Tipranavir-d₇  (Synonyms: PNU-140690-d7)

Tipranavir-d₇ is deuterated labeled Tipranavir (HY-15148). Tipranavir (PNU-140690) 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^[1][2]. Tipranavir inhibits SARS-CoV-2 3CL^pro activity^[3].

Stable heavy isotopes of hydrogen, carbon, and other elements have been incorporated into drug molecules, largely as tracers for quantitation during the drug development process. Deuteration has gained attention because of its potential to affect the pharmacokinetic and metabolic profiles of drugs^[1].
Tipranavir (PNU-140690) 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 (HIV_11MIX), which include HIV_B and HIV_C, is selected against Tipranavir, HIV_11MIX rapidly (by 10 passages [HIV_11MIX^P10]) acquires high-level Tipranavir (PNU-140690) resistance and replicates at high concentrations of Tipranavir (PNU-140690). cHIV_B^I54V and cHIV_B^I54V/V82T are significantly resistant to Tipranavir (PNU-140690), with IC₅₀s of 2.9 and 3.2 μM, respectively, which are 11- and 12-fold increases in comparison to the IC₅₀ against cHIV_B, respectively^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Tipranavir (PNU-140690) 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 (PNU-140690) abundance in the liver, spleen, and eyes is significantly higher than that in mice treated with Tipranavir alone. Tipranavir (PNU-140690) metabolites accounts for 31 and 38% in the serum and liver in the Tipranavir-alone group. In Tipranavir (PNU-140690) 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 (PNU-140690) 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^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

623.73

C₃₂H₂₈D₇F₃N₂O₅S

174484-41-4

FC(F)(C1=CC=C(S(=O)(NC2=CC([C@H](C(C(O3)=O)=C(C[C@]3(CC(C(C4=C([2H])C([2H])=C([2H])C([2H])=C4[2H])[2H])[2H])CCC)O)CC)=CC=C2)=O)N=C1)F

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Russak EM, et al. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019 Feb;53(2):211-216.  [Content Brief]

  [2]. Qi Sun, et al. Bardoxolone and bardoxolone methyl, two Nrf2 activators in clinical trials, inhibit SARS-CoV-2 replication and its 3C-like protease. Signal Transduct Target Ther. 2021 May 29;6(1):212.  [Content Brief]

  [3]. Li F, et al. Metabolism-mediated drug interactions associated with ritonavir-boosted tipranavir in mice. Drug Metab Dispos. 2010 May;38(5):871-8.  [Content Brief]

  [4]. Aoki M, et al. Loss of the protease dimerization inhibition activity of tipranavir (TPV) and its association with the acquisition of resistance to TPV by HIV-1. J Virol. 2012 Dec;86(24):13384-96.  [Content Brief]