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- W1988525115 abstract "Efforts to develop therapeutically relevant HIV protease inhibitors as medicinal agents in confronting the AIDS crisis have been aided by the wealth of fundamental information acquired during related drug discovery campaigns against other aspartyl proteases. This knowledge base was brought to full force with the broad screening identification of small, nonpeptidic, inhibitory molecules as templates for chemical elaboration. Significantly, the ability to collect crystallographic data on the inhibitor-enzyme complexes in a rapid fashion afforded the opportunity for a structure-based approach to drug discovery. Iterative cycles of synthesis, biological testing, and structural information gathering followed by prudent design modifications afforded compounds suitable for clinical evaluation. Displaying high enzymatic inhibition (Ki = 8 pM), potent in vitro antiviral cell culture activity (IC90 = 100 nM), and a useful pharmacokinetic profile, PNU-140690E (Tipranavir disodium) has entered into clinical studies. Promising results from these early trials supported further evaluation of this compound in HIV-infected individuals. PNU-140690E is currently under extensive clinical study." @default.
- W1988525115 created "2016-06-24" @default.
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- W1988525115 date "1999-01-01" @default.
- W1988525115 modified "2023-09-24" @default.
- W1988525115 title "Structure-based discovery of tipranavir disodium (PNU-140690E): A potent, orally bioavailable, nonpeptidic HIV protease inhibitor" @default.
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- W1988525115 doi "https://doi.org/10.1002/(sici)1097-0282(1999)51:1<51::aid-bip6>3.0.co;2-u" @default.
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