Lersivirine (UK-453061)

製品コード：S8055 純度：99.50%

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

CAS No. 473921-12-9

サイズ	価格(税別)	在庫状況
5mg	JPY 33500	国内在庫あり
25mg	JPY 96600	国内在庫あり

代表番号: 045-509-1970\|電子メール：[email protected] よく尋ねられる質問

製品安全説明書

現在のバッチを見る：純度： 99.50%

99.50

Lersivirine (UK-453061)関連製品

関連ターゲット	HBV RT HIV RT RT	もっと見る
関連化合物ライブラリー	Anti-infection Compound Library Antibiotics compound Library Antiviral Compound Library Anti-parasitic Compound Library Gut Microbial Metabolite Library	もっと見る

シグナル伝達経路

Reverse Transcriptaseシグナル伝達経路

Reverse Transcriptase阻害剤の選択性比較

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.

Targets

NNRT ^[2]

In Vitro
In vitro	Lersivirine binds to HIV-1 wt reverse transcriptase (RT) with K_d 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]
Kinase Assay	RT enzyme assays
Kinase Assay	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.
細胞実験	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.

In Vivo
In Vivo	Lersivirine is not teratogenic in mice.^[3]
動物実験	動物モデル	Mated Crl:CD1(ICR) mice
	投与量	150 mg/kg, 350 mg/kg, 500 mg/kg
	投与経路	Oral gavage

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-01-11)
NCT01220232	Completed	Healthy Volunteers	Pfizer\|ViiV Healthcare	November 2010	Phase 1
NCT01230385	Completed	Healthy Volunteers	Pfizer\|ViiV Healthcare	October 2010	Phase 1
NCT00925535	Completed	Healthy Volunteers	Pfizer	May 2010	Phase 1
NCT01050751	Completed	Healthy Volunteers	Pfizer	February 2010	Phase 1

参考
[1] Corbau R, et al. Antimicrob Agents Chemother, 2010, 54(10), 4451-4463. [2] Charles E Mowbray, et al. Bioorg Med Chem Lett. 2009 Oct 15;19(20):5857-60. [3] Gregg D Cappon, et al. Birth Defects Res B Dev Reprod Toxicol. 2012 Jun;95(3):225-30.

参考

化学情報

分子量	310.35	化学式	C₁₇H₁₈N₄O₂
CAS No.	473921-12-9	SDF	--
Smiles	CCC1=C(C(=NN1CCO)CC)OC2=CC(=CC(=C2)C#N)C#N
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1年-80°Cin solvent
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1个月-20°Cin solvent

In vitro
Batch:

DMSO : 62 mg/mL ( (199.77 mM)；吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Ethanol : 62 mg/mL

Water : Insoluble

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機

実験計算

モル濃度計算器

質量	濃度	体積	分子量
=	×	×

希釈計算器分子量計算器

投与溶液組成計算機(クリア溶液)

ステップ１：実験データを入力してください。（実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します）

投与量 mg/kg 動物平均体重 g 投与体積（動物毎）μL 動物数匹

ステップ２：投与溶媒の組成を入力してください。（ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください）

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

計算結果：

投与溶媒濃度： mg/ml;

DMSOストック溶液調製方法： mg 試薬を μL DMSOに溶解する（濃度 mg/mL, 注：濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法：Take μL DMSOストック溶液に μL PEG300，を加え、完全溶解後μL Tween 80，を加えて完全溶解させた後 μL ddH₂O，を加え完全に溶解させます。

投与溶媒調製方法：μL DMSOストック溶液に μL Corn oil，を加え、完全溶解。

注意：１.ストック溶液に沈殿、混濁などがないことをご確認ください；
２.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

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Handling Instructions

他に質問がある場合は、お気軽にお問い合わせください。

* 必須

C1=C0/X	C1:	LOG(C1):
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C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):