生物活性

• 描述Darunavir is an antiretroviral protease inhibitor that is used in the therapy and prevention of human immunodeficiency virus (HIV) infection and the acquired immunodeficiency syndrome (AIDS). Darunavir is a proteinomimetic, azapeptide that blocks the catalytic site of the HIV protease preventing cleavage of viral polyprotein precursors into mature, functional proteins that are necessary for viral replication. Ritonavir-boosted darunavir, as a component of antiretroviral therapy (ART), is indicated for the treatment of HIV-1 infection in adult and paediatric patients Boosted darunavir is generally well tolerated, with gastrointestinal disturbances and lipid abnormalities among the most common tolerability issues^[3]. Darunavir is a nonpeptidic inhibitor of protease (PR) that lodges itself in the active site of PR through a number of hydrogen bonds. Darunavir interacts with these catalytic aspartates and the backbone of the active site through hydrogen bonds, specifically binding to residues Asp25, Asp25', Asp 29, Asp 30, Asp 30', and Gly 27. This interaction prevents viral replication, as it competitively inhibits the viral polypeptides from gaining access to the active site and strongly binds to the enzymatic portions of this protein ^[4].
• 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
  NCT03042390	-	-	Completed	-	Spain ... more >> Hospital Costa del Sol Malaga, Marbella, Spain Hospital Clinic i Provincial Barcelona, Spain Hospital de la Santa Creu i Sant Pau Barcelona, Spain Hospital del Mar Barcelona, Spain Hospital del Vall d'Hebron Barcelona, Spain Hospital Germans Trias i Pujol Barcelona, Spain Hospital de Guadalajara Guadalajara, Spain Hospital Infanta Leonor Madrid, Spain Hospital La Paz Madrid, Spain Hospital La Princesa Madrid, Spain Hospital Príncipe de Asturias Madrid, Spain Hospital Puerta de Hierro Madrid, Spain Hospital Ramón y Cajal Madrid, Spain Hospital Virgen de la Victoria Malaga, Spain Hospital de Son Llatzer Palma de Mallorca, Spain Hospital de Valme Sevilla, Spain Complejo Hospitalario de Toledo Toledo, Spain Hospital Clínico de Valencia Valencia, Spain Hospital La Fe Valencia, Spain Complejo Hospitalaria Alvaron Cunqueiro Vigo, Spain Collapse <<
  NCT01449929	Infection, Human Immunodeficie... more >>ncy Virus Collapse <<	Phase 3	Completed	-	-
  NCT00854204	HIV-I	Phase 1	Completed	-	-

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• 参考文献

• [1] Meher BR, Wang Y. Interaction of I50V mutant and I50L/A71V double mutant HIV-protease with inhibitor TMC114 (darunavir): molecular dynamics simulation and binding free energy studies. J Phys Chem B. 2012 Feb 16;116(6):1884-900.

  [2] Kovalevsky AY, Louis JM, et al. Structural evidence for effectiveness of darunavir and two related antiviral inhibitors against HIV-2 protease. J Mol Biol. 2008 Dec 5;384(1):178-92.

  [3] Deeks ED. Darunavir: a review of its use in the management of HIV-1 infection. Drugs. 2014 Jan;74(1):99-125. doi: 10.1007/s40265-013-0159-3. PMID: 24338166.

  [4] Leonis G, Czyżnikowska Ż, Megariotis G, Reis H, Papadopoulos MG. Computational studies of darunavir into HIV-1 protease and DMPC bilayer: necessary conditions for effective binding and the role of the flaps. J Chem Inf Model. 2012 Jun 25;52(6):1542-58. doi: 10.1021/ci300014z. Epub 2012 May 30. PMID: 22587384.