|S1185||Ritonavir||<1 mg/mL||100 mg/mL||3 mg/mL|
|S1380||Lopinavir||<1 mg/mL||126 mg/mL||126 mg/mL|
|S1457||Atazanavir Sulfate||<1 mg/mL||104 mg/mL||<1 mg/mL|
|S1620||Darunavir Ethanolate||<1 mg/mL||100 mg/mL||<1 mg/mL|
|S1639||Amprenavir||<1 mg/mL||16 mg/mL||100 mg/mL|
|S2319||Limonin||<1 mg/mL||44 mg/mL||<1 mg/mL|
|S4662||Atazanavir||<1 mg/mL||71 mg/mL||32 mg/mL|
|S4282||Nelfinavir Mesylate||<1 mg/mL||100 mg/mL||100 mg/mL|
|S7381||Pepstatin A||<1 mg/mL||57 mg/mL||1 mg/mL|
- HIV Protease抑制剂（9）
Ritonavir是Cytochrome P450 3A和HIV蛋白酶抑制剂，用于治疗HIV感染和AIDS。抑制Cytochrome P450 2D6, P-Glycoprotein，诱导Cytochrome P450 2C19, Cytochrome P450 1A2, Cytochrome P450 2C9, Cytochrome P450 2B6和UDP Glucuronosyltransferases。
(A) KMS11 and (B) L363 cells were plated in 5mM glucose medium with ritonavir or DMSO (D) for 17 hours. Glucose consumption rates are normalized to untreated cells (not shown). (C) KMS11 and (D) L363 cells were treated with ritonavir or DMSO for 72 hours. Relative viable cell numbers were determined by MTS assay and normalized to untreated cells (not shown).
Lopinavir是一种有效的HIV protease抑制剂，无细胞试验中Ki为1.3 pM。
Sodium butyrate and lopinavir treatment represent pharmacological aging models that reproduce key properties of cellular aging. LLC-PK1 cells were incubated with vehicle (controls), sodium butyrate or lopinavir and assessed for different indicators of aging. (A) The number of cells that scored positive for SA-β-galactosidase activity increased significantly upon treatment with sodium butyrate or lopinavir. Data are shown for three independent experiments as average + SEM. Results were normalized to controls and depicted as arbitrary units (AU). (B) Sodium butyrate and lopinavir increase cell size, cause nuclear dysmorphy, reduce cell proliferation, while lamin A becomes more abundant. Confocal images were acquired for 5-ethynyl-2′-deoxyuridine (EdU) and lamin A (Materials and methods). Representative images are shown for control and treated samples. Scale bar, 20 μm. (C) Nuclear fluorescence was quantified for EdU and lamin A for at least three independent experiments. Pixel intensities were measured for > 100 cells for each experiment per condition. NaBu, sodium butyrate, D, DMSO, Lopi, lopinavir. **, p < 0.01; ***, p < 0.001.
Atazanavir Sulfate是一种HIV protease抑制剂，无细胞试验中Ki值为2.66 nM。
Protease inhibitors induce macroautophagy. JEG3 were seeded on glass chamber slides (1 x 104 cell per chamber; 8-well μ slides; Ibidi, Martinsried, Germany), grown for 24 h under cell culture conditions, and treated for 24 h with 0-10 ug/ml of either lopinavir/ritonavir or atazanavir. Cells were then incubated for 30 min with the blue-green fluorescent autophagy marker monodansylcadaverine and viewed under a fluorescence microscope.
HIV PIs variably alter intracellular HIV epitope stability. (A) HLA-A02–restricted SL9 epitope (SLYNTVATL, aa 77–85 in HIV-1 Gag p17) was degraded in PBMC extracts pretreated with DMSO (control, circles), 5 µM of Nelfinavir (triangles) or 5 µM of Saquinavir (squares). Remaining peptide was quantified by RP-HPLC analysis after 0, 10, 30 and 60 minutes. 100% represents the amount of peptide at time 0 calculated as the surface under the peptide peak detected by RP-HPLC (815.986, 821.569, and 813.118 for DMSO, Saquinavir, and Nelfinavir, respectively). Times at which 50% of the SL9 peptide remained correspond to peptide half-lives (37 min, 52 min and 24 min for Control, Saquinavir and Nelfinavir respectively). (B–F) HLA-A02–SL9, HLA-B57-KF11, HLAB57-ISW9, HLA-B57-TW10 and HLA-A11-ATK9 epitopes (from B to F respectively) were degraded in PBMC extracts pretreated with DMSO, 2 µM or 5 µM PI (Saquinavir, Ritonavir, Nelfinavir, Atazanavir or Darunavir). The cytosolic half-lives in control condition were 33.87, 25.66, 14.83, 119.4 and 37.21 minutes for SL9, KF11, ISW9, TW10 and ATK9 respectively. Fold differences of each epitope half-life upon treatment compared to control are presented in each panel. All data represent the average of 4 different experiments using 4 different PBMC extracts. *P < 0.05, **P < 0.01, ***P < 0.001, 1-way ANOVA with Dunnett’s post-test.
Amprenavir 是一种人类免疫缺陷病毒(HIV)蛋白酶抑制剂，作用于野生型HIV分离株，IC50为14.6 ng/ml。
Limonin又称Limonoate D-ring-lactone 和 Limonoic acid di-delta-lactone，化学上属于Furanolactone类化合物。
Nelfinavir Mesylate 是强效的HIV protease抑制剂，Ki为2 nM。
Pepstatin A 是一种强效的aspartic protease抑制剂, 并可抑制HIV的复制。