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Tipranavir

CAS No. : 174484-41-4

MCE 国际站：Tipranavir

产品活性：Tipranavir (PNU-140690) 有效抑制 HIV-1 蛋白酶 酶活性和二聚化，对抗多种蛋白酶抑制剂(PI)的HIV-1分离株具有有效的活性，IC₅₀ 为 66-410 nM。Tipranavir 抑制 SARS-CoV-2 3CL^pro 活性。

研究领域：Anti-infection  |  Metabolic Enzyme/Protease

作用靶点：HIV Protease  |  HIV  |  SARS-CoV

In Vitro: 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.

In Vivo: 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.

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