Tipranavir

Summary

Tipranavir (CHEMBL222559) is an approved small-molecule HIV protease inhibitor (ATC J05AE09); indicated across 3 conditions including hiv infectious disease and viral infectious disease.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: J05AE09
• Indications: 3 conditions
• Clinical trials: 44
• Chemistry: 602.7 Da · C31H33F3N2O5S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL222559
Name	Tipranavir
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	54682461
ChEBI	CHEBI:63628
ATC	J05AE09
Molecular formula	C31H33F3N2O5S
Molecular weight	602.7
InChIKey	SUJUHGSWHZTSEU-FYBSXPHGSA-N

SMILES: CCC[C@]1(CC(=C(C(=O)O1)[C@H](CC)C2=CC(=CC=C2)NS(=O)(=O)C3=NC=C(C=C3)C(F)(F)F)O)CCC4=CC=CC=C4

IUPAC name: N-[3-[(1R)-1-[(2R)-4-hydroxy-6-oxo-2-(2-phenylethyl)-2-propyl-3H-pyran-5-yl]propyl]phenyl]-5-(trifluoromethyl)pyridine-2-sulfonamide

ChEBI definition: A pyridine-2-sulfonamide substituted at C-5 by a trifluoromethyl group and at the sulfonamide nitrogen by a dihydropyrone-containing m-tolyl substituent. It is an HIV-1 protease inhibitor.

Pharmacological roles (ChEBI): HIV protease inhibitor, antiviral drug.

Also known as: Aptivus, Tipranavir, U-140690, tipranavir, TIPRANAVIR, SID144206515

Parent form; salt/anhydrous children: CHEMBL445699, CHEMBL2103936

Patent coverage: 4,388 distinct patent families (17,513 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 17,435 (100%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Broader ChEMBL bioactivity targets: 26 (assay-derived). Sample: CAAX prenyl protease 1 homolog, 5-hydroxytryptamine receptor 2B, Alpha-2A adrenergic receptor, Cholecystokinin receptor type A, Alpha-2C adrenergic receptor, D(1A) dopamine receptor, Progesterone receptor, Muscarinic acetylcholine receptor M2, Motilin receptor, 5-hydroxytryptamine receptor 2A.

Bioactivity

ChEMBL activities: 14 potent at pChembl ≥ 5 of 26 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
NR1I2	6.58	AC50	260	nM	CHEMBL_ACT_25224315
Q80W54	5.92	IC50	1200	nM	CHEMBL_ACT_2150018
PGA5	5.7	Ki	2000	nM	CHEMBL_ACT_625544
ABCB11	5.5	AC50	3200	nM	CHEMBL_ACT_25126984
PTGS2	5.42	AC50	3800	nM	CHEMBL_ACT_25166143
ADRA1A	5.33	AC50	4700	nM	CHEMBL_ACT_25218034
Q63921	5.24	AC50	5800	nM	CHEMBL_ACT_25174346
CHRM2	5.2	AC50	6300	nM	CHEMBL_ACT_25213688
ADORA3	5.19	AC50	6400	nM	CHEMBL_ACT_25134159
PPARG	5.16	AC50	6900	nM	CHEMBL_ACT_25113935
P0DTD1	5.13	IC50	7380	nM	CHEMBL_ACT_26139531
HTR2B	5.12	AC50	7500	nM	CHEMBL_ACT_25227473
ADRA2A	5.07	AC50	8600	nM	CHEMBL_ACT_25219842
CTSE	5.05	Ki	9000	nM	CHEMBL_ACT_625546

Target pathways

No target-pathway data for this drug (no mapped target genes).

Indications & clinical

Indications

3 indications (3 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
HIV infectious disease	4	MONDO:0005109	EFO:0000764
viral infectious disease	4	MONDO:0005108	EFO:0000763

1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 44.

Phase distribution

Phase	Trials
PHASE1	22
Not specified	8
PHASE3	6
PHASE2	4
PHASE4	2
PHASE2/PHASE3	1
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00192660	PHASE4	COMPLETED	HIV Infection And Metabolic Abnormalities Protocol 1 (HAMA001)
NCT00607958	PHASE4	COMPLETED	Clinical Trial to Assess the Security of the Dose Reduction of Ritonavir in HIV-Infected Patients in Treatment With Tipranavir/Ritonavir 500/200 mg Every 12 Hours
NCT00054717	PHASE3	COMPLETED	Randomized Evaluation of Strategic Intervention in Multidrug Resistant Patients With Tipranavir (RESIST)
NCT00144287	PHASE3	COMPLETED	Safety Study of Tipranavir Co-administered With Low-dose Ritonavir (TPV/r) in Patients With Advanced HIV-1 Infection and Limited Treatment Options
NCT00146328	PHASE2/PHASE3	COMPLETED	Rollover Trial Safety and Tolerability of Combination Tipranavir and Ritonavir Use in HIV 1 Infected Subjects
NCT00440271	PHASE3	TERMINATED	SPRING: Safety, Efficacy, Pharmacokinetics of tipRanavir/r IN Race/Gender HIV+ Patients Randomized to TDM or SoC
NCT00447902	PHASE3	TERMINATED	Safety and Antiviral Activity of TPV in HCV and/or HBV HIV Coinfected Patients TDM Randomised Pilot Evaluation
NCT00517192	PHASE3	TERMINATED	Comparison of TPV/r to DRV/r in Triple Class Experienced Patient With Resistance to > 1 PI
NCT00537394	PHASE3	COMPLETED	Optimizing Treatment for Treatment-Experienced, HIV-Infected People
NCT00056641	PHASE2	COMPLETED	Dual Boosted - Protease Inhibitor (PI) Pharmacokinetics (PK) Trial (Tipranavir / Ritonavir) in Highly Treatment-experienced HIV-1 Infected Patients
NCT00275444	PHASE2	COMPLETED	3 TPV/RTV Doses in Multiple ARV Experienced Patients - Tipranavir Dose Defining Study
NCT00530920	PHASE2	COMPLETED	Tipranavir/Ritonavir Low Dose Pharmacokinetics in Treatment Naive Patients
NCT02229760	PHASE1/PHASE2	TERMINATED	Effect of Steady State TPV/r on Intracellular Concentrations of Zidovudine and Carbovir for Patients With HIV
NCT02249130	PHASE2	COMPLETED	Tipranavir Dose-response Study Using a Prototype Self-emulsifying Drug Delivery System (SEDDS) Formulation in Treatment-naive HIV-1 Infected Patients Report on the Post-study Option, a Treatment of Triple Therapy With Delavirdine, ZDV and 3TC Without Tipranavir
NCT00307502	PHASE1	COMPLETED	Study to Determine the Pharmacokinetic Behavior of Antiretroviral Drugs in Patients Infected by HIV
NCT00344123	PHASE1	COMPLETED	Pharmacokinetic (PK) Study of Single-dose Rosuvastatin and Tipranavir/Ritonavir in Healthy Subjects
NCT02195466	PHASE1	COMPLETED	Effects of Single-dose and Steady-state TPV/RTV on the Steady-state Pharmacokinetics of Fluconazole in Healthy Adult Volunteers
NCT02226978	PHASE1	COMPLETED	Pharmacokinetic Interaction Study of Steady-state Tipranavir/Ritonavir (TPV/r) With Single-dose Valaciclovir (VAL) in Healthy Volunteers
NCT02226991	PHASE1	COMPLETED	Effects of Steady-state Efavirenz 600 mg QD (Sustiva®) on Tipranavir Concentration at Steady-state in Healthy Adult Volunteers
NCT02243553	PHASE1	COMPLETED	Effects of Tipranavir (With Ritonavir) Capsule and Liquid Formulation on Cytochrome P450 and P-glycoprotein Activity in Healthy Volunteers
NCT02244190	PHASE1	COMPLETED	Bioequivalence of Two Different Oral Solutions Tipranavir Administered in Combination With Ritonavir to Healthy Volunteers
NCT02245269	PHASE1	COMPLETED	Pharmacokinetics of Atorvastatin With Tipranavir/Ritonavir and the Effect of Antacid on the Pharmacokinetics of Single-Dose Tipranavir/Ritonavir in Healthy Volunteers
NCT02245451	PHASE1	COMPLETED	Study of Tipranavir and Ritonavir on the Pharmacokinetic Characteristics of Methadone Administered in Healthy Volunteers
NCT02249442	PHASE1	COMPLETED	Study to Determine the Pharmacokinetics on TPV/r in Subjects With Mild and Moderate Hepatic Insufficiency
NCT02251119	PHASE1	COMPLETED	The Pharmacodynamic/Pharmacokinetic Interaction of Tipranavir and Ritonavir With Loperamide in Healthy Volunteers
NCT02251158	PHASE1	COMPLETED	Bioavailability of Tipranavir/Ritonavir Paediatric Solution Compared to Tipranavir/Ritonavir Capsules in Healthy Female and Male Subjects
NCT02251171	PHASE1	COMPLETED	Effects of Steady-state TPV/RTV on the Single-dose Pharmacokinetics of Rifabutin and the Effects of Single-dose Rifabutin on the Steady-state Pharmacokinetics of TPV in Healthy Adult Volunteers
NCT02251769	PHASE1	COMPLETED	Effects of Single-dose and Steady-state TPV/r on the Steady-state Pharmacokinetics of Clarithromycin and a Preliminary Assessment of the Effects of a Standard High-fat Test Meal on the Steady-state Pharmacokinetics of Tipranavir
NCT02251795	PHASE1	COMPLETED	Effects of Steady State Tipranavir/Ritonavir or Darunavir/Ritonavir or Ritonavir on Platelet Function, Coagulation and Fibrinolysis Biomarkers in Healthy Subjects
NCT02253797	PHASE1	COMPLETED	Pharmacokinetics of Tipranavir/Ritonavir and Its Metabolites in Healthy Male Subjects
NCT02253836	PHASE1	COMPLETED	Pharmacokinetic Study in Healthy Adult Volunteers to Assess the Interactions Between Steady-State Tipranavir and Atazanavir in the Presence of Ritonavir
NCT02253849	PHASE1	COMPLETED	Effects of TPV/r on the Pharmacokinetics of Carbamazepine in Healthy Adult Volunteers
NCT02253862	PHASE1	COMPLETED	Pharmacokinetic of Tadalafil Co-administered With Tipranavir/Ritonavir to Healthy Male Volunteers
NCT02253875	PHASE1	COMPLETED	Study to Determine the Effects of Multiple-dose Omeprazole on the Single-dose Pharmacokinetics of Tipranavir (TPV) Coadministered With Ritonavir (RTV) in Healthy Adult Volunteers
NCT02257021	PHASE1	COMPLETED	Pharmacokinetic Interaction Between Tipranavir and BILR 355 BS Plus Ritonavir in Healthy Male Volunteers
NCT02259855	PHASE1	COMPLETED	Pharmacokinetics (PK) of Tipranavir/Ritonavir, Ribavirin, Pegylated Interferon (Peg INF) in Hepatitis C (HCV) Subjects With Mild Hepatic Impairment and in HCV, Hepatitis B (HBV), Hepatitis D Infected Subjects or Alcoholic Cirrhosis With Moderate Hepatic Impairment
NCT00042289	Not specified	COMPLETED	Pharmacokinetic Study of Antiretroviral Drugs and Related Drugs During and After Pregnancy
NCT00062660	Not specified	APPROVED_FOR_MARKETING	Tipranavir in Patients With Progressive, Systemic HIV-1 Disease Who Have Failed or Are Intolerant to Currently Approved Treatments for HIV Infection
NCT00097799	Not specified	APPROVED_FOR_MARKETING	Tipranavir Expanded Access Program (EAP) in PI-experienced Patients With HIV-1 Infection
NCT00531206	Not specified	COMPLETED	Observational Non-interventional Study (Anwendungsbeobachtung) With Aptivus® (Tipranavir) in HIV-infected Patients.

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Related molecules

Related molecules

No competitor molecules sharing a primary target (ChEMBL phase ≥2 or PubChem drug-class).