Identification

Name
Darunavir
Accession Number
DB01264  (EXPT00002)
Type
Small Molecule
Groups
Approved
Description

Darunavir is a protease inhibitor used to treat HIV. It acts on the HIV aspartyl protease which the virus needs to cleave the HIV polyprotein into its functional fragments.

Structure
Thumb
Synonyms
  • (3R,3AS,6ar)-hexahydrofuro[2,3-b]furan-3-yl N-((1S,2R)-1-benzyl-2-hydroxy-3-(N(1)-isobutylsulfanilamido)propyl)carbamate
  • (3R,3AS,6ar)-hexahydrofuro[2,3-b]furan-3-yl(1S,2R)-3-[[(4-aminophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropylcarbamate
  • (3R,3AS,6ar)-tetrahydro-2H-furo[2,3-b]furan-3-yl (2S,3R)-4-(4-amino-N-isobutylphenylsulfonamido)-3-hydroxy-1-phenylbutan-2-ylcarbamate
  • (3R,3AS,6ar)-tetrahydro-2H-furo[2,3-b]furan-3-yl (2S,3R)-4-(4-amino-N-neopentylphenylsulfonamido)-3-hydroxy-1-phenylbutan-2-ylcarbamate
  • [(S)-3-[(4-Amino-benzenesulfonyl)-isobutyl-amino]-2-hydroxy-1-((R)-phenylmethyl)-propyl]-carbamic acid (3R,3as,6ar)-(hexahydro-furo[2,3-b]furan-3-yl) ester
  • {(1S,2R)-3-[(4-amino-benzenesulfonyl)-isobutyl-amino]-1-benzyl-2-hydroxy-propyl}-carbamic acid (3R,3as,6ar)-(hexahydro-furo[2,3-b]furan-3-yl) ester
  • Darunavir
  • Darunavirum
  • N-((1S,2R)-3-(((4-Aminophenyl)sulfonyl)(2-methylpropyl)amino)-2-hydroxy-1-benzylpropyl)((1S,2R,5R)-4,6-dioxabicyclo(3.3.0)oct-2-yloxy)carboxamide
External IDs
AIDS073035 / TMC 114 / TMC-114 / TMC-41629 / TMC114 / UIC-94017
Product Ingredients
IngredientUNIICASInChI Key
Darunavir ethanolate33O78XF0BW635728-49-3QWSHKNICRJHQCY-VBTXLZOXSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
PrezistaTablet, film coated800 mgOralJanssen Cilag International Nv2007-02-12Not applicableEu
PrezistaTablet, film coated800 mg/1OralAvera McKennan Hospital2015-10-052018-07-05Us
PrezistaTablet, film coated400 mg/1OralPhysicians Total Care, Inc.2008-12-09Not applicableUs
PrezistaTablet, film coated150 mg/1OralJanssen Products LP2009-04-27Not applicableUs
PrezistaTablet600 mgOralJanssen Pharmaceuticals2009-03-17Not applicableCanada
PrezistaTablet, film coated300 mgOralJanssen Cilag International Nv2007-02-12Not applicableEu
PrezistaTablet150 mgOralJanssen Pharmaceuticals2012-04-16Not applicableCanada
PrezistaTablet, film coated400 mgOralJanssen Cilag International Nv2007-02-12Not applicableEu
PrezistaTablet400 mgOralJanssen Pharmaceuticals2009-04-012016-09-01Canada
PrezistaTablet, film coated600 mg/1OralRemedy Repack2017-08-21Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Pat-darunavirTablet150 mgOralPatriot A Division Of Janssen IncNot applicableNot applicableCanada
Pat-darunavirTablet400 mgOralPatriot A Division Of Janssen IncNot applicableNot applicableCanada
Pat-darunavirTablet800 mgOralPatriot A Division Of Janssen IncNot applicableNot applicableCanada
Pat-darunavirTablet75 mgOralPatriot A Division Of Janssen IncNot applicableNot applicableCanada
Pat-darunavirTablet600 mgOralPatriot A Division Of Janssen IncNot applicableNot applicableCanada
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
PrezcobixDarunavir ethanolate (800 mg/1) + Cobicistat (150 mg/1)Tablet, film coatedOralREMEDYREPACK INC.2017-08-28Not applicableUs
PrezcobixDarunavir (800 mg) + Cobicistat (150 mg)TabletOralJanssen Pharmaceuticals2014-08-28Not applicableCanada
PrezcobixDarunavir ethanolate (800 mg/1) + Cobicistat (150 mg/1)Tablet, film coatedOralA-S Medication Solutions2015-01-31Not applicableUs
PrezcobixDarunavir ethanolate (800 mg/1) + Cobicistat (150 mg/1)Tablet, film coatedOralJanssen Products LP2015-01-31Not applicableUs
PrezcobixDarunavir ethanolate (800 mg/1) + Cobicistat (150 mg/1)Tablet, film coatedOralA-S Medication Solutions2015-01-31Not applicableUs
RezolstaDarunavir (800 mg) + Cobicistat (150 mg)Tablet, film coatedOralJanssen Cilag International Nv2014-11-19Not applicableEu
SymtuzaDarunavir (800 mg) + Cobicistat (150 mg) + Emtricitabine (200 mg) + Tenofovir alafenamide (10 mg)TabletOralJanssen PharmaceuticalsNot applicableNot applicableCanada
SymtuzaDarunavir (800 mg/1) + Cobicistat (150 mg/1) + Emtricitabine (200 mg/1) + Tenofovir alafenamide (10 mg/1)Tablet, film coatedOralJanssen, Lp2018-07-17Not applicableUs
Categories
UNII
YO603Y8113
CAS number
206361-99-1
Weight
Average: 547.664
Monoisotopic: 547.235221243
Chemical Formula
C27H37N3O7S
InChI Key
CJBJHOAVZSMMDJ-HEXNFIEUSA-N
InChI
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
IUPAC Name
(3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl N-[(2S,3R)-3-hydroxy-4-[N-(2-methylpropyl)4-aminobenzenesulfonamido]-1-phenylbutan-2-yl]carbamate
SMILES
[H][C@@]12CCO[C@]1([H])OC[C@@H]2OC(=O)N[C@@H](CC1=CC=CC=C1)[C@H](O)CN(CC(C)C)S(=O)(=O)C1=CC=C(N)C=C1

Pharmacology

Indication

Darunavir, co-administered with ritonavir, and with other antiretroviral agents, is indicated for the treatment of human immunodeficiency virus (HIV) infection in antiretroviral treatment-experienced adult patients, such as those with HIV-1 strains resistant to more than one protease inhibitor.

Associated Conditions
Pharmacodynamics

Darunavir is an inhibitor of the human immunodeficiency virus (HIV) protease. In studies, the drug, co-administered with ritonavir in combination therapy, significantly reduced viral load and increased CD4 cell counts in this treatment-experienced patient population (Tibotec, 2006, Product Monograph, Prezista 2006). Darunavir is used as an adjunct therapy with low dose ritonavir, which inhibits cytochrome P450 3A (CYP3A) which increases the bioavailability and half life of darunavir.

Mechanism of action

Darunavir is a HIV protease inhibitor which prevents HIV replication by binding to the enzyme's active site, thereby preventing the dimerization and the catalytic activity of the HIV-1 protease. Darunavir selectively inhibits the cleavage of HIV encoded Gag-Pol polyproteins in virus-infected cells, which prevents the formation of mature infectious virus particles. Structual analyses suggests that the close contact that darunavir has with the main chains of the protease active site amino acids (Asp-29 and Asp-30) is an important contributing factor to its potency and wide spectrum of activity against multi-protease inhibitor resistant HIV-1 variants. Darunavir can also adapt to the changing shape of a protease enzyme because of its molecular flexibility. Darunavir is known to bind to two distinct sites on the enzyme: the active site cavity and the surface of one of the flexible flaps in the protease dimer.

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

The absolute oral bioavailability of a single 600 mg dose of darunavir alone and after co-administration with 100 mg ritonavir twice daily was 37% and 82%, respectively.

Volume of distribution
Not Available
Protein binding

Darunavir is approximately 95% bound to plasma proteins. Darunavir binds primarily to plasma alpha 1-acid glycoprotein (AAG).

Metabolism

Hepatic. Darunavir is extensively metabolized by CYP enzymes, primarily by CYP3A.

Route of elimination

Darunavir is primarily metabolized by CYP3A. Darunavir is extensively metabolized by CYP enzymes, primarily by CYP3A. A mass balance study in healthy volunteers showed that after single dose administration of 400 mg 14C-darunavir, co-administered with 100 mg ritonavir, approximately 79.5% and 13.9% of the administered dose of 14C-darunavir was recovered in the feces and urine, respectively.

Half life

The terminal elimination half-life of darunavir was approximately 15 hours when combined with ritonavir.

Clearance
  • 32.8 L/hr [Healthy volunteers receiving intravenous administration of 400 mg of darunavir]
  • 5.9 L/hr [Healthy volunteers receiving intravenous administrations of 400 mg of darunavir and 100 mg of ritonavir twice daily]
Toxicity
Not Available
Affected organisms
  • Human Immunodeficiency Virus
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of Darunavir can be decreased when combined with (R)-warfarin.
(S)-WarfarinThe metabolism of Darunavir can be decreased when combined with (S)-Warfarin.
2,4-thiazolidinedioneThe therapeutic efficacy of 2,4-thiazolidinedione can be increased when used in combination with Darunavir.
3,5-diiodothyropropionic acidThe metabolism of Darunavir can be decreased when combined with 3,5-diiodothyropropionic acid.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Darunavir.
5-androstenedioneThe metabolism of Darunavir can be decreased when combined with 5-androstenedione.
6-Deoxyerythronolide BThe metabolism of Darunavir can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of Darunavir can be decreased when combined with 6-O-benzylguanine.
9-aminocamptothecinThe metabolism of Darunavir can be decreased when combined with 9-aminocamptothecin.
AbacavirThe serum concentration of Abacavir can be decreased when it is combined with Darunavir.
Food Interactions
  • Take with food - better absorption (+30%).

References

Synthesis Reference
US05158713
General References
  1. Back D, Sekar V, Hoetelmans RM: Darunavir: pharmacokinetics and drug interactions. Antivir Ther. 2008;13(1):1-13. [PubMed:18389894]
  2. Tremblay CL: Combating HIV resistance - focus on darunavir. Ther Clin Risk Manag. 2008 Aug;4(4):759-66. [PubMed:19209258]
  3. Koh Y, Matsumi S, Das D, Amano M, Davis DA, Li J, Leschenko S, Baldridge A, Shioda T, Yarchoan R, Ghosh AK, Mitsuya H: Potent inhibition of HIV-1 replication by novel non-peptidyl small molecule inhibitors of protease dimerization. J Biol Chem. 2007 Sep 28;282(39):28709-20. Epub 2007 Jul 17. [PubMed:17635930]
  4. Kovalevsky AY, Tie Y, Liu F, Boross PI, Wang YF, Leshchenko S, Ghosh AK, Harrison RW, Weber IT: Effectiveness of nonpeptide clinical inhibitor TMC-114 on HIV-1 protease with highly drug resistant mutations D30N, I50V, and L90M. J Med Chem. 2006 Feb 23;49(4):1379-87. [PubMed:16480273]
  5. De Meyer S, Azijn H, Surleraux D, Jochmans D, Tahri A, Pauwels R, Wigerinck P, de Bethune MP: TMC114, a novel human immunodeficiency virus type 1 protease inhibitor active against protease inhibitor-resistant viruses, including a broad range of clinical isolates. Antimicrob Agents Chemother. 2005 Jun;49(6):2314-21. [PubMed:15917527]
  6. Link [Link]
External Links
Human Metabolome Database
HMDB0015393
KEGG Drug
D03656
PubChem Compound
213039
PubChem Substance
46506908
ChemSpider
184733
BindingDB
8125
ChEBI
367163
ChEMBL
CHEMBL1323
Therapeutic Targets Database
DAP001086
PharmGKB
PA163522472
HET
017
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Darunavir
ATC Codes
J05AR14 — Darunavir and cobicistatJ05AE10 — DarunavirG01AE10 — Combinations of sulfonamides
AHFS Codes
  • 08:18.08.08 — HIV Protease Inhibitors
PDB Entries
1t3r / 1t7i / 2f80 / 2f81 / 2f8g / 2hs1 / 2hs2 / 2idw / 2ien / 2ieo
show 44 more
FDA label
Download (281 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableHealthy Volunteers1
1CompletedNot AvailableHepatitis C Viral Infection1
1CompletedBasic ScienceHealthy Volunteers1
1CompletedBasic ScienceHealthy Volunteers / Human Immunodeficiency Virus (HIV) Infections1
1CompletedBasic ScienceHuman Immunodeficiency Virus (HIV) Infections / Human Immunodeficiency Virus Infection(HIV)/Acquired Immunodeficiency Syndrome (AIDS)1
1CompletedBasic ScienceInfection, Human Immunodeficiency Virus I1
1CompletedHealth Services ResearchHuman Immunodeficiency Virus (HIV)1
1CompletedOtherHuman Immunodeficiency Virus (HIV) Infections / Human Immunodeficiency Virus Infection(HIV)/Acquired Immunodeficiency Syndrome (AIDS)1
1CompletedPreventionAsthma Bronchial / Human Immunodeficiency Virus (HIV)1
1CompletedTreatmentAcquired Immune Deficiency Syndrome (AIDS) / Human Immunodeficiency Virus (HIV)1
1CompletedTreatmentDrug-drug Interaction Study / Human Immunodeficiency Virus (HIV) Infections1
1CompletedTreatmentHIV-I1
1CompletedTreatmentHealthy Participants1
1CompletedTreatmentHealthy Volunteers7
1CompletedTreatmentHepatitis C Viral Infection / Human Immunodeficiency Virus (HIV) / Telaprevir1
1CompletedTreatmentHepatitis C Virus (HCV) Infection1
1CompletedTreatmentHuman Immunodeficiency Virus (HIV)3
1CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections3
1CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Opioid Dependency1
1CompletedTreatmentHuman Immunodeficiency Virus Type 1 (HIV-1)1
1CompletedTreatmentInsulin Resistance1
1CompletedTreatmentPharmacokinetics1
1Enrolling by InvitationTreatmentAmyotrophic Lateral Sclerosis (ALS)1
1RecruitingOtherHealthy Volunteers1
1Unknown StatusNot AvailableHuman Immunodeficiency Virus (HIV) / Hyperlipidemias1
1, 2CompletedTreatmentAcute HIV Infection1
1, 2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
1, 2Unknown StatusTreatmentHuman Immunodeficiency Virus (HIV) Infections1
2Active Not RecruitingTreatmentHIV-1-infection1
2Active Not RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections1
2Active Not RecruitingTreatmentInfection, Human Immunodeficiency Virus I1
2CompletedTreatmentAcquired Immune Deficiency Syndrome (AIDS) / Human Immunodeficiency Virus (HIV) Infections1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV)3
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections5
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Human Immunodeficiency Virus Type 1 (HIV-1)1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Infection, Human Immunodeficiency Virus I1
2CompletedTreatmentHuman Immunodeficiency Virus Type 1 (HIV-1)2
2CompletedTreatmentInfection, Human Immunodeficiency Virus I4
2Not Yet RecruitingTreatmentContraception / Human Immunodeficiency Virus (HIV)1
2RecruitingTreatmentContraception / HIV-1-infection1
2, 3CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
2, 3RecruitingTreatmentAcquired Immune Deficiency Syndrome (AIDS) / Human Immunodeficiency Virus (HIV) Infections1
2, 3WithdrawnTreatmentHuman Immunodeficiency Virus Infection(HIV)/Acquired Immunodeficiency Syndrome (AIDS)1
3Active Not RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections1
3Active Not RecruitingTreatmentHuman Immunodeficiency Virus Type 1 (HIV-1)1
3Active Not RecruitingTreatmentInfection, Human Immunodeficiency Virus I3
3Approved for MarketingNot AvailableHuman Immunodeficiency Virus (HIV) Infections1
3CompletedTreatmentAcquired Immunodeficiency Syndrome Virus / AIDS Virus / Human Immunodeficiency Virus (HIV) / Human Immunodeficiency Virus (HIV) Infections1
3CompletedTreatmentAcquired Immune Deficiency Syndrome (AIDS) / Human Immunodeficiency Virus (HIV) Infections2
3CompletedTreatmentAcquired Immunodeficiency Syndrome (AIDS) Virus / Human Immunodeficiency Virus (HIV) Infections1
3CompletedTreatmentHuman Immunodeficiency Virus (HIV)2
3CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections7
3CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Infection, Human Immunodeficiency Virus I1
3CompletedTreatmentHuman Immunodeficiency Virus (HIV) / Human Immunodeficiency Virus (HIV) Infections1
3CompletedTreatmentHuman Immunodeficiency Virus (HIV) / Human Immunodeficiency Virus (HIV) Infections / Pregnancy1
3CompletedTreatmentHuman Immunodeficiency Virus (HIV) / Infectious1
3CompletedTreatmentHuman Immunodeficiency Virus Infection(HIV)/Acquired Immunodeficiency Syndrome (AIDS)1
3CompletedTreatmentHuman Immunodeficiency Virus Type 1 (HIV-1)1
3CompletedTreatmentInfection, Human Immunodeficiency Virus I2
3Not Yet RecruitingTreatmentHuman Immunodeficiency Virus Infection(HIV)/Acquired Immunodeficiency Syndrome (AIDS)1
3RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections1
3TerminatedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
3TerminatedTreatmentHuman Immunodeficiency Virus Type 1 (HIV-1)1
3TerminatedTreatmentInfection, Human Immunodeficiency Virus I / Treatment Resistant Disorders / Viral sepsis1
3WithdrawnTreatmentHuman Immunodeficiency Virus (HIV)1
4Active Not RecruitingOtherInfection, Human Immunodeficiency Virus I1
4Active Not RecruitingTreatmentAcquired Immune Deficiency Syndrome Virus1
4Active Not RecruitingTreatmentInfection, Human Immunodeficiency Virus I1
4CompletedNot AvailableAcquired Immune Deficiency Syndrome (AIDS)1
4CompletedNot AvailableHealthy Volunteers1
4CompletedNot AvailableHuman Immunodeficiency Virus (HIV)2
4CompletedNot AvailableHuman Immunodeficiency Virus (HIV) / Proteinuria1
4CompletedOtherHealthy Volunteers1
4CompletedTreatmentCardiovascular Disease (CVD) / Human Immunodeficiency Virus (HIV)1
4CompletedTreatmentHealthy Volunteers1
4CompletedTreatmentHuman Immunodeficiency Virus (HIV)2
4CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections4
4CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Hyperlipidemias1
4CompletedTreatmentHuman Immunodeficiency Virus Type 1 (HIV-1)2
4CompletedTreatmentImmunosuppression-related Infectious Disease / Infection, Human Immunodeficiency Virus I1
4CompletedTreatmentInfection, Human Immunodeficiency Virus I1
4Not Yet RecruitingTreatmentHIV test positive1
4Not Yet RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections2
4RecruitingTreatmentAntiretroviral Therapy Intolerance / Patients Compliance1
4RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections2
4TerminatedTreatmentAIDS-Related Dementia Complex1
4TerminatedTreatmentAcute HIV Infection / Human Immunodeficiency Virus (HIV) Infections1
4TerminatedTreatmentHuman Immunodeficiency Virus (HIV)1
4TerminatedTreatmentHuman Immunodeficiency Virus (HIV) / Human Immunodeficiency Virus (HIV) Infections1
4Unknown StatusTreatmentAcquired Immune Deficiency Syndrome (AIDS) / HIV-1 Adults Patients / Triple Class Failure1
4WithdrawnNot AvailableHuman Immunodeficiency Virus Type 1 (HIV-1)1
Not AvailableCompletedNot AvailableHIV Integrase, HIV Protease1
Not AvailableCompletedNot AvailableHuman Immunodeficiency Virus (HIV) Infections3
Not AvailableCompletedNot AvailableInfection, Human Immunodeficiency Virus I1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
Not AvailableRecruitingNot AvailableHuman Immunodeficiency Virus (HIV)1
Not AvailableRecruitingNot AvailableMinor Patient Treated by One or More Antiretroviral and for Which a Blood Test Has Been Performed1
Not AvailableRecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections1
Not AvailableUnknown StatusBasic ScienceHuman Immunodeficiency Virus (HIV) Infections1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • A-S Medication Solutions LLC
  • Centocor Ortho Biotech Inc.
  • Janssen-Ortho Inc.
  • Lake Erie Medical and Surgical Supply
  • Physicians Total Care Inc.
  • Quality Care
  • Remedy Repack
Dosage forms
FormRouteStrength
TabletOral400 mg
TabletOral
SuspensionOral100 mg/ml
SuspensionOral100 mg
SuspensionOral100 mg/1mL
TabletOral150 mg
TabletOral300 mg
TabletOral600 mg
TabletOral75 mg
TabletOral800 mg
Tablet, film coatedOral150 mg
Tablet, film coatedOral150 mg/1
Tablet, film coatedOral300 mg/1
Tablet, film coatedOral300 mg
Tablet, film coatedOral400 mg/1
Tablet, film coatedOral400 mg
Tablet, film coatedOral600 mg/1
Tablet, film coatedOral600 mg
Tablet, film coatedOral75 mg/1
Tablet, film coatedOral75 mg
Tablet, film coatedOral800 mg
Tablet, film coatedOral800 mg/1
Tablet, film coatedOral
Prices
Unit descriptionCostUnit
Prezista 600 mg tablet25.75USD tablet
Prezista 400 mg tablet18.74USD tablet
Prezista 300 mg tablet16.2USD tablet
Prezista 150 mg tablet4.59USD tablet
Prezista 75 mg tablet2.3USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6335460No2002-01-012012-08-25Us
CA2469343No2008-05-132022-12-12Canada
CA2224738No2002-08-272016-06-28Canada
US6703403Yes2004-03-092016-12-26Us
US6037157Yes2000-03-142016-12-26Us
US6642245Yes2003-11-042021-05-04Us
US6703396Yes2004-03-092021-09-09Us
US5843946Yes1998-12-012016-06-01Us
US7470506Yes2008-12-302019-12-23Us
USRE43802Yes2012-11-132017-04-19Us
US8597876Yes2013-12-032019-12-23Us
US7700645Yes2010-04-202027-06-26Us
USRE42889Yes2011-11-012017-04-19Us
US8518987Yes2013-08-272024-08-16Us
USRE43596Yes2012-08-212017-11-09Us
US8148374No2012-04-032029-09-03Us
US9296769No2016-03-292032-08-15Us
US7803788No2010-09-282022-02-02Us
US8754065No2014-06-172032-08-15Us
US7390791No2008-06-242022-05-07Us
US9889115No2018-02-132019-06-23Us
US10039718No2012-10-042032-10-04Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityApproximately 0.15 mg/mL at 20 °C as ethanolate saltNot Available
logP1.8Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0668 mg/mLALOGPS
logP1.76ALOGPS
logP2.82ChemAxon
logS-3.9ALOGPS
pKa (Strongest Acidic)13.59ChemAxon
pKa (Strongest Basic)2.39ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area140.42 Å2ChemAxon
Rotatable Bond Count11ChemAxon
Refractivity142.34 m3·mol-1ChemAxon
Polarizability57.24 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9636
Blood Brain Barrier-0.5518
Caco-2 permeable+0.7274
P-glycoprotein substrateSubstrate0.7464
P-glycoprotein inhibitor IInhibitor0.7588
P-glycoprotein inhibitor IINon-inhibitor0.8683
Renal organic cation transporterNon-inhibitor0.8847
CYP450 2C9 substrateNon-substrate0.5747
CYP450 2D6 substrateSubstrate0.6809
CYP450 3A4 substrateSubstrate0.6496
CYP450 1A2 substrateNon-inhibitor0.7328
CYP450 2C9 inhibitorNon-inhibitor0.6999
CYP450 2D6 inhibitorNon-inhibitor0.8784
CYP450 2C19 inhibitorNon-inhibitor0.6587
CYP450 3A4 inhibitorNon-inhibitor0.5076
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7132
Ames testNon AMES toxic0.5933
CarcinogenicityNon-carcinogens0.7991
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.5482 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9824
hERG inhibition (predictor II)Non-inhibitor0.857
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-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0aor-0900800000-e427a102e3a7551cc732
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0a4i-0900000000-8ab8c2b3421f4a277282
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0a4i-2900000000-eddacc917eaf16abe9d2
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0a4i-2900000000-86c785caeafe3b4a10c3
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0a4l-5900000000-69bc90a59383cb5a804b
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0a4l-8900000000-f481d0932a99692c87d9
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-000g-0009760000-f730e27547a482694ebc
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0006-0009000000-fcd18a6f4e9084f0f8f1
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0006-0469000000-716a2ae87ad9df6765fb
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0a4i-0941000000-5e0dbe51025009642b33
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0a4i-0910000000-2411514d55bfa3c4e81f
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0006-2309000000-e6767f5d8648334c41c9
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-9621000000-3a7c794f5e3f473b9ad5
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-9400000000-16b363cdd836532460ce
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4i-2900000000-98bfa9c688e4cb2dbbc3
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4l-4900000000-05c5a10ff111a5d1c9bf
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-052f-6900000000-f59c1c0d97f0a8ab00d7

Taxonomy

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 / Furofurans / Organosulfonamides / Tetrahydrofurans / Aminosulfonyl compounds / Carbamate esters / Secondary alcohols
show 8 more
Substituents
Aminobenzenesulfonamide / Phenylbutylamine / Amphetamine or derivatives / Benzenesulfonyl group / Furofuran / Aniline or substituted anilines / Organosulfonic acid amide / Organic sulfonic acid or derivatives / Organosulfonic acid or derivatives / Sulfonyl
show 21 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
carbamate ester, sulfonamide, furofuran (CHEBI:367163)

Targets

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. Dierynck I, De Wit M, Gustin E, Keuleers I, Vandersmissen J, Hallenberger S, Hertogs K: Binding kinetics of darunavir to human immunodeficiency virus type 1 protease explain the potent antiviral activity and high genetic barrier. J Virol. 2007 Dec;81(24):13845-51. Epub 2007 Oct 10. [PubMed:17928344]
  2. Ghosh AK, Dawson ZL, Mitsuya H: Darunavir, a conceptually new HIV-1 protease inhibitor for the treatment of drug-resistant HIV. Bioorg Med Chem. 2007 Dec 15;15(24):7576-80. Epub 2007 Sep 14. [PubMed:17900913]
  3. Wang YF, Tie Y, Boross PI, Tozser J, Ghosh AK, Harrison RW, Weber IT: Potent new antiviral compound shows similar inhibition and structural interactions with drug resistant mutants and wild type HIV-1 protease. J Med Chem. 2007 Sep 6;50(18):4509-15. Epub 2007 Aug 16. [PubMed:17696515]
  4. McKeage K, Perry CM, Keam SJ: Darunavir: a review of its use in the management of HIV infection in adults. Drugs. 2009;69(4):477-503. doi: 10.2165/00003495-200969040-00007. [PubMed:19323590]
  5. Tremblay CL: Combating HIV resistance - focus on darunavir. Ther Clin Risk Manag. 2008 Aug;4(4):759-66. [PubMed:19209258]
  6. Kovalevsky AY, Tie Y, Liu F, Boross PI, Wang YF, Leshchenko S, Ghosh AK, Harrison RW, Weber IT: Effectiveness of nonpeptide clinical inhibitor TMC-114 on HIV-1 protease with highly drug resistant mutations D30N, I50V, and L90M. J Med Chem. 2006 Feb 23;49(4):1379-87. [PubMed:16480273]
  7. De Meyer S, Azijn H, Surleraux D, Jochmans D, Tahri A, Pauwels R, Wigerinck P, de Bethune MP: TMC114, a novel human immunodeficiency virus type 1 protease inhibitor active against protease inhibitor-resistant viruses, including a broad range of clinical isolates. Antimicrob Agents Chemother. 2005 Jun;49(6):2314-21. [PubMed:15917527]
  8. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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. McKeage K, Perry CM, Keam SJ: Darunavir: a review of its use in the management of HIV infection in adults. Drugs. 2009;69(4):477-503. doi: 10.2165/00003495-200969040-00007. [PubMed:19323590]
  2. Tremblay CL: Combating HIV resistance - focus on darunavir. Ther Clin Risk Manag. 2008 Aug;4(4):759-66. [PubMed:19209258]
  3. Busse KH, Penzak SR: Darunavir: a second-generation protease inhibitor. Am J Health Syst Pharm. 2007 Aug 1;64(15):1593-602. doi: 10.2146/ajhp060668. [PubMed:17646561]
  4. Brown KC, Paul S, Kashuba AD: Drug interactions with new and investigational antiretrovirals. Clin Pharmacokinet. 2009;48(4):211-41. [PubMed:19492868]

Transporters

Kind
Protein
Organism
Human
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. Annaert P, Ye ZW, Stieger B, Augustijns P: Interaction of HIV protease inhibitors with OATP1B1, 1B3, and 2B1. Xenobiotica. 2010 Mar;40(3):163-76. doi: 10.3109/00498250903509375. [PubMed:20102298]
  2. Darunavir FDA [File]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
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. Darunavir FDA label [File]

Drug created on May 16, 2007 11:43 / Updated on December 11, 2018 09:50