Amprenavir

Identification

Summary

Amprenavir is a protease inhibitor used to treat HIV infection.

Generic Name
Amprenavir
DrugBank Accession Number
DB00701
Background

Amprenavir is a protease inhibitor used to treat HIV infection.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 505.627
Monoisotopic: 505.224656557
Chemical Formula
C25H35N3O6S
Synonyms
  • (3S)-Tetrahydro-3-furanyl ((1S,2R)-3-(((4-aminophenyl)sulfonyl)(2-methylpropyl)amino)-2-hydroxy-1-(phenylmethyl)propyl)carbamate
  • Amprenavir
  • Amprénavir
  • Amprenavirum
External IDs
  • 141 W 94
  • 141W94
  • KVX 478
  • KVX-478
  • VX-478

Pharmacology

Indication

For the treatment of HIV-1 infection in combination with other antiretroviral agents.

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Contraindications & Blackbox Warnings
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Pharmacodynamics

Amprenavir is a protease inhibitor with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Protease inhibitors block the part of HIV called protease. HIV-1 protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins found in infectious HIV-1. Amprenavir binds to the protease active site and inhibits the activity of the enzyme. This inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature non-infectious viral particles. Protease inhibitors are almost always used in combination with at least two other anti-HIV drugs.

Mechanism of action

Amprenavir inhibits the HIV viral proteinase enzyme which prevents cleavage of the gag-pol polyprotein, resulting in noninfectious, immature viral particles.

TargetActionsOrganism
AHuman immunodeficiency virus type 1 protease
inhibitor
Human immunodeficiency virus 1
Absorption

Rapidly 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.

Volume of distribution

Not Available

Protein binding

Very high (90%). Amprenavir has the highest affinity for alpha(1)-acid glycoprotein.

Metabolism

Hepatic. 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.

Route of elimination

Not Available

Half-life

7.1-10.6 hours

Clearance

Not Available

Adverse Effects
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Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
1,2-BenzodiazepineThe metabolism of 1,2-Benzodiazepine can be decreased when combined with Amprenavir.
AbametapirThe serum concentration of Amprenavir can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Amprenavir can be increased when combined with Abatacept.
AbemaciclibThe metabolism of Abemaciclib can be decreased when combined with Amprenavir.
AbirateroneThe metabolism of Abiraterone can be decreased when combined with Amprenavir.
Food Interactions
  • Avoid alcohol. Drug impairs alcohol metabolism.
  • Avoid fatty foods.
  • Take with or without food.

Products

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International/Other Brands
Agemerase (GlaxoSmithKline) / Prozei (Kissei Pharmaceuticals Co., Ltd.)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AgeneraseCapsule150 mgOralGlaxo Group Limited2016-09-072011-06-21EU flag
AgeneraseCapsule150 mgOralGlaxosmithkline Inc2001-03-162008-05-27Canada flag
AgeneraseCapsule50 mg/1OralGlaxosmithkline Inc1999-04-152008-02-26US flag
AgeneraseSolution15 mg/mlOralGlaxo Group Limited2016-09-072011-06-21EU flag
AgeneraseCapsule50 mgOralGlaxo Group Limited2016-09-072011-06-21EU flag

Categories

ATC Codes
J05AE05 — Amprenavir
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound 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.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzenesulfonamides
Direct Parent
Aminobenzenesulfonamides
Alternative Parents
Phenylbutylamines / Amphetamines and derivatives / Benzenesulfonyl compounds / Aniline and substituted anilines / Organosulfonamides / Tetrahydrofurans / Aminosulfonyl compounds / Carbamate esters / Secondary alcohols / Organic carbonic acids and derivatives
show 7 more
Substituents
Alcohol / Amine / Aminobenzenesulfonamide / Aminosulfonyl compound / Amphetamine or derivatives / Aniline or substituted anilines / Aromatic heteromonocyclic compound / Benzenesulfonyl group / Carbamic acid ester / Carbonic acid derivative
show 21 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
carbamate ester, sulfonamide, tetrahydrofuryl ester (CHEBI:40050)
Affected organisms
  • Human Immunodeficiency Virus

Chemical Identifiers

UNII
5S0W860XNR
CAS number
161814-49-9
InChI Key
YMARZQAQMVYCKC-OEMFJLHTSA-N
InChI
InChI=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
IUPAC Name
(3S)-oxolan-3-yl N-[(2S,3R)-3-hydroxy-4-[N-(2-methylpropyl)4-aminobenzenesulfonamido]-1-phenylbutan-2-yl]carbamate
SMILES
CC(C)CN(C[C@@H](O)[C@H](CC1=CC=CC=C1)NC(=O)O[C@H]1CCOC1)S(=O)(=O)C1=CC=C(N)C=C1

References

Synthesis Reference
US5585397
General References
Not Available
Human Metabolome Database
HMDB0014839
KEGG Drug
D00894
KEGG Compound
C08086
PubChem Compound
65016
PubChem Substance
46507537
ChemSpider
58532
BindingDB
577
RxNav
228656
ChEBI
40050
ChEMBL
CHEMBL116
ZINC
ZINC000003809192
Therapeutic Targets Database
DAP000170
PharmGKB
PA448422
PDBe Ligand
478
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Amprenavir
PDB Entries
1hpv / 1t7j / 3ekp / 3ekv / 3nu3 / 3nu6 / 3nu9 / 3nuj / 3nuo / 3oxv
show 12 more
FDA label
Download (120 KB)

Clinical Trials

Clinical Trials

Pharmacoeconomics

Manufacturers
  • Glaxosmithkline
Packagers
  • Catalent Pharma Solutions
Dosage Forms
FormRouteStrength
CapsuleOral
CapsuleOral150 mg
CapsuleOral50 mg/1
CapsuleOral50 mg
LiquidOral15 mg / mL
SolutionOral
SolutionOral15 mg/1mL
SolutionOral15 mg/ml
SolutionOral1.5 g
Capsule, liquid filledOral150 mg
Prices
Unit descriptionCostUnit
Agenerase 50 mg capsule0.65USD capsule
Agenerase 15 mg/ml Solution0.21USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5585397No1996-12-172013-12-17US flag
US6730679No2004-05-042017-11-11US flag

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0491 mg/mLALOGPS
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 Å2Chemaxon
Rotatable Bond Count11Chemaxon
Refractivity134.08 m3·mol-1Chemaxon
Polarizability53.57 Å3Chemaxon
Number of Rings3Chemaxon
Bioavailability0Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleYesChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9132
Blood Brain Barrier-0.5886
Caco-2 permeable+0.8866
P-glycoprotein substrateSubstrate0.7175
P-glycoprotein inhibitor IInhibitor0.7973
P-glycoprotein inhibitor IINon-inhibitor0.8383
Renal organic cation transporterNon-inhibitor0.8815
CYP450 2C9 substrateNon-substrate0.5
CYP450 2D6 substrateSubstrate0.8919
CYP450 3A4 substrateSubstrate0.6176
CYP450 1A2 substrateNon-inhibitor0.7641
CYP450 2C9 inhibitorNon-inhibitor0.6591
CYP450 2D6 inhibitorNon-inhibitor0.8821
CYP450 2C19 inhibitorNon-inhibitor0.6641
CYP450 3A4 inhibitorInhibitor0.6185
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7229
Ames testNon AMES toxic0.6097
CarcinogenicityNon-carcinogens0.8218
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.4787 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9884
hERG inhibition (predictor II)Non-inhibitor0.8733
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
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-022d-8491400000-418cbb7f08471fa84619
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-05mk-2692510000-696582f37a165753c2f5
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0040-0059730000-9f3c7e5afb73a73640f6
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-0309230000-ca1462ef0636801c2aec
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4i-4952110000-60b1805ca1c3730e46eb
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4i-7820910000-d0bbeb297156f1401870
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0006-9233100000-af8cec22007a8e721905
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0bt9-8911300000-e353230f84239c7f373a
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-239.3044098
predicted
DarkChem Lite v0.1.0
[M-H]-218.90154
predicted
DeepCCS 1.0 (2019)
[M+H]+238.4493098
predicted
DarkChem Lite v0.1.0
[M+H]+220.90411
predicted
DeepCCS 1.0 (2019)
[M+Na]+238.8571098
predicted
DarkChem Lite v0.1.0
[M+Na]+226.81706
predicted
DeepCCS 1.0 (2019)

Targets

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insights and accelerate drug research.
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Kind
Protein
Organism
Human immunodeficiency virus 1
Pharmacological action
Yes
Actions
Inhibitor
General Function
Aspartic-type endopeptidase activity
Specific Function
Not Available
Gene Name
pol
Uniprot ID
Q72874
Uniprot Name
Pol polyprotein
Molecular Weight
10778.7 Da
References
  1. Wittayanarakul K, Hannongbua S, Feig M: Accurate prediction of protonation state as a prerequisite for reliable MM-PB(GB)SA binding free energy calculations of HIV-1 protease inhibitors. J Comput Chem. 2008 Apr 15;29(5):673-85. [Article]
  2. 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. [Article]
  3. Sadler BM, Hanson CD, Chittick GE, Symonds WT, Roskell NS: Safety and pharmacokinetics of amprenavir (141W94), a human immunodeficiency virus (HIV) type 1 protease inhibitor, following oral administration of single doses to HIV-infected adults. Antimicrob Agents Chemother. 1999 Jul;43(7):1686-92. [Article]
  4. Authors unspecified: Amprenavir: a new HIV protease inhibitor. Med Lett Drugs Ther. 1999 Jul 16;41(1057):64-6. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid 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 oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. Hesse LM, von Moltke LL, Shader RI, Greenblatt DJ: Ritonavir, efavirenz, and nelfinavir inhibit CYP2B6 activity in vitro: potential drug interactions with bupropion. Drug Metab Dispos. 2001 Feb;29(2):100-2. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Amprenavir at high concentrations has been shown to inhibit CYP2C19 in vitro. The clinical correlation is unknown.
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Veronese L, Rautaureau J, Sadler BM, Gillotin C, Petite JP, Pillegand B, Delvaux M, Masliah C, Fosse S, Lou Y, Stein DS: Single-dose pharmacokinetics of amprenavir, a human immunodeficiency virus type 1 protease inhibitor, in subjects with normal or impaired hepatic function. Antimicrob Agents Chemother. 2000 Apr;44(4):821-6. doi: 10.1128/aac.44.4.821-826.2000. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid 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 oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Fung HB, Kirschenbaum HL, Hameed R: Amprenavir: a new human immunodeficiency virus type 1 protease inhibitor. Clin Ther. 2000 May;22(5):549-72. doi: 10.1016/S0149-2918(00)80044-2. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Fung HB, Kirschenbaum HL, Hameed R: Amprenavir: a new human immunodeficiency virus type 1 protease inhibitor. Clin Ther. 2000 May;22(5):549-72. doi: 10.1016/S0149-2918(00)80044-2. [Article]
Details
5. Cytochrome P450 3A5
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
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 un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Treluyer JM, Bowers G, Cazali N, Sonnier M, Rey E, Pons G, Cresteil T: Oxidative metabolism of amprenavir in the human liver. Effect of the CYP3A maturation. Drug Metab Dispos. 2003 Mar;31(3):275-81. [Article]
Details
6. Cytochrome P450 3A4
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Inducer
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. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
  2. Brophy DF, Israel DS, Pastor A, Gillotin C, Chittick GE, Symonds WT, Lou Y, Sadler BM, Polk RE: Pharmacokinetic interaction between amprenavir and clarithromycin in healthy male volunteers. Antimicrob Agents Chemother. 2000 Apr;44(4):978-84. doi: 10.1128/aac.44.4.978-984.2000. [Article]
  3. Granfors MT, Wang JS, Kajosaari LI, Laitila J, Neuvonen PJ, Backman JT: Differential inhibition of cytochrome P450 3A4, 3A5 and 3A7 by five human immunodeficiency virus (HIV) protease inhibitors in vitro. Basic Clin Pharmacol Toxicol. 2006 Jan;98(1):79-85. doi: 10.1111/j.1742-7843.2006.pto_249.x. [Article]
  4. Fung HB, Kirschenbaum HL, Hameed R: Amprenavir: a new human immunodeficiency virus type 1 protease inhibitor. Clin Ther. 2000 May;22(5):549-72. doi: 10.1016/S0149-2918(00)80044-2. [Article]
  5. Treluyer JM, Bowers G, Cazali N, Sonnier M, Rey E, Pons G, Cresteil T: Oxidative metabolism of amprenavir in the human liver. Effect of the CYP3A maturation. Drug Metab Dispos. 2003 Mar;31(3):275-81. [Article]
  6. Wire MB, Shelton MJ, Studenberg S: Fosamprenavir : clinical pharmacokinetics and drug interactions of the amprenavir prodrug. Clin Pharmacokinet. 2006;45(2):137-68. doi: 10.2165/00003088-200645020-00002. [Article]

Transporters

Details
1. P-glycoprotein 1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inducer
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
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Perloff MD, von Moltke LL, Fahey JM, Daily JP, Greenblatt DJ: Induction of P-glycoprotein expression by HIV protease inhibitors in cell culture. AIDS. 2000 Jun 16;14(9):1287-9. [Article]
  2. Polli JW, Wring SA, Humphreys JE, Huang L, Morgan JB, Webster LO, Serabjit-Singh CS: Rational use of in vitro P-glycoprotein assays in drug discovery. J Pharmacol Exp Ther. 2001 Nov;299(2):620-8. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transporter activity
Specific Function
Mediates export of organic anions and drugs from the cytoplasm. Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotre...
Gene Name
ABCC1
Uniprot ID
P33527
Uniprot Name
Multidrug resistance-associated protein 1
Molecular Weight
171589.5 Da
References
  1. Olson DP, Scadden DT, D'Aquila RT, De Pasquale MP: The protease inhibitor ritonavir inhibits the functional activity of the multidrug resistance related-protein 1 (MRP-1). AIDS. 2002 Sep 6;16(13):1743-7. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. Karlgren M, Ahlin G, Bergstrom CA, Svensson R, Palm J, Artursson P: In vitro and in silico strategies to identify OATP1B1 inhibitors and predict clinical drug-drug interactions. Pharm Res. 2012 Feb;29(2):411-26. doi: 10.1007/s11095-011-0564-9. Epub 2011 Aug 23. [Article]

Drug created at June 13, 2005 13:24 / Updated at December 02, 2023 06:54