U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C31H33F3N2O5S
Molecular Weight 602.664
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TIPRANAVIR

SMILES

CCC[C@@]2(CCC1=CC=CC=C1)CC(O)=C([C@H](CC)C3=CC=CC(NS(=O)(=O)C4=NC=C(C=C4)C(F)(F)F)=C3)C(=O)O2

InChI

InChIKey=SUJUHGSWHZTSEU-FYBSXPHGSA-N
InChI=1S/C31H33F3N2O5S/c1-3-16-30(17-15-21-9-6-5-7-10-21)19-26(37)28(29(38)41-30)25(4-2)22-11-8-12-24(18-22)36-42(39,40)27-14-13-23(20-35-27)31(32,33)34/h5-14,18,20,25,36-37H,3-4,15-17,19H2,1-2H3/t25-,30-/m1/s1

HIDE SMILES / InChI
Molecular Formula C31H33F3N2O5S
Molecular Weight 602.664
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
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/16802849 | https://www.ncbi.nlm.nih.gov/pubmed/9719600 | http://adisinsight.springer.com/drugs/800008750

Tipranavir (PNU-140690, trade mark APTIVUS) is a potent, orally bioavailable nonpeptidic HIV protease inhibitor of the 5,6-dihydro-4-hydroxy-2-pyrone sulfonamide class. Tipranavir has potent in vitro activity against a variety of HIV-1 laboratory strains and clinical isolates, including those resistant to ritonavir, as well as HIV-2. The drug is launched in several countries, including the US and in the EU. APTIVUS, co-administered with ritonavir, is indicated for combination antiretroviral treatment of HIV-1 infected patients who are treatment-experienced and infected with HIV-1 strains resistant to more than one protease inhibitor.

CNS Activity

CNS Non-penetrant
1040
Curator's Comment: Tipranavir do not reach therapeutical concentrations in CSF

Originator

Pfizer
420
Curator's Comment: # Pharmacia & Upjohn (now Pfizer)

Approval Year

2005
130
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8504
 8.0 pM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Approved
8583
APTIVUS

Approved Use

APTIVUS, co-administered with ritonavir, is indicated for combination antiretroviral treatment of HIV-1 infected patients who are treatment-experienced and infected with HIV-1 strains resistant to more than one protease inhibitor (PI). This indication is based on analyses of plasma HIV-1 RNA levels in two controlled studies of APTIVUS/ritonavir of 48 weeks duration in treatment-experienced adults and one open-label 48-week study in pediatric patients age 2 to 18 years. The adult studies were conducted in clinically advanced, 3-class antiretroviral (NRTI, NNRTI, PI) treatment-experienced adults with evidence of HIV-1 replication despite ongoing antiretroviral therapy. The following points should be considered when initiating therapy with APTIVUS/ritonavir: The use of APTIVUS/ritonavir in treatment-naïve patients is not recommended [ see Warnings and Precautions (5.1)

Launch Date

2005
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
94.8 μM
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021814s011lbl.pdf
500 mg 2 times / day steady-state, oral
dose: 500 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: Ritonavir
Ritonavir
 TIPRANAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE
food status: FED
77.6 μM
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021814s011lbl.pdf
500 mg 2 times / day steady-state, oral
dose: 500 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: Ritonavir
Ritonavir
 TIPRANAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: FED
135 μM
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021814s011lbl.pdf
375 mg/m² 2 times / day steady-state, oral
dose: 375 mg/m²
route of administration: Oral
experiment type: STEADY-STATE
co-administered: Ritonavir
Ritonavir
 TIPRANAVIR plasma
Homo sapiens
population: UNHEALTHY
age: CHILD
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
851 μM × h
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021814s011lbl.pdf
500 mg 2 times / day steady-state, oral
dose: 500 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: Ritonavir
Ritonavir
 TIPRANAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE
food status: FED
710 μM × h
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021814s011lbl.pdf
500 mg 2 times / day steady-state, oral
dose: 500 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: Ritonavir
Ritonavir
 TIPRANAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: FED
1190 μM × h
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021814s011lbl.pdf
375 mg/m² 2 times / day steady-state, oral
dose: 375 mg/m²
route of administration: Oral
experiment type: STEADY-STATE
co-administered: Ritonavir
Ritonavir
 TIPRANAVIR plasma
Homo sapiens
population: UNHEALTHY
age: CHILD
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
5.5 h
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021814s011lbl.pdf
500 mg 2 times / day steady-state, oral
dose: 500 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: Ritonavir
Ritonavir
 TIPRANAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE
food status: FED
6 h
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021814s011lbl.pdf
500 mg 2 times / day steady-state, oral
dose: 500 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: Ritonavir
Ritonavir
 TIPRANAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: MALE
food status: FED
8.1 h
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021814s011lbl.pdf
375 mg/m² 2 times / day steady-state, oral
dose: 375 mg/m²
route of administration: Oral
experiment type: STEADY-STATE
co-administered: Ritonavir
Ritonavir
 TIPRANAVIR plasma
Homo sapiens
population: UNHEALTHY
age: CHILD
sex: FEMALE / MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
0.1%
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021814s011lbl.pdf
500 mg 2 times / day steady-state, oral
dose: 500 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: Ritonavir
Ritonavir
 TIPRANAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE
food status: FED
Doses

Doses

DosePopulationAdverse events​
500 mg 2 times / day multiple, oral
Recommended
Dose: 500 mg, 2 times / day
Route: oral
Route: multiple
Dose: 500 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/26730818
unhealthy, 18–65
Health Status: unhealthy
Age Group: 18–65
Sex: M+F
Sources:
https://pubmed.ncbi.nlm.nih.gov/26730818
Disc. AE: Gastrointestinal disorder NOS, Gastrointestinal disorder NOS...
AEs leading to
discontinuation/dose reduction:
Gastrointestinal disorder NOS (grade 1, 1%)
Gastrointestinal disorder NOS (moderate, 2.1%)
Gastrointestinal disorder NOS (severe, 1%)
Transaminases increased (grade 1, 1%)
Transaminases increased (moderate, 1.6%)
Transaminases increased (severe, 4.8%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/26730818
1200 mg 2 times / day multiple, oral
Highest studied dose
Dose: 1200 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1200 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/15097154
unhealthy, 35.2
Health Status: unhealthy
Age Group: 35.2
Sex: M+F
Sources:
https://pubmed.ncbi.nlm.nih.gov/15097154
Sources:
https://pubmed.ncbi.nlm.nih.gov/15097154
500 mg 2 times / day multiple, oral
Recommended
Dose: 500 mg, 2 times / day
Route: oral
Route: multiple
Dose: 500 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021814s011lbl.pdf
unhealthy
Health Status: unhealthy
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021814s011lbl.pdf
Disc. AE: Hepatitis, Hepatic decompensation...
AEs leading to
discontinuation/dose reduction:
Hepatitis
Hepatic decompensation
Intracranial hemorrhage
Platelet aggregation
Coagulation abnormal
Diabetes mellitus
Hyperglycemia
Immune reconstitution syndrome
Fat redistribution
Lipids increased
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021814s011lbl.pdf
500 mg 2 times / day multiple, oral
Recommended
Dose: 500 mg, 2 times / day
Route: oral
Route: multiple
Dose: 500 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021814s011lbl.pdf
unhealthy
Health Status: unhealthy
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021814s011lbl.pdf
Disc. AE: Rash...
AEs leading to
discontinuation/dose reduction:
Rash (0.5%)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021814s011lbl.pdf
AEs

AEs

AESignificanceDosePopulation
Gastrointestinal disorder NOS grade 1, 1%
Disc. AE
500 mg 2 times / day multiple, oral
Recommended
Dose: 500 mg, 2 times / day
Route: oral
Route: multiple
Dose: 500 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/26730818
unhealthy, 18–65
Health Status: unhealthy
Age Group: 18–65
Sex: M+F
Sources:
https://pubmed.ncbi.nlm.nih.gov/26730818
Transaminases increased grade 1, 1%
Disc. AE
500 mg 2 times / day multiple, oral
Recommended
Dose: 500 mg, 2 times / day
Route: oral
Route: multiple
Dose: 500 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/26730818
unhealthy, 18–65
Health Status: unhealthy
Age Group: 18–65
Sex: M+F
Sources:
https://pubmed.ncbi.nlm.nih.gov/26730818
Transaminases increased moderate, 1.6%
Disc. AE
500 mg 2 times / day multiple, oral
Recommended
Dose: 500 mg, 2 times / day
Route: oral
Route: multiple
Dose: 500 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/26730818
unhealthy, 18–65
Health Status: unhealthy
Age Group: 18–65
Sex: M+F
Sources:
https://pubmed.ncbi.nlm.nih.gov/26730818
Gastrointestinal disorder NOS moderate, 2.1%
Disc. AE
500 mg 2 times / day multiple, oral
Recommended
Dose: 500 mg, 2 times / day
Route: oral
Route: multiple
Dose: 500 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/26730818
unhealthy, 18–65
Health Status: unhealthy
Age Group: 18–65
Sex: M+F
Sources:
https://pubmed.ncbi.nlm.nih.gov/26730818
Gastrointestinal disorder NOS severe, 1%
Disc. AE
500 mg 2 times / day multiple, oral
Recommended
Dose: 500 mg, 2 times / day
Route: oral
Route: multiple
Dose: 500 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/26730818
unhealthy, 18–65
Health Status: unhealthy
Age Group: 18–65
Sex: M+F
Sources:
https://pubmed.ncbi.nlm.nih.gov/26730818
Transaminases increased severe, 4.8%
Disc. AE
500 mg 2 times / day multiple, oral
Recommended
Dose: 500 mg, 2 times / day
Route: oral
Route: multiple
Dose: 500 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/26730818
unhealthy, 18–65
Health Status: unhealthy
Age Group: 18–65
Sex: M+F
Sources:
https://pubmed.ncbi.nlm.nih.gov/26730818
Coagulation abnormal Disc. AE
500 mg 2 times / day multiple, oral
Recommended
Dose: 500 mg, 2 times / day
Route: oral
Route: multiple
Dose: 500 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021814s011lbl.pdf
unhealthy
Health Status: unhealthy
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021814s011lbl.pdf
Diabetes mellitus Disc. AE
500 mg 2 times / day multiple, oral
Recommended
Dose: 500 mg, 2 times / day
Route: oral
Route: multiple
Dose: 500 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021814s011lbl.pdf
unhealthy
Health Status: unhealthy
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021814s011lbl.pdf
Fat redistribution Disc. AE
500 mg 2 times / day multiple, oral
Recommended
Dose: 500 mg, 2 times / day
Route: oral
Route: multiple
Dose: 500 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021814s011lbl.pdf
unhealthy
Health Status: unhealthy
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021814s011lbl.pdf
Hepatic decompensation Disc. AE
500 mg 2 times / day multiple, oral
Recommended
Dose: 500 mg, 2 times / day
Route: oral
Route: multiple
Dose: 500 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021814s011lbl.pdf
unhealthy
Health Status: unhealthy
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021814s011lbl.pdf
Hepatitis Disc. AE
500 mg 2 times / day multiple, oral
Recommended
Dose: 500 mg, 2 times / day
Route: oral
Route: multiple
Dose: 500 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021814s011lbl.pdf
unhealthy
Health Status: unhealthy
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021814s011lbl.pdf
Hyperglycemia Disc. AE
500 mg 2 times / day multiple, oral
Recommended
Dose: 500 mg, 2 times / day
Route: oral
Route: multiple
Dose: 500 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021814s011lbl.pdf
unhealthy
Health Status: unhealthy
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021814s011lbl.pdf
Immune reconstitution syndrome Disc. AE
500 mg 2 times / day multiple, oral
Recommended
Dose: 500 mg, 2 times / day
Route: oral
Route: multiple
Dose: 500 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021814s011lbl.pdf
unhealthy
Health Status: unhealthy
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021814s011lbl.pdf
Intracranial hemorrhage Disc. AE
500 mg 2 times / day multiple, oral
Recommended
Dose: 500 mg, 2 times / day
Route: oral
Route: multiple
Dose: 500 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021814s011lbl.pdf
unhealthy
Health Status: unhealthy
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021814s011lbl.pdf
Lipids increased Disc. AE
500 mg 2 times / day multiple, oral
Recommended
Dose: 500 mg, 2 times / day
Route: oral
Route: multiple
Dose: 500 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021814s011lbl.pdf
unhealthy
Health Status: unhealthy
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021814s011lbl.pdf
Platelet aggregation Disc. AE
500 mg 2 times / day multiple, oral
Recommended
Dose: 500 mg, 2 times / day
Route: oral
Route: multiple
Dose: 500 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021814s011lbl.pdf
unhealthy
Health Status: unhealthy
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021814s011lbl.pdf
Rash 0.5%
Disc. AE
500 mg 2 times / day multiple, oral
Recommended
Dose: 500 mg, 2 times / day
Route: oral
Route: multiple
Dose: 500 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021814s011lbl.pdf
unhealthy
Health Status: unhealthy
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021814s011lbl.pdf
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
inhibitor
2252

substrate
1946

inducer
1087
inducer
440

inhibitor
2438
inhibitor
2507

substrate
1388
inhibitor
2217

OverviewOther

Other InhibitorOther SubstrateOther Inducer
CYP3A
227

P-gp
1741

CYP1A2
2153

CYP2C19
2057

OATP2B1
157

UGT enzymes
4

Ca2+ channels
59
P-gp
2052
P-gp
301

CYP1A2
832

UGT enzymes
2

CYP2C19
329
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP1A2
2333
 inconclusive
CYP2C19
2141
 inconclusive
CYP2C9
2497
 inconclusive
Ca2+ channels
62
 inconclusive
UGT enzymes
4
 inconclusive
UGT enzymes
4
 inconclusive
P-gp
1932
 likely
CYP2D6
2546
 moderate [IC50 16.3 uM]
yes (co-administration study)
Comment: coadministration with dextromethorphan led to potent inhibition of CYP2D5
Page: 100.0
CYP3A4
2633
 moderate
P-gp
1932
 weak
CYP2C9
2497
 yes [IC50 0.26 uM]
no (co-administration study)
Comment: coadministration with warfarin had no effect
Page: 100.0
CYP3A4
2633
 yes [IC50 2.3 uM]
CYP2C19
2141
 yes [IC50 2.7 uM]
CYP1A2
2333
 yes [IC50 >50 uM]
yes (co-administration study)
Comment: coadministration with caffeine led to moderate induction at steady state
Page: 100.0
CYP3A
317
 yes
OATP2B1
162
 yes
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
CYP2D6
1388
 no
P-gp
2052
 yes
CYP3A4
1946
 yes
yes (co-administration study)
Comment: coadministration with ketaconazole inhibited the metabolism of tipranavir by 90%
Page: 96.0
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
2263
Sourcing

Sourcing

Vendor/AggregatorIDURL
ChEBI
CHEBI:63628
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:63628
ChemicalBook
CB9501005
https://www.chemicalbook.com/ChemicalProductProperty_EN_CB9501005
eMolecules
36754763
https://www.emolecules.com/cgi-bin/more?vid=36754763
MolPort
MolPort-003-850-561
https://www.molport.com/shop/molecule-link/MolPort-003-850-561
ZINC
ZINC000100016058
http://zinc15.docking.org/substances/ZINC000100016058
PubMed

PubMed

TitleDatePubMed
Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11).
2013-12
P2' benzene carboxylic acid moiety is associated with decrease in cellular uptake: evaluation of novel nonpeptidic HIV-1 protease inhibitors containing P2 bis-tetrahydrofuran moiety.
2013-10
Substrate envelope-designed potent HIV-1 protease inhibitors to avoid drug resistance.
2013-09-19
GRL-0519, a novel oxatricyclic ligand-containing nonpeptidic HIV-1 protease inhibitor (PI), potently suppresses replication of a wide spectrum of multi-PI-resistant HIV-1 variants in vitro.
2013-05
Novel method to assess antiretroviral target trough concentrations using in vitro susceptibility data.
2012-11
Activity of human immunodeficiency virus type 1 protease inhibitors against the initial autocleavage in Gag-Pol polyprotein processing.
2012-07
In vitro activity of antiretroviral drugs against Plasmodium falciparum.
2011-11
Novel protease inhibitors (PIs) containing macrocyclic components and 3(R),3a(S),6a(R)-bis-tetrahydrofuranylurethane that are potent against multi-PI-resistant HIV-1 variants in vitro.
2010-08
Evaluating the substrate-envelope hypothesis: structural analysis of novel HIV-1 protease inhibitors designed to be robust against drug resistance.
2010-05
Hepatic profile analyses of tipranavir in Phase II and III clinical trials.
2009-12-14
Cytotoxicological analysis of a gp120 binding aptamer with cross-clade human immunodeficiency virus type 1 entry inhibition properties: comparison to conventional antiretrovirals.
2009-07
Intracranial hemorrhage and liver-associated deaths associated with tipranavir/ritonavir: review of cases from the FDA's Adverse Event Reporting System.
2008-11
Characterization of a novel human immunodeficiency virus type 1 protease inhibitor, A-790742.
2008-04
Tipranavir: the first nonpeptidic protease inhibitor for the treatment of protease resistance.
2007-11
Potent inhibition of HIV-1 replication by novel non-peptidyl small molecule inhibitors of protease dimerization.
2007-09-28
Tipranavir: a new option for the treatment of drug-resistant HIV infection.
2007-09-15
Susceptibility to protease inhibitors in HIV-2 primary isolates from patients failing antiretroviral therapy.
2006-04
Tipranavir: PNU 140690, tipranivir.
2006
Selection and characterization of HIV-1 showing reduced susceptibility to the non-peptidic protease inhibitor tipranavir.
2005-10
Design of HIV-1 protease inhibitors active on multidrug-resistant virus.
2005-03-24
Analysis of protease inhibitor combinations in vitro: activity of lopinavir, amprenavir and tipranavir against HIV type 1 wild-type and drug-resistant isolates.
2004-03
In vitro antiviral interaction of lopinavir with other protease inhibitors.
2002-07
Two sulfonamides-containing dihydropyrone derivatives as HIV protease inhibitors.
2001-07
6-Hydroxy-1,3-dioxin-4-ones as non-peptidic HIV protease inhibitors.
2000-12-04
Tipranavir inhibits broadly protease inhibitor-resistant HIV-1 clinical samples.
2000-09-08
In-vitro tipranavir susceptibility of HIV-1 isolates with reduced susceptibility to other protease inhibitors.
2000-01-07
Tipranavir (PNU-140690): a potent, orally bioavailable nonpeptidic HIV protease inhibitor of the 5,6-dihydro-4-hydroxy-2-pyrone sulfonamide class.
1998-08-27
In vitro combination of PNU-140690, a human immunodeficiency virus type 1 protease inhibitor, with ritonavir against ritonavir-sensitive and -resistant clinical isolates.
1997-11
Antiviral activity of the dihydropyrone PNU-140690, a new nonpeptidic human immunodeficiency virus protease inhibitor.
1997-05
Structure-based design of HIV protease inhibitors: sulfonamide-containing 5,6-dihydro-4-hydroxy-2-pyrones as non-peptidic inhibitors.
1996-10-25
Patents

Patents

20010044451
27
JP2006511554A
19
JP2006512339A
22
JP2007516260A
16
JP2007536237A
19
JP2009525265A
19
JP2009531441A
18
JP2010521465A
6
JP2011508747A
62
JP2011508748A
30
JP4676536B2
29
JP4738172B2
29

Sample Use Guides

In Vivo Use Guide
Adults: 500 mg APTIVUS® (tipranavir), co-administered with 200 mg ritonavir, twice daily. Pediatric patients (age 2 to 18 years): Dosing is based on body weight or body surface area not to exceed adult dose.
Route of Administration: Oral
In Vitro Use Guide
Tipranavir inhibits the replication of laboratory strains of HIV-1 and clinical isolates in acute models of T-cell infection, with EC50 ranging from 0.03 to 0.07 µM (18-42 ng/mL)
Substance Class Chemical
Created
by admin
on Mon Mar 31 18:28:09 GMT 2025
Edited
by admin
on Mon Mar 31 18:28:09 GMT 2025
Record UNII
ZZT404XD09
Record Status Validated (UNII)
Record Version
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Name Type Language
TIPRANAVIR
EMA EPAR   INN   MART.   MI   ORANGE BOOK   VANDF   WHO-DD  
INN  
Official Name English
APTIVUS
Preferred Name English
3'-((1R)-1-((6R)-5,6-DIHYDRO-4-HYDROXY-2-OXO-6-PHENETHYL-6-PROPYL-2H-PYRAN-3-YL)PROPYL)-5-(TRIFLUOROMETHYL)-2-PYRIDINESULFONANILIDE
Systematic Name English
TIPRANAVIR [MART.]
Common Name English
TIPRANAVIR [EMA EPAR]
Common Name English
TIPRANAVIR [ORANGE BOOK]
Common Name English
tipranavir [INN]
Common Name English
Tipranavir [WHO-DD]
Common Name English
TIPRANAVIR [VANDF]
Common Name English
TIPRANAVIR [MI]
Common Name English
Classification Tree Code System Code
NDF-RT N0000000246
Created by admin on Mon Mar 31 18:28:09 GMT 2025 , Edited by admin on Mon Mar 31 18:28:09 GMT 2025
NCI_THESAURUS C97366
Created by admin on Mon Mar 31 18:28:09 GMT 2025 , Edited by admin on Mon Mar 31 18:28:09 GMT 2025
EMA ASSESSMENT REPORTS APTIVUS (AUTHORIZED: HIV INFECTIONS)
Created by admin on Mon Mar 31 18:28:09 GMT 2025 , Edited by admin on Mon Mar 31 18:28:09 GMT 2025
WHO-VATC QJ05AE09
Created by admin on Mon Mar 31 18:28:09 GMT 2025 , Edited by admin on Mon Mar 31 18:28:09 GMT 2025
LIVERTOX NBK548389
Created by admin on Mon Mar 31 18:28:09 GMT 2025 , Edited by admin on Mon Mar 31 18:28:09 GMT 2025
WHO-ATC J05AE09
Created by admin on Mon Mar 31 18:28:09 GMT 2025 , Edited by admin on Mon Mar 31 18:28:09 GMT 2025
NDF-RT N0000175889
Created by admin on Mon Mar 31 18:28:09 GMT 2025 , Edited by admin on Mon Mar 31 18:28:09 GMT 2025
Code System Code Type Description
RXCUI
190548
Created by admin on Mon Mar 31 18:28:09 GMT 2025 , Edited by admin on Mon Mar 31 18:28:09 GMT 2025
PRIMARY RxNorm
CHEBI
63628
Created by admin on Mon Mar 31 18:28:09 GMT 2025 , Edited by admin on Mon Mar 31 18:28:09 GMT 2025
PRIMARY
CAS
174484-41-4
Created by admin on Mon Mar 31 18:28:09 GMT 2025 , Edited by admin on Mon Mar 31 18:28:09 GMT 2025
PRIMARY
SMS_ID
100000085237
Created by admin on Mon Mar 31 18:28:09 GMT 2025 , Edited by admin on Mon Mar 31 18:28:09 GMT 2025
PRIMARY
WIKIPEDIA
TIPRANAVIR
Created by admin on Mon Mar 31 18:28:09 GMT 2025 , Edited by admin on Mon Mar 31 18:28:09 GMT 2025
PRIMARY
PUBCHEM
54682461
Created by admin on Mon Mar 31 18:28:09 GMT 2025 , Edited by admin on Mon Mar 31 18:28:09 GMT 2025
PRIMARY
MESH
C107201
Created by admin on Mon Mar 31 18:28:09 GMT 2025 , Edited by admin on Mon Mar 31 18:28:09 GMT 2025
PRIMARY
LACTMED
Tipranavir
Created by admin on Mon Mar 31 18:28:09 GMT 2025 , Edited by admin on Mon Mar 31 18:28:09 GMT 2025
PRIMARY
FDA UNII
ZZT404XD09
Created by admin on Mon Mar 31 18:28:09 GMT 2025 , Edited by admin on Mon Mar 31 18:28:09 GMT 2025
PRIMARY
DAILYMED
ZZT404XD09
Created by admin on Mon Mar 31 18:28:09 GMT 2025 , Edited by admin on Mon Mar 31 18:28:09 GMT 2025
PRIMARY
HSDB
8083
Created by admin on Mon Mar 31 18:28:09 GMT 2025 , Edited by admin on Mon Mar 31 18:28:09 GMT 2025
PRIMARY
MERCK INDEX
m10885
Created by admin on Mon Mar 31 18:28:09 GMT 2025 , Edited by admin on Mon Mar 31 18:28:09 GMT 2025
PRIMARY Merck Index
ChEMBL
CHEMBL222559
Created by admin on Mon Mar 31 18:28:09 GMT 2025 , Edited by admin on Mon Mar 31 18:28:09 GMT 2025
PRIMARY
EVMPD
SUB04883MIG
Created by admin on Mon Mar 31 18:28:09 GMT 2025 , Edited by admin on Mon Mar 31 18:28:09 GMT 2025
PRIMARY
EPA CompTox
DTXSID6048622
Created by admin on Mon Mar 31 18:28:09 GMT 2025 , Edited by admin on Mon Mar 31 18:28:09 GMT 2025
PRIMARY
NCI_THESAURUS
C66603
Created by admin on Mon Mar 31 18:28:09 GMT 2025 , Edited by admin on Mon Mar 31 18:28:09 GMT 2025
PRIMARY
DRUG BANK
DB00932
Created by admin on Mon Mar 31 18:28:09 GMT 2025 , Edited by admin on Mon Mar 31 18:28:09 GMT 2025
PRIMARY
DRUG CENTRAL
3609
Created by admin on Mon Mar 31 18:28:09 GMT 2025 , Edited by admin on Mon Mar 31 18:28:09 GMT 2025
PRIMARY
INN
7774
Created by admin on Mon Mar 31 18:28:09 GMT 2025 , Edited by admin on Mon Mar 31 18:28:09 GMT 2025
PRIMARY
Related Record Type Details
Structure of TIPRANAVIR DISODIUM
SALT/SOLVATE -> PARENT
MULTIDRUG RESISTANCE PROTEIN 1
TRANSPORTER -> INDUCER
HUMAN IMMUNODEFICIENCY VIRUS TYPE 1
TARGET ORGANISM->INHIBITOR
Tipranavir (TPV) is a non-peptidic HIV-1 protease inhibitor that inhibits the virus-specific processing of the viral Gag and Gag-Pol polyproteins in HIV-1 infected cells, thus preventing formation of mature virions.
Structure of TIPRANAVIR
EXCRETED UNCHANGED
MAJOR
FECAL
CYTOCHROME P450 3A4
METABOLIC ENZYME -> SUBSTRATE
COADMINSTERED WITH RITONAVIR TO INCREASE BIOAVAILABILITY
MULTIDRUG RESISTANCE PROTEIN 1
TRANSPORTER -> SUBSTRATE
COADMINSTERED WITH RITONAVIR TO INCREASE BIOAVAILABILITY
PLASMA PROTEIN FRACTION (HUMAN)
BINDER->LIGAND
BINDING
Related Record Type Details
Structure of (2R)-3,6-DIHYDRO-6-OXO-2-(2-PHENYLETHYL)-2-PROPYL-5-((1R)-1-(3-(((5-(TRIFLUOROMETHYL)-2-PYRIDINYL)SULFONYL)AMINO)PHENYL)PROPYL)-2H-PYRAN-4-YL .BETA.-D-GLUCOPYRANOSIDURONIC ACID
METABOLITE -> PARENT
MINOR
Related Record Type Details
Structure of TIPRANAVIR
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC
Biological Half-life
NIH
NCATS
PRIVACY NOTICE
ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
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