Lomibuvir (VX-222)

製品コードS1480 バッチS148001

印刷

化学情報

Synonyms

VCH-222

Storage
(From the date of receipt)

3 years -20°C powder
1 years -80°C in solvent

化学式

C₂₅H₃₅NO₄S

分子量

445.61

CAS No.

1026785-59-0

Solubility (25°C)*

体外

DMSO

89 mg/mL (199.72 mM)

Ethanol

89 mg/mL (199.72 mM)

Water

Insoluble

体内（毎回新しく調製した物を用意してください）

Clear solution

30%PEG400 1 0.5%Tween80 2 5%propylene glycol

30.0mg/ml

Taking the 1 mL working solution as an example, add 300 μL of 100 mg/ml clarified PEG400 stock solution to 5 μL of Tween80, mix evenly to clarify it; add 50 μL Propylene glycol to the above system, mix evenly to clarify it; then continue to add 645 μL ddH2O to adjust the volume. to 1 mL. 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	Lomibuvir (VX-222, VCH-222) is a novel, potent and selective inhibitor of HCV polymerase with IC50 of 0.94-1.2 μM, 15.3-fold less effective for mutant M423T, and 108-fold less effective for mutant I482L. Phase 2.
in vitro	VX-222 binds to the thumb II allosteric pocket of the HCV RNA-dependent RNA polymerase. VX-222 exhibits non-competitive and selective inhibition in HCV NS5B of genotype 1a and 1b, with IC50 of 0.94 and 1.2 μM, respectively. VX-222 selectively inhibits the replication of subgenomic HCV genotype 1a and 1b with an EC50 of 22.3 and 11.2 nM, respectively. ^[1] Similarly, a recent study shows that VX-222 inhibits the 1b/Con1 HCV subgenomic replicon, with an EC50 of 5 nM. VX-222 preferentially inhibits primer-dependent RNA synthesis, showing only a modest or no effect on de novo-initiated RNA synthesis. ^[2]
in vivo	In rats and dogs, VCH-222 displays fine pharmacokinetic proﬁle, including low total body clearance and excellent oral bioavailability (greater than 30%) and good ADME properties. VCH-222 is biotransformed by several enzymes (CYP1A1, 2A6, 2B6, 2C8, CYP 3A4, UGT1A3) and is predicted to be actively transported in liver and excreted mainly intact in bile or as glucuronide adducts. ^[3]
特徴	A novel, potent and selective inhibitor of non-nucleoside polymerase, specifically the HCV RNA-dependent RNA polymerase.

プロトコル(参考用のみ)

キナーゼアッセイ	Anti-NS5B activity assay
キナーゼアッセイ	The inhibitory effect of VX-222 on HCV NS5B activity is measured by evaluating the amount of radiolabeled UTP incorporated by the C-terminal ∆21 truncated version of enzyme in a newly synthesized RNA using a homopolymeric RNA template / primer namely poly rA / oligo dT. Quantitative detection of incorporated radioactivity is done using a liquid scintillation counter. The in vitro kinetics of inhibition of HCV NS5B from genotype 1b strain BK by VX-222 are determined using the C-terminal ∆21 truncated version of NS5B. VX-222 (1 to 1.5 μM) is tested in the presence of 10 to 75 μM nonradioactive UTP mixed with 0.89 to 6.70 μCi of [α-³³P]-labeled UTP. RNA-dependent-RNA polymerase reactions are allowed to proceed for 18 min at 22 °C.
細胞アッセイ	細胞株	Huh7.5 cells
	濃度	0.01 nM -10 μM
	反応時間	48 hours
	実験の流れ	Huh7.5 cells harboring HCV RNA replicons are trypsinized and plated into 48-well plates at a concentration of 4 × 10⁴ cells/well. The next day the medium is changed and VX-222 is added in 200 μL of complete medium. After 48 hours, total RNA is extracted and viral RNAs are quantiﬁed by real-time reverse transcription-PCR (RT-PCR). The effective drug concentrations that reduced HCV RNA replicon levels by 50% (EC50) are calculated by nonlinear regression analysis with log curve ﬁtting.
動物実験	動物モデル	Rats or dogs
	投薬量	5 mg/kg for rats or 10 mg/kg for dogs
	投与方法	By oral gavage

参考

カスタマーフィードバック

: Data from [Intervirology, 2013, 56(5), 302-9]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

SMG6 regulates DNA damage and cell survival in Hippo pathway kinase LATS2-inactivated malignant mesothelioma [ Cell Death Discov, 2022, 8(1:446)]	PubMed: 36335095
Development of recombinant infectious hepatitis E virus harboring the nanoKAZ gene and its application in drug screening [ J Virol, 2022, jvi0190621]	PubMed: 35107380
Characterization of fluorescent probe substrates to develop an efficient high-throughput assay for neonatal hepatic CYP3A7 inhibition screening [ Sci Rep, 2021, 11(1):19443]	PubMed: 34593846
Antiviral Candidates for Treating Hepatitis E Virus Infection. [ Antimicrob Agents Chemother, 2019, 63(6)]	PubMed: 30885901
PI4KIII inhibitor enviroxime impedes the replication of the hepatitis C virus by inhibiting PI3 kinases [ J Antimicrob Chemother, 2018, 73(12):3375-3384]	PubMed: 30219827
Differential modulation of hepatitis C virus replication and innate immune pathways by synthetic calcitriol-analogs [ J Steroid Biochem Mol Biol, 2018, 183:142-151]	PubMed: 29885880
Quantifying antiviral activity optimizes drug combinations against hepatitis C virus infection. [ Proc Natl Acad Sci U S A, 2017, 114(8):1922-1927]	PubMed: 28174263
The Tumor Suppressor p53 Limits Ferroptosis by Blocking DPP4 Activity [ Cell Rep, 2017, 20(7):1692-1704]	PubMed: 28813679
Broad-spectrum non-nucleoside inhibitors for caliciviruses. [ Antiviral Res, 2017, 146:65-75]	PubMed: 28757394
De Novo RNA Synthesis by RNA-Dependent RNA Polymerase Activity of Telomerase Reverse Transcriptase. [ Mol Cell Biol, 2016, 36(8):1248-59]	PubMed: 26830230

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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