1. Metabolic Enzyme/Protease
    Anti-infection
  2. HIV Protease
    HIV

Tipranavir 

Cat. No.: HY-15148 Purity: 99.54%
Data Sheet SDS Handling Instructions

Tipranavir inhibits the enzymatic activity and dimerization of HIV-1 protease, exerts potent activity against multi-protease inhibitor (PI)-resistant HIV-1 isolates with IC50s of 66-410 nM.

For research use only. We do not sell to patients.
Tipranavir Chemical Structure

Tipranavir Chemical Structure

CAS No. : 174484-41-4

Size Price Stock Quantity
10 mM * 1 mL in DMSO $530 In-stock
1 mg $128 In-stock
5 mg $400 In-stock
10 mg $600 In-stock
50 mg   Get quote  
100 mg   Get quote  

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Description

Tipranavir inhibits the enzymatic activity and dimerization of HIV-1 protease, exerts potent activity against multi-protease inhibitor (PI)-resistant HIV-1 isolates with IC50s of 66-410 nM.

IC50 & Target

IC50: 66-410 nM (HIV-1 isolates)[1]

In Vitro

Tipranavir (TPV) inhibits the enzymatic activity of HIV-1 protease, blocks the dimerization of protease subunits, and exerts potent activity against a wide spectrum of wild-type and multi-PI-resistant HIV-1 variants. When a mixture of 11 multi-PI-resistant (but TPV-sensitive) clinical isolates (HIV11MIX), which include HIVB and HIVC, is selected against Tipranavir, HIV11MIX rapidly (by 10 passages [HIV11MIXP10]) acquires high-level Tipranavir resistance and replicates at high concentrations of Tipranavir. cHIVBI54V and cHIVBI54V/V82T are significantly resistant to TPV, with IC50s of 2.9 and 3.2 μM, respectively, which are 11- and 12-fold increases in comparison to the IC50 against cHIVB, respectively[1].

In Vivo

Tipranavir (TPV) is administered orally twice daily and must be given in combination with low-dose ritonavir (RTV) to boost Tipranavir bioavailability. In Tipranavir/r-cotreated mice, the Tipranavir abundance in the liver, spleen, and eyes is significantly higher than that in mice treated with Tipranavir alone. Tipranavir metabolites accounts for 31 and 38% in the serum and liver in the Tipranavir-alone group. In Tipranavir and Tipranavir (TPV/r)-cotreated mice, only 1 and 2% of metabolites are detected in the serum and liver. Sprague-Dawley rats are administered a single dose of [14C]Tipranavir with coadministration of RTV. The most abundant metabolite in feces is an oxidation metabolite. In urine, no single metabolite is found to be significantly present[2].

Clinical Trial
NCT Number Sponsor Condition Start Date Phase
NCT00486330 Yale University|Boehringer Ingelheim HIV Infections May 2006
NCT00344123 Johns Hopkins University|Boehringer Ingelheim HIV Infections February 2007 Phase 1
NCT00607958 Germans Trias i Pujol Hospital|Fundacio Lluita Contra la SIDA HIV Infections December 2007 Phase 4
NCT02244190 Boehringer Ingelheim Healthy April 2008 Phase 1
NCT00062660 Boehringer Ingelheim HIV Infections May 2003
NCT02257021 Boehringer Ingelheim Healthy February 2005 Phase 1
NCT00146328 Boehringer Ingelheim HIV Infections April 2001 Phase 2|Phase 3
NCT02253875 Boehringer Ingelheim Healthy November 2005 Phase 1
NCT02251158 Boehringer Ingelheim Healthy October 2003 Phase 1
NCT02253797 Boehringer Ingelheim Healthy July 2003 Phase 1
NCT00275444 Boehringer Ingelheim HIV Infections March 2002 Phase 2
NCT00034866 Boehringer Ingelheim HIV Infections April 2002 Phase 2
NCT02251795 Boehringer Ingelheim Healthy August 2007 Phase 1
NCT00144287 Boehringer Ingelheim HIV Infections May 2004 Phase 3
NCT00530920 Boehringer Ingelheim HIV Infections October 2007 Phase 2
NCT02251145 Boehringer Ingelheim Healthy May 2002 Phase 1
NCT00144170 Boehringer Ingelheim HIV Infections February 2003 Phase 3
NCT02226991 Boehringer Ingelheim Healthy April 2006 Phase 1
NCT00054717 Boehringer Ingelheim HIV Infections January 2003 Phase 3
NCT02238314 Boehringer Ingelheim HIV Infections January 1999 Phase 2
NCT02245451 Boehringer Ingelheim Healthy January 2005 Phase 1
NCT00531206 Boehringer Ingelheim HIV Infections August 2006
NCT02253862 Boehringer Ingelheim Healthy December 2005 Phase 1
NCT02249130 Boehringer Ingelheim HIV Infections March 1999 Phase 2
NCT00933205 Boehringer Ingelheim HIV Infections May 2004
NCT02226978 Boehringer Ingelheim Healthy February 2007 Phase 1
NCT00615290 Boehringer Ingelheim HIV Infections June 2007
NCT02251119 Boehringer Ingelheim Healthy July 2002 Phase 1
NCT00805857 Boehringer Ingelheim HIV Infections June 2008
NCT02251223 Boehringer Ingelheim HIV Infections February 2001 Phase 1|Phase 2
NCT00097799 Boehringer Ingelheim HIV Infections December 2004
NCT00976950 Boehringer Ingelheim HIV Infections September 2009
NCT02239835 Boehringer Ingelheim HIV Infections December 1999 Phase 2
NCT02251769 Boehringer Ingelheim Healthy August 2003 Phase 1
NCT02249416 Boehringer Ingelheim Healthy November 2001 Phase 1
NCT02243553 Boehringer Ingelheim Healthy January 2006 Phase 1
NCT02245269 Boehringer Ingelheim Healthy July 2003 Phase 1
NCT00056641 Boehringer Ingelheim HIV Infections January 2003 Phase 2
NCT00440271 Boehringer Ingelheim HIV Infections February 2007 Phase 3
NCT02253836 Boehringer Ingelheim Healthy January 2005 Phase 1
NCT02259855 Boehringer Ingelheim Hepatic Insufficiency January 2006 Phase 1
NCT00517192 Boehringer Ingelheim HIV Infections September 2007 Phase 3
NCT02229760 Boehringer Ingelheim HIV Infections August 2006 Phase 1|Phase 2
NCT02245438 Boehringer Ingelheim Healthy May 2002 Phase 1
NCT02251171 Boehringer Ingelheim Healthy August 2003 Phase 1
NCT02249442 Boehringer Ingelheim Hepatic Insufficiency October 2003 Phase 1
NCT02253849 Boehringer Ingelheim Healthy November 2005 Phase 1
NCT00447902 Boehringer Ingelheim HIV Infections March 2007 Phase 3
NCT02195466 Boehringer Ingelheim Healthy June 2003 Phase 1
NCT00307502 Germans Trias i Pujol Hospital|Fundacio Lluita Contra la SIDA HIV Infections January 2005 Phase 1
NCT00537394 National Institute of Allergy and Infectious Diseases (NIAID)|AIDS Clinical Trials Group HIV Infections January 2008 Phase 3
NCT00192660 Kirby Institute|St Vincent's Hospital, Sydney|National Heart, Lung, and Blood Institute (NHLBI) HIV-Associated Lipodystrophy Syndrome|Cardiovascular Disease February 2003 Phase 4
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References
Preparing Stock Solutions
Concentration Volume (DMSO) Mass 1 mg 5 mg 10 mg
1 mM 1.6593 mL 8.2966 mL 16.5931 mL
5 mM 0.3319 mL 1.6593 mL 3.3186 mL
10 mM 0.1659 mL 0.8297 mL 1.6593 mL
Kinase Assay
[1]

Thirty 50% tissue culture infectious doses (TCID50s) of each of the 11 highly multi-PI-resistant HIV-1 isolates is mixed and propagated in a mixture of an equal number of PHA-PBMCs (5×105) and MT-4 cells (5×105), in an attempt to adapt them for replication in MT-4 cells. The cell-free supernatant is harvested on day 7 of coculture (PHA-PBMCs and MT-4 cells), and the viruses (designated HIV11MIXP0, where P0 represents passage 0) are further propagated in fresh MT-4 cells for the selection experiment. On the first passage, MT-4 cells (5×105) are exposed to culture supernatant of mixed viruses or 500 TCID50s of each infectious molecular HIV-1 clone and cultured in the presence of Tipranavir at initial concentrations of 0.1 to 0.4 μM. On the last day of each passage (approximately day 7), 1 mL of the cell-free supernatant is harvested and transferred to a culture of fresh uninfected MT-4 cells in the presence of increased concentrations of the drug for the following round of culture. In this round of culture, three drug concentrations (increased by 1-, 2-, and 3-fold compared to the previous concentration) are employed. When the replication of HIV-1 in the culture is confirmed by substantial Gag protein production (greater than 200 ng/mL), the highest drug concentration among the three concentrations is used to continue the selection (for the next round of culture). This protocol is repetitively used until the drug concentration reaches the targeted concentration. Proviral DNA samples obtained from the lysates of infected cells are subjected to nucleotide sequencing[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[2]

Tipranavir (TPV) is dissolved in DMSO and then diluted in water or PBS (Mice)[2].

Mice[2]
All mice (2-4 months old) are maintained under a standard 12-h dark and 12-h light cycle with water and chow provided ad libitum. For metabolomic analysis, Tipranavir (40 mg/kg) is administered via ball-tipped gavage needles, and the mice are housed in separate metabolic cages for 18 h. Urine and feces samples are collected and stored at −20°C for further analysis. For tissue distribution and inhibition studies, three groups of mice are used and are orally treated with Tipranavir (100 mg/kg), RTV (40 mg/kg), and Tipranavir/r (100 mg/kg Tipranavir and 40 mg/kg RTV), respectively. Tissues including the liver, brain, lung, kidney, spleen, and eyes are collected 30 min after treatment and stored at −20°C for further analysis. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
M.Wt

602.66

Formula

C₃₁H₃₃F₃N₂O₅S

CAS No.

174484-41-4

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

10 mM in DMSO

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

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Tipranavir
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