U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS
This repository is under review for potential modification in compliance with Administration directives.

Details

Stereochemistry ABSOLUTE
Molecular Formula C27H37N3O7S
Molecular Weight 547.664
Optical Activity ( - )
Defined Stereocenters 5 / 5
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DARUNAVIR

SMILES

CC(C)CN(C[C@@H](O)[C@H](CC1=CC=CC=C1)NC(=O)O[C@H]2CO[C@H]3OCC[C@@H]23)S(=O)(=O)C4=CC=C(N)C=C4

InChI

InChIKey=CJBJHOAVZSMMDJ-HEXNFIEUSA-N
InChI=1S/C27H37N3O7S/c1-18(2)15-30(38(33,34)21-10-8-20(28)9-11-21)16-24(31)23(14-19-6-4-3-5-7-19)29-27(32)37-25-17-36-26-22(25)12-13-35-26/h3-11,18,22-26,31H,12-17,28H2,1-2H3,(H,29,32)/t22-,23-,24+,25-,26+/m0/s1

HIDE SMILES / InChI

Molecular Formula C27H37N3O7S
Molecular Weight 547.664
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 5 / 5
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/23708741 | http://adisinsight.springer.com/drugs/800016726

Darunavir (trade name Prezista) is an orally active bis-furan-sulfonamide inhibitor of human immunodeficiency virus (HIV-1) protease. Darunavir was developed by Tibotec Pharmaceuticals (now Janssen R&D Ireland). Darunavir is indicated for the treatment of HIV-1 infection in adult and pediatric patients 3 years of age and older. The drug is co-administered with low-dose ritonavir and other anti-HIV agents. It is the only antiretroviral that has been registered at two different doses, 800/100 mg once-daily or 600/100 mg twice-daily, allowing its administration throughout the entire course of HIV disease, from naive subjects without any HIV-1 resistance to heavily treatment-experienced subjects with widespread triple-class family resistance.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
4.5 pM [Kd]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
PREZISTA

Approved Use

PREZISTA is a human immunodeficiency virus (HIV-1) protease inhibitor indicated for the treatment of HIV-1 infection in adult patients. PREZISTA is also indicated for the treatment of HIV-1 infection in pediatric patients 3 years of age and older. PREZISTA must be co-administered with ritonavir (PREZISTA/ritonavir) and with other antiretroviral agents.

Launch Date

2006
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
5272 ng/mL
800 mg 1 times / day steady-state, oral
dose: 800 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: Ritonavir
DARUNAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
57055 ng × h/mL
800 mg 1 times / day steady-state, oral
dose: 800 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: Ritonavir
DARUNAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
93026 ng × h/mL
800 mg 1 times / day steady-state, oral
dose: 800 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: Ritonavir
DARUNAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
124698 ng × h/mL
600 mg 2 times / day steady-state, oral
dose: 600 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: Ritonavir
DARUNAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
126377 ng × h/mL
600 mg 2 times / day steady-state, oral
dose: 600 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: Ritonavir
DARUNAVIR plasma
Homo sapiens
population: UNHEALTHY
age: CHILD
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
15 h
800 mg 1 times / day steady-state, oral
dose: 800 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: Ritonavir
DARUNAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
15 h
600 mg 2 times / day steady-state, oral
dose: 600 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: Ritonavir
DARUNAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
5%
800 mg 1 times / day steady-state, oral
dose: 800 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: Ritonavir
DARUNAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
5%
600 mg 2 times / day steady-state, oral
dose: 600 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: Ritonavir
DARUNAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
unhealthy, 43
Health Status: unhealthy
Age Group: 43
Sex: M+F
Sources:
Disc. AE: Headache, Gastrointestinal disorder NOS...
AEs leading to
discontinuation/dose reduction:
Headache (grade 3, 0.79%)
Gastrointestinal disorder NOS (5.51%)
Sources:
3200 mg single, oral
Overdose
Dose: 3200 mg
Route: oral
Route: single
Dose: 3200 mg
Sources:
healthy
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
unhealthy
Disc. AE: Drug-induced hepatitis, Hepatitis acute...
AEs leading to
discontinuation/dose reduction:
Drug-induced hepatitis
Hepatitis acute
Cytolytic hepatitis
Reaction skin (grade 1-3)
Stevens-Johnson syndrome
Toxic epidermal necrolysis
Diabetes mellitus
Hyperglycemia
Fat redistribution
Fat tissue increased
Immune reconstitution syndrome
Sources:
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
unhealthy
Disc. AE: Rash...
AEs leading to
discontinuation/dose reduction:
Rash (grade 1-2, 0.5%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Gastrointestinal disorder NOS 5.51%
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
unhealthy, 43
Health Status: unhealthy
Age Group: 43
Sex: M+F
Sources:
Headache grade 3, 0.79%
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
unhealthy, 43
Health Status: unhealthy
Age Group: 43
Sex: M+F
Sources:
Cytolytic hepatitis Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
unhealthy
Diabetes mellitus Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
unhealthy
Drug-induced hepatitis Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
unhealthy
Fat redistribution Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
unhealthy
Fat tissue increased Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
unhealthy
Hepatitis acute Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
unhealthy
Hyperglycemia Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
unhealthy
Immune reconstitution syndrome Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
unhealthy
Stevens-Johnson syndrome Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
unhealthy
Toxic epidermal necrolysis Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
unhealthy
Reaction skin grade 1-3
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
unhealthy
Rash grade 1-2, 0.5%
Disc. AE
800 mg 1 times / day multiple, oral
Recommended
Dose: 800 mg, 1 times / day
Route: oral
Route: multiple
Dose: 800 mg, 1 times / day
Sources:
unhealthy
PubMed

PubMed

TitleDatePubMed
Anti-HIV agents. What the future holds for TMC114.
2005 Aug-Sep
Anti-HIV agents. Interactions with TMC114.
2005 Aug-Sep
Anti-HIV agents. TMC114--an overview.
2005 Aug-Sep
New drugs.
2005 Jul
TMC114, a novel human immunodeficiency virus type 1 protease inhibitor active against protease inhibitor-resistant viruses, including a broad range of clinical isolates.
2005 Jun
TMC114/ritonavir substitution for protease inhibitor(s) in a non-suppressive antiretroviral regimen: a 14-day proof-of-principle trial.
2005 Jun 10
New protease inhibitor TMC-114. Preliminary 24-week late breaker results of the phase II trial.
2005 Mar-Apr
New PI may offer hope to triple class patients.
2005 May
A lame duck, a dark horse, and a goat.
2005 May-Jun
Meeting notes from the 3rd IAS Conference. New drugs.
2005 Oct
HIV Pathogenesis and Treatment - Third International AIDS Society Conference.
2005 Oct
Molecular basis for substrate recognition and drug resistance from 1.1 to 1.6 angstroms resolution crystal structures of HIV-1 protease mutants with substrate analogs.
2005 Oct
FDA clears HIV drug for patients with resistant virus.
2006 Aug
Anti-HIV agents. Darunavir shows its strength.
2006 Aug-Sep
Drug interactions. Interactions with TMC114 and TMC125.
2006 Jun-Jul
TMC114 approved for resistant patients.
2006 Oct
Ultra-high resolution crystal structure of HIV-1 protease mutant reveals two binding sites for clinical inhibitor TMC114.
2006 Oct 13
Bis-tetrahydrofuran: a privileged ligand for darunavir and a new generation of hiv protease inhibitors that combat drug resistance.
2006 Sep
Darunavir (Prezista) for HIV infection.
2006 Sep 11
New HIV treatment.
2006 Sep-Oct
Fast and simultaneous determination of darunavir and eleven other antiretroviral drugs for therapeutic drug monitoring: method development and validation for the determination of all currently approved HIV protease inhibitors and non-nucleoside reverse transcriptase inhibitors in human plasma by liquid chromatography coupled with electrospray ionization tandem mass spectrometry.
2007
Pharmacokinetics of darunavir (TMC114) and atazanavir during coadministration in HIV-negative, healthy volunteers.
2007
Darunavir (TMC114) approved by the FDA.
2007 Feb
No patient left behind--better treatments for resistant HIV infection.
2007 Jul 7
Safety, tolerability, and efficacy of darunavir (TMC114) with low-dose ritonavir in treatment-experienced, hepatitis B or C co-infected patients in POWER 1 and 3.
2007 Jul-Aug
A novel bis-tetrahydrofuranylurethane-containing nonpeptidic protease inhibitor (PI), GRL-98065, is potent against multiple-PI-resistant human immunodeficiency virus in vitro.
2007 Jun
Relative antiviral efficacy of ritonavir-boosted darunavir and ritonavir-boosted tipranavir vs. control protease inhibitor in the POWER and RESIST trials.
2007 May
Predicting HIV care costs using CD4 counts from clinical trials.
2007 Sep
Design of HIV protease inhibitors targeting protein backbone: an effective strategy for combating drug resistance.
2008 Jan
Quality control of protease inhibitors.
2008 Jun
Patents

Sample Use Guides

Treatment-naïve adult patients and treatment-experienced adult patients with no darunavir resistance associated substitutions: 800 mg (two 400 mg tablets) taken with ritonavir 100 mg once daily and with food. Treatment-experienced adult patients with at least one darunavir resistance associated substitution: 600 mg (one 600 mg tablet) taken with ritonavir 100 mg twice daily and with food. Pediatric patients (3 to less than 18 years of age and weighing at least 10 kg): dosage of PREZISTA and ritonavir is based on body weight and should not exceed the treatmentexperienced adult dose. Do not use once daily dosing in pediatric patients. PREZISTA should be taken with ritonavir twice daily and with food.
Route of Administration: Oral
Darunavir exhibits activity against laboratory strains and clinical isolates of HIV-1 and laboratory strains of HIV-2 in acutely infected T-cell lines, human peripheral blood mononuclear cells and human monocytes/macrophages with median EC50 values ranging from 1.2 to 8.5 nM (0.7 to 5.0 ng/mL). Darunavir demonstrates antiviral activity in cell culture against a broad panel of HIV-1 group M (A, B, C, D, E, F, G), and group O primary isolates with EC50 values ranging from less than 0.1 to 4.3 nM.
Substance Class Chemical
Created
by admin
on Mon Mar 31 18:28:49 GMT 2025
Edited
by admin
on Mon Mar 31 18:28:49 GMT 2025
Record UNII
YO603Y8113
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
(3R,3AS,6AR)-HEXAHYDROFURO(2,3-B)FURAN-3-YL ((1S,2R)-3-(((4-AMINOPHENYL)SULFONYL)(ISOBUTYL)AMINO)-1-BENZYL-2-HYDROXYPROPYL)CARBAMATE
Preferred Name English
DARUNAVIR
EMA EPAR   HSDB   INN   MART.   MI   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
Darunavir [WHO-DD]
Common Name English
((1S,2R)-3-(((4-AMINOPHENYL)SULFONYL)(2-METHYLPROPYL)AMINO)-2-HYDROXY-1-(PHENYLMETHYL)PROPYL)-CARBAMIC ACID (3R,3AS,6AR)-HEXAHYDROFURO(2,3-B)FURAN-3-YL ESTER
Common Name English
Carbamic acid, [(1S,2R)-3-[[(4-aminophenyl)sulfonyl](2-methylpropyl)amino]-2-hydroxy-1-(phenylmethyl)propyl]-, (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl ester
Systematic Name English
DARUNAVIR [MART.]
Common Name English
(3R,3AS,6AR)-HEXAHYDROFURO(2,3-B)FURAN-3-YL ((2S,3R)-4-((4-AMINO-N-ISOBUTYLPHENYL)SULFONAMIDO)-3-HYDROXY-1-PHENYLBUTAN-2-YL)CARBAMATE
Systematic Name English
TMC114
Code English
(-)-DARUNAVIR
Common Name English
DARUNAVIR [USAN]
Common Name English
DARUNAVIR [ORANGE BOOK]
Common Name English
darunavir [INN]
Common Name English
DRV
Common Name English
DARUNAVIR [MI]
Common Name English
DARUNAVIR [EMA EPAR]
Common Name English
TMC-41629
Code English
DARUNAVIR [HSDB]
Common Name English
TMC-114
Code English
DARUNAVIR [VANDF]
Common Name English
UIC-94017
Code English
TMC 114
Code English
Classification Tree Code System Code
WHO-ATC J05AE10
Created by admin on Mon Mar 31 18:28:49 GMT 2025 , Edited by admin on Mon Mar 31 18:28:49 GMT 2025
LIVERTOX NBK547994
Created by admin on Mon Mar 31 18:28:49 GMT 2025 , Edited by admin on Mon Mar 31 18:28:49 GMT 2025
NDF-RT N0000175889
Created by admin on Mon Mar 31 18:28:49 GMT 2025 , Edited by admin on Mon Mar 31 18:28:49 GMT 2025
WHO-ATC J05AR14
Created by admin on Mon Mar 31 18:28:49 GMT 2025 , Edited by admin on Mon Mar 31 18:28:49 GMT 2025
NDF-RT N0000000246
Created by admin on Mon Mar 31 18:28:49 GMT 2025 , Edited by admin on Mon Mar 31 18:28:49 GMT 2025
WHO-VATC QJ05AE10
Created by admin on Mon Mar 31 18:28:49 GMT 2025 , Edited by admin on Mon Mar 31 18:28:49 GMT 2025
NCI_THESAURUS C783
Created by admin on Mon Mar 31 18:28:49 GMT 2025 , Edited by admin on Mon Mar 31 18:28:49 GMT 2025
Code System Code Type Description
CAS
206361-99-1
Created by admin on Mon Mar 31 18:28:49 GMT 2025 , Edited by admin on Mon Mar 31 18:28:49 GMT 2025
PRIMARY
EPA CompTox
DTXSID0046779
Created by admin on Mon Mar 31 18:28:49 GMT 2025 , Edited by admin on Mon Mar 31 18:28:49 GMT 2025
PRIMARY
DAILYMED
YO603Y8113
Created by admin on Mon Mar 31 18:28:49 GMT 2025 , Edited by admin on Mon Mar 31 18:28:49 GMT 2025
PRIMARY
NDF-RT
N0000190114
Created by admin on Mon Mar 31 18:28:49 GMT 2025 , Edited by admin on Mon Mar 31 18:28:49 GMT 2025
PRIMARY Cytochrome P450 3A Inhibitors [MoA]
LACTMED
Darunavir
Created by admin on Mon Mar 31 18:28:49 GMT 2025 , Edited by admin on Mon Mar 31 18:28:49 GMT 2025
PRIMARY
WIKIPEDIA
DARUNAVIR
Created by admin on Mon Mar 31 18:28:49 GMT 2025 , Edited by admin on Mon Mar 31 18:28:49 GMT 2025
PRIMARY
INN
8305
Created by admin on Mon Mar 31 18:28:49 GMT 2025 , Edited by admin on Mon Mar 31 18:28:49 GMT 2025
PRIMARY
HSDB
7788
Created by admin on Mon Mar 31 18:28:49 GMT 2025 , Edited by admin on Mon Mar 31 18:28:49 GMT 2025
PRIMARY
ChEMBL
CHEMBL1323
Created by admin on Mon Mar 31 18:28:49 GMT 2025 , Edited by admin on Mon Mar 31 18:28:49 GMT 2025
PRIMARY
FDA UNII
YO603Y8113
Created by admin on Mon Mar 31 18:28:49 GMT 2025 , Edited by admin on Mon Mar 31 18:28:49 GMT 2025
PRIMARY
USAN
RR-31
Created by admin on Mon Mar 31 18:28:49 GMT 2025 , Edited by admin on Mon Mar 31 18:28:49 GMT 2025
PRIMARY
MERCK INDEX
m4099
Created by admin on Mon Mar 31 18:28:49 GMT 2025 , Edited by admin on Mon Mar 31 18:28:49 GMT 2025
PRIMARY Merck Index
EVMPD
SUB25394
Created by admin on Mon Mar 31 18:28:49 GMT 2025 , Edited by admin on Mon Mar 31 18:28:49 GMT 2025
PRIMARY
NCI_THESAURUS
C65364
Created by admin on Mon Mar 31 18:28:49 GMT 2025 , Edited by admin on Mon Mar 31 18:28:49 GMT 2025
PRIMARY
DRUG CENTRAL
4143
Created by admin on Mon Mar 31 18:28:49 GMT 2025 , Edited by admin on Mon Mar 31 18:28:49 GMT 2025
PRIMARY
DRUG BANK
DB01264
Created by admin on Mon Mar 31 18:28:49 GMT 2025 , Edited by admin on Mon Mar 31 18:28:49 GMT 2025
PRIMARY
CHEBI
367163
Created by admin on Mon Mar 31 18:28:49 GMT 2025 , Edited by admin on Mon Mar 31 18:28:49 GMT 2025
PRIMARY
SMS_ID
100000089367
Created by admin on Mon Mar 31 18:28:49 GMT 2025 , Edited by admin on Mon Mar 31 18:28:49 GMT 2025
PRIMARY
RXCUI
460132
Created by admin on Mon Mar 31 18:28:49 GMT 2025 , Edited by admin on Mon Mar 31 18:28:49 GMT 2025
PRIMARY RxNorm
PUBCHEM
213039
Created by admin on Mon Mar 31 18:28:49 GMT 2025 , Edited by admin on Mon Mar 31 18:28:49 GMT 2025
PRIMARY
MESH
C482292
Created by admin on Mon Mar 31 18:28:49 GMT 2025 , Edited by admin on Mon Mar 31 18:28:49 GMT 2025
PRIMARY
Related Record Type Details
METABOLIC ENZYME -> SUBSTRATE
SOLVATE->ANHYDROUS
METABOLIC ENZYME -> INHIBITOR
Ki
SOLVATE->ANHYDROUS
TRANSPORTER -> INHIBITOR
BINDER->LIGAND
BINDING
TARGET ORGANISM->INHIBITOR
SALT/SOLVATE -> PARENT
EXCRETED UNCHANGED
AMOUNT EXCRETED
URINE
TRANSPORTER -> INHIBITOR
EXCRETED UNCHANGED
AMOUNT EXCRETED
FECAL
SALT/SOLVATE -> PARENT
TRANSPORTER -> SUBSTRATE
SALT/SOLVATE -> PARENT
SOLVATE->ANHYDROUS
Related Record Type Details
IMPURITY -> PARENT
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC INTRAVENOUS ADMINISTRATION

Tmax PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC