Pregnenolone

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'''Pregnenolone''' is a [[steroid]] hormone involved in the [[steroidogenesis]] of [[progesterone]], [[mineralocorticoids]], [[glucocorticoids]], [[androgen]]s, and [[estrogen]]s. As such it is a [[prohormone]].  Pregnenolone is a [[GABAB receptor|GABA<sub>B</sub>]] antagonist and increases neurogenesis in the hippocampus.<ref name=Mayo2005>{{cite journal
 
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| pmid = 15585350
 
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| pmc = 15585350
 
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| title = Pregnenolone Sulfate Enhances Neurogenesis and Psa-Ncam in Young and Aged Hippocampus
 
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| year = 2005
 
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| journal = Neurobiology of Aging
 
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| volume = 26
 
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| issue = 1
 
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| pages = 103–14
 
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| doi = 10.1016/j.neurobiolaging.2004.03.013
 
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| month = Jan
 
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| author = Mayo, W; Lemaire, V; Malaterre, J; Rodriguez, Jj; Cayre, M; Stewart, Mg; Kharouby, M; Rougon, G; Le, Moal, M; Piazza, Pv; Abrous, Dn
 
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}}</ref>
 
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Pubchem(8955)
 
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A 21-carbon steroid, derived from CHOLESTEROL and found in steroid hormone-producing tissues. Pregnenolone is the precursor to GONADAL STEROID HORMONES and the adrenal CORTICOSTEROIDS.
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==Description==
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A 21-carbon steroid, derived from CHOLESTEROL and found in steroid   hormone-producing tissues. Pregnenolone is the precursor to GONADAL   STEROID HORMONES and the adrenal CORTICOSTEROIDS.
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==General Properties==
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'''Drug Type''':  Small Molecule; Experimental
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<b>*Molecular Weight</b>
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'''KEGG Pathway'''(C01953,D00143)
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316.48
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*C21-Steroid hormone metabolism
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{| border="1;width:100%; height:200px;style=text-align:center"
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|+'''Physiochemical properties of Estriol:'''
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|-
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! style="background:brown; color:white" |Physical Property
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! style="background:brown; color:white" |Value
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! style="background:brown; color:white" |Units
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! style="background:brown; color:white" |Temp (deg C)
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! style="background:brown; color:white" |Source
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|-
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|Melting Point
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|192
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|deg C
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|  
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|EXP
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|-
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|log P (octanol-water)
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|4.22
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|(none)
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|
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|EXP
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|-
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|Water Solubility
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|7.06
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|mg/L
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|37
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|EXP
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|-
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|Vapor Pressure
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|1.03E-08
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|mm Hg
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|25
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|EST
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|-
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|Henry's Law Constant
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|1.17E-08
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|atm-m3/mole
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|25
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|EST
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|-
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|Atmospheric OH Rate Constant
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|1.20E-10
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|cm3/molecule-sec
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|25
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|EST
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|-
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|}
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{| border="1;width:100%; height:200px;style=text-align:center"
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|+'''Toxicity:'''
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|-
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! style="background:brown; color:white" |Organism
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! style="background:brown; color:white" |Test Type 
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! style="background:brown; color:white" |Route 
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! style="background:brown; color:white" |Reported Dose (Normalized Dose)
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! style="background:brown; color:white" |Effect
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! style="background:brown; color:white" |Source
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|-
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|mouse
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|LD
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|intraperitoneal
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|> 200mg/kg (200mg/kg)
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|  
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|Journal of Medicinal Chemistry. Vol. 11, Pg. 117, 1968.
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|-
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|}
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<b>*Molecular Formula</b>
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C<sub>2</sub><sub>1</sub>H<sub>3</sub><sub>2</sub>O<sub>2</sub>
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==Chemistry==
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<b>*IUPAC NAME</b>
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Like other [[steroid]]s, pregnenolone consists of four interconnected [[cyclic hydrocarbon]]s. It contains [[ketone]] and [[hydroxyl]] functional groups, two [[methyl]] branches, and a double bond at C5, in the B cyclic hydrocarbon ring. Like all steroid hormones, it is [[hydrophobic]]. Its esterified version, pregnenolone sulfate, is water-soluble.
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==Synthesis==
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1-[(3S,8S,9S,10R,13S,14S,17S)-3-hydroxy-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl]ethanone
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[[Image:DHEA1.svg|thumb|350px|''Production of Pregnenolone from Cholesteol and further metabolism'']]
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[[Image:Reaction-Pregnenolone-Progesterone2.png|thumb|350px|Reaction: Pregnenolone-[[Progesterone]]]]
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Pregnenolone is synthesized from [[cholesterol]]. This conversion involves  hydroxylation at the [[side-chain]] at C20 and C22 positions, with cleavage of the side-chain. The [[enzyme]] performing this task is [[P450 scc|cytochrome P450scc]], located in the [[mitochondria]], and controlled by pituitary tropic hormones, such as [[ACTH]], [[FSH]], [[LH]].
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<b>*Canonical Smiles</b>
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==Prohormone==
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CC(=O)C1CCC2C1(CCC3C2CC=C4C3(CCC(C4)O)C)C
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Pregnenolone undergoes further steroid metabolism in one of three ways.
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* Pregnenolone can be converted to [[progesterone]]. The critical enzyme step is two-fold using a [[3-beta-hydroxysteroid dehydrogenase]] and a [[delta 4-5 isomerase]]. The latter transfers the [[double bond]] from C5 to C4 on the A ring.  Progesterone is the entry into the [[delta-4-pathway]], resulting in production of 17-hydroxy progesterone and [[androstenedione]], precursor to [[testosterone]] and [[estrone]]. [[Aldosterone]] and [[corticosteroid]]s are also derived from progesterone or its derivatives.
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<b>*Isomeric Smiles</b>
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* Pregnenolone can be converted to [[17-hydroxy-pregnenolone]] by the enzyme 17α-hydroxylase ([[CYP17A1]]). Using this pathway, termed [[delta-5 pathway]], the next step is conversion to [[dehydroepiandrosterone]] (DHEA) using a [[desmolase]]. DHEA is the precursor of androstenedione.
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CC(=O)[C@H]1CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2CC=C4[C@@]3(CC[C@@H](C4)O)C)C
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* Pregnenolone can be converted to androsta-5,16-dien-3 beta-ol by 16-ene synthetase.
 
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==Neurosteroid==
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==PhysioChemical Properties==
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Pregnenolone and its sulfate, like [[dehydroepiandrosterone]] and its sulfate and progesterone, belong to the group of [[neuroactive steroid|neurosteroid]]s that are found in high concentrations in certain areas in the brain, and are synthesized there. Neurosteroids affect synaptic functioning, are [[neuroprotective]], and enhance [[myelin]]ization. Pregnenolone and its sulfate ester are under investigation for their potential to improve cognitive and [[memory]] functioning.<ref>{{cite journal | author = Vallée M, Mayo W, Le Moal M | title = Role of pregnenolone, dehydroepiandrosterone and their sulfate esters on learning and memory in cognitive aging. | journal = Brain Res Brain Res Rev | volume = 37 | issue = 1-3 | pages = 301–12 | year = 2001 | pmid = 11744095 | doi = 10.1016/S0165-0173(01)00135-7}}</ref>
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==Additional images==
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<b>*Melting Point</b>
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<gallery>
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Image:Steroidogenesis.svg|[[Steroidogenesis]]
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Image:Cholesterol.svg|[[Cholesterol]]
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Image:Progesterone-2D-skeletal.png|[[Progesterone]]
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</gallery>
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==References==
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192(EXP)
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{{Reflist}}
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{{Steroids}}
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<b>*LogP</b>
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[[Category:Steroid hormones]]
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[[Category:Neurosteroids]]
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4.22(EXP)
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<b>*Water Solubility</b>
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7.06(EXP) at 37C
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==External Links==
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*[http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=8955]Pubchem
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*[http://www.genome.jp/dbget-bin/www_bget?compound+C01953]KEGG Compound
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*[http://www.genome.jp/dbget-bin/www_bget?drug+D00143]KEGG Drug
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*[http://www.drugbank.ca/drugs/DB02789]Drugbank
 +
 
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[[Categories:Hormones]]

Revision as of 00:00, 15 January 2001


Contents

Description

A 21-carbon steroid, derived from CHOLESTEROL and found in steroid hormone-producing tissues. Pregnenolone is the precursor to GONADAL STEROID HORMONES and the adrenal CORTICOSTEROIDS.

General Properties

*Molecular Weight

316.48

*Molecular Formula

C21H32O2

*IUPAC NAME

1-[(3S,8S,9S,10R,13S,14S,17S)-3-hydroxy-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl]ethanone

*Canonical Smiles

CC(=O)C1CCC2C1(CCC3C2CC=C4C3(CCC(C4)O)C)C

*Isomeric Smiles

CC(=O)[C@H]1CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2CC=C4[C@@]3(CC[C@@H](C4)O)C)C


PhysioChemical Properties

*Melting Point

192(EXP)

*LogP

4.22(EXP)

*Water Solubility

7.06(EXP) at 37C

External Links

Categories:Hormones

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