Ritonavir
Ritonavir is an HIV protease inhibitor that is commonly used as a component of highly active anti-retroviral therapy (HAART) in the treatment of HIV infection. Ritonavir exhibits antiviral, anti-angiogenic, neuroprotective, and hyperlipidemic activities. Ritonavir inhibits expression of VEGF and HIF-1α, decreasing proliferation in retinal epithelial cells and indicating potential use as a treatment for ocular diseases. Ritonavir also inhibits translocation of apoptosis-inducing factor (AIF), activates caspase 9, and inhibits permeability alterations in the mitochondrial membrane potential, preventing apoptosis in retinal photoreceptor cells and macrophages. This compound decreases levels of sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) and intracellular Ca2+, increasing endoplasmic reticular stress and injury. Additionally, ritonavir increases levels of IL-6 and decreases levels of adiponectin, GLUT4, and fatty acid synthase, inhibiting lipogenesis and increasing lipodystrophy; this compound also increases levels of VLDL.
References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/18961645
| Cas No. |
155213-67-5 |
|---|---|
| Purity |
≥98% |
| Formula |
C37H48N6O5S2 |
| Formula Wt. |
720.95 |
| IUPAC Name |
1,3-thiazol-5-ylmethylN-[(2S,3S,5S)-3-hydroxy-5-[[(2S)-3-methyl-2-[[methyl-[(2-propan-2-yl-1,3-thiazol-4-yl)methyl]carbamoyl]amino]butanoyl]amino]-1,6-diphenylhexan-2-yl]carbamate |
| Synonym |
Norvir |
| Melting Point |
120-123°C |
| Solubility |
DMSO to 10 mg/mL, Ethanol to 3 mg/mL, Methanol |
| Appearance |
White to off white powder |
Vadlapatla RK, Vadlapudi AD, Pal D, et al. Ritonavir inhibits HIF-1α-mediated VEGF expression in retinal pigment epithelial cells in vitro. Eye (Lond). 2013 Nov 8. [Epub ahead of print]. PMID: 24202050.
Kao E, Shinohara M, Feng M, et al. Human immunodeficiency virus protease inhibitors modulate Ca2+ homeostasis and potentiate alcoholic stress and injury in mice and primary mouse and human hepatocytes. Hepatology. 2012 Aug;56(2):594-604. PMID: 22407670.
Hisatomi T, Nakazawa T, Noda K, et al. HIV protease inhibitors provide neuroprotection through inhibition of mitochondrial apoptosis in mice. J Clin Invest. 2008 Jun;118(6):2025-38. PMID: 18497877.
Grigem S, Fischer-Posovszky P, Debatin KM, et al. The effect of the HIV protease inhibitor ritonavir on proliferation, differentiation, lipogenesis, gene expression and apoptosis of human preadipocytes and adipocytes. Horm Metab Res. 2005 Oct;37(10):602-9. PMID: 16278782.
Riddle TM, Schildmeyer NM, Phan C, et al. The HIV protease inhibitor ritonavir increases lipoprotein production and has no effect on lipoprotein clearance in mice. J Lipid Res. 2002 Sep;43(9):1458-63. PMID: 12235177.
Beach JW. Chemotherapeutic agents for human immunodeficiency virus infection: mechanism of action, pharmacokinetics, metabolism, and adverse reactions. Clin Ther. 1998 Jan-Feb;20(1):2-25. PMID: 9522101.
Kawakami K, Harada T, Yoshihashi Y, et al. Correlation between glass-forming ability and fragility of pharmaceutical compounds. J Phys Chem B. 2015 Apr 9;119(14):4873-4880. PMID: 25781503.
