BMS-707035 是一种有效的口服活性 HIV-1 整合酶链转移抑制剂 (INSTI)。
BMS-707035 is a specific HIV-I integrase (IN) inhibitor with IC50 value of 15 nM [1].
Retroviral IN is an enzyme produced by a retrovirus (such as HIV) that enables its genetic material to be integrated into the DNA of the infected cell. IN is a key component in the retroviral pre-integration complex (PIC) [1].
BMS-707035 is an investigational IN inhibitor. However, the IN mutations V75I, Q148R, V151I, and G163R are found to have resistance to BMS-707035. The inhibition of strand transfer activity by BMS-707035 is overcome when increasing amount of target DNA, so the binding of BMS-707035 to IN and target DNA to IN are mutually exclusive. The four terminal bases at the 5' end of LTR can affect the binding of BMS-707035 to IN [3]. The 3' terminus of the viral LTR can regulate the kinetics of binding and dissociation, which will then retard the rate of BMS-707035 association with IN [2].
参考文献:
[1]. Cotelle P. 3-Hydroxy-6,7-dihydropyrimido[2,1-c][1,4]oxazin-4(9H)-ones as new HIV-1 integrase inhibitors WO2011046873 A1. Expert Opin. Ther Patents, 2011, 21(11): 1799-1804.
[2]. Langley DR, Samanta HK, Lin Z, et al. The terminal (catalytic) adenosine of the HIV LTR controls the kinetics of binding and dissociation of HIV integrase strand transfer inhibitors. Biochemistry, 2008, 47(51): 13481-13488.
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Cell lines |
Human immunodeficiency virus (HIV) |
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Preparation method |
The solubility of this compound in DMSO is > 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
IC50: 15 nM |
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Applications |
BMS-707035 was a potent, specific, and reversible HIV-I integrase (IN) inhibitor that blocked HIV IN strand transfer activity with IC50 of 15 nM. Several IN mutations, including V75I, Q148R, V151I, and G163R were resistant to HIV IN inhibitors. The binding of BMS-707035 and target DNA to IN was mutually exclusive events, as revealed by the fact that the inhibition of strand transfer catalysis by BMS-707035 was overcome by increasing amount of target DNA. The binding affinity of BMS-707035 to IN was affected by the four terminal bases at the 5' end of the pre-processed U5 long terminal repeat (LTR). Gln148 of IN was crucial for the binding of BMS-707035 to IN. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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参考文献: [1]. Dicker I B, Samanta H K, Li Z, et al. Changes to the HIV long terminal repeat and to HIV integrase differentially impact HIV integrase assembly, activity, and the binding of strand transfer inhibitors[J]. Journal of Biological Chemistry, 2007, 282(43): 31186-31196. | |
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