Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C21H30O2 |
Molecular Weight | 314.4617 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 6 / 6 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CC(=O)[C@H]1CC[C@H]2[C@@H]3CCC4=CC(=O)CC[C@]4(C)[C@H]3CC[C@]12C
InChI
InChIKey=RJKFOVLPORLFTN-LEKSSAKUSA-N
InChI=1S/C21H30O2/c1-13(22)17-6-7-18-16-5-4-14-12-15(23)8-10-20(14,2)19(16)9-11-21(17,18)3/h12,16-19H,4-11H2,1-3H3/t16-,17+,18-,19-,20-,21+/m0/s1
DescriptionSources: http://www.accessdata.fda.gov/drugsatfda_docs/anda/2001/75-906_Progesterone_prntlbl.pdfCurator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/8282004
http://www.rxlist.com/endometrin-drug/clinical-pharmacology.htm
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/anda/2001/75-906_Progesterone_prntlbl.pdf
Curator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/8282004
http://www.rxlist.com/endometrin-drug/clinical-pharmacology.htm
Progesterone is indicated in amenorrhea and abnormal uterine bleeding due to hormonal imbalance in the absence of organic pathology, such as submucous fibroids of uterine cancer. Progesterone, converted from pregnenolone, also serves as an intermediate in the biosynthesis of gonadal steroid hormones and adrenal corticosteroids. Progesterone is a naturally occurring steroid that is secreted by the ovary, placenta, and adrenal gland. In the presence of adequate estrogen, progesterone transforms a proliferative endometrium into a secretory endometrium. Progesterone is necessary to increase endometrial receptivity for implantation of an embryo. Once an embryo is implanted, progesterone acts to maintain a pregnancy. Progesterone shares the pharmacological actions of the progestins. Progesterone binds to the progesterone and estrogen receptors. Target cells include the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. Once bound to the receptor, progesterone will slow the frequency of release of gonadotropin releasing hormone (GnRH) from the hypothalamus and blunt the pre-ovulatory LH (luteinizing hormone) surge. In women who have adequate endogenous estrogen, progesterone transforms a proliferative endometrium into a secretory one. Progesterone is metabolized primarily by the liver largely to pregnanediols and pregnanolones. Pregnanediols and pregnanolones are conjugated in the liver to glucuronide and sulfate metabolites. Progesterone metabolites that are excreted in the bile may be deconjugated and may be further metabolized in the gut via reduction, dehydroxylation, and epimerization. Common progesterone side effects may include: drowsiness, dizziness; breast pain; mood changes; headache; constipation, diarrhea, heartburn; bloating, swelling in your hands or feet; joint pain; hot flashes; or vaginal discharge.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL208 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17015480 |
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Target ID: CHEMBL206 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17118173 |
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Target ID: CHEMBL1994 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8282004 |
0.01 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | PROGESTERONE Approved UseIs indicated in amenorrhea and abnormal uterine bleeding due to hormonal imbalance in the absence of organic pathology, such as submucous fibroids of uterine cancer. Launch Date2007 |
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Primary | PROGESTERONE Approved UseIs indicated in amenorrhea and abnormal uterine bleeding due to hormonal imbalance in the absence of organic pathology, such as submucous fibroids of uterine cancer. Launch Date2007 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
60.6 ng/mL |
300 mg 1 times / day multiple, oral dose: 300 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
PROGESTERONE plasma | Homo sapiens population: UNKNOWN age: ADULT sex: FEMALE food status: UNKNOWN |
|
14.87 ng/mL |
90 mg single, vaginal dose: 90 mg route of administration: Vaginal experiment type: SINGLE co-administered: |
PROGESTERONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN |
|
15.97 ng/mL |
90 mg 1 times / day steady-state, vaginal dose: 90 mg route of administration: Vaginal experiment type: STEADY-STATE co-administered: |
PROGESTERONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
175.7 ng × h/mL |
300 mg 1 times / day multiple, oral dose: 300 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
PROGESTERONE plasma | Homo sapiens population: UNKNOWN age: ADULT sex: FEMALE food status: UNKNOWN |
|
296.78 ng × h/mL |
90 mg single, vaginal dose: 90 mg route of administration: Vaginal experiment type: SINGLE co-administered: |
PROGESTERONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN |
|
391.98 ng × h/mL |
90 mg 1 times / day steady-state, vaginal dose: 90 mg route of administration: Vaginal experiment type: STEADY-STATE co-administered: |
PROGESTERONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
34.8 h |
90 mg single, vaginal dose: 90 mg route of administration: Vaginal experiment type: SINGLE co-administered: |
PROGESTERONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN |
|
45 h |
90 mg 1 times / day steady-state, vaginal dose: 90 mg route of administration: Vaginal experiment type: STEADY-STATE co-administered: |
PROGESTERONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
yes [IC50 10.5 uM] | ||||
yes [IC50 4.8 uM] | ||||
yes [IC50 42.1 uM] | ||||
yes [Inhibition 100 uM] | ||||
Sources: https://pubmed.ncbi.nlm.nih.gov/9328296/ Page: 3.0 |
yes [Ki 17 uM] | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/9328296/ Page: 3.0 |
yes [Ki 9 uM] | |||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
yes | ||||
Sources: https://pubmed.ncbi.nlm.nih.gov/19813763/ |
yes | |||
yes |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
yes | ||||
Sources: https://pubmed.ncbi.nlm.nih.gov/9328296/ Page: 5.0 |
yes | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/9328296/ Page: 5.0 |
yes | |||
yes | ||||
yes | likely (co-administration study) Comment: Ketoconazole is a known inhibitor of cytochrome P450 3A4, hence these data suggest that ketoconazole or other known inhibitors of this enzyme may increase the bioavailability of progesterone Sources: https://pubmed.ncbi.nlm.nih.gov/8424894/ |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
PubMed
Title | Date | PubMed |
---|---|---|
Elevation of steroid 5 alpha-reductase mRNA levels in rat cerebellum by toluene inhalation: possible relation to GFAP expression. | 2000 Aug |
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Estrogen activation of the nuclear orphan receptor CAR (constitutive active receptor) in induction of the mouse Cyp2b10 gene. | 2000 Nov |
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Progestins, progesterone receptor modulators, and progesterone antagonists change VEGF release of endometrial cells in culture. | 2000 Oct-Nov |
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Dexamethasone up-regulates type II IL-1 receptor in mouse primary activated astrocytes. | 2001 Feb |
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Human types 1 and 3 3 alpha-hydroxysteroid dehydrogenases: differential lability and tissue distribution. | 2001 Feb |
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Endothelins enhance prostaglandin (PGE(2) and PGF(2alpha)) biosynthesis and release by human luteal cells: evidence of a new paracrine/autocrine regulation of luteal function. | 2001 Feb |
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Enhanced verbal memory in nondemented elderly women receiving hormone-replacement therapy. | 2001 Feb |
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Use of salivary biomarkers in biobehavioral research: cotton-based sample collection methods can interfere with salivary immunoassay results. | 2001 Feb |
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Prognostic and predictive significance of ErbB-2 breast tumor levels measured by enzyme immunoassay. | 2001 Feb 1 |
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Re: Randomized trial of fenretinide to prevent second breast malignancy in women with early breast cancer. | 2001 Feb 7 |
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Concordance in judgments among c-erbB-2 (HER2/neu) overexpression detected by two immunohistochemical tests and gene amplification detected by Southern blot hybridization in breast carcinoma. | 2001 Jan |
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The APC is dispensable for first meiotic anaphase in Xenopus oocytes. | 2001 Jan |
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The octadecaneuropeptide ODN stimulates neurosteroid biosynthesis through activation of central-type benzodiazepine receptors. | 2001 Jan |
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Targeted disruption of luteinizing hormone/human chorionic gonadotropin receptor gene. | 2001 Jan |
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Mutations at the boundary of the hinge and ligand binding domain of the androgen receptor confer increased transactivation function. | 2001 Jan |
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Separable features of the ligand-binding domain determine the differential subcellular localization and ligand-binding specificity of glucocorticoid receptor and progesterone receptor. | 2001 Jan |
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Estrogen receptor beta regulates sexually dimorphic neural responses to estradiol. | 2001 Jan |
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Establishment and characterization of a steroidogenic human granulosa-like tumor cell line, KGN, that expresses functional follicle-stimulating hormone receptor. | 2001 Jan |
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Glucocorticoids regulate plasma membrane potential during rat thymocyte apoptosis in vivo and in vitro. | 2001 Jan |
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Assessment of mechanisms of thyroid hormone action in mouse Leydig cells: regulation of the steroidogenic acute regulatory protein, steroidogenesis, and luteinizing hormone receptor function. | 2001 Jan |
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Biphasic action of prolactin in the regulation of murine Leydig tumor cell functions. | 2001 Jan |
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Differential regulation of two forms of gonadotropin-releasing hormone messenger ribonucleic acid in human granulosa-luteal cells. | 2001 Jan |
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Molecular cytogenetic comparison of apocrine hyperplasia and apocrine carcinoma of the breast. | 2001 Jan |
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Prostaglandin receptors and role of G protein-activated pathways on corpora lutea of pseudopregnant rabbit in vitro. | 2001 Jan |
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In vitro regulation of local secretion and contraction of the bovine oviduct: stimulation by luteinizing hormone, endothelin-1 and prostaglandins, and inhibition by oxytocin. | 2001 Jan |
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Granulosa-luteal cell function in vitro and ovarian stimulation protocols. | 2001 Jan |
|
Charcoal treatment and risk of escape ovulation in oral contraceptive users. | 2001 Jan |
|
Reproductive hormones and blood pressure during pregnancy. | 2001 Jan |
|
Hormones and the brain: more studies. | 2001 Jan |
|
Low peripheral blood levels of the immunosuppressive cytokine interleukin 10 (IL-10) at the start of gonadotrophin stimulation indicates increased risk for development of ovarian hyperstimulation syndrome (OHSS). | 2001 Jan |
|
Clinical relevance of urokinase-type plasminogen activator, its receptor, and its inhibitor type 1 in endometrial cancer. | 2001 Jan |
|
Dual effects of nitric oxide in functional and regressing rat corpus luteum. | 2001 Jan |
|
Inhibition of ovulation in the rat by a leukotriene B(4) receptor antagonist. | 2001 Jan |
|
Feed restriction and insulin treatment affect subsequent luteal function in the immediate postovulatory period in pigs: progesterone production in vitro and messenger ribonucleic acid expression for key steroidogenic enzymes. | 2001 Jan |
|
Regulation of progesterone receptors and decidualization in uterine stroma of the estrogen receptor-alpha knockout mouse. | 2001 Jan |
|
Equine P450 cholesterol side-chain cleavage and 3 beta-hydroxysteroid dehydrogenase/delta(5)-delta(4) isomerase: molecular cloning and regulation of their messenger ribonucleic acids in equine follicles during the ovulatory process. | 2001 Jan |
|
Lysyl oxidase and MMP-2 expression in dehydroepiandrosterone-induced polycystic ovary in rats. | 2001 Jan |
|
Follicle-stimulating hormone regulation of inhibin alpha- and beta(B)-subunit and follistatin messenger ribonucleic acid in cultured avian granulosa cells. | 2001 Jan |
|
Metabolism of estradiol, ethynylestradiol, and moxestrol in rat uterus, vagina, and aorta: influence of sex steroid treatment. | 2001 Jan |
|
Influence of gender and sex hormones on nicotine acute pharmacological effects in mice. | 2001 Jan |
|
Evaluation of a vincristine resistant Caco-2 cell line for use in a calcein AM extrusion screening assay for P-glycoprotein interaction. | 2001 Jan |
|
17beta-oestradiol acutely regulates Cl- secretion in rat distal colonic epithelium. | 2001 Jan 1 |
|
Tumor variants by hormone receptor expression in white patients with node-negative breast cancer from the surveillance, epidemiology, and end results database. | 2001 Jan 1 |
|
Prolactin, growth hormone, and epidermal growth factor activate Stat5 in different compartments of mammary tissue and exert different and overlapping developmental effects. | 2001 Jan 1 |
|
Effect of medroxyprogesterone acetate plus estradiol on endothelium-dependent vasodilation in postmenopausal women. | 2001 Jan 15 |
|
Functional involvement of Xenopus LIM kinases in progression of oocyte maturation. | 2001 Jan 15 |
|
Evidence that epithelial and mesenchymal estrogen receptor-alpha mediates effects of estrogen on prostatic epithelium. | 2001 Jan 15 |
|
Evaluation of in vitro methods for detecting the effects of various chemicals on the human progesterone receptor, with a focus on pyrethroid insecticides. | 2001 Jan 3 |
|
Effects of low-frequency magnetic fields on implantation in rats. | 2001 Jan-Feb |
|
Identification of a phosphorylation site in the hinge region of the human progesterone receptor and additional amino-terminal phosphorylation sites. | 2001 Mar 16 |
Patents
Sample Use Guides
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/20540763
Curator's Comment: As a resule 34% reduction in cell proliferation was observed in the MB468 cells with treatment of P4, as compared with the cells with treatment of vehicle alone. As expected, P4 had no effects on cell proliferation of the parental MB231. However, the treatment of the mPRα stably-expressing MB231 cells with P4 induced a significant reduction of cell proliferation (28.1%). These data suggest that mPRα is also involved in regulating cell proliferation of BPBC cells.
To test whether the female sex hormone controls cell proliferation of MB468 (basal phenotype breast cancers) cells, cell were incubated the with progesterone (P4) (30 ng/ml) for 24 hours.
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Classification Tree | Code System | Code | ||
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FDA ORPHAN DRUG |
664818
Created by
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WHO-VATC |
QG03FA04
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NDF-RT |
N0000005934
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LIVERTOX |
803
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LOINC |
83109-9
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FDA ORPHAN DRUG |
82694
Created by
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CFR |
21 CFR 556.540
Created by
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LOINC |
83110-7
Created by
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DSLD |
4218 (Number of products:3)
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LOINC |
12820-7
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LOINC |
44729-2
Created by
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CFR |
21 CFR 522.1940
Created by
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LOINC |
24109-1
Created by
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CFR |
21 CFR 862.1430
Created by
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WHO-ATC |
G03FA04
Created by
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LOINC |
14890-8
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EU-Orphan Drug |
EU/3/13/1101
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LOINC |
17483-9
Created by
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WHO-VATC |
QG03DA04
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CFR |
21 CFR 310.530
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NDF-RT |
N0000005934
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LOINC |
44730-0
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LOINC |
35223-7
Created by
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CFR |
21 CFR 862.1620
Created by
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NCI_THESAURUS |
C2296
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NDF-RT |
N0000175601
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NDF-RT |
N0000005934
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LOINC |
2838-1
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LOINC |
2839-9
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WHO-ATC |
G03DA04
Created by
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FDA ORPHAN DRUG |
284809
Created by
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Code System | Code | Type | Description | ||
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2377
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PRIMARY | |||
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17026
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PRIMARY | |||
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1568007
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PRIMARY | |||
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64377
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PRIMARY | |||
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PROGESTERONE
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PRIMARY | |||
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57-83-0
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PRIMARY | |||
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CHEMBL103
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PRIMARY | |||
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DTXSID3022370
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PRIMARY | |||
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4G7DS2Q64Y
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PRIMARY | |||
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5994
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DB00396
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PRIMARY | |||
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D011374
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PRIMARY | |||
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100000090354
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PRIMARY | |||
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PROGESTERONE
Created by
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PRIMARY | Description: Colourless crystals or a white to slightly yellowish white, crystalline powder; odourless. Solubility: Practically insoluble in water; soluble in 8 parts of ethanol (~750 g/l) TS. Category: Progestational steroid. Storage: Progesterone should be kept in a well-closed container, protected from light. Additional information: Progesterone may exist in 2 polymorphic forms, one of which melts at about 130?C, the other at about 121?C. Definition: Progesterone contains not less than 97.0% and not more than 102.0% of C21H30O2, calculated with reference to the dried substance. | ||
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m9159
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PRIMARY | Merck Index | ||
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SUB10076MIG
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PRIMARY | |||
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2279
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PRIMARY | |||
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200-350-6
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PRIMARY | |||
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Progesterone
Created by
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PRIMARY | |||
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C777
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PRIMARY | |||
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4G7DS2Q64Y
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PRIMARY | |||
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417
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PRIMARY | |||
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3389
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PRIMARY | |||
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9704
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PRIMARY | |||
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8727
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PRIMARY | |||
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C400424
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259409
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ALTERNATIVE | |||
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Progesterone (medication)
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PRIMARY |
ACTIVE MOIETY