Amprenavir (T3D2863)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (5)XML
Targets (5)
Record Information
Version2.0
Creation Date2009-07-21 20:27:27 UTC
Update Date2014-12-24 20:25:52 UTC
Accession NumberT3D2863
Identification
Common NameAmprenavir
ClassSmall Molecule
DescriptionAmprenavir is only found in individuals that have used or taken this drug. It is a protease inhibitor used to treat HIV infection.Amprenavir inhibits the HIV viral proteinase enzyme which prevents cleavage of the gag-pol polyprotein, resulting in noninfectious, immature viral particles.
Compound Type
  • Amide
  • Amine
  • Anti-HIV Agent
  • Antibiotic, Antitubercular
  • Drug
  • Ester
  • Ether
  • HIV Protease Inhibitor
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDF3D-SDFPDBSMILESInChI View 3D Structure
Synonyms
Synonym
(3S)-Tetrahydro-3-furanyl ((1S,2R)-3-(((4-aminophenyl)sulfonyl)(2-methylpropyl)amino)-2-hydroxy-1-(phenylmethyl)propyl)carbamate
Agemerase
Agenerase
AMP
Amprenavirum
AMV
Prozei
VX-478
Chemical FormulaC25H35N3O6S
Average Molecular Mass505.627 g/mol
Monoisotopic Mass505.225 g/mol
CAS Registry Number161814-49-9
IUPAC Name(3S)-oxolan-3-yl N-[(2S,3R)-3-hydroxy-4-[N-(2-methylpropyl)4-aminobenzenesulfonamido]-1-phenylbutan-2-yl]carbamate
Traditional Nameamprenavir
SMILES[H][C@@](O)(CN(CC(C)C)S(=O)(=O)C1=CC=C(N)C=C1)[C@]([H])(CC1=CC=CC=C1)N=C(O)O[C@@]1([H])CCOC1
InChI IdentifierInChI=1S/C25H35N3O6S/c1-18(2)15-28(35(31,32)22-10-8-20(26)9-11-22)16-24(29)23(14-19-6-4-3-5-7-19)27-25(30)34-21-12-13-33-17-21/h3-11,18,21,23-24,29H,12-17,26H2,1-2H3,(H,27,30)/t21-,23-,24+/m0/s1
InChI KeyInChIKey=YMARZQAQMVYCKC-OEMFJLHTSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as aminobenzenesulfonamides. These are organic compounds containing a benzenesulfonamide moiety with an amine group attached to the benzene ring.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBenzenesulfonamides
Direct ParentAminobenzenesulfonamides
Alternative Parents
Substituents
  • Aminobenzenesulfonamide
  • Phenylbutylamine
  • Amphetamine or derivatives
  • Benzenesulfonyl group
  • Aniline or substituted anilines
  • Organosulfonic acid amide
  • Organic sulfonic acid or derivatives
  • Organosulfonic acid or derivatives
  • Aminosulfonyl compound
  • Carbamic acid ester
  • Tetrahydrofuran
  • Sulfonyl
  • Carbonic acid derivative
  • Secondary alcohol
  • Dialkyl ether
  • Ether
  • Oxacycle
  • Organoheterocyclic compound
  • Organic oxide
  • Organosulfur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Organopnictogen compound
  • Amine
  • Alcohol
  • Carbonyl group
  • Primary amine
  • Hydrocarbon derivative
  • Organic nitrogen compound
  • Organic oxygen compound
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical Roles
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
Solubility4.91e-02 g/L
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.049 g/LALOGPS
logP1.85ALOGPS
logP2.43ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)13.61ChemAxon
pKa (Strongest Basic)2.39ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area131.19 ŲChemAxon
Rotatable Bond Count11ChemAxon
Refractivity134.08 m³·mol⁻¹ChemAxon
Polarizability53.6 ųChemAxon
Number of Rings3ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-022d-8491400000-418cbb7f08471fa846192017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-03kc-7192320000-fa264cdbd41779709c302017-10-06View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-05mk-2692510000-696582f37a165753c2f52017-09-14View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0a4r-9000500000-e60fa95c31e43c49b0312016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a4i-9001100000-2c5d3283dd48ceae82dd2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a4i-9010000000-cd15933ef1ecd45d9b1c2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0gbi-4304930000-6cf1884fae8acb8332ab2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0173-9432500000-a4d70ca4c7ac6bd2930d2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-052f-9825100000-b5b4efee0204074368f42016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000i-0046920000-a443e441b8dc951bec992021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a4i-2922000000-15960e61915142ff5b1e2021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0006-9200000000-78c87a49bf59b5f6c0142021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0uxr-2302980000-1c2dbf56f0de2b3df5972021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a4i-3911710000-48ad17f577dc556faafc2021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4i-7900200000-41ad730c9ba505f337932021-10-11View Spectrum
Toxicity Profile
Route of ExposureRapidly absorbed after oral administration in HIV-1-infected patients with a time to peak concentration (Tmax) typically between 1 and 2 hours after a single oral dose. The absolute oral bioavailability of amprenavir in humans has not been established.
Mechanism of ToxicityAmprenavir inhibits the HIV viral proteinase enzyme which prevents cleavage of the gag-pol polyprotein, resulting in noninfectious, immature viral particles.
MetabolismHepatic. Amprenavir is metabolized in the liver by the cytochrome P450 3A4 (CYP3A4) enzyme system. The 2 major metabolites result from oxidation of the tetrahydrofuran and aniline moieties. Glucuronide conjugates of oxidized metabolites have been identified as minor metabolites in urine and feces. Half Life: 7.1-10.6 hours
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the treatment of HIV-1 infection in combination with other antiretroviral agents.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentIf overdosage occurs, the patient should be monitored for evidence of toxicity and standard supportive treatment applied as necessary. (2)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00701
HMDB IDHMDB14839
PubChem Compound ID65016
ChEMBL IDCHEMBL116
ChemSpider ID58532
KEGG IDC08086
UniProt IDNot Available
OMIM ID
ChEBI ID2684
BioCyc IDNot Available
CTD IDNot Available
Stitch IDAmprenavir
PDB ID478
ACToR IDNot Available
Wikipedia LinkAmprenavir
References
Synthesis Reference

DrugSyn.org

MSDST3D2863.pdf
General References
  1. Drugs.com [Link]
  2. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Cytochrome P450 3A4
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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide (PubMed:11159812). Catalyzes 4-beta-hydroxylation of cholesterol. May catalyze 25-hydroxylation of cholesterol in vitro (PubMed:21576599).
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.26 uMNot AvailableBindingDB 577
Inhibitory0.37 uMNot AvailableBindingDB 577
References
  1. Fontana E, Dansette PM, Poli SM: Cytochrome p450 enzymes mechanism based inhibitors: common sub-structures and reactivity. Curr Drug Metab. 2005 Oct;6(5):413-54. [16248836 ]
  2. Orr ST, Ripp SL, Ballard TE, Henderson JL, Scott DO, Obach RS, Sun H, Kalgutkar AS: Mechanism-based inactivation (MBI) of cytochrome P450 enzymes: structure-activity relationships and discovery strategies to mitigate drug-drug interaction risks. J Med Chem. 2012 Jun 14;55(11):4896-933. doi: 10.1021/jm300065h. Epub 2012 Mar 27. [22409598 ]
Target Details
2. Cathepsin D
General Function:
Aspartic-type endopeptidase activity
Specific Function:
Acid protease active in intracellular protein breakdown. Involved in the pathogenesis of several diseases such as breast cancer and possibly Alzheimer disease.
Gene Name:
CTSD
Uniprot ID:
P07339
Molecular Weight:
44551.845 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC5015.2 uMNot AvailableBindingDB 577
References
  1. Dandache S, Sevigny G, Yelle J, Stranix BR, Parkin N, Schapiro JM, Wainberg MA, Wu JJ: In vitro antiviral activity and cross-resistance profile of PL-100, a novel protease inhibitor of human immunodeficiency virus type 1. Antimicrob Agents Chemother. 2007 Nov;51(11):4036-43. Epub 2007 Jul 16. [17638694 ]
Target Details
3. Cytochrome P450 3A5
General Function:
Oxygen binding
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 oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP3A5
Uniprot ID:
P20815
Molecular Weight:
57108.065 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.2 uMNot AvailableBindingDB 577
References
  1. Fontana E, Dansette PM, Poli SM: Cytochrome p450 enzymes mechanism based inhibitors: common sub-structures and reactivity. Curr Drug Metab. 2005 Oct;6(5):413-54. [16248836 ]
Target Details
4. Multidrug resistance protein 1
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular Weight:
141477.255 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC50>100 uMNot AvailableBindingDB 577
References
  1. Tong L, Phan TK, Robinson KL, Babusis D, Strab R, Bhoopathy S, Hidalgo IJ, Rhodes GR, Ray AS: Effects of human immunodeficiency virus protease inhibitors on the intestinal absorption of tenofovir disoproxil fumarate in vitro. Antimicrob Agents Chemother. 2007 Oct;51(10):3498-504. Epub 2007 Jul 30. [17664327 ]
Target Details
5. Cytosolic 10-formyltetrahydrofolate dehydrogenase
General Function:
Methyltransferase activity
Specific Function:
Not Available
Gene Name:
ALDH1L1
Uniprot ID:
O75891
Molecular Weight:
98828.505 Da