生物活性

• 靶点	HIV-1 Protease Ki:2nM

• 描述The HIV-1 protease belongs to the family of aspartyl protease. It cleaves the newly synthesized polyproteins, which is the vital step to create the mature protein components of an infectious HIV-1 virus^[3]. Nelfinavir is a selective, nonpeptidic competitive inhibitor of the HIV-1 protease{{Kaldor SW, Kalish VJ, Davies JF II, et al. Viracept (nelfinavir mesylate, AG1343): a potent, orally bioavailable inhibitor of HIV-1 protease. J Med Chem 1997 Nov 21; 40: 3979-85.|https://pubmed.ncbi.nlm.nih.gov/9397180/}}. Nelfinavir has an in vitro inhibition constant(Ki) of 1.7 nM against HIV-1 protease, but no significant activity against human aspartic proteases including pepsin, renin and gastricin. Very weak affinity for cathepsin E (74 μM) and cathepsin D (435 nM) has been observed. The mean nelfinavir concentration producing 95% inhibition of viral replication (IC95) in a variety of i in vitro HIV infection models was 59 nM (range 7 to 130 nM). Nelfinavir was also effective at inhibiting replication of the zidovudine-resistant HIV-1 strain G910-6 and the NNRTI-resistant strain A17^[4]. The mean plasma nelfinavir concentration exceeded the 95% antiviral effective dose (ED95 =40 μg/L) for up to 8 hours after a single 100mg dose, and up to 24 hours after an 800mg dose. The area under the concentration-time curve (AUC) after administration in the fasted state was 27 to 50% of the AUC when the drug was administered with food^[5]. Nelfinavir is metabolised in the liver by the cytochrome P450 (CYP) enzyme system. Nelfinavir is metabolically converted to its major hydroxy-t-butylamide metabolite M8, which has anti-HIV activity comparable to nelfinavir i in vitro ^[6].
• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT00624195	HIV Infections	Phase 2 Phase 3	Completed	-	United States, California ... more >> HIV Neurobehavioral Research Center, University of California San Diego San Diego, California, United States, 92103 University of California, San Francisco San Francisco, California, United States, 94110 United States, Maryland Johns Hopkins University- School of Medicine Baltimore, Maryland, United States, 21287 United States, Missouri Washington University St. Louis, Missouri, United States, 63110 United States, New York Mount Sinai Medical Center New York, New York, United States, 10024 Collapse <<
  NCT00002411	HIV Infections	Not Applicable	Completed	-	-
  NCT00624195	-	-	Completed	-	-

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• 参考文献

• [1] Mondal D, Liu K, et al. Nelfinavir suppresses insulin signaling and nitric oxide production by human aortic endothelial cells: protective effects of thiazolidinediones. Ochsner J. 2013 Spring;13(1):76-90.

  [2] Kaldor SW, Kalish VJ, et al. Viracept (nelfinavir mesylate, AG1343): a potent, orally bioavailable inhibitor of HIV-1 protease. J Med Chem. 1997 Nov 21;40(24):3979-85.

  [3] Davies, D. R. The structure and function of the aspartic proteinases. Annu. Rev. Biophys. Biophys. Chem. 19, 189–215,

  [4] A K Patick,et al. Antiviral and resistance studies of AG1343, an orally bioavailable inhibitor of human immunodeficiency virus protease. Antimicrob Agents Chemother.1996 Feb;40(2):292-7.

  [5] Caroline M Perry,et al. Nelfinavir: a review of its use in the management of HIV infection. Drugs.2005;65(15):2209-44.

  [6] A Bardsley-Elliot,et al. Nelfinavir: an update on its use in HIV infection. Drugs. 2000 Mar;59(3):581-620.

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