Compound Info
NAs Base Info
ID Cluster Name Target MolWt
Compound Structure
NAs.004450 0 GS-461203
Target name Tax id
DNA-directed RNA polymerase II subunit RPB1
DNA-directed RNA polymerase
mitochondrial
DNA polymerase alpha subunit
Hepatitis C virus NS5B RNA-dependent RNA polymerase
DNA polymerase gamma subunit 1
DNA polymerase beta
Nonstructural protein 5
500.158
Chemical Representations
InChI InChI=1S/C10H16FN2O14P3/c1-10(11)7(15)5(25-8(10)13-3-2-6(14)12-9(13)16)4-24-29(20,21)27-30(22,23)26-28(17,18)19/h2-3,5,7-8,15H,4H2,1H3,(H,20,21)(H,22,23)(H,12,14,16)(H2,17,18,19)/t5-,7-,8-,10-/m1/s1
InChI Key IPHULAIUXUVCHH-VPCXQMTMSA-N
SMILES C[C@@]1(F)[C@H](O)[C@@H](COP(=O)(O)OP(=O)(O)OP(=O)(O)O)O[C@H]1n1ccc(=O)[nH]c1=O
Molecular Formula C10H16FN2O14P3
Functional Fragments
Base Ribose Phosphate
Base Structure
Match
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Match
Calculated Properties
logP -1.134 Computed by RDKit
Heavy Atom Count 30 Computed by RDKit
Ring Count 2 Computed by RDKit
Hydrogen Bond Acceptor Count 11 Computed by RDKit
Hydrogen Bond Donor Count 6 Computed by RDKit
Rotatable Bond Count 8 Computed by RDKit
Topological Polar Surface Area 244.140 Computed by RDKit
Activity Data
Target Activity type Relation Value Unit Assay Source
Hepatitis C virus IC50 = 1190.0 nM Inhibition of RNA synthesis activity of HSV 1b Con1 replicase CHEMBL1156500
Hepatitis C virus IC50 Antiviral activity against HCV 1b Con1 in 2209-23 cells after 72 hrs by luciferase based replicon assay CHEMBL1156500
Hepatitis C virus IC50 = 520.0 nM Inhibition of RNA synthesis activity of HSV 1b Con1 NS5B polymerase CHEMBL1156500
Hepatitis C virus Ki = 141.0 nM Inhibition of RNA synthesis activity of HSV 1b Con1 NS5B polymerase CHEMBL1156500
Hepatocyte T1/2 = 38.0 hr Drug uptake in human hepatocyte assessed as time needed for triphosphate to be reduced to half of maximum level CHEMBL1156500
Unchecked Ki = 420.0 nM Inhibition of wild type HCV NS5B polymerase assessed as incorporation of [alpha32P]UTP into newly synthesized RNA by liquid scintillation counting CHEMBL1152990
Unchecked Ki = 68.0 nM Activity of wild type HCV NS5B polymerase CHEMBL1152990
Unchecked Ki/Km = 6.2 Ratio of Ki to Km for wild type HCV NS5B polymerase CHEMBL1152990
Hepatitis C virus NS5B RNA-dependent RNA polymerase Ki = 22000.0 nM Inhibition of HCV NS5B polymerase S282T mutant assessed as incorporation of [alpha32P]UTP into newly synthesized RNA by liquid scintillation counting CHEMBL1152990
Hepatitis C virus NS5B RNA-dependent RNA polymerase Km = 150.0 nM Activity of HCV NS5B polymerase S282T mutant CHEMBL1152990
Hepatitis C virus NS5B RNA-dependent RNA polymerase Ki/Km = 147.0 Ratio of Ki to Km for HCV NS5B polymerase S282T mutant CHEMBL1152990
Unchecked Ratio = 23.7 Fold resistance, ratio of Ki/Km for HCV NS5B polymerase S282T mutant to Ki/Km for wild type HCV NS5B polymerase CHEMBL1152990
Hepatocyte T1/2 = 38.0 hr Metabolic stability in human hepatocytes assessed as PSI-6130 triphosphate half life at 2 uM CHEMBL1152990
DNA-directed RNA polymerase II subunit RPB1 Inhibition = 85.0 % Inhibition of human RNA polymerase 2 assessed as synthesis of RNA products at 500 uM CHEMBL1629705
DNA-directed RNA polymerase II subunit RPB1 IC50 > 500000.0 nM Inhibition of human RNA polymerase 2 CHEMBL1629705
DNA-directed RNA polymerase II subunit RPB1 Inhibition % Inhibition of human RNA polymerase 2 assessed as synthesis of RNA products at 1 uM CHEMBL1629705
Hepatitis C virus IC50 = 1600.0 nM Inhibition of Hepatitis C virus Con1 recombinant NS5B polymerase after 30 mins by phosphor imaging CHEMBL1629705
Unchecked IC50 = 2800.0 nM Inhibition of Hepatitis C virus genotype 1a JFH-1 recombinant NS5B polymerase after 30 mins by phosphor imaging CHEMBL1629705
Unchecked IC50 = 700.0 nM Inhibition of Hepatitis C virus genotype 3a recombinant NS5B polymerase after 3 hrs by phosphor imaging CHEMBL1629705
Unchecked IC50 = 2600.0 nM Inhibition of Hepatitis C virus genotype 4a recombinant NS5B polymerase after 3 hrs by phosphor imaging CHEMBL1629705
Hepatocyte T1/2 = 38.0 hr Half life in human hepatocytes CHEMBL1629705
DNA polymerase alpha subunit IC50 = 550000.0 nM Inhibition of human DNA polymerase alpha assessed as incorporation of [alpha-32P]dCTP up to 1mM preincubated for 30 mins by whatman DE81 paper binding assay CHEMBL1629705
DNA polymerase beta IC50 > 1000000.0 nM Inhibition of human DNA polymerase beta assessed as incorporation of [alpha-32P]dCTP up to 1mM preincubated for 30 mins by whatman DE81 paper binding assay CHEMBL1629705
DNA polymerase gamma subunit 1 IC50 > 1000000.0 nM Inhibition of human DNA polymerase gamma assessed as incorporation of [alpha-32P]dCTP up to 1mM preincubated for 30 mins by whatman DE81 paper binding assay CHEMBL1629705
ADMET T1/2 = 38.0 hr Half life in primary human hepatocytes treated with PSI-6130 at 2 uM by HPLC method CHEMBL4011639
Unchecked IC50 > 100000.0 nM Inhibition of RNA polymerase 2 isolated from human HeLa cell nuclear extract assessed as decrease in incorporation of P32-alpha-CTP after 2 hrs by scintillation counting method CHEMBL4014354
DNA-directed RNA polymerase, mitochondrial Activity = 3.1 % Inhibition of human POLRMT using 5'-P32-RNA/DNA hybrid assessed as incorporation of UTP at 100 uM after 2 hrs by scintillation counting method relative to control CHEMBL4014354
DNA polymerase alpha subunit IC50 > 100000.0 nM Inhibition of human DNA polymerase alpha using 5' end radiolabeled 24nt DNA/48nt DNA as primer/template after 5 mins by PAGE analysis CHEMBL4014354
DNA polymerase beta IC50 > 100000.0 nM Inhibition of human DNA polymerase beta using 5' end radiolabeled 24nt DNA/48nt DNA as primer/template after 5 mins by PAGE analysis CHEMBL4014354
Unchecked IC50 > 100000.0 nM Inhibition of human DNA polymerase gamma using 5' end radiolabeled 24nt DNA/36nt DNA as primer/template after 120 mins by PAGE analysis CHEMBL4014354
Unchecked Ratio IC50 = 7.7 Selectivity ratio of IC50 for HCV genotype 1b NS5B RNA dependent RNA polymerase S282T mutant to IC50 for wild-type HCV genotype 1b NS5B RNA dependent RNA polymerase CHEMBL4043192
Hepatitis C virus NS5B RNA-dependent RNA polymerase IC50 = 606.0 nM Inhibition of HCV genotype 1b NS5B RNA dependent RNA polymerase S282T mutant CHEMBL4043192
Unchecked IC50 = 79.0 nM Inhibition of wild-type HCV genotype 1b NS5B RNA dependent RNA polymerase CHEMBL4043192
Unchecked Ki = 490.0 nM Inhibition of HCV genotype 1b NS5B RNA dependent RNA polymerase CHEMBL4052672
Nonstructural protein 5 IC50 = 18000.0 nM Inhibition of Dengue virus RdRp activity using 5'-(TCAG)20(TCCAAG)14(TCAG)20-3' as template measured after 120 mins CHEMBL4118212
DNA-directed RNA polymerase, mitochondrial Activity = 1.8 % Inhibition of human POLRMT using 5'-FAM labelled RNA primer/DNA template duplex assessed as single nucleotide incorporation rate at 500 uM after 5 mins by SDS-PAGE analysis relative to control CHEMBL4118212
DNA polymerase alpha subunit Inhibition = 58.2 % Inhibition of human DNA polymerase-alpha assessed as reduction in [3H]dTTP incorporation in to activated calf thymus DNA substrate at 100 uM by scintillation counting method relative to control CHEMBL4393666
DNA polymerase beta Inhibition = 14.0 % Inhibition of human DNA polymerase-beta assessed as reduction in [3H]dTTP incorporation in to activated calf thymus DNA substrate at 100 uM by scintillation counting method relative to control CHEMBL4393666
DNA polymerase gamma subunit 1 Inhibition = 9.2 % Inhibition of human DNA polymerase-gamma assessed as reduction in [3H]dTTP incorporation in to activated calf thymus DNA substrate at 100 uM by scintillation counting method relative to control CHEMBL4393666
Unchecked IC50 > 100000.0 nM Inhibition of RNA polymerase 2 in human HeLa cell nuclear extract assessed as reduction in RNA transcription by PAGE analysis CHEMBL4393666
Unchecked IC50 > 100000.0 nM Inhibition of human DNA polymerase gamma using 5-end radiolabeled 24nt to 48nt DNA as primer template after 120 mins in presence of dCTP/dGTP/dTTP/dATP by PAGE analysis CHEMBL4411318
DNA polymerase beta IC50 > 100000.0 nM Inhibition of human DNA polymerase beta using 5-end radiolabeled 24nt to 48nt DNA as primer template after 5 mins in presence of dCTP/dGTP/dTTP/dATP by PAGE analysis CHEMBL4411318
DNA polymerase alpha subunit IC50 > 100000.0 nM Inhibition of human DNA polymerase alpha using 5-end radiolabeled 24nt to 48nt DNA as primer template after 5 mins in presence of dCTP/dGTP/dTTP/dATP by PAGE analysis CHEMBL4411318
DNA-directed RNA polymerase, mitochondrial Activity = 3.1 % Substrate activity at human POLRMT assessed as 5-radiolabled RNA/DNA incorporation levels at 100 uM after 2 hrs by PAGE analysis CHEMBL4411318
Unchecked Ratio IC50 = 0.53 Selectivity ratio of IC50 for HCV genotype 1a NS5B polymerase to IC50 for wild type HCV genotype 1b NS5B polymerase CHEMBL4411318
Hepatitis C virus NS5B RNA-dependent RNA polymerase IC50 = 180.0 nM Inhibition of NS5B polymerase in HCV genotype 1b infected in human HuH7 replicon cells after 96 hrs by RT-PCR analysis CHEMBL4411318
Hepatitis C virus NS5B RNA-dependent RNA polymerase IC50 = 96.0 nM Inhibition of NS5B polymerase in HCV genotype 1a infected in human HuH7 replicon cells after 96 hrs by RT-PCR analysis CHEMBL4411318
Hepatitis C virus NS5B RNA-dependent RNA polymerase IC50 = 380.0 nM Inhibition of NS5B polymerase in HCV genotype 3a infected in human HuH7 replicon cells after 96 hrs by RT-PCR analysis CHEMBL4411318
Hepatitis C virus NS5B RNA-dependent RNA polymerase IC50 = 130.0 nM Inhibition of NS5B polymerase in HCV genotype 6a infected in human HuH7 replicon cells after 96 hrs by RT-PCR analysis CHEMBL4411318
Hepatitis C virus NS5B RNA-dependent RNA polymerase IC50 = 7300.0 nM Inhibition of NS5B polymerase S282T mutant in HCV genotype 1b infected in human HuH7 replicon cells after 96 hrs by RT-PCR analysis CHEMBL4411318
Hepatitis C virus NS5B RNA-dependent RNA polymerase IC50 = 290.0 nM Inhibition of NS5B polymerase in HCV genotype 2a infected in human HuH7 replicon cells after 96 hrs by RT-PCR analysis CHEMBL4411318
Hepatitis C virus NS5B RNA-dependent RNA polymerase IC50 = 570.0 nM Inhibition of NS5B polymerase in HCV genotype 4a infected in human HuH7 replicon cells after 96 hrs by RT-PCR analysis CHEMBL4411318
Hepatitis C virus NS5B RNA-dependent RNA polymerase IC50 = 430.0 nM Inhibition of NS5B polymerase in HCV genotype 5a infected in human HuH7 replicon cells after 96 hrs by RT-PCR analysis CHEMBL4411318
Unchecked Ratio IC50 = 2.1 Selectivity ratio of IC50 for HCV genotype 3a NS5B polymerase to IC50 for wild type HCV genotype 1b NS5B polymerase CHEMBL4411318
Unchecked Ratio IC50 = 3.2 Selectivity ratio of IC50 for HCV genotype 4a NS5B polymerase to IC50 for wild type HCV genotype 1b NS5B polymerase CHEMBL4411318
Unchecked Ratio IC50 = 2.4 Selectivity ratio of IC50 for HCV genotype 5a NS5B polymerase to IC50 for wild type HCV genotype 1b NS5B polymerase CHEMBL4411318
Unchecked Ratio IC50 = 0.72 Selectivity ratio of IC50 for HCV genotype 6a NS5B polymerase to IC50 for wild type HCV genotype 1b NS5B polymerase CHEMBL4411318
Unchecked Ratio IC50 = 1.6 Selectivity ratio of IC50 for HCV genotype 2a NS5B polymerase to IC50 for wild type HCV genotype 1b NS5B polymerase CHEMBL4411318
Unchecked Ratio IC50 = 41.0 Selectivity ratio of IC50 for HCV genotype 1b NS5B polymerase S282T mutant to IC50 for wild type HCV genotype 1b NS5B polymerase CHEMBL4411318