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 35 Target ID: CHEMBL3401 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23519392	Agonist 2662	8.6 µM [EC50]
Cytochrome P450 3A 22 Target ID: CHEMBL2364675 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10952482	Inhibitor 8228	2.5 µM [IC50]
Human immunodeficiency virus type 1 protease 35 Target ID: CHEMBL243 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/21007s11,21039s10lbl.pdf	Inhibitor 8228

Conditions

Condition	Modality	Targets	Highest Phase	Product
HIV-1 infection 150 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/21007s11,21039s10lbl.pdf	Primary		Approved 8360	AGENERASE Approved Use AGENERASE (amprenavir) is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection. Launch Date 9.2404803E11

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 Co-administed with:: lamivudine, po(150 mg, BID) zidovudine, po(300 mg, BID) Sources: https://pubmed.ncbi.nlm.nih.gov/11192131 Page: p.1387	unhealthy, 21-62 n = 113 Health Status: unhealthy Condition: HIV-1 infection Age Group: 21-62 Sex: M+F Population Size: 113 Sources: https://pubmed.ncbi.nlm.nih.gov/11192131 Page: p.1387	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 Page: p.1387
1200 mg single, oral Recommended Dose: 1200 mg Route: oral Route: single Dose: 1200 mg Sources: https://pubmed.ncbi.nlm.nih.gov/10390223 Page: p.1688	unhealthy, 33+/-6.7 n = 12 Health Status: unhealthy Condition: HIV-1 infection Age Group: 33+/-6.7 Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/10390223 Page: p.1688	Sources: https://pubmed.ncbi.nlm.nih.gov/10390223 Page: p.1688
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 Page: p.11	unhealthy Health Status: unhealthy Condition: HIV-1 infection Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021007s017lbl.pdf Page: p.11	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 Page: p.11

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 Co-administed with:: lamivudine, po(150 mg, BID) zidovudine, po(300 mg, BID) Sources: https://pubmed.ncbi.nlm.nih.gov/11192131 Page: p.1387	unhealthy, 21-62 n = 113 Health Status: unhealthy Condition: HIV-1 infection Age Group: 21-62 Sex: M+F Population Size: 113 Sources: https://pubmed.ncbi.nlm.nih.gov/11192131 Page: p.1387
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 Co-administed with:: lamivudine, po(150 mg, BID) zidovudine, po(300 mg, BID) Sources: https://pubmed.ncbi.nlm.nih.gov/11192131 Page: p.1387	unhealthy, 21-62 n = 113 Health Status: unhealthy Condition: HIV-1 infection Age Group: 21-62 Sex: M+F Population Size: 113 Sources: https://pubmed.ncbi.nlm.nih.gov/11192131 Page: p.1387
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 Co-administed with:: lamivudine, po(150 mg, BID) zidovudine, po(300 mg, BID) Sources: https://pubmed.ncbi.nlm.nih.gov/11192131 Page: p.1387	unhealthy, 21-62 n = 113 Health Status: unhealthy Condition: HIV-1 infection Age Group: 21-62 Sex: M+F Population Size: 113 Sources: https://pubmed.ncbi.nlm.nih.gov/11192131 Page: p.1387
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 Co-administed with:: lamivudine, po(150 mg, BID) zidovudine, po(300 mg, BID) Sources: https://pubmed.ncbi.nlm.nih.gov/11192131 Page: p.1387	unhealthy, 21-62 n = 113 Health Status: unhealthy Condition: HIV-1 infection Age Group: 21-62 Sex: M+F Population Size: 113 Sources: https://pubmed.ncbi.nlm.nih.gov/11192131 Page: p.1387
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 Co-administed with:: lamivudine, po(150 mg, BID) zidovudine, po(300 mg, BID) Sources: https://pubmed.ncbi.nlm.nih.gov/11192131 Page: p.1387	unhealthy, 21-62 n = 113 Health Status: unhealthy Condition: HIV-1 infection Age Group: 21-62 Sex: M+F Population Size: 113 Sources: https://pubmed.ncbi.nlm.nih.gov/11192131 Page: p.1387
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 Co-administed with:: lamivudine, po(150 mg, BID) zidovudine, po(300 mg, BID) Sources: https://pubmed.ncbi.nlm.nih.gov/11192131 Page: p.1387	unhealthy, 21-62 n = 113 Health Status: unhealthy Condition: HIV-1 infection Age Group: 21-62 Sex: M+F Population Size: 113 Sources: https://pubmed.ncbi.nlm.nih.gov/11192131 Page: p.1387
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 Page: p.11	unhealthy Health Status: unhealthy Condition: HIV-1 infection Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021007s017lbl.pdf Page: p.11
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 Page: p.11	unhealthy Health Status: unhealthy Condition: HIV-1 infection Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021007s017lbl.pdf Page: p.11

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
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
eMolecules	877446	https://www.emolecules.com/cgi-bin/more?vid=877446

PubMed

Title	Date	PubMed
Four new antiretroviral medications will soon offer more options to HIV patients.	1998 Jul-Aug	11365545
Structural and kinetic analyses of the protease from an amprenavir-resistant human immunodeficiency virus type 1 mutant rendered resistant to saquinavir and resensitized to amprenavir.	2000 Aug	10906218
BMS-232632, a highly potent human immunodeficiency virus protease inhibitor that can be used in combination with other available antiretroviral agents.	2000 Aug	10898681
Novel inhibitors of HIV protease: design, synthesis and biological evaluation of picomolar inhibitors containing cyclic P1/P2 scaffolds.	2000 Jun 5	10866371
Inhibition of HIV-1 protease by a boron-modified polypeptide.	2000 Oct 1	10974201
A phase II trial of dual protease inhibitor therapy: amprenavir in combination with indinavir, nelfinavir, or saquinavir.	2001 Apr 15	11391165
Liquid chromatographic-tandem mass spectrometric determination of amprenavir (agenerase) in serum/plasma of human immunodeficiency virus type-1 infected patients receiving combination antiretroviral therapy.	2001 Apr 20	11358202
Combination of protease inhibitors for the treatment of HIV-1-infected patients: a review of pharmacokinetics and clinical experience.	2001 Dec	11878403
Therapeutic drug monitoring of HIV protease inhibitors using high-performance liquid chromatography with ultraviolet or photodiode array detection.	2001 Dec	11802104
[Resistance to protease inhibitors].	2001 Feb	11428058
New developments in anti-HIV chemotherapy.	2001 Jan-Feb	11347962
Antiretroviral activity and safety of abacavir in combination with selected HIV-1 protease inhibitors in therapy-naive HIV-1-infected adults.	2001 Jun	11491415
Simultaneous determination of the HIV-protease inhibitors indinavir, amprenavir, ritonavir, saquinavir and nelfinavir in human plasma by reversed-phase high-performance liquid chromatography.	2001 Jun 15	11417878
Phase III trials for new PI.	2001 Mar	11313031
Resistant to everything.	2001 May	11682786
Simultaneous determination of the HIV protease inhibitors indinavir, amprenavir, saquinavir, ritonavir and nelfinavir in human plasma by high-performance liquid chromatography.	2001 May 5	11393736
[Drug interactions with antiretroviral agents].	2001 May-Jun	11475806
From amprenavir to GW433908.	2001 Nov	11740410
DPC 681 and DPC 684: potent, selective inhibitors of human immunodeficiency virus protease active against clinically relevant mutant variants.	2001 Nov	11600351
New developments in anti-HIV chemotherapy.	2001 Nov	11562282
Anti-human immunodeficiency virus drugs are ineffective against Pneumocystis carinii in vitro and in vivo.	2001 Nov 15	11679930
Methadone blood concentrations are decreased by the administration of abacavir plus amprenavir.	2001 Oct	11591903
Effectors of HIV-1 protease peptidolytic activity.	2001 Sep 18	11551211
Amping amprenavir with ritonavir.	2001 Spring	11570075
Retroviral proteases.	2002	11983066
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 Apr	11897976
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 Feb 22	11741936
Clinical pharmacology and pharmacokinetics of amprenavir.	2002 Jan	11816239
Unfavourable interaction of amprenavir and lopinavir in combination with ritonavir?	2002 Jan 25	11807318
Longitudinal use of phenotypic resistance testing to HIV-1 protease inhibitors in patients developing HAART failure.	2002 Jul	12116020
Dual vs single protease inhibitor therapy following antiretroviral treatment failure: a randomized trial.	2002 Jul 10	12095381
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 Jul 15	12134255
Synthesis and antiviral activity of new anti-HIV amprenavir bioisosteres.	2002 Jul 18	12109915
Efavirenz-induced skin eruption and successful desensitization.	2002 Mar	11895054
Delavirdine increases drug exposure of ritonavir-boosted protease inhibitors.	2002 Mar 29	11964540
Salvage therapy with amprenavir and ritonavir: prospective study in 17 heavily pretreated patients.	2002 Mar-Apr	11976990
Prevalence of the HIV protease mutation N88S causing hypersensitivity to amprenavir.	2002 May 1	11941567
Amprenavir-resistant HIV-1 exhibits lopinavir cross-resistance and reduced replication capacity.	2002 May 3	11953467
Therapeutic vaccination in primary HIV infection, the Quest trial.	2002 May 6	11983263

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 `Wed Jul 05 23:17:12 UTC 2023` Edited by `admin` on `Wed Jul 05 23:17:12 UTC 2023`
Record UNII	5S0W860XNR
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

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

J05AE05

Code

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 [(αS)-α-[(1R-1-hydroxy-2-(N1-isobutylsulfanilamido)ethyl]phenethyl]carbamate

Common Name

English

Classification Tree Code System Code

EMA ASSESSMENT REPORTS

AGENERASE (WITHDRAWN: HIV INFECTIONS)