817204-33-4

817204-33-4 structure

Name: PSI-6130
Chemical Name: 4-amino-1-[(2R,3R,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)-3-methyloxolan-2-yl]pyrimidin-2-one
CAS Number: 817204-33-4
Molecular Formula: C₁₀H₁₄FN₃O₄
Molecular Weight: 259.234
Catalog: Signaling Pathways Anti-infection HCV
Create Date: 2018-12-30 17:54:46
Modify Date: 2024-01-04 01:03:42
PSI-6130 is a potent and selective inhibitor of HCV NS5B polymerase, and inhibits HCV replication with a mean IC50 of 0.6 μM.

Name	4-amino-1-[(2R,3R,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)-3-methyloxolan-2-yl]pyrimidin-2-one
Synonyms	2'-Deoxy-2'-fluoro-2'-methylcytidine Cytidine, 2'-deoxy-2'-fluoro-2'-methyl- 2'-Fluoro-2'-C-methylcytidine 2'-deoxy-2'-fluoro-2'-C-methylcytidine PSI6130 R-1656 PSI-6130

Description	PSI-6130 is a potent and selective inhibitor of HCV NS5B polymerase, and inhibits HCV replication with a mean IC50 of 0.6 μM.
Related Catalog	Signaling Pathways >> Metabolic Enzyme/Protease >> HCV Protease Signaling Pathways >> Anti-infection >> HCV Research Areas >> Infection
Target	IC50: 0.6 μM (HCV replication)[2]
In Vitro	PSI-6130 exhibits potent and specific inhibitory activity against HCV RNA replication mediated by the NS5B polymerase. Both PSI-6130 inhibit HCV GT-1b (Con1 strain) and GT-1a (H77 strain) subgenomic RNA replication, with mean EC50 values of 0.51 and 0.30 μM, respectively. PSI-6130 inhibits 40% human serum with EC50 of 0.51 μM[1]. PSI-6130 inhibits HCV replication with a mean IC50 of 0.6 μM, PSI-6130-TP inhibits HCV replicase with a mean IC50 of 0.34 μM. PSI-6130-TP inhibits recombinant HCV Con1 NS5B on a heteropolymeric RNA template derived from the 3′-end of the negative strand of the HCV genome with an IC50 of 0.13 μM and Ki of 0.023 μM[2].
Kinase Assay	The inhibition potency of compounds with respect to the RdRp activity of recombinant NS5B570-BK, NS5B570-Con1, and NS5B570-H77 proteins is determined by measuring the incorporation of radiolabeled NMP into acid-insoluble RNA products by use of a complement strand of internal ribosomal entry site (cIRES) RNA template. Briefly, 50% inhibitory concentration (IC50) determinations are carried out using 200 nM in vitro-transcribed cIRES RNA template, 1 μCi of tritiated UTP (42 Ci/mmol), 500 μM ATP, 500 μM GTP, 1 μM CTP, 1× TMDN buffer (40 mM Tris-HCl [pH 8.0], 4 mM MgCl2, 4 mM dithiothreitol, 40 mM NaCl), and 200 nM enzyme. The inhibition potency of compounds with respect to the RdRp activity of NS5B570-S282T-Con1 is determined under GT-1b assay conditions as. NS5B570-BK and NS5B570-Con1 enzymes are used as controls. The final reaction volume is 50 μL under all assay conditions. All reactions contain a final 10% dimethyl sulfoxide. Km and Ki values are measured.
References	[1]. Ali S, et al. Selected replicon variants with low-level in vitro resistance to the hepatitis C virus NS5B polymerase inhibitor PSI-6130 lack cross-resistance with R1479. Antimicrob Agents Chemother. 2008 Dec;52(12):4356-69. [2]. Ma H, et al. Characterization of the metabolic activation of hepatitis C virus nucleoside inhibitor beta-D-2'-Deoxy-2'-fluoro-2'-C-methylcytidine (PSI-6130) and identification of a novel active 5'-triphosphate species. J Biol Chem. 2007 Oct 12;282(41):29812-20. Epub 2007 Aug 13.

Density	1.7±0.1 g/cm3
Boiling Point	482.4±55.0 °C at 760 mmHg
Molecular Formula	C₁₀H₁₄FN₃O₄
Molecular Weight	259.234
Flash Point	245.5±31.5 °C
Exact Mass	259.096832
PSA	110.60000
LogP	-0.72
Vapour Pressure	0.0±2.7 mmHg at 25°C
Index of Refraction	1.653

817204-32-3

~93%

817204-33-4

Literature: Carr, Robert; Hildbrand, Stefan; Hodges, Mark L.; Kammerer, Michael; Lang, John F.; Lawrimore, III, William J.; Nguyen, Dieu Patent: US2013/324709 A1, 2013 ; Location in patent: Paragraph 0053; 0054 ;

Precursor 1
817204-32-3
DownStream 1
817204-32-3

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