectrical & Electronic EquipmentNot Available
515Discharge Tubes With Liquid Pool CathodesElectrical & Electronic EquipmentNot Available
516Electric Hearing AidsElectrical & Electronic EquipmentNot Available
517Electric SwitchesElectrical & Electronic EquipmentNot Available
518Electrically Stimulated Smoking DevicesElectrical & Electronic EquipmentNot Available
519ElectrodesElectrical & Electronic EquipmentNot Available
520Emergency Protective DevicesElectrical & Electronic EquipmentNot Available
521Fixed Capacitors And Their ManufactureElectrical & Electronic EquipmentNot Available
523Gas Filled Discharge Tubes With Solid CathodeElectrical & Electronic EquipmentNot Available
524Hybrid CapacitorsElectrical & Electronic EquipmentNot Available
525Line Transmission SystemsElectrical & Electronic EquipmentNot Available
527MagnetsElectrical & Electronic EquipmentNot Available
529Power CablesElectrical & Electronic EquipmentNot Available
530Radio Transmission SystemsElectrical & Electronic EquipmentNot Available
531RelaysElectrical & Electronic EquipmentNot Available
532SelectorsElectrical & Electronic EquipmentNot Available
533Sparking PlugsElectrical & Electronic EquipmentNot Available
534Still Video CamerasElectrical & Electronic EquipmentNot Available
537Television SystemsElectrical & Electronic EquipmentNot Available
539Video GamesElectrical & Electronic EquipmentNot Available
544Fermentation Processes For BeerFood, food processing & cookwareNot Available
545Food PreservationFood, food processing & cookwareNot Available
547Preparation Of MaltFood, food processing & cookwareNot Available
549Preparation Of Wine Or Sparkling WineFood, food processing & cookwareNot Available
550Preparation Of WortFood, food processing & cookwareNot Available
551Processing FishFood, food processing & cookwareNot Available
552Processing MeatsFood, food processing & cookwareNot Available
554Ash TraysHousehold cleaning & consumer productsNot Available
555Bleaching AgentsHousehold cleaning & consumer productsNot Available
556Cigar CigarettesHousehold cleaning & consumer productsNot Available
559Non Electric Simulated Smoking DevicesHousehold cleaning & consumer productsNot Available
561Perfumes Within Detergents And SoapsHousehold cleaning & consumer productsNot Available
562Pipe AccessoriesHousehold cleaning & consumer productsNot Available
563Soap DetergentsHousehold cleaning & consumer productsNot Available
564Soap DispensersHousehold cleaning & consumer productsNot Available
566Tobacco PipesHousehold cleaning & consumer productsNot Available
569Tobacco Smoke FiltersHousehold cleaning & consumer productsNot Available
575RosariesHousehold itemsNot Available
577Watch ChainsHousehold itemsNot Available
578Making CigarsIndustrial manufacturing & chemical processingNot Available
579Manufacture Of Iron Or SteelIndustrial manufacturing & chemical processingNot Available
580Manufacture Preparation Of Tobacco ProductsIndustrial manufacturing & chemical processingNot Available
581Paper Making MachinesIndustrial manufacturing & chemical processingNot Available
583Anchoring EquipmentMarine, shipping & aquacultureNot Available
589Life BuoysMarine, shipping & aquacultureNot Available
590Lifeboat EquipmentMarine, shipping & aquacultureNot Available
592Marine Propulsion Or SteeringMarine, shipping & aquacultureNot Available
594Ship HullsMarine, shipping & aquacultureNot Available
596AcaricidesAgriculture & land managementNot Available
598Fertiliser DistributorsAgriculture & land managementNot Available
599Harvesters For PeanutsAgriculture & land managementNot Available
600Herbicides And AlgicidesAgriculture & land managementNot Available
601Lawn MowersAgriculture & land managementNot Available
602MolluscicidesAgriculture & land managementNot Available
603NematocidesAgriculture & land managementNot Available
605Pest RepellantsAgriculture & land managementNot Available
606Plant Growth RegulatorsAgriculture & land managementNot Available
609AftershavePersonal care & cosmeticsNot Available
610Aftersun ProductsPersonal care & cosmeticsNot Available
611Anti Perspirants Or Body DeoderantsPersonal care & cosmeticsNot Available
613DepilatoriesPersonal care & cosmeticsNot Available
614Essential Oils Or PerfumesPersonal care & cosmeticsNot Available
615Eye Makeup ProductsPersonal care & cosmeticsNot Available
617Lip Care ProductsPersonal care & cosmeticsNot Available
618Lip Makeup ProductsPersonal care & cosmeticsNot Available
619Manicure PedicurePersonal care & cosmeticsNot Available
620Card GamesRecreation & sports surfacesNot Available
621Chutes And SlidesRecreation & sports surfacesNot Available
622Game AccessoriesRecreation & sports surfacesNot Available
624Merry Go RoundsRecreation & sports surfacesNot Available
628See SawsRecreation & sports surfacesNot Available
629SwingsRecreation & sports surfacesNot Available
630ToysRecreation & sports surfacesNot Available
632ApparelTextiles, leather & furnishingsNot Available
633Azo DyesTextiles, leather & furnishingsNot Available
634BucklesTextiles, leather & furnishingsNot Available
638Decorating TextilesTextiles, leather & furnishingsNot Available
640Embroidering And TuftingTextiles, leather & furnishingsNot Available
642FootwearTextiles, leather & furnishingsNot Available
643HeadwearTextiles, leather & furnishingsNot Available
644Hook Or Eye FastenersTextiles, leather & furnishingsNot Available
647Multicolour DyeingTextiles, leather & furnishingsNot Available
649Pins ClothesTextiles, leather & furnishingsNot Available
650Purses Luggage Hand BagsTextiles, leather & furnishingsNot Available
651Purses Money Bags WalletsTextiles, leather & furnishingsNot Available
652RopesTextiles, leather & furnishingsNot Available
653SewingTextiles, leather & furnishingsNot Available
655Slide FastenersTextiles, leather & furnishingsNot Available
656Snap FastenersTextiles, leather & furnishingsNot Available
657Surface Finishing Of LeatherTextiles, leather & furnishingsNot Available
658Touch FastenersTextiles, leather & furnishingsNot Available
659Transfer PrintingTextiles, leather & furnishingsNot Available
661UmbrellasTextiles, leather & furnishingsNot Available
662Yarns Or ThreadsTextiles, leather & furnishingsNot Available
Pathways
1 pathway
Targets
StructureProteinUniProt IDOrganismRelationshipDetails
Glucocorticoid receptor structureClick to view 3D structureGlucocorticoid receptorP04150HumansPredicted (SEA)1.40129
Click to view 3D structureAndrogen receptorP15207Rattus norvegicusPredicted (SEA)0.856341
Click to view 3D structureProgesterone receptorQ690N0Bos taurusPredicted (SEA)0.233548
Sex hormone-binding globulin structureClick to view 3D structureSex hormone-binding globulinP04278HumansPredicted (SEA)1.16774
Androgen receptor structureClick to view 3D structureAndrogen receptorP10275HumansPredicted (SEA)5.99439
Progesterone receptor structureClick to view 3D structureProgesterone receptorP06401HumansPredicted (SEA)4.12601
Mineralocorticoid receptor structureClick to view 3D structureMineralocorticoid receptorP08235HumansPredicted (SEA)3.11397
Click to view 3D structureAndrogen receptorP19091Mus musculusPredicted (SEA)0.778492
Corticosteroid-binding globulin structureClick to view 3D structureCorticosteroid-binding globulinP08185HumansPredicted (SEA)8.56341
Aldo-keto reductase family 1 member C3 structureClick to view 3D structureAldo-keto reductase family 1 member C3P42330HumansPredicted (SEA)14.3243
Bile salt export pump structureClick to view 3D structureBile salt export pumpO95342HumansPredicted (SEA)10.5875
Cytochrome P450 2C9 structureClick to view 3D structureCytochrome P450 2C9P11712HumansPredicted (SEA)434.632
Estrogen receptor structureClick to view 3D structureEstrogen receptorP03372HumansPredicted (SEA)61.0338
Aldo-keto reductase family 1 member C2 structureClick to view 3D structureAldo-keto reductase family 1 member C2P52895HumansPredicted (SEA)22.3427
Aromatase structureClick to view 3D structureAromataseP11511HumansPredicted (SEA)46.9431
Cytochrome P450 2C19 structureClick to view 3D structureCytochrome P450 2C19P33261HumansPredicted (SEA)327.745
Click to view 3D structure3-oxo-5-alpha-steroid 4-dehydrogenase 1P18405HumansPredicted (SEA)4.7488
Steroid 17-alpha-hydroxylase/17,20 lyase structureClick to view 3D structureSteroid 17-alpha-hydroxylase/17,20 lyaseP05093HumansPredicted (SEA)16.0369
3-oxo-5-alpha-steroid 4-dehydrogenase 2 structureClick to view 3D structure3-oxo-5-alpha-steroid 4-dehydrogenase 2P31213HumansPredicted (SEA)6.61718
Aldo-keto reductase family 1 member C1 structureClick to view 3D structureAldo-keto reductase family 1 member C1Q04828HumansPredicted (SEA)12.0666
Click to view 3D structure3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1P14060HumansPredicted (SEA)3.26967
G-protein coupled bile acid receptor 1 structureClick to view 3D structureG-protein coupled bile acid receptor 1Q8TDU6HumansPredicted (SEA)49.5121
Click to view 3D structureSolute carrier organic anion transporter family member 1A1P46720Rattus norvegicusPredicted (SEA)9.10836
Estrogen receptor beta structureClick to view 3D structureEstrogen receptor betaQ92731HumansPredicted (SEA)147.914
Click to view 3D structure3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomeraseP9WQP7Mycobacterium tuberculosisPredicted (SEA)8.40772
Progesterone receptor structureClick to view 3D structureProgesterone receptorP06401HumansKnownNot Available
Estrogen receptor structureClick to view 3D structureEstrogen receptorP03372HumansKnownNot Available
Concentrations
Not Available
External Links
DrugBank IDDB00603
HMDB IDNot Available
FooDB IDNot Available
Phenol Explorer IDNot Available
KNApSAcK IDNot Available
BiGG IDNot Available
BioCyc IDNot Available
METLIN IDNot Available
PDB IDNot Available
Wikipedia LinkMedroxyprogesterone_acetate
Chemspider IDNot Available
ChEBI ID6716
PubChem Compound ID6279
Kegg Compound IDC08150
YMDB IDNot Available
ECMDB IDNot Available
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.

MSDSNot Available
General References
1. https://www.ncbi.nlm.nih.gov/pubmed/?term=11156860
2. https://www.ncbi.nlm.nih.gov/pubmed/?term=11925144
3. https://www.ncbi.nlm.nih.gov/pubmed/?term=15973592
4. https://www.ncbi.nlm.nih.gov/pubmed/?term=16645869
5. https://www.ncbi.nlm.nih.gov/pubmed/?term=18497975
6. https://www.ncbi.nlm.nih.gov/pubmed/?term=18541028
7. https://www.ncbi.nlm.nih.gov/pubmed/?term=19017820
8. https://www.ncbi.nlm.nih.gov/pubmed/?term=19181558
9. https://www.ncbi.nlm.nih.gov/pubmed/?term=20173089
10. https://www.ncbi.nlm.nih.gov/pubmed/?term=29386945
11. https://www.ncbi.nlm.nih.gov/pubmed/?term=29393479
12. https://www.ncbi.nlm.nih.gov/pubmed/?term=29694506
13. https://www.ncbi.nlm.nih.gov/pubmed/?term=30452655
14. https://www.ncbi.nlm.nih.gov/pubmed/?term=30585733
15. https://www.ncbi.nlm.nih.gov/pubmed/?term=30633132
16. https://www.ncbi.nlm.nih.gov/pubmed/?term=30721635
17. https://www.ncbi.nlm.nih.gov/pubmed/?term=30741807
18. https://www.ncbi.nlm.nih.gov/pubmed/?term=30866773
19. https://www.ncbi.nlm.nih.gov/pubmed/?term=30894394
20. https://www.ncbi.nlm.nih.gov/pubmed/?term=30927417
21. https://www.ncbi.nlm.nih.gov/pubmed/?term=31019626
22. https://www.ncbi.nlm.nih.gov/pubmed/?term=31077968
23. https://www.ncbi.nlm.nih.gov/pubmed/?term=31127826
24. https://www.ncbi.nlm.nih.gov/pubmed/?term=31171559
25. https://www.ncbi.nlm.nih.gov/pubmed/?term=31228485
26. https://www.ncbi.nlm.nih.gov/pubmed/?term=31403601
27. https://www.ncbi.nlm.nih.gov/pubmed/?term=31421164
28. https://www.ncbi.nlm.nih.gov/pubmed/?term=31479152
29. https://www.ncbi.nlm.nih.gov/pubmed/?term=31491645
30. https://www.ncbi.nlm.nih.gov/pubmed/?term=31504342
31. https://www.ncbi.nlm.nih.gov/pubmed/?term=31537512
32. https://www.ncbi.nlm.nih.gov/pubmed/?term=31635772
33. https://www.ncbi.nlm.nih.gov/pubmed/?term=31718641
34. https://www.ncbi.nlm.nih.gov/pubmed/?term=31732107
35. https://www.ncbi.nlm.nih.gov/pubmed/?term=31805393
36. https://www.ncbi.nlm.nih.gov/pubmed/?term=31838718
37. https://www.ncbi.nlm.nih.gov/pubmed/?term=31928370
38. https://www.ncbi.nlm.nih.gov/pubmed/?term=31935387
39. https://www.ncbi.nlm.nih.gov/pubmed/?term=7502690