Darunavir Ethanolate (DRV, TMC-114; UIC-94017; Trade name: Prezista), the ethanolate salt of darunavir, is a nonpeptidic HIV protease inhibitor/PI used in combination with other HIV medications to control HIV infection. Darunavir was approved by FDA in 2006 to treat and prevent HIV/AIDS infection. Darunavir is an OARAC (Office of AIDS Research Advisory Council) recommended treatment option for treatment-naive and treatment-experienced adults and adolescents. It was developed by pharmaceutical company Tibotec and was named after Arun K. Ghosh, the chemist who discovered the molecule at the University of Illinois at Chicago (now a Professor at Purdue Univeristy). Darunavir is generally recommended for use with other antiretrovirals, for example, it is often used with low doses of ritonavir or cobicistat to increase darunavir levels. It may be used for prevention after a needlestick injury or other potential exposure. It is taken by mouth once to twice a day.
理化性质和储存条件
| Molecular Weight (MW) | 593.73 |
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| Formula | C27H37N3O7S.C2H5OH |
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| CAS No. | 635728-49-3 (Ethanolate); |
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| Storage | -20℃ for 3 years in powder form |
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| -80℃ for 2 years in solvent |
| Solubility (In vitro) | DMSO: 100 mg/mL (168.4 mM) |
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| Water: <1 mg/mL |
| Ethanol: <1 mg/mL |
| SMILES Code | O=C(O[C@@H]1[C@@]2([H])[C@@](OCC2)([H])OC1)N[C@@H](CC3=CC=CC=C3)[C@H](O)CN(S(=O)(C4=CC=C(N)C=C4)=O)CC(C)C.CCO |
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| Synonyms | Darunavir Ethanolate; TMC-114 Ethanolate; TMC114 Ethanolate; TMC 114 Ethanolate; UIC-94017 Ethanolate; UIC 94017 Ethanolate; UIC94017 Ethanolate; Trade name: Prezista. |
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实验参考方法
| In Vitro | In vitro activity: Darunavir displays potent activity against HIV strains resistant to other available protease inhibitor. Darunavir inhibits P-glycoprotein-mediated efflux of calcein-acetoxymethyl ester in L-MDR1 cells with the inhibitory potency of 121 mM. Darunavir is a protein inhibits that mimics the phenylalanine sequences at positions 167 and 168 of the gag-pol polypeptide and binds to the active sites of the HIV protease, thereby inhibiting its activity. Darunavir blocks the infectivity and replication of each of the HIV-1 variants at concentrations up to 5 μM. Darunavir shows strong ARV activity against a selected panel of 19 recombinant clinical isolates carrying multiple protease mutations conferring resistance to an average of five other protien inhibitors. Darunavir inhibits 75% of 1501 PI-resistant viruses tested with a half maximal effective concentration (EC50) of < 10 nM.
Kinase Assay: Darunavir has a Ki of 1 nM for wild type HIV-1 protease.
Cell Assay: In an in vitro study in MT-2 cells, the potency of darunavir is greater than that of saquinavir, amprenavir, nelfinavir, indinavir, lopinavir and ritonavir. Darunavir is primarily metabolized by the hepatic cytochrome P450 (CYP) enzymes, primarily CYP3A. The ‘boosting’ dose of ritonavir acts an an inhibitor of CYP3A, thereby increasing darunavir bioavailability |
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| In Vivo | Darunavir is effective against wild-type and PI-resistant HIV, and has an oral bioavailability of 37%. It is often used in combination with ritonavir, which increases the bioavailability to 82% |
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| References | Biol Pharm Bull. 2009 Sep;32(9):1588-93; Expert Opin Pharmacother. 2007 Aug;8(12):1951-64. |
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生物活性
| Biological activity-darunavir |
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