AMPRENAVIR

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C25H35N3O6S
Molecular Weight	505.627
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)CN(C[C@@H](O)[C@H](CC1=CC=CC=C1)NC(=O)O[C@H]2CCOC2)S(=O)(=O)C3=CC=C(N)C=C3

InChI

InChIKey=YMARZQAQMVYCKC-OEMFJLHTSA-N

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

HIDE SMILES / InChI

Molecular Formula	C25H35N3O6S
Molecular Weight	505.627
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	3 / 3
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/21007s11,21039s10lbl.pdf
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/23519392 | https://www.ncbi.nlm.nih.gov/pubmed/11152018 | https://www.ncbi.nlm.nih.gov/pubmed/15341507

Amprenavir is an inhibitor of HIV-1 protease. Amprenavir binds to the active site of HIV-1 protease and thereby prevents the processing of viral gag and gag-pol polyprotein precursors, resulting in the formation of immature non-infectious viral particles. Amprenavir-containing combination regimens have shown virological efficacy, and have generally been well tolerated, in patients with HIV infection (primarily treatment-naive or protease inhibitor-naive). Fosamprenavir (GW433908, Lexiva, Telzir) is an oral prodrug of amprenavir, with a reduced daily pill burden. The use of protease inhibitors has also been associated with dyslipidemia and an increased risk of cardiovascular disease. Amprenavir activates Pregnane X receptor to mediate dyslipidemia.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Pregnane X receptor 36 Target ID: CHEMBL3401 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23519392	Agonist 2752	8.6 µM [EC50]
Cytochrome P450 3A 22 Target ID: CHEMBL2364675 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10952482	Inhibitor 8504	2.5 µM [IC50]
Human immunodeficiency virus type 1 protease 36 Target ID: CHEMBL243 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/21007s11,21039s10lbl.pdf	Inhibitor 8504

Conditions

Condition	Modality	Targets	Highest Phase	Product
HIV-1 infection 156 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/21007s11,21039s10lbl.pdf	Primary		Approved 8583	AGENERASE Approved Use AGENERASE (amprenavir) is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection. Launch Date 1999

C_max

Value	Dose	Analyte	Population
5.36 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/21007lbl.pdf	1200 mg 2 times / day multiple, oral dose: 1200 mg route of administration: Oral experiment type: MULTIPLE co-administered:	AMPRENAVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
6.18 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/21007lbl.pdf	1200 mg single, oral dose: 1200 mg route of administration: Oral experiment type: SINGLE co-administered:	AMPRENAVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: HIGH-FAT
9.72 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/21007lbl.pdf	1200 mg single, oral dose: 1200 mg route of administration: Oral experiment type: SINGLE co-administered:	AMPRENAVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
6.77 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/21007lbl.pdf	20 mg/kg bw 2 times / day multiple, oral dose: 20 mg/kg bw route of administration: Oral experiment type: MULTIPLE co-administered:	AMPRENAVIR plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: UNKNOWN food status: UNKNOWN
3.99 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/21007lbl.pdf	15 mg/kg bw 3 times / day multiple, oral dose: 15 mg/kg bw route of administration: Oral experiment type: MULTIPLE co-administered:	AMPRENAVIR plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
18.5 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/21007lbl.pdf	1200 mg 2 times / day multiple, oral dose: 1200 mg route of administration: Oral experiment type: MULTIPLE co-administered:	AMPRENAVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
22.06 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/21007lbl.pdf	1200 mg single, oral dose: 1200 mg route of administration: Oral experiment type: SINGLE co-administered:	AMPRENAVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: HIGH-FAT
28.05 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/21007lbl.pdf	1200 mg single, oral dose: 1200 mg route of administration: Oral experiment type: SINGLE co-administered:	AMPRENAVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED
15.46 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/21007lbl.pdf	20 mg/kg bw 2 times / day multiple, oral dose: 20 mg/kg bw route of administration: Oral experiment type: MULTIPLE co-administered:	AMPRENAVIR plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: UNKNOWN food status: UNKNOWN
8.73 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/21007lbl.pdf	15 mg/kg bw 3 times / day multiple, oral dose: 15 mg/kg bw route of administration: Oral experiment type: MULTIPLE co-administered:	AMPRENAVIR plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
8.85 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/21007lbl.pdf	1200 mg 2 times / day multiple, oral dose: 1200 mg route of administration: Oral experiment type: MULTIPLE co-administered:		AMPRENAVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
10% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/21007lbl.pdf	1200 mg 2 times / day multiple, oral dose: 1200 mg route of administration: Oral experiment type: MULTIPLE co-administered:		AMPRENAVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
1200 mg 2 times / day multiple, oral Recommended Dose: 1200 mg, 2 times / day Route: oral Route: multiple Dose: 1200 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11192131	unhealthy, 21-62 Health Status: unhealthy Age Group: 21-62 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/11192131	Disc. AE: Nausea, Vomiting... AEs leading to discontinuation/dose reduction: Nausea (12%) Vomiting (6%) Loose stools (3%) Abdominal pain (2%) Abdominal discomfort (2%) Rash (3%) Sources: https://pubmed.ncbi.nlm.nih.gov/11192131
1200 mg single, oral Recommended Dose: 1200 mg Route: oral Route: single Dose: 1200 mg Sources: https://pubmed.ncbi.nlm.nih.gov/10390223	unhealthy, 33+/-6.7 Health Status: unhealthy Age Group: 33+/-6.7 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/10390223	Sources: https://pubmed.ncbi.nlm.nih.gov/10390223
1200 mg 2 times / day multiple, oral Recommended Dose: 1200 mg, 2 times / day Route: oral Route: multiple Dose: 1200 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021007s017lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021007s017lbl.pdf	Disc. AE: Reaction skin, Stevens-Johnson syndrome... AEs leading to discontinuation/dose reduction: Reaction skin (grade 3-4) Stevens-Johnson syndrome (grade 3-4) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021007s017lbl.pdf

AEs

AE	Significance	Dose	Population
Nausea	12% Disc. AE	1200 mg 2 times / day multiple, oral Recommended Dose: 1200 mg, 2 times / day Route: oral Route: multiple Dose: 1200 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11192131	unhealthy, 21-62 Health Status: unhealthy Age Group: 21-62 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/11192131
Abdominal discomfort	2% Disc. AE	1200 mg 2 times / day multiple, oral Recommended Dose: 1200 mg, 2 times / day Route: oral Route: multiple Dose: 1200 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11192131	unhealthy, 21-62 Health Status: unhealthy Age Group: 21-62 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/11192131
Abdominal pain	2% Disc. AE	1200 mg 2 times / day multiple, oral Recommended Dose: 1200 mg, 2 times / day Route: oral Route: multiple Dose: 1200 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11192131	unhealthy, 21-62 Health Status: unhealthy Age Group: 21-62 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/11192131
Loose stools	3% Disc. AE	1200 mg 2 times / day multiple, oral Recommended Dose: 1200 mg, 2 times / day Route: oral Route: multiple Dose: 1200 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11192131	unhealthy, 21-62 Health Status: unhealthy Age Group: 21-62 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/11192131
Rash	3% Disc. AE	1200 mg 2 times / day multiple, oral Recommended Dose: 1200 mg, 2 times / day Route: oral Route: multiple Dose: 1200 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11192131	unhealthy, 21-62 Health Status: unhealthy Age Group: 21-62 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/11192131
Vomiting	6% Disc. AE	1200 mg 2 times / day multiple, oral Recommended Dose: 1200 mg, 2 times / day Route: oral Route: multiple Dose: 1200 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11192131	unhealthy, 21-62 Health Status: unhealthy Age Group: 21-62 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/11192131
Reaction skin	grade 3-4 Disc. AE	1200 mg 2 times / day multiple, oral Recommended Dose: 1200 mg, 2 times / day Route: oral Route: multiple Dose: 1200 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021007s017lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021007s017lbl.pdf
Stevens-Johnson syndrome	grade 3-4 Disc. AE	1200 mg 2 times / day multiple, oral Recommended Dose: 1200 mg, 2 times / day Route: oral Route: multiple Dose: 1200 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021007s017lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021007s017lbl.pdf

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:40050	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:40050
ChemicalBook	CB4186139	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB4186139
eMolecules	877446	https://www.emolecules.com/cgi-bin/more?vid=877446
MolPort	MolPort-000-883-856	https://www.molport.com/shop/molecule-link/MolPort-000-883-856
Selleck Chemicals	Amprenavir-(Agenerase)	http://www.selleckchem.com/products/Amprenavir-(Agenerase).html
ZINC	ZINC000003809192	http://zinc15.docking.org/substances/ZINC000003809192

PubMed

Title	Date	PubMed
Synthesis and antiviral activity of new anti-HIV amprenavir bioisosteres.	2002-07-18	12109915
New developments in anti-HIV chemotherapy.	2002-07-18	12084468
The pharmacokinetics of amprenavir, zidovudine, and lamivudine in the genital tracts of men infected with human immunodeficiency virus type 1 (AIDS clinical trials group study 850).	2002-07-15	12134255
Determination of lopinavir and nevirapine by high-performance liquid chromatography after solid-phase extraction: application for the assessment of their transplacental passage at delivery.	2002-07-15	12076682
Dual vs single protease inhibitor therapy following antiretroviral treatment failure: a randomized trial.	2002-07-10	12095381
Longitudinal use of phenotypic resistance testing to HIV-1 protease inhibitors in patients developing HAART failure.	2002-07	12116020
In vitro antiviral interaction of lopinavir with other protease inhibitors.	2002-07	12069982
High-performance liquid chromatographic method for the simultaneous determination of the six HIV-protease inhibitors and two non-nucleoside reverse transcriptase inhibitors in human plasma.	2002-06	12021635
Sensitive and simultaneous determination of HIV protease inhibitors in rat biological samples by liquid chromatography-mass spectrometry.	2002-06	11933027
Select HIV protease inhibitors alter bone and fat metabolism ex vivo.	2002-05-31	11937496
Therapeutic vaccination in primary HIV infection, the Quest trial.	2002-05-06	11983263
Amprenavir-resistant HIV-1 exhibits lopinavir cross-resistance and reduced replication capacity.	2002-05-03	11953467
Prevalence of the HIV protease mutation N88S causing hypersensitivity to amprenavir.	2002-05-01	11941567
Salvage therapy with amprenavir and ritonavir: prospective study in 17 heavily pretreated patients.	2002-04-27	11976990
New dosing regimen approved.	2002-04	12015873
Simultaneous determination of the six HIV protease inhibitors (amprenavir, indinavir, lopinavir, nelfinavir, ritonavir, and saquinavir) plus M8 nelfinavir metabolite and the nonnucleoside reverse transcription inhibitor efavirenz in human plasma by solid-phase extraction and column liquid chromatography.	2002-04	11897976
The utility of inhibitory quotients in determining the relative potency of protease inhibitors.	2002-03-29	11964541
Delavirdine increases drug exposure of ritonavir-boosted protease inhibitors.	2002-03-29	11964540
Drug interaction between amprenavir and lopinavir/ritonavir in salvage therapy.	2002-03-29	11964539
FDA approves new dosing for amprenavir and ritonavir combination.	2002-03-08	11965920
Parallel decline of CD8+/CD38++ T cells and viraemia in response to quadruple highly active antiretroviral therapy in primary HIV infection.	2002-03-08	11873002
Fosamprenavir. Vertex Pharmaceuticals/GlaxoSmithKline.	2002-03	12054084
Lipodystrophy update.	2002-03	12038302
Resistance testing in children changing human immunodeficiency virus type 1 protease inhibitor.	2002-03	12005085
Drug interactions between HIV protease inhibitors based on physiologically-based pharmacokinetic model.	2002-03	11920753
Efavirenz-induced skin eruption and successful desensitization.	2002-03	11895054
Amino acid substitutions in Gag protein at non-cleavage sites are indispensable for the development of a high multitude of HIV-1 resistance against protease inhibitors.	2002-02-22	11741936
HIV-1 genotype and phenotype correlate with virological response to abacavir, amprenavir and efavirenz in treatment-experienced patients.	2002-02-15	11834950
In-vitro and in-vivo pharmacokinetic interactions of amprenavir, an HIV protease inhibitor, with other current HIV protease inhibitors in rats.	2002-02	11848286
A potent human immunodeficiency virus type 1 protease inhibitor, UIC-94003 (TMC-126), and selection of a novel (A28S) mutation in the protease active site.	2002-02	11773409
Determination of amprenavir, a HIV-1 protease inhibitor, in human seminal plasma using high-performance liquid chromatography-tandem mass spectrometry.	2002-01-25	11824819
Unfavourable interaction of amprenavir and lopinavir in combination with ritonavir?	2002-01-25	11807318
[Advances in the domain of HIV].	2002-01-19	11850992
Beta-strand mimicking macrocyclic amino acids: templates for protease inhibitors with antiviral activity.	2002-01-17	11784141
Central nervous system toxicity and amprenavir oral solution.	2002-01	11816252
Clinical pharmacology and pharmacokinetics of amprenavir.	2002-01	11816239
Retroviral proteases.	2002	11983066
Interaction potential of lercanidipine, a new vasoselective dihydropyridine calcium antagonist.	2002	11963641
Human immunodeficiency virus type 1 hypersusceptibility to amprenavir in vitro can be associated with virus load response to treatment in vivo.	2001-12-15	11700580
Genotypic correlates of resistance to HIV-1 protease inhibitors on longitudinal data: the role of secondary mutations.	2001-12	11878405
Combination of protease inhibitors for the treatment of HIV-1-infected patients: a review of pharmacokinetics and clinical experience.	2001-12	11878403
Therapeutic drug monitoring of HIV protease inhibitors using high-performance liquid chromatography with ultraviolet or photodiode array detection.	2001-12	11802104
Pharmacokinetics of amprenavir and lopinavir in combination with nevirapine in highly pretreated HIV-infected patients.	2001-11-23	11698713
Anti-human immunodeficiency virus drugs are ineffective against Pneumocystis carinii in vitro and in vivo.	2001-11-15	11679930
From amprenavir to GW433908.	2001-11	11740410
In vitro activity of amprenavir against Pneumocystis carinii.	2001-09	11708264
HIV and drug allergy.	2001-08	11964706
Amprenavir: new preparation. Another HIV protease inhibitor: no proven advance.	2001-06	11718166
Resistant to everything.	2001-05	11682786
Principles and practice of HIV-protease inhibitor pharmacoenhancement.	2001-04	11737387

Patents

Sample Use Guides

In Vivo Use Guide

Adults: The recommended oral dose of AGENERASE Capsules for adults is 1200 mg (eight 150-mg capsules) twice daily in combination with other antiretroviral agents. Concomitant Therapy: If AGENERASE and ritonavir are used in combination, the recommended dosage regimens are: AGENERASE 1200 mg with ritonavir 200 mg once daily or AGENERASE 600 mg with ritonavir 100 mg twice daily. Pediatric Patients: For adolescents (13 to 16 years), the recommended oral dose of AGENERASE Capsules is 1200 mg (eight 150-mg capsules) twice daily in combination with other antiretroviral agents. For patients between 4 and 12 years of age or for patients 13 to 16 years of age with weight of <50 kg, the recommended oral dose of AGENERASE Capsules is 20 mg/kg twice daily or 15 mg/kg 3 times daily (to a maximum daily dose of 2400 mg) in combination with other antiretroviral agents.

Route of Administration: Oral

In Vitro Use Guide

The in vitro antiviral activity of amprenavir was evaluated against HIV-1 IIIB in both acutely and chronically infected lymphoblastic cell lines (MT-4, CEM-CCRF, 43 H9) and in peripheral blood lymphocytes. The 50% inhibitory concentration (IC50) of amprenavir ranged from 0.012 to 0.08 µM in acutely infected cells and was 0.41 µM in chronically infected cells (1 µM = 0.50 mcg/mL).

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:09:31 GMT 2025` Edited by `admin` on `Mon Mar 31 18:09:31 GMT 2025`
Record UNII	5S0W860XNR
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

J05AE05

Preferred Name

English

AMPRENAVIR

Official Name

English

AMPRENAVIR [EMA EPAR]

Common Name

English

VX-478

Code

English

AMPRENAVIR [VANDF]

Common Name

English

AMPRENAVIR [MART.]

Common Name

English

KVX-478

Code

English

(3S-(3R*(1R*,2S*)))-(3-(((4-AMINOPHENYL)SULFONYL)(2-METHYLPROPYL)AMINO)-2-HYDROXY-1-(PHENYLMETHYL)PROPYL) TETRAHYDRO-3-FURANYL CARBAMATE

Common Name

English

AMPRENAVIR [MI]

Common Name

English

AMPRENAVIR [HSDB]

Common Name

English

141W94

Code

English

AMPRENAVIR [ORANGE BOOK]

Common Name

English

AMPRENAVIR [USAN]

Common Name

English

AGENERASE

Brand Name

English

AMPRENAVIR [JAN]

Common Name

English

Amprenavir [WHO-DD]

Common Name

English

amprenavir [INN]

Common Name

English

141W94

Code

English

(3S)-Tetrahydro-3-furyl [(?S)-?-[(1R-1-hydroxy-2-(N1-isobutylsulfanilamido)ethyl]phenethyl]carbamate

Common Name

English

Classification Tree Code System Code

EMA ASSESSMENT REPORTS

AGENERASE (WITHDRAWN: HIV INFECTIONS)