Progestrone

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(New page: Pubchem(5994) The major progestational steroid that is secreted primarily by the CORPUS LUTEUM and the PLACENTA. Progesterone acts on the UTERUS, the MAMMARY GLANDS and the BRAIN. It is r...)
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Pubchem(5994)
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The major progestational steroid that is secreted primarily by the CORPUS LUTEUM and the PLACENTA. Progesterone acts on the UTERUS, the MAMMARY GLANDS and the BRAIN. It is required in EMBRYO IMPLANTATION; PREGNANCY maintenance, and the development of mammary tissue for MILK production. Progesterone, converted from PREGNENOLONE, also serves as an intermediate in the biosynthesis of GONADAL STEROID HORMONES and adrenal CORTICOSTEROIDS.
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<table align='right' border=1>
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Therapeutic Uses
-
<tr><td>
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* hormonal agent
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<jmol><jmolApplet>
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<size>200</size>
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<script>spin on;color atoms amino;</script>
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<uploadedFileContents>NPH208.SDF</uploadedFileContents>
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<color>black</color>
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</jmolApplet>
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</jmol>
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</td></tr></table>
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==Description==
+
-
The major progestational steroid that is secreted primarily by the  CORPUS LUTEUM and the PLACENTA. Progesterone acts on the UTERUS, the  MAMMARY GLANDS and the BRAIN. It is required in EMBRYO IMPLANTATION;  PREGNANCY maintenance, and the development of mammary tissue for MILK  production. Progesterone, converted from PREGNENOLONE, also serves as  an intermediate in the biosynthesis of GONADAL STEROID HORMONES and  adrenal CORTICOSTEROIDS.
+
-
==General Properties==
+
-
<b>*Molecular Weight</b>
+
Lipinski’s “Rule of Five” Prediction for a Compound’s ABSORPTION OR PERMEABILITY PROPERTIES
 +
{| border="1;width:100%; height:200px;style=text-align:center"
 +
|+'''Table I:'''
 +
|-
 +
! style="background:brown; color:white" |4
 +
! style="background:brown; color:white" |3
 +
! style="background:brown; color:white" |2
 +
! style="background:brown; color:white" |1
 +
! style="background:brown; color:white" |0
 +
|-
-
314.46
+
|GOOD
 +
|INDETERMINATE
 +
|INDETERMINATE
 +
|INDETERMINATE
 +
|POOR
 +
|-
 +
|}
-
<b>*Molecular Formula</b>
+
KEGG Pathway(C00410,D00066)
 +
C21-Steroid hormone metabolism
 +
Progesterone-mediated oocyte maturation
 +
Prostate cancer
 +
Activity Progestin
 +
DrugBank: DB00396
 +
LigandBox: D00066
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C<sub>2</sub><sub>1</sub>H<sub>3</sub><sub>0</sub>O<sub>2</sub>
+
{| border="1;width:100%; height:200px;style=text-align:center"
-
 
+
|+'''Table I:'''
-
<b>*IUPAC NAME</b>
+
|-
-
 
+
! style="background:brown; color:white" |MMDB ID
-
(8S,9S,10R,13S,14S,17S)-17-acetyl-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-one
+
! style="background:brown; color:white" |PDB ID
-
 
+
! style="background:brown; color:white" |Reference
-
<b>*Canonical Smiles</b>
+
|-
-
 
+
|28824
-
CC(=O)C1CCC2C1(CCC3C2CCC4=CC(=O)CCC34C)C
+
|1W0F
-
 
+
|Williams PA, Cosme J, Vinkovic DM, Ward A, Angove HC, Day PJ, Vonrhein C, Tickle IJ, Jhoti HCrystal structures of human cytochrome P450 3A4 bound to metyrapone and progesteroneScience v305, p.683-686
-
<b>*Isomeric Smiles</b>
+
Cytochromes P450 (P450s) metabolize a wide range of endogenous compounds and xenobiotics, such as pollutants, environmental compounds, and drug molecules. The microsomal, membrane-associated, P450 isoforms CYP3A4, CYP2D6, CYP2C9, CYP2C19, CYP2E1, and CYP1A2 are responsible for the oxidative metabolism of more than 90% of marketed drugs...
-
 
+
|-
-
CC(=O)[C@H]1CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2CCC4=CC(=O)CC[C@]34C)C
+
|33238
-
 
+
|1YA3
-
 
+
|Fagart J, Huyet J, Pinon GM, Rochel M, Mayer C, Rafestin-Oblin MECrystal structure of a mutant mineralocorticoid receptor responsible for hypertensionNat. Struct. Mol. Biol. v12, p.554-555
-
==PhysioChemical Properties==
+
The S810L mutation within the human mineralocorticoid receptor (MR S810L) induces severe hypertension and switches progesterone from antagonist to agonist. Here we report the crystal structures of the ligand-binding domain of MR S810L in complex with progesterone and deoxycorticosterone, an agonist of both wild-type and mutant MRs....
-
 
+
|-
-
<b>*Melting Point</b>
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|34428
-
 
+
|2AA5
-
121(EXP)
+
|
-
 
+
|-
-
<b>*LogP</b>
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|34429
-
 
+
|2AA6
-
3.87(EXP)
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|-Bledsoe RK, Madauss KP, Holt JA, Apolito CJ, Lambert MH, Pearce KH, Stanley TB, Stewart EL, Trump RP, Willson TM, Williams SPA ligand-mediated hydrogen bond network required for the activation of the mineralocorticoid receptorJ. Biol. Chem. v280, p.31283-31293
-
 
+
Ligand binding is the first step in hormone regulation of mineralocorticoid receptor (MR) activity. Here, we report multiple crystal structures of MR (NR3C2) bound to both agonist and antagonists. These structures combined with mutagenesis studies reveal that maximal receptor activation involves an intricate ligand-mediated hydrogen bond network with Asn770 which serves dual roles: stabilization of the loop preceding the C-terminal activation function-2 helix and direct contact with the hormone ligand....
-
<b>*Water Solubility</b>
+
|-
-
 
+
|35596
-
8.81(EXP) at 25C
+
|2ABA
-
 
+
|Khan H, Barna T, Bruce NC, Munro AW, Leys D, Scrutton NSProton transfer in the oxidative half-reaction of pentaerythritol tetranitrate reductase. Structure of the reduced enzyme-progesterone complex and the roles of residues Tyr186, His181, His184FEBS J. v272, p.4660-4671
-
==External Links==
+
The roles of His181, His184 and Tyr186 in PETN reductase have been examined by mutagenesis, spectroscopic and stopped-flow kinetics, and by determination of crystallographic structures for the Y186F PETN reductase and reduced wild-type enzyme-progesterone complex. Residues His181 and His184 are important in the binding of coenzyme, steroids, nitroaromatic ligands and the substrate 2-cyclohexen-1-one....
-
*[http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5994]Pubchem
+
|-
-
*[http://www.rcsb.org/pdb/cgi/explore.cgi?pdbId=1W0F]]1W0F,[[http://www.rcsb.org/pdb/cgi/explore.cgi?pdbId=1YA3]]1YA3,[[http://www.rcsb.org/pdb/cgi/explore.cgi?pdbId=2AA5]]2AA5,[[http://www.rcsb.org/pdb/cgi/explore.cgi?pdbId=2AA6]]2AA6,[[http://www.rcsb.org/pdb/cgi/explore.cgi?pdbId=2ABA]]2ABA,[[http://www.rcsb.org/pdb/cgi/explore.cgi?pdbId=2HZQ]]2HZQ,[[http://www.rcsb.org/pdb/cgi/explore.cgi?pdbId=2O5Y]]2O5Y,[[http://www.rcsb.org/pdb/cgi/explore.cgi?pdbId=1DBB]]1DBB,[[http://www.rcsb.org/pdb/cgi/explore.cgi?pdbId=1A28]]1A28,
+
|53437
-
*[http://www.genome.jp/dbget-bin/www_bget?compound+C00410]KEGG Compound
+
|2HZQ
-
*[http://www.genome.jp/dbget-bin/www_bget?drug+D00066]KEGG Drug
+
|Eichinger A, Nasreen A, Kim HJ, Skerra AStructural insight into the dual ligand specificity and mode of high density lipoprotein association of apolipoprotein DJ. Biol. Chem. v282, p.31068-31075
-
*[http://www.hmdb.ca/metabolites/HMDB01830]Human Metabolome DataBase
+
Human apolipoprotein D (ApoD) occurs in plasma associated with high density lipoprotein. Apart from the involvement in lipid metabolism, its binding activity for progesterone and arachidonic acid plays a role in cancer development and neurological diseases. The crystal structures of free ApoD and its complex with progesterone were determined at 1.8A resolution and reveal a lipocalin fold....
-
*[http://www.drugbank.ca/drugs/DB00396]Drugbank
+
|-
-
 
+
|61329
-
[[Categories:Hormones]]
+
|2O5Y
 +
|Verdino P, Aldag C, Hilvert D, Wilson IAClosely related antibody receptors exploit fundamentally different strategies for steroid recognitionProc. Natl. Acad. Sci. U. S. A. v105, p.11725-11730
 +
Molecular recognition by the adaptive immune system relies on specific high-affinity antibody receptors that are generated from a restricted set of starting sequences through homologous recombination and somatic mutation. The steroid binding antibody DB3 and the catalytic Diels-Alderase antibody 1E9 derive from the same germ line sequences but exhibit very distinct specificities and functions....
 +
|-
 +
|733
 +
|1DBB
 +
|Arevalo JH, Stura EA, Taussig MJ, Wilson IAThree-dimensional structure of an anti-steroid Fab' and progesterone-Fab' complexJ. Mol. Biol. v231, p.103-118.The monoclonal anti-progesterone antibody DB3 binds progesterone with nanomolar affinity (Ka approximately 10(9) M-1), suggesting high specificity. However, DB3 also cross-reacts with similar affinity with a subgroup of structurally distinct, progesterone-like steroids. Crystals of the unliganded Fab" and various steroid-Fab" complexes are isomorphous and belong to the hexagonal space group, P6(4)22, with unit cell dimensions of a = b = 135 A, c = 124 A....
 +
|-
 +
|8232
 +
|1A28
 +
|Williams SP, Sigler PBAtomic structure of progesterone complexed with its receptorNature v393, p.392-396
 +
The physiological effects of progestins are mediated by the progesterone receptor, a member of the steroid/nuclear receptor superfamily. As progesterone is required for maintenance of pregnancy, its receptor has been a target for pharmaceuticals. Here we report the 1.8 A crystal structure of a progesterone-bound ligand-binding domain of the human progesterone receptor....
 +
|-
 +
|}
 +
{| border="1;width:100%; height:200px;style=text-align:center"
 +
|+'''Table I:'''
 +
|-
 +
! style="background:brown; color:white" |Physical Property
 +
! style="background:brown; color:white" |Value
 +
! style="background:brown; color:white" |Units
 +
! style="background:brown; color:white" |Temp (deg C)
 +
! style="background:brown; color:white" |Source
 +
|-
 +
|Melting Point  
 +
|121
 +
|deg C
 +
|
 +
|EXP
 +
|-
 +
log P (octanol-water)
 +
|3.87  
 +
|none
 +
|-
 +
|EXP
 +
|Water Solubility  
 +
|8.81
 +
|mg/L
 +
|25
 +
|EXP
 +
|-
 +
|Vapor Pressure
 +
|1.30E-06
 +
|mm Hg
 +
|25
 +
|EST
 +
|-
 +
|Henry's Law Constant
 +
|6.49E-08
 +
|atm-m3/mole
 +
|25
 +
|EST
 +
|-
 +
|Atmospheric OH Rate Constant
 +
|1.04E-10
 +
|cm3/molecule-sec
 +
|25
 +
|EST
 +
|-
 +
|}
 +
{| border="1;width:100%; height:200px;style=text-align:center"
 +
|+'''Table I:'''
 +
|-
 +
! style="background:brown; color:white" |Organism
 +
! style="background:brown; color:white" |Test Type 
 +
! style="background:brown; color:white" |Route 
 +
! style="background:brown; color:white" |Reported Dose (Normalized Dose)
 +
! style="background:brown; color:white" |Effect
 +
! style="background:brown; color:white" |Source
 +
|-
 +
|mouse
 +
|LDLo
 +
|intravenous
 +
|100mg/kg (100mg/kg)
 +
|BEHAVIORAL: CONVULSIONS OR EFFECT ON SEIZURE THRESHOLD.BEHAVIORAL: ATAXIA
 +
|LUNGS, THORAX, OR RESPIRATION: DYSPNEA Journal of Medicinal Chemistry. Vol. 11, Pg. 117, 1968.
 +
|-
 +
|rat
 +
|LD50
 +
|intraperitoneal
 +
|327mg/kg (327mg/kg)
 +
|
 +
|Drugs in Japan Vol. -, Pg. 1183, 1995.
 +
|-
 +
|}
 +
Major Use:
 +
DRUGS (HORMONES)

Revision as of 08:35, 24 October 2008

Pubchem(5994)

The major progestational steroid that is secreted primarily by the CORPUS LUTEUM and the PLACENTA. Progesterone acts on the UTERUS, the MAMMARY GLANDS and the BRAIN. It is required in EMBRYO IMPLANTATION; PREGNANCY maintenance, and the development of mammary tissue for MILK production. Progesterone, converted from PREGNENOLONE, also serves as an intermediate in the biosynthesis of GONADAL STEROID HORMONES and adrenal CORTICOSTEROIDS.

Therapeutic Uses

  • hormonal agent

Lipinski’s “Rule of Five” Prediction for a Compound’s ABSORPTION OR PERMEABILITY PROPERTIES

Table I:
4 3 2 1 0
GOOD INDETERMINATE INDETERMINATE INDETERMINATE POOR

KEGG Pathway(C00410,D00066) C21-Steroid hormone metabolism Progesterone-mediated oocyte maturation Prostate cancer Activity Progestin DrugBank: DB00396 LigandBox: D00066

Ligand binding is the first step in hormone regulation of mineralocorticoid receptor (MR) activity. Here, we report multiple crystal structures of MR (NR3C2) bound to both agonist and antagonists. These structures combined with mutagenesis studies reveal that maximal receptor activation involves an intricate ligand-mediated hydrogen bond network with Asn770 which serves dual roles: stabilization of the loop preceding the C-terminal activation function-2 helix and direct contact with the hormone ligand....
Table I:
MMDB ID PDB ID Reference
28824 1W0F Williams PA, Cosme J, Vinkovic DM, Ward A, Angove HC, Day PJ, Vonrhein C, Tickle IJ, Jhoti HCrystal structures of human cytochrome P450 3A4 bound to metyrapone and progesteroneScience v305, p.683-686

Cytochromes P450 (P450s) metabolize a wide range of endogenous compounds and xenobiotics, such as pollutants, environmental compounds, and drug molecules. The microsomal, membrane-associated, P450 isoforms CYP3A4, CYP2D6, CYP2C9, CYP2C19, CYP2E1, and CYP1A2 are responsible for the oxidative metabolism of more than 90% of marketed drugs...

33238 1YA3 Fagart J, Huyet J, Pinon GM, Rochel M, Mayer C, Rafestin-Oblin MECrystal structure of a mutant mineralocorticoid receptor responsible for hypertensionNat. Struct. Mol. Biol. v12, p.554-555

The S810L mutation within the human mineralocorticoid receptor (MR S810L) induces severe hypertension and switches progesterone from antagonist to agonist. Here we report the crystal structures of the ligand-binding domain of MR S810L in complex with progesterone and deoxycorticosterone, an agonist of both wild-type and mutant MRs....

34428 2AA5
34429 2AA6
35596 2ABA Khan H, Barna T, Bruce NC, Munro AW, Leys D, Scrutton NSProton transfer in the oxidative half-reaction of pentaerythritol tetranitrate reductase. Structure of the reduced enzyme-progesterone complex and the roles of residues Tyr186, His181, His184FEBS J. v272, p.4660-4671

The roles of His181, His184 and Tyr186 in PETN reductase have been examined by mutagenesis, spectroscopic and stopped-flow kinetics, and by determination of crystallographic structures for the Y186F PETN reductase and reduced wild-type enzyme-progesterone complex. Residues His181 and His184 are important in the binding of coenzyme, steroids, nitroaromatic ligands and the substrate 2-cyclohexen-1-one....

53437 2HZQ Eichinger A, Nasreen A, Kim HJ, Skerra AStructural insight into the dual ligand specificity and mode of high density lipoprotein association of apolipoprotein DJ. Biol. Chem. v282, p.31068-31075

Human apolipoprotein D (ApoD) occurs in plasma associated with high density lipoprotein. Apart from the involvement in lipid metabolism, its binding activity for progesterone and arachidonic acid plays a role in cancer development and neurological diseases. The crystal structures of free ApoD and its complex with progesterone were determined at 1.8A resolution and reveal a lipocalin fold....

61329 2O5Y Verdino P, Aldag C, Hilvert D, Wilson IAClosely related antibody receptors exploit fundamentally different strategies for steroid recognitionProc. Natl. Acad. Sci. U. S. A. v105, p.11725-11730

Molecular recognition by the adaptive immune system relies on specific high-affinity antibody receptors that are generated from a restricted set of starting sequences through homologous recombination and somatic mutation. The steroid binding antibody DB3 and the catalytic Diels-Alderase antibody 1E9 derive from the same germ line sequences but exhibit very distinct specificities and functions....

733 1DBB Arevalo JH, Stura EA, Taussig MJ, Wilson IAThree-dimensional structure of an anti-steroid Fab' and progesterone-Fab' complexJ. Mol. Biol. v231, p.103-118.The monoclonal anti-progesterone antibody DB3 binds progesterone with nanomolar affinity (Ka approximately 10(9) M-1), suggesting high specificity. However, DB3 also cross-reacts with similar affinity with a subgroup of structurally distinct, progesterone-like steroids. Crystals of the unliganded Fab" and various steroid-Fab" complexes are isomorphous and belong to the hexagonal space group, P6(4)22, with unit cell dimensions of a = b = 135 A, c = 124 A....
8232 1A28 Williams SP, Sigler PBAtomic structure of progesterone complexed with its receptorNature v393, p.392-396

The physiological effects of progestins are mediated by the progesterone receptor, a member of the steroid/nuclear receptor superfamily. As progesterone is required for maintenance of pregnancy, its receptor has been a target for pharmaceuticals. Here we report the 1.8 A crystal structure of a progesterone-bound ligand-binding domain of the human progesterone receptor....

log P (octanol-water)
Table I:
Physical Property Value Units Temp (deg C) Source
Melting Point 121 deg C EXP
3.87 none
EXP Water Solubility 8.81 mg/L 25 EXP
Vapor Pressure 1.30E-06 mm Hg 25 EST
Henry's Law Constant 6.49E-08 atm-m3/mole 25 EST
Atmospheric OH Rate Constant 1.04E-10 cm3/molecule-sec 25 EST
Table I:
Organism Test Type Route Reported Dose (Normalized Dose) Effect Source
mouse LDLo intravenous 100mg/kg (100mg/kg) BEHAVIORAL: CONVULSIONS OR EFFECT ON SEIZURE THRESHOLD.BEHAVIORAL: ATAXIA LUNGS, THORAX, OR RESPIRATION: DYSPNEA Journal of Medicinal Chemistry. Vol. 11, Pg. 117, 1968.
rat LD50 intraperitoneal 327mg/kg (327mg/kg) Drugs in Japan Vol. -, Pg. 1183, 1995.

Major Use: DRUGS (HORMONES)

Retrieved from "http://277988.efsst.group/drugpedia/index.php/Progestrone"