Lersivirine (UK-453061)

製品コードS8055 バッチS805501

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C17H18N4O2
分子量 310.35 CAS No. 473921-12-9
Solubility (25°C)* 体外 DMSO 62 mg/mL (199.77 mM)
Ethanol 62 mg/mL (199.77 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

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生物活性

製品説明 Lersivirine (UK-453061) is a potent and selective inhibitor of nonnucleoside reverse transcriptase (NNRTI) with IC50 of 0.119 μM.

生物活性

製品説明 Lersivirine (UK-453061) is a potent and selective inhibitor of nonnucleoside reverse transcriptase (NNRTI) with IC50 of 0.119 μM.
in vitro

Lersivirine binds to HIV-1 wt reverse transcriptase (RT) with Kd of 624 nM. Lersivirine is a very weak inhibitor of human DNA polymerase beta, with an extrapolated geometric mean IC50 of approximately 20 mM resulting in a predicted selectivity index of 166,000. Lersivirine is able to inhibit HIV-1 virus replication in MT-2 cells infected with wt NL4-3, with an EC50 ranging from 5 nM to 35 nM against an MOI ranging from 0.005 to 0.5. Lersivirine retains activity against 80% of viruses with genotypes containing K103N as a single NNRTI mutation (versus 7% for efavirenz), 57% of viruses with genotypes containing Y181C as a single NNRTI mutation (43% for efavirenz), and 46% of viruses with genotypes containing G190A as a single NNRTI mutation (0% for efavirenz). Lersivirine inhibits the replication of strain Ba-L in PBL, with a geometric mean EC50 equal to 3.38 nM (95% CI, 2.26 to 5.05 nM) and an EC90 equal to 9.87 nM (95% CI, 6.63 to 14.7 nM), with no cytotoxicity observed up to 50 μM. Combinations of lersivirine with drugs of the NRTI class (abacavir, didanosine, emtricitabine, lamivudine, tenofovir, and zidovudine) results in synergistic interactions. [1]
in vivo

Lersivirine is not teratogenic in mice.[3]

プロトコル(参考用のみ)

キナーゼアッセイ RT enzyme assays
The activities of lersivirine and efavirenz against wt RT (BH10 strain) are determined using a primer extension assay incorporating a DNA/RNA primer/template. The 5’biotinylated primer DNA is a 16mer oligo(dT), which is annealed to a poly(rA) template of approximately 300 bases in length. Incorporation of [3H]TTP(dTTP) by reverse transcription results in extension of the primer. During the reaction the primer/template is bound to a streptavidin-coated flashplate (NEN). The incorporated tritiated nucleotides can then stimulate the scintillant to produce a signal that is measured using a scintillation counter. Compounds that inhibit the RNA-dependent DNA polymerase activity of RT produce a reduced signal.
細胞アッセイ 細胞株 SupT1 cells
濃度 increasing concentrations from 5 nM
反応時間 Every 7 days
実験の流れ

For inhibitor escalation studies, SupT1 cells are initially infected with HIV-1 NL4-3 wt for 1 h at 37°C and the virus-infected cells are passaged weekly in SupT1 cells in the presence of increasing concentrations of lersivirine from a starting concentration of 5 nM (IC50 in this assay system) in 12-well plates (6 × 105 cells/well). Throughout the passaging period, ongoing virus replication is monitored weekly by observing cytopathic effects (syncytia). Every 7 days, virus supernatant is passaged onto fresh cells at the same density with fresh lersivirine-containing medium. The concentration of lersivirine is increased by 2-fold and 5-fold that of the previous concentration upon subsequent passage whenever evidence of viral replication is observed. Virus stocks for phenotypic characterization are produced in SupT1 cells in the absence of compound and are tested for their sensitivity to lersivirine in an antiviral assay using HeLaP4 cells.
動物実験 動物モデル Mated Crl:CD1(ICR) mice
投薬量 150 mg/kg, 350 mg/kg, 500 mg/kg
投与方法 Oral gavage

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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