BMS-707035 is a novel, potent, specific, and reversible inhibitor of HIV-I integrase (IN) with IC50 of 15 nM. 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.
理化性质和储存条件
| Molecular Weight (MW) | 410.42 |
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| Formula | C17H19FN4O5S |
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| CAS No. | 729607-74-3 |
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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: 38 mg/mL (92.6 mM) |
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| Water:<1 mg/mL |
| Ethanol:<1 mg/mL |
| SMILES | FC1=CC=C(C=C1)CNC(C(N=C(N2C)N3S(CCCC3)(=O)=O)=C(C2=O)O)=O |
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| Synonyms | BMS-707035; BMS-707035; BMS-707035; 2-(1,1-dioxido-1,2-thiazinan-2-yl)-N-(4-fluorobenzyl)-5-hydroxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide |
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实验参考方法
| In Vitro | In vitro activity: BMS-707035 is a pyrimidine carboxamide similar to Raltegravir, the first integrase inhibitor licensed for clinical use. BMS-707035 is a potent, specific, and reversible HIV-I integrase (IN) inhibitor that blocks HIV IN strand transfer activity with IC50 of 15 nM. However, several IN mutations, including V75I, Q148R, V151I, and G163R are found to confer resistance to HIV IN inhibitors. The binding of BMS-707035 and target DNA to IN are mutually exclusive events, as revealed by the fact that the inhibition of strand transfer catalysis by BMS-707035 is overcome by increasing amount of target DNA. The binding affinity of BMS-707035 to IN is also affected by the four terminal bases at the 5' end of the pre-processed U5 long terminal repeat (LTR). Gln148 of IN is crucial for the binding of BMS-707035 to IN. The 3' terminus of the viral LTR, on the other hand, retards the rate of BMS-707035 association with IN, by regulating the kinetics of binding and dissociation.
Kinase Assay: BMS-707035 is an HIV-1 integrase (IN) inhibitor with an IC50 value of 15 nM. |
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| References | J Biol Chem. 2007 Oct 26;282(43):31186-96; Biochemistry. 2008 Dec 23;47(51):13481-8. |
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