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Lopinavir

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Chemical Structure| 192725-17-0 同义名 : ABT-378;A-157378.0;Koletra;Aluviran
CAS号 : 192725-17-0
货号 : A330804
分子式 : C37H48N4O5
纯度 : 99+%
分子量 : 628.801
MDL号 : MFCD22628840
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 250 mg/mL(397.58 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

30% PEG400+0.5% Tween80+5% propylene glycol+water 30 mg/mL suspension

生物活性
靶点

  • HIV Protease

    HIV protease, Ki:1.3 pM
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
细胞系 浓度 检测类型 检测时间 活动说明 数据源
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
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... 展开 >>ble to achieve the number of patients defined by protocol) 收起 << - Spain ... 展开 >> 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 收起 <<
NCT00262522 Human Immunodeficiency Virus I... 展开 >>nfections 收起 << Phase 3 Completed - -
NCT00105079 HIV Infections Phase 3 Completed - -
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.59mL

0.32mL

0.16mL

7.95mL

1.59mL

0.80mL

15.90mL

3.18mL

1.59mL
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.