Tipranavir-d₇  (Synonyms: 替拉那韦-d₇; 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].

氢、碳和其他元素的稳定重同位素已被纳入药物分子中，主要作为药物开发过程中定量的示踪剂。氘化引起了人们的关注，因为它可能影响药物的药代动力学和代谢谱^[1]。

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].

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

623.73

C₃₂H₂₈D₇F₃N₂O₅S

174484-41-4

替拉那韦-d₇

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]