Sofosbuvir

製品コードS2794 バッチS279402

化学情報

	Synonyms	GS-7977, PSI-7977	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₂₂H₂₉FN₃O₉P
	分子量	529.45	CAS No.	1190307-88-0
Solubility (25°C)*	体外	DMSO	100 mg/mL warmed with 50ºC water bath (188.87 mM)
		Ethanol	100 mg/mL (188.87 mM)
		Water	11 mg/mL warmed with 50ºC water bath (20.77 mM)
* <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	Sofosbuvir is a HCV NS5B polymerase inhibitor for the treatment of chronic hepatitis C virus (HCV) infection.
in vitro	As HCV NS5B polymerase inhibitor, PSI-7977 displays more potent inhibitory activity against HCV RNA replication than PSI-7976 with EC50 of 92 nM versus 1.07 μM and EC90 of 0.29 μM versus 2.99 μM, consistent with that incubating clone A cells with PSI-7977 leads to a higher concentration of PSI-7409 than clone A cells incubated with PSI-7976. PSI-7977 is an effective substrate for CatA to form PSI-352707 with 18-30 fold more potency as compared with PSI-7976. Unlike GS-7976, however, the CES1-mediated hydrolysis of PSI-7977 does not progress in a time-dependent manner. ^[1] The S282T NS5B polymerase mutation but not S96T mutation confers resistance to PSI-7977 with EC90 increases from 0.42 μM to 7.8 μM. When assessed in an 8-day cytotoxicity assay, PSI-7977 displays no cytotoxicity against Huh7, HepG2, BxPC3, and CEM cells even at concentrations up to 100 μM. PSI-7977 treatment for 14 days shows a IC90 of 72.1 μM and 68.6 μM for the inhibition of mtDNA and rDNA, respectively, in HepG2 cells. ^[2] PSI-7977 exhibits potent activity against genotype (GT) 1a, 1b, and 2a (strain JFH-1) replicons and chimeric replicons containing GT 2a (strain J6), 2b, and 3a NS5B polymerase. Sequence analysis of the JFH-1 NS5B region indicates that additional amino acid changes including T179A, M289L, I293L, M434T, and H479P are selected both prior to and after the emergence of S282T, which are required to confer resistance to PSI-7977. ^[3]

製品説明

Sofosbuvir is a HCV NS5B polymerase inhibitor for the treatment of chronic hepatitis C virus (HCV) infection.

in vitro

As HCV NS5B polymerase inhibitor, PSI-7977 displays more potent inhibitory activity against HCV RNA replication than PSI-7976 with EC50 of 92 nM versus 1.07 μM and EC90 of 0.29 μM versus 2.99 μM, consistent with that incubating clone A cells with PSI-7977 leads to a higher concentration of PSI-7409 than clone A cells incubated with PSI-7976. PSI-7977 is an effective substrate for CatA to form PSI-352707 with 18-30 fold more potency as compared with PSI-7976. Unlike GS-7976, however, the CES1-mediated hydrolysis of PSI-7977 does not progress in a time-dependent manner. ^[1] The S282T NS5B polymerase mutation but not S96T mutation confers resistance to PSI-7977 with EC90 increases from 0.42 μM to 7.8 μM. When assessed in an 8-day cytotoxicity assay, PSI-7977 displays no cytotoxicity against Huh7, HepG2, BxPC3, and CEM cells even at concentrations up to 100 μM. PSI-7977 treatment for 14 days shows a IC90 of 72.1 μM and 68.6 μM for the inhibition of mtDNA and rDNA, respectively, in HepG2 cells. ^[2] PSI-7977 exhibits potent activity against genotype (GT) 1a, 1b, and 2a (strain JFH-1) replicons and chimeric replicons containing GT 2a (strain J6), 2b, and 3a NS5B polymerase. Sequence analysis of the JFH-1 NS5B region indicates that additional amino acid changes including T179A, M289L, I293L, M434T, and H479P are selected both prior to and after the emergence of S282T, which are required to confer resistance to PSI-7977. ^[3]

プロトコル(参考用のみ)

細胞アッセイ	細胞株	Huh7, HepG2, BxPC3, and CEM
	濃度	Dissolved in DMSO, final concentrations ~100 μM
	反応時間	8 days
	実験の流れ	Cells are exposed to various concentrations of PSI-7977 for 8 days. At the end of the growth period, MTS dye from the CellTiter 96 AQueous One Solution Cell Proliferation Assay kit is added to each well, and the plate is incubated for an additional 2 hours. The absorbance at 490 nm is read with a Victor3 plate reader using themedium only controlwells as blanks. The 50% inhibition value (IC50) is determined by comparing the absorbance in wells containing cells and PSI-7977 to untreated cell control wells.

参考

カスタマーフィードバック

: Data from [Data independently produced by , , Hepatology, 2017, 66(3):758-771]

: Data from [Data independently produced by , , Antimicrob Agents Chemother, 2016, 60(6):3786-3793.]

: Data from [Data independently produced by , , PLoS One, 2018, 13(11):e0198226]

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：

Hepatitis C virus infects and perturbs liver stem cells [ mBio, 2023, 10.1128/mbio.01318-23]	PubMed: 37938000
Activation of the urotensin-II receptor by remdesivir induces cardiomyocyte dysfunction [ Commun Biol, 2023, 6(1):511]	PubMed: 37173432
An anti-influenza A virus microbial metabolite acts by degrading viral endonuclease PA [ Nat Commun, 2022, 13(1):2079]	PubMed: 35440123
Therapeutic targeting of organelles for inhibition of Zika virus replication in neurons [ Antiviral Res, 2022, S0166-3542(22)00233-9]	PubMed: 36396026
Efficacy decrease of antiviral agents when administered to ongoing hepatitis C virus infections in cell culture [ Front Microbiol, 2022, 13:960676]	PubMed: 35992670
Processing and Subcellular Localization of the Hepatitis E Virus Replicase: Identification of Candidate Viral Factories [ Front Microbiol, 2022, 13:828636]	PubMed: 35283856
Pre-Senescence Induction in Hepatoma Cells Favors Hepatitis C Virus Replication and Can Be Used in Exploring Antiviral Potential of Histone Deacetylase Inhibitors [ Int J Mol Sci, 2021, 22(9)4559]	PubMed: 33925399
HCV Interplay With Mir34a: Implications in Hepatocellular Carcinoma [ Front Oncol, 2021, 11:803278]	PubMed: 35127513
Chronic cardiotoxicity assessment of BMS-986094, a guanosine nucleotide analogue, using human iPS cell-derived cardiomyocytes [ J Toxicol Sci, 2021, 46(8):359-369]	PubMed: 34334557
A bacterial artificial chromosome (BAC)-vectored noninfectious replicon of SARS-CoV-2 [ Antiviral Res, 2020, 185:104974]	PubMed: 33217430

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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