Identification

Name
Pregnenolone
Accession Number
DB02789  (EXPT02608)
Type
Small Molecule
Groups
Approved, Experimental
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.

Structure
Thumb
Synonyms
Not Available
Categories
UNII
73R90F7MQ8
CAS number
145-13-1
Weight
Average: 316.4776
Monoisotopic: 316.240230268
Chemical Formula
C21H32O2
InChI Key
ORNBQBCIOKFOEO-QGVNFLHTSA-N
InChI
InChI=1S/C21H32O2/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/h4,15-19,23H,5-12H2,1-3H3/t15-,16-,17+,18-,19-,20-,21+/m0/s1
IUPAC Name
1-[(1S,3aS,3bS,7S,9aR,9bS,11aS)-7-hydroxy-9a,11a-dimethyl-1H,2H,3H,3aH,3bH,4H,6H,7H,8H,9H,9aH,9bH,10H,11H,11aH-cyclopenta[a]phenanthren-1-yl]ethan-1-one
SMILES
[H][C@@]12CC[C@H](C(C)=O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CC=C2C[C@@H](O)CC[C@]12C

Pharmacology

Indication
Not Available
Pharmacodynamics
Not Available
Mechanism of action
TargetActionsOrganism
USulfotransferase family cytosolic 2B member 1Not AvailableHuman
UNuclear receptor subfamily 1 group I member 2Not AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Pregnenolone.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Pregnenolone.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Pregnenolone.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Pregnenolone.
5-androstenedioneThe metabolism of Pregnenolone can be decreased when combined with 5-androstenedione.
6-Deoxyerythronolide BThe metabolism of Pregnenolone can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Pregnenolone.
AbemaciclibThe metabolism of Abemaciclib can be decreased when combined with Pregnenolone.
AbirateroneThe metabolism of Abiraterone can be decreased when combined with Pregnenolone.
AcalabrutinibThe metabolism of Pregnenolone can be decreased when combined with Acalabrutinib.
Food Interactions
Not Available

References

Synthesis Reference

Alexander James Bridges, "Efficient Process for Preparing Steroids and Vitamin D Derivatives With the Unnatural Configuration at C20 (20 Alpha-Methyl) from Pregnenolone." U.S. Patent US20080171728, issued July 17, 2008.

US20080171728
General References
  1. Geyer J, Doring B, Meerkamp K, Ugele B, Bakhiya N, Fernandes CF, Godoy JR, Glatt H, Petzinger E: Cloning and functional characterization of human sodium-dependent organic anion transporter (SLC10A6). J Biol Chem. 2007 Jul 6;282(27):19728-41. Epub 2007 May 9. [PubMed:17491011]
External Links
Human Metabolome Database
HMDB0000253
KEGG Drug
D00143
KEGG Compound
C01953
PubChem Compound
8955
PubChem Substance
46506718
ChemSpider
8611
BindingDB
50375319
ChEBI
16581
ChEMBL
CHEMBL253363
Therapeutic Targets Database
DNC001147
HET
PLO
Wikipedia
Pregnenolone
PDB Entries
1q20 / 4j6b / 4nkw

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentSchizophrenic Disorders1
1Not Yet RecruitingBasic ScienceMajor Depressive Disorder (MDD)1
1, 2RecruitingTreatmentMajor Depressive Disorder (MDD) / Menopause / Perimenopause / Pregnenolone1
2Active Not RecruitingTreatmentCognitive Decline / Painful musculoskeletal conditions / Tiredness1
2CompletedTreatmentAutistic Disorder1
2CompletedTreatmentBack Pain Lower Back1
2CompletedTreatmentBrain Injuries,Traumatic1
2CompletedTreatmentMarijuana Dependence1
2RecruitingBasic SciencePerceived Social Isolation1
2RecruitingTreatmentAutism Spectrum Conditions/Disorders / Autism, Early Infantile1
2WithdrawnTreatmentMajor Depressive Disorder (MDD) / Post Traumatic Stress Disorder (PTSD)1
2, 3CompletedTreatmentSchizophrenic Disorders1
4CompletedTreatmentBipolar Disorder (BD) / Major Depressive Disorder (MDD)1
4CompletedTreatmentBipolar Disorder (BD) / Major Depressive Disorder (MDD) / Substance Abuse1
4RecruitingTreatmentAlcohol Use Disorder (AUD) / Bipolar Disorder (BD)1
Not AvailableCompletedTreatmentPost Traumatic Stress Disorder (PTSD)1
Not AvailableCompletedTreatmentSchizophrenic Disorders1
Not AvailableCompletedTreatmentTraumatic Brain Injury (TBI)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0136 mg/mLALOGPS
logP4.06ALOGPS
logP3.58ChemAxon
logS-4.4ALOGPS
pKa (Strongest Acidic)18.2ChemAxon
pKa (Strongest Basic)-1.4ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area37.3 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity93.76 m3·mol-1ChemAxon
Polarizability38.09 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9671
Caco-2 permeable+0.8568
P-glycoprotein substrateSubstrate0.6106
P-glycoprotein inhibitor IInhibitor0.6721
P-glycoprotein inhibitor IINon-inhibitor0.7531
Renal organic cation transporterNon-inhibitor0.7825
CYP450 2C9 substrateNon-substrate0.8333
CYP450 2D6 substrateNon-substrate0.8417
CYP450 3A4 substrateSubstrate0.7594
CYP450 1A2 substrateNon-inhibitor0.9179
CYP450 2C9 inhibitorNon-inhibitor0.9333
CYP450 2D6 inhibitorNon-inhibitor0.9558
CYP450 2C19 inhibitorNon-inhibitor0.9023
CYP450 3A4 inhibitorNon-inhibitor0.8332
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9076
Ames testNon AMES toxic0.9439
CarcinogenicityNon-carcinogens0.9346
BiodegradationNot ready biodegradable0.9379
Rat acute toxicity1.9852 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8779
hERG inhibition (predictor II)Non-inhibitor0.7239
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
GC-MS Spectrum - GC-MS (1 MEOX; 1 TMS)GC-MSsplash10-0fic-5910000000-4b4de0891180a420522a
GC-MS Spectrum - EI-BGC-MSsplash10-05o0-2982000000-90eb349ceb4f7cdf4bf0
Mass Spectrum (Electron Ionization)MSsplash10-052f-6920000000-2b11c86505b10fe4485f
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
1H NMR Spectrum1D NMRNot Applicable
13C NMR Spectrum1D NMRNot Applicable

Taxonomy

Description
This compound 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.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Steroids and steroid derivatives
Sub Class
Pregnane steroids
Direct Parent
Gluco/mineralocorticoids, progestogins and derivatives
Alternative Parents
20-oxosteroids / 3-beta-hydroxysteroids / 3-beta-hydroxy delta-5-steroids / Delta-5-steroids / Secondary alcohols / Ketones / Cyclic alcohols and derivatives / Organic oxides / Hydrocarbon derivatives
Substituents
Progestogin-skeleton / 20-oxosteroid / 3-hydroxy-delta-5-steroid / 3-hydroxysteroid / 3-beta-hydroxysteroid / 3-beta-hydroxy-delta-5-steroid / Oxosteroid / Hydroxysteroid / Delta-5-steroid / Cyclic alcohol
Molecular Framework
Aliphatic homopolycyclic compounds
External Descriptors
3beta-hydroxy steroid, 20-oxo steroid, C21-steroid (CHEBI:16581) / Pregnane and derivatives [Fig], Progestagens (C01953) / C21 steroids (gluco/mineralocorticoids, progestogins) and derivatives (LMST02030088)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Steroid sulfotransferase activity
Specific Function
Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of many hormones, neurotransmitters, drugs and xenobiotic compounds. Sulf...
Gene Name
SULT2B1
Uniprot ID
O00204
Uniprot Name
Sulfotransferase family cytosolic 2B member 1
Molecular Weight
41307.32 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Zinc ion binding
Specific Function
Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism an...
Gene Name
NR1I2
Uniprot ID
O75469
Uniprot Name
Nuclear receptor subfamily 1 group I member 2
Molecular Weight
49761.245 Da
References
  1. Kretschmer XC, Baldwin WS: CAR and PXR: xenosensors of endocrine disrupters? Chem Biol Interact. 2005 Aug 15;155(3):111-28. [PubMed:16054614]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Felmlee MA, Lon HK, Gonzalez FJ, Yu AM: Cytochrome P450 expression and regulation in CYP3A4/CYP2D6 double transgenic humanized mice. Drug Metab Dispos. 2008 Feb;36(2):435-41. doi: 10.1124/dmd.107.018838. Epub 2007 Nov 29. [PubMed:18048490]
  2. Wang H, Huang H, Li H, Teotico DG, Sinz M, Baker SD, Staudinger J, Kalpana G, Redinbo MR, Mani S: Activated pregnenolone X-receptor is a target for ketoconazole and its analogs. Clin Cancer Res. 2007 Apr 15;13(8):2488-95. [PubMed:17438109]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Sodium-dependent organic anion transmembrane transporter activity
Specific Function
Transports sulfoconjugated steroid hormones, as well as taurolithocholic acid-3-sulfate and sulfoconjugated pyrenes in a sodium-dependent manner.
Gene Name
SLC10A6
Uniprot ID
Q3KNW5
Uniprot Name
Solute carrier family 10 member 6
Molecular Weight
41258.24 Da
References
  1. Geyer J, Doring B, Meerkamp K, Ugele B, Bakhiya N, Fernandes CF, Godoy JR, Glatt H, Petzinger E: Cloning and functional characterization of human sodium-dependent organic anion transporter (SLC10A6). J Biol Chem. 2007 Jul 6;282(27):19728-41. Epub 2007 May 9. [PubMed:17491011]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 05:22