Tmic
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Record Information
Version2.0
Creation Date2014-09-11 05:17:25 UTC
Update Date2014-12-24 20:26:57 UTC
Accession NumberT3D4806
Identification
Common NameAminoglutethimide
ClassSmall Molecule
DescriptionAn aromatase inhibitor that produces a state of 'medical' adrenalectomy by blocking the production of adrenal steroids. It also blocks the conversion of androgens to estrogens. Aminoglutethimide has been used in the treatment of advanced breast and prostate cancer. It was formerly used for its weak anticonvulsant properties.
Compound Type
  • Amide
  • Amine
  • Antineoplastic Agent, Hormonal
  • Aromatase Inhibitor
  • Drug
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
2-(p-Aminophenyl)-2-ethylglutarimide
3-Ethyl-3-(P-aminophenyl)-2,6-dioxopiperidine
alpha-(P-Aminophenyl)-alpha-ethylglutarimide
Aminoglutethimid
Aminoglutéthimide
Aminoglutethimidum
Aminoglutetimida
Aminoglutetimide
Cytadren
Dl-Aminoglutethimide
Elipten
Mamomit
Orimeten
P-Aminoglutethimide
Rogluten
Chemical FormulaC13H16N2O2
Average Molecular Mass232.278 g/mol
Monoisotopic Mass232.121 g/mol
CAS Registry Number125-84-8
IUPAC Name3-(4-aminophenyl)-3-ethylpiperidine-2,6-dione
Traditional Nameaminoglutethimide
SMILESCCC1(CCC(O)=NC1=O)C1=CC=C(N)C=C1
InChI IdentifierInChI=1/C13H16N2O2/c1-2-13(8-7-11(16)15-12(13)17)9-3-5-10(14)6-4-9/h3-6H,2,7-8,14H2,1H3,(H,15,16,17)
InChI KeyInChIKey=ROBVIMPUHSLWNV-UHFFFAOYNA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as aniline and substituted anilines. These are organic compounds containing an aminobenzene moiety.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassAniline and substituted anilines
Direct ParentAniline and substituted anilines
Alternative Parents
Substituents
  • Aniline or substituted anilines
  • Tetrahydropyridine
  • Hydropyridine
  • Amino acid or derivatives
  • N-acylimine
  • Lactim
  • Organoheterocyclic compound
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Carboxylic acid derivative
  • Azacycle
  • Organopnictogen compound
  • Amine
  • Organic oxygen compound
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Organic nitrogen compound
  • Carbonyl group
  • Hydrocarbon derivative
  • Organic oxide
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point223-225°C
Boiling PointNot Available
SolubilityPractically insoluble in water
LogP1.3
Predicted Properties
PropertyValueSource
Water Solubility0.37 g/LALOGPS
logP1.49ALOGPS
logP1.3ChemAxon
logS-2.8ALOGPS
pKa (Strongest Acidic)11.69ChemAxon
pKa (Strongest Basic)4.28ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area72.19 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity65.35 m³·mol⁻¹ChemAxon
Polarizability24.69 ųChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0ue9-5960000000-f9b33cb2d18e6b01ae76View in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0ue9-5960000000-f9b33cb2d18e6b01ae76View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-01q9-0930000000-1559858da10d4930e919View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-0540-2960000000-949d8dddc3981b8c3e63View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-0uxr-0905000000-155a653652a8dc132b5cView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-001j-3910000000-d92bbd37c74ab8b7828dView in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0540-1970000000-fc41c032a79d79173387View in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0540-2960000000-949d8dddc3981b8c3e63View in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-001j-3910000000-d92bbd37c74ab8b7828dView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00lr-0190000000-bd92b28e06f9a2c94ab1View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00lr-0590000000-2ecccc66bf459b9dff9bView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00l2-2900000000-486145b0245b40ea818cView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-001i-0090000000-b5c20a34adc0796f60c2View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-01q9-1190000000-e50243f982300e3ad740View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9410000000-a3860f54f1f49a280fb8View in MoNA
MSMass Spectrum (Electron Ionization)splash10-0f89-3950000000-013571ce504af9a2d603View in MoNA
Toxicity Profile
Route of ExposureRapidly and completely absorbed from gastrointestinal tract. The bioavailability of tablets is equivalent to equal doses given as a solution.
Mechanism of ToxicityAminoglutethimide reduces the production of D5-pregnenolone and blocks several other steps in steroid synthesis, including the C-11, C-18, and C-21 hydroxylations and the hydroxylations required for the aromatization of androgens to estrogens, mediated through the binding of aminoglutethimide to cytochrome P-450 complexes. Specifically, the drug binds to and inhibits aromatase which is essential for the generation of estrogens from androstenedione and testosterone. A decrease in adrenal secretion of cortisol is followed by an increased secretion of pituitary adrenocorticotropic hormone (ACTH), which will overcome the blockade of adrenocortical steroid synthesis by aminoglutethimide. The compensatory increase in ACTH secretion can be suppressed by the simultaneous administration of hydrocortisone. Since aminoglutethimide increases the rate of metabolism of dexamethasone but not that of hydrocortisone, the latter is preferred as the adrenal glucocorticoid replacement. Although aminoglutethimide inhibits the synthesis of thyroxine by the thyroid gland, the compensatory increase in thyroid-stimulating hormone (TSH) is frequently of sufficient magnitude to overcome the inhibition of thyroid synthesis due to aminoglutethimide. In spite of an increase in TSH, aminoglutethimide has not been associated with increased prolactin secretion.
MetabolismHepatic. 34-54% of the administered dose is excreted in the urine as unchanged drug during the first 48 hours, and an additional fraction as an N-acetyl derivative. Route of Elimination: After ingestion of a single oral dose, 34%-54% is excreted in the urine as unchanged drug during the first 48 hours, and an additional fraction as the N-acetyl derivative. Half Life: 12.5 ± 1.6 hours
Toxicity ValuesOral LD50s (mg/kg): rats, 1800; dogs, >100. Intravenous LD50s (mg/kg): rats, 156; dogs, >100.
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the suppression of adrenal function in selected patients with Cushing's syndrome, malignant neoplasm of the female breast, and carcinoma in situ of the breast.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsSymptoms of overdose include respiratory depression, hypoventilation, hypotension, hypovolemic shock due to dehydration, somnolence, lethargy, coma, ataxia, dizziness, fatigue, nausea, and vomiting.
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00357
HMDB IDHMDB14501
PubChem Compound ID2145
ChEMBL IDCHEMBL488
ChemSpider ID2060
KEGG IDC07617
UniProt IDNot Available
OMIM ID
ChEBI ID2654
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkAminoglutethimide
References
Synthesis Reference

Hoffmann, K.and Urech, E.; U.S. Patent 2,848,455; August 19,1958; assigned to Ciba Pharmaceutical Products, Inc.

MSDSNot Available
General ReferencesNot Available
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, nad(p)h as one donor, and incorporation of one atom of oxygen
Specific Function:
Catalyzes the side-chain cleavage reaction of cholesterol to pregnenolone.
Gene Name:
CYP11A1
Uniprot ID:
P05108
Molecular Weight:
60101.87 Da
References
  1. Slominski A, Semak I, Wortsman J, Zjawiony J, Li W, Zbytek B, Tuckey RC: An alternative pathway of vitamin D metabolism. Cytochrome P450scc (CYP11A1)-mediated conversion to 20-hydroxyvitamin D2 and 17,20-dihydroxyvitamin D2. FEBS J. 2006 Jul;273(13):2891-901. [16817851 ]
  2. Oka H, Emori Y, Hayashi Y, Nomoto K: Breakdown of Th cell immune responses and steroidogenic CYP11A1 expression in CD4+ T cells in a murine model implanted with B16 melanoma. Cell Immunol. 2000 Nov 25;206(1):7-15. [11161433 ]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
General Function:
Oxygen binding
Specific Function:
Catalyzes the formation of aromatic C18 estrogens from C19 androgens.
Gene Name:
CYP19A1
Uniprot ID:
P11511
Molecular Weight:
57882.48 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC503.8 uMNVS_ADME_hCYP19A1Novascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]