Lersivirine (UK-453061)

製品コードS8055 バッチS805502

印刷

化学情報

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

31 mg/mL (99.88 mM)

Ethanol

16 mg/mL (51.55 mM)

Water

Insoluble

体内（毎回新しく調製した物を用意してください）

Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	1.550mg/ml (4.99mM)	Taking the 1 mL working solution as an example, add 50 μL of 31 mg/ml clarified DMSO stock solution to 400 μL PEG300, mix evenly to clarify it; add 50 μL Tween80 to the above system, mix evenly to clarify it; then continue to add 500 μL ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% corn oil この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	1.550mg/ml (4.99mM)	Taking the 1 mL working solution as an example, add 50 μL of 31 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

* <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.

溶剤液（一定の濃度）を調合する

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 (UK-453061) binds to HIV-1 wt reverse transcriptase (RT) with K_d of 624 nM. It 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. This compound 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. It 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 this compound with drugs of the NRTI class (abacavir, didanosine, emtricitabine, lamivudine, tenofovir, and zidovudine) results in synergistic interactions. ^[1]
in vivo	In mice, Lersivirine (UK-453061) is not teratogenic.^[3]

プロトコル(参考用のみ)

キナーゼアッセイ	RT enzyme assays
キナーゼアッセイ	The activities of lersivirine (UK-453061) 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. This compound inhibits the RNA-dependent DNA polymerase activity of RT, producing 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 (UK-453061) 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 medium containing this compound. The concentration of it 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

参考

https://pubmed.ncbi.nlm.nih.gov/20660667/
https://pubmed.ncbi.nlm.nih.gov/19748778/
https://pubmed.ncbi.nlm.nih.gov/22447726/

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。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。