DARUNAVIR

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 Search

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
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021976s021lbl.pdf
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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Human immunodeficiency virus type 1 protease 36 Target ID: CHEMBL243 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15479840	Inhibitor 8504		4.5 pM [Kd]

Conditions

Condition	Modality	Targets	Highest Phase	Product
HIV-1 infection 156 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021976s021lbl.pdf	Primary		Approved 8583	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

C_max

Value	Dose	Co-administered	Analyte	Population
5272 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21926632/	800 mg 1 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered: Ritonavir	Ritonavir	DARUNAVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
57055 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21926632/	800 mg 1 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered: Ritonavir	Ritonavir	DARUNAVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
93026 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021976s021lbl.pdf	800 mg 1 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered: Ritonavir	Ritonavir	DARUNAVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
124698 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021976s021lbl.pdf	600 mg 2 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered: Ritonavir	Ritonavir	DARUNAVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
126377 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021976s021lbl.pdf	600 mg 2 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered: Ritonavir	Ritonavir	DARUNAVIR plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
15 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021976s021lbl.pdf	800 mg 1 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered: Ritonavir	Ritonavir	DARUNAVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
15 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021976s021lbl.pdf	600 mg 2 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered: Ritonavir	Ritonavir	DARUNAVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
5% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021976s021lbl.pdf	800 mg 1 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered: Ritonavir	Ritonavir	DARUNAVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
5% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021976s021lbl.pdf	600 mg 2 times / day steady-state, oral dose: 600 mg route of administration: Oral experiment type: STEADY-STATE co-administered: Ritonavir	Ritonavir	DARUNAVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse 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: https://pubmed.ncbi.nlm.nih.gov/20010070	unhealthy, 43 Health Status: unhealthy Age Group: 43 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/20010070	Disc. AE: Headache, Gastrointestinal disorder NOS... AEs leading to discontinuation/dose reduction: Headache (grade 3, 0.79%) Gastrointestinal disorder NOS (5.51%) Sources: https://pubmed.ncbi.nlm.nih.gov/20010070
3200 mg single, oral Overdose Dose: 3200 mg Route: oral Route: single Dose: 3200 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021976s021lbl.pdf	healthy Health Status: healthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021976s021lbl.pdf	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021976s021lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021976s021lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021976s021lbl.pdf	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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021976s021lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021976s021lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021976s021lbl.pdf	Disc. AE: Rash... AEs leading to discontinuation/dose reduction: Rash (grade 1-2, 0.5%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021976s021lbl.pdf

AEs

AE	Significance	Dose	Population
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: https://pubmed.ncbi.nlm.nih.gov/20010070	unhealthy, 43 Health Status: unhealthy Age Group: 43 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/20010070
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: https://pubmed.ncbi.nlm.nih.gov/20010070	unhealthy, 43 Health Status: unhealthy Age Group: 43 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/20010070
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021976s021lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021976s021lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021976s021lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021976s021lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021976s021lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021976s021lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021976s021lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021976s021lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021976s021lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021976s021lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021976s021lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021976s021lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021976s021lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021976s021lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021976s021lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021976s021lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021976s021lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021976s021lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021976s021lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021976s021lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021976s021lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021976s021lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021976s021lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021976s021lbl.pdf

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:367163	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:367163
ChemicalBook	CB51176244	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB51176244
eMolecules	35833368	https://www.emolecules.com/cgi-bin/more?vid=35833368
eMolecules	36557635	https://www.emolecules.com/cgi-bin/more?vid=36557635
MolPort	MolPort-003-846-141	https://www.molport.com/shop/molecule-link/MolPort-003-846-141
ZINC	ZINC000003955219	http://zinc15.docking.org/substances/ZINC000003955219

PubMed

Title	Date	PubMed
Anti-HIV agents. What the future holds for TMC114.	2005 Aug-Sep	17219656
Anti-HIV agents. Interactions with TMC114.	2005 Aug-Sep	17219655
Anti-HIV agents. TMC114--an overview.	2005 Aug-Sep	17219654
New drugs.	2005 Jul	16011526
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	15917527
TMC114/ritonavir substitution for protease inhibitor(s) in a non-suppressive antiretroviral regimen: a 14-day proof-of-principle trial.	2005 Jun 10	15905675
New protease inhibitor TMC-114. Preliminary 24-week late breaker results of the phase II trial.	2005 Mar-Apr	15828108
New PI may offer hope to triple class patients.	2005 May	15948276
A lame duck, a dark horse, and a goat.	2005 May-Jun	16193576
Meeting notes from the 3rd IAS Conference. New drugs.	2005 Oct	16276591
HIV Pathogenesis and Treatment - Third International AIDS Society Conference.	2005 Oct	16254799
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	16218957
FDA clears HIV drug for patients with resistant virus.	2006 Aug	16933372
Anti-HIV agents. Darunavir shows its strength.	2006 Aug-Sep	17205651
Drug interactions. Interactions with TMC114 and TMC125.	2006 Jun-Jul	17211920
TMC114 approved for resistant patients.	2006 Oct	17052143
Ultra-high resolution crystal structure of HIV-1 protease mutant reveals two binding sites for clinical inhibitor TMC114.	2006 Oct 13	16962136
Bis-tetrahydrofuran: a privileged ligand for darunavir and a new generation of hiv protease inhibitors that combat drug resistance.	2006 Sep	16927344
Darunavir (Prezista) for HIV infection.	2006 Sep 11	16977286
New HIV treatment.	2006 Sep-Oct	17326304
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	17610214
Pharmacokinetics of darunavir (TMC114) and atazanavir during coadministration in HIV-negative, healthy volunteers.	2007	17596110
Darunavir (TMC114) approved by the FDA.	2007 Feb	17763549
No patient left behind--better treatments for resistant HIV infection.	2007 Jul 7	17617250
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	17720661
A novel bis-tetrahydrofuranylurethane-containing nonpeptidic protease inhibitor (PI), GRL-98065, is potent against multiple-PI-resistant human immunodeficiency virus in vitro.	2007 Jun	17371811
Relative antiviral efficacy of ritonavir-boosted darunavir and ritonavir-boosted tipranavir vs. control protease inhibitor in the POWER and RESIST trials.	2007 May	17461854
Predicting HIV care costs using CD4 counts from clinical trials.	2007 Sep	17803366
Design of HIV protease inhibitors targeting protein backbone: an effective strategy for combating drug resistance.	2008 Jan	17722874
Quality control of protease inhibitors.	2008 Jun	17828738

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

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

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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

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