生物活性

• 靶点	HIV Protease Ki:1.3pM

• 描述Lopinavir (ABT-378) is an antiretroviral of the HIV protease inhibitor class, as well as an inhibitor of P-Glycoprotein, Cytochrome P450 3A and Organic Anion Transporting Polypeptide 1B1. It has a mean oral bioavailability of less than 20 % due to extensive hepatic metabolism by cytochrome P450 3A4. The reported half-life of Lopinavir is 5-6 hours and the maximum recommended daily dose is 400 mg/day^[3]. In a randomised controlled trial done in HIV-infected adults or adolescents, at 144 weeks, 86% participants in the protease inhibitor plus nucleoside reverse-transcriptase inhibitor (NRTI) group (lopinavir 400 mg with ritonavir 100 mg, twice per day plus two or three clinician-selected NRTIs) had viral loads of less than 400 copies per mL compared with 81% in the protease inhibitor plus raltegravir (400 mg twice per day) group^[4]. Promastigotes of L. amazonensis (the cause of tropical disease Leishmaniasis) treated with increasing concentrations of lopinavir (7.5, 15 and 30 µM) exhibited accumulation of lipid inclusions and increased amounts of cholesterol-ester in a dose-dependent manner, which reinforced that lopinavir can be useful in leishmaniasis treatment^[5]. In Human Glioblastoma U-87 MG cell line, co-treatment with Lopinavir and Ritonavir (25 and 50 µM) for 24 h promoted a significant increase in ROS production, caused mitochondrial network damage and induced apoptosis in a caspase-independent manner^[6]. In the latest study, Lopinavir was found to have anti-2019-novel coronavirus activity.
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  HEK293 cells	-	Function assay	48 h	Antiviral activity against wild type HIV1 NL4-3 in HEK293 cells after 48 hrs by replication-deffective luciferase reporter gene-based phenotypic assay, EC50=0.0028 μM	17638694
  human MT4 cells	-	Function assay	5 days	Antiviral activity against HIV2 MS infected in human MT4 cells assessed as inhibition of virus production after 5 days by Lenti-RT activity assay, EC50=0.006 μM	17576848
  human PBMC cells	-	Function assay	5 days	Antiviral activity against HIV2 MS infected in human PBMC cells assessed as inhibition of virus production after 5 days by Lenti-RT activity assay, EC50=0.015 μM	17576848

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• 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
  NCT00661349	HIV Infections	Phase 4	Terminated(It has been impossi... more >>ble to achieve the number of patients defined by protocol) Collapse <<	-	Spain ... more >> Hospital Son Dureta Palma de Mallorca, Baleares, Spain, 07014 H.U. Germans Trias i Pujol - Unitat VIH, Fundació Lluita contra la Sida Badalona, Barcelona, Spain, 08916 Hospital General Universitario de Alicante Alicante, Spain, 03010 Hospital Clínic i Provincial de Barcelona Barcelona, Spain, 08036 Hospital Universitario Príncipe de Asturias Madrid, Spain, 28005 Hospital Clínico San Carlos Madrid, Spain, 28040 Hospital Universitario la Paz Madrid, Spain, 28046 Hospital Clínico de Salamanca Salamanca, Spain, 37007 Hospital Universitario de Valme Sevilla, Spain, 41014 Collapse <<
  NCT00262522	Human Immunodeficiency Virus I... more >>nfections Collapse <<	Phase 3	Completed	-	-
  NCT00105079	HIV Infections	Phase 3	Completed	-	-

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• 参考文献

• [1] Vishnuvardhan D, Moltke LL, et al. Lopinavir: acute exposure inhibits P-glycoprotein; extended exposure induces P-glycoprotein. AIDS. 2003 May 2;17(7):1092-4.

  [2] Sham HL, Kempf DJ, et al. ABT-378, a highly potent inhibitor of the human immunodeficiency virus protease. Antimicrob Agents Chemother. 1998 Dec;42(12):3218-24.

  [3] Ansari H, Singh P. Formulation and in-vivo Evaluation of Novel Topical Gel of Lopinavir for Targeting HIV. Curr HIV Res. 2018;16(4):270-279. doi: 10.2174/1570162X16666180924101650. PMID: 30246641; PMCID: PMC6416462.

  [4] Hakim JG, Thompson J, Kityo C, Hoppe A, Kambugu A, van Oosterhout JJ, Lugemwa A, Siika A, Mwebaze R, Mweemba A, Abongomera G, Thomason MJ, Easterbrook P, Mugyenyi P, Walker AS, Paton NI; Europe Africa Research Network for Evaluation of Second-line Therapy (EARNEST) Trial Team. Lopinavir plus nucleoside reverse-transcriptase inhibitors, lopinavir plus raltegravir, or lopinavir monotherapy for second-line treatment of HIV (EARNEST): 144-week follow-up results from a randomised controlled trial. Lancet Infect Dis. 2018 Jan;18(1):47-57. doi: 10.1016/S1473-3099(17)30630-8. Epub 2017 Nov 3. PMID: 29108797; PMCID: PMC5739875.

  [5] Rebello KM, Andrade-Neto VV, Zuma AA, Motta MCM, Gomes CRB, de Souza MVN, Atella GC, Branquinha MH, Santos ALS, Torres-Santos EC, d'Avila-Levy CM. Lopinavir, an HIV-1 peptidase inhibitor, induces alteration on the lipid metabolism of Leishmania amazonensis promastigotes. Parasitology. 2018 Sep;145(10):1304-1310. doi: 10.1017/S0031182018000823. Epub 2018 May 28. PMID: 29806577; PMCID: PMC6137378.

  [6] Gratton R, Tricarico PM, Guimaraes RL, Celsi F, Crovella S. Lopinavir/Ritonavir Treatment Induces Oxidative Stress and Caspaseindependent Apoptosis in Human Glioblastoma U-87 MG Cell Line. Curr HIV Res. 2018;16(2):106-112. doi: 10.2174/1570162X16666180528100922. PMID: 29804534.

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