Tipranavir (Synonyms: PNU-140690) |
Catalog No.GC14454
One-Click Copy Product Info
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A nonpeptidic HIV protease inhibitor
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 174484-41-4
Sample solution is provided at 25 µL, 10mM.
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Tipranavir is a potent HIV protease inhibitor, which has been proven effective in inhibiting the HIV protease with a Ki value of 8 pM and showing an IC90 value of 100 nM [1].
It is believed that tipranavir can block the replication of numbers of viruses resistant to the current range of protease inhibitor. And the major amino acid substitutions of HIV-1 protease were identified to be associated with tipranavir sensitivity and resistance .[2]
As a highly potent HIV protease inhibitor , tipranavir inhibited HIV-2 protease with high potency (Ki < 1 nM) and was also effective against V82A and V82F/I84V mutants (Ki 3.0 and 0.25 nM, respectively). High Ki values against other aspartyl proteases such as human pepsin, cathepsins D and E illustrated the selectivity for HIV protease. An investigation of the effect of protein binding on antiviral activity was performed in HIV-1IIIB infected cells in a medium of 10% fetal bovine serum and 75% human plasma, where above 99% of the inhibitor is protein bound and an IC90 value of 1.4 µM was observed [1] . Additionally, a study of antiviral activities of tipranavir was operated with 134 clinical isolates in vitro, which showed the attractive properties of broadly protease inhibitor resistant HIV clinical samples [2].
In a mouse model with 5 mg/kg tipranavir dosing, as a result, CLtot was 0.17 ± 0.10 L/h/kg, Vss was 0.51 ± 0.14 L/kg, and t1/2 was 5.4 ±0. 3h. And following 10 mg/kg oral dosing in rats, got the result of F was 30% compared to 5 mg/kg tipranavir dosing [1]. After being proved an effective therapeutic agent for treatment of AIDS. An evaluating of the long-term (up to week 292) safety, efficacy and tolerability of ritonavir-boosted tipranavir was carried out in HIV-1-infected pediatric patients. The result of the evaluating indicated that the pediatric patients do well with regard to safety, tolerability and virologic efficacy when they are stable on a tipranavir-based regimen [3].
References:
1.Turner SR, Strohbach JW, Tommasi RA , et al.Tipranavir (PNU-140690): A Potent, Orally Bioavailable Nonpeptidic HIV Protease Inhibitor of the 5,6-Dihydro-4-hydroxy-2-pyrone Sulfonamide Class. Journal of Medicinal Chemistry, 1998,41 (18), 3467-3476.
2.Larder BA , Hertogs K , Bloor S ,et al. Tipranavir inhibits broadly protease inhibitor-resistant HIV-1 clinical samples. AIDS, 14 (13), 1943-1948.
3.Salazar JC, Cahn P, Della Negra M, et al. Efficacy and safety of tipranavir coadministered with ritonavir in HIV-1-infected children and adolescents: 5 years of experience. The Pediatric Infectious Disease Journal, 2014, 33 (4), 396-400.
| Kinase experiment [1]: | |
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Inhibitory activities |
The inhibition constant (Ki) for tipranavir (TPV) was determined by measuring the change in fluorescence associated with the cleavage of the fluorogenic substrate Arg-Glu(EDANS)-Ser-Gln-Asn-Tyr-Pro-Ile-Val-Gln-Lys(DABCYL)-Arg. Enzymatic assays were performed in 10 mM sodium acetate buffer, pH 5.0, with 40 μM substrate and 1 to 400 nM protease at 25℃. The inhibitor concentration varied between 2 nM and 1 μM, depending on the type of inhibitor and mutant used. Several aliquots at different concentrations were prepared by diluting the stock solution (15 mM) in 100% DMSO. The final concentration of DMSO was 2% (vol/vol) in all reaction mixtures. Fluorescence was measured on a CytoFluor fluorescence multiwell plate reader with an excitation wavelength of 360 nm and an emission wavelength of 508 nm. Hydrolysis rates were obtained from the initial portion of the data, where at least 80% of the substrate remained nonhydrolyzed. |
| Human experiment [2]: | |
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Patients |
HIV-1-infected patients. |
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Dosage form |
500 mg twice daily or 1000 mg twice daily administered with ritonavir (100 mg twice daily); 80 weeks. |
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Applications |
TPV induces a consistent and durable reduction in viral load and increases the amount of CD4+ cells. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Muzammil S, Armstrong AA, Kang LW, et al. Unique thermodynamic response of tipranavir to human immunodeficiency virus type 1 protease drug resistance mutations. J Virol, 2007, 81(10): 5144-5154. [2]. Markowitz M, Slater LN, Schwartz R, et al. Long-term efficacy and safety of tipranavir boosted with ritonavir in HIV-1-infected patients failing multiple protease inhibitor regimens: 80-week data from a phase 2 study. J Acquir Immune Defic Syndr, 2007, 45(4): 401-410. | |
| Cas No. | 174484-41-4 | SDF | |
| Synonyms | PNU-140690 | ||
| Chemical 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 | ||
| Canonical SMILES | CCCC1(CC(=C(C(=O)O1)C(CC)C2=CC(=CC=C2)NS(=O)(=O)C3=NC=C(C=C3)C(F)(F)F)O)CCC4=CC=CC=C4 | ||
| Formula | C31H33F3N2O5S | M.Wt | 602.66 |
| Solubility | DMSO: 10 mM,Methanol: | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.6593 mL | 8.2966 mL | 16.5931 mL |
| 5 mM | 331.9 μL | 1.6593 mL | 3.3186 mL |
| 10 mM | 165.9 μL | 829.7 μL | 1.6593 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)