Compound Info
NAs Base Info
ID Cluster Name Target MolWt
Compound Structure
NAs.004200 0
Target name Tax id
Hepatitis C virus NS5B RNA-dependent RNA polymerase 10090.0
Acyl coenzyme A:cholesterol acyltransferase 10090.0
UMP-CMP kinase 10090.0
Histidine triad nucleotide-binding protein 1 10090.0
598.565
Chemical Representations
InChI InChI=1S/C26H36FN4O9P/c1-6-10-21(32)28-20-13-14-31(25(35)29-20)24-26(5,27)22(33)19(39-24)15-37-41(36,40-18-11-8-7-9-12-18)30-17(4)23(34)38-16(2)3/h7-9,11-14,16-17,19,22,24,33H,6,10,15H2,1-5H3,(H,30,36)(H,28,29,32,35)/t17-,19+,22+,24+,26+,41-/m0/s1
InChI Key JBZNUSDZMYOPGK-FVXPEPLUSA-N
SMILES CCCC(=O)Nc1ccn([C@@H]2O[C@H](CO[P@@](=O)(N[C@@H](C)C(=O)OC(C)C)Oc3ccccc3)[C@@H](O)[C@@]2(C)F)c(=O)n1
Molecular Formula C26H36FN4O9P
Functional Fragments
Base Ribose Phosphate
Base Structure
Match
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Match
Calculated Properties
logP 3.102 Computed by RDKit
Heavy Atom Count 41 Computed by RDKit
Ring Count 3 Computed by RDKit
Hydrogen Bond Acceptor Count 11 Computed by RDKit
Hydrogen Bond Donor Count 3 Computed by RDKit
Rotatable Bond Count 13 Computed by RDKit
Topological Polar Surface Area 167.310 Computed by RDKit
Activity Data
Target Activity type Relation Value Unit Assay Source
Huh-7 Activity Cytotoxicity against human HuH7 cells assessed as reduction in cell viability up to 100 uM after 72 hrs by Cell Titer-Fluor Cell assay CHEMBL4011639
Unchecked EC50 = 240.0 nM Inhibition of wild type NS5B in HCV genotype 1b replicon expressed in human HuH7 cells after 72 hrs by bright Glo-luciferase reporter gene assay CHEMBL4011639
Acyl coenzyme A:cholesterol acyltransferase Drug metabolism Drug metabolism in human HuH7 cells assessed as carboxylesterase 1-mediated (S)-2-((R)-(((2R,3R,4R,5R)-5-(4-butyramido-2-oxopyrimidin-1(2H)-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(hydroxy)phosphorylamino)propanoic acid metabolite formation at 50 uM after 24 hrs by LC/MS/MS analysis CHEMBL4011639
Unchecked Drug metabolism Drug metabolism in human HuH7 cells assessed as carboxylesterase-mediated (S)-2-((S)-(((2R,3R,4R,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(hydroxy)phosphoryloxy)propanoic acid metabolite formation at 50 uM after 24 hrs by LC/MS/MS analysis CHEMBL4011639
Histidine triad nucleotide-binding protein 1 Drug metabolism Drug metabolism in human HuH7 cells assessed as HINT1-mediated ((2R,3R,4R,5R)-5-(4-butyramido-2-oxopyrimidin-1(2H)-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methyl dihydrogen phosphate metabolite formation at 50 uM after 48 hrs by LC/MS/MS analysis CHEMBL4011639
Unchecked Drug metabolism Drug metabolism in human HuH7 cells assessed as carboxylesterase-mediated (S)-2-((S)-(((2R,3R,4R,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(hydroxy)phosphoryloxy)propanoic acid metabolite formation at 50 uM after 48 hrs by LC/MS/MS analysis CHEMBL4011639
Mus musculus Activity Subacute toxicity in ICR mouse assessed as macroscopic pathologic findings at 100 to 1000 mg/kg, administered once a day via oral gavage for 14 days CHEMBL4011639
Mus musculus Activity Subacute toxicity in ICR mouse assessed as weight change in kidney at 100 to 1000 mg/kg, administered once a day via oral gavage for 14 days CHEMBL4011639
Mus musculus Activity Subacute toxicity in ICR mouse assessed as weight change in liver at 100 to 1000 mg/kg, administered once a day via oral gavage for 14 days CHEMBL4011639
Mus musculus Activity Subacute toxicity in ICR mouse assessed as body weight loss at 100 to 1000 mg/kg, administered once a day via oral gavage for 14 days CHEMBL4011639
Mus musculus Activity Subacute toxicity in ICR mouse assessed as clinical signs of toxicity at 100 to 1000 mg/kg, administered once a day via oral gavage for 14 days CHEMBL4011639
Mus musculus Activity Acute toxicity in ICR mouse assessed as body weight loss at 150 to 1800 mg/kg, administered via oral gavage measured once a day over 14 days CHEMBL4011639
Mus musculus Activity Acute toxicity in ICR mouse assessed as mortality at 150 to 1800 mg/kg, administered via oral gavage measured once a day over 14 days CHEMBL4011639
Canis familiaris Activity Toxicity in Beagle dog at 150 mg/kg, administered via oral gavage measured up to 24 hrs post dose CHEMBL4011639
Canis familiaris AUC = 411.3 ng.hr.mL-1 AUC (0 to infinity) in Beagle dog at 150 mg/kg, administered via oral gavage measured up to 24 hrs post dose by LC/MS/MS analysis CHEMBL4011639
Canis familiaris AUC = 248.1 ng.hr.mL-1 AUClast in Beagle dog at 150 mg/kg, administered via oral gavage measured up to 24 hrs post dose by LC/MS/MS analysis CHEMBL4011639
Canis familiaris Cmax = 85.71 nM Cmax in Beagle dog at 150 mg/kg, administered via oral gavage measured up to 24 hrs post dose by LC/MS/MS analysis CHEMBL4011639
Canis familiaris Tmax = 0.9 hr Tmax in Beagle dog at 150 mg/kg, administered via oral gavage measured up to 24 hrs post dose by LC/MS/MS analysis CHEMBL4011639
Canis familiaris T1/2 = 14.2 hr Half life in Beagle dog at 150 mg/kg, administered via oral gavage measured up to 24 hrs post dose by LC/MS/MS analysis CHEMBL4011639
Liver T1/2 = 0.16 hr Half life in human liver S9 fraction at 10 uM by LC/MS/MS analysis CHEMBL4011639
Plasma T1/2 > 3.85 hr Half life in human plasma at 200 uM by LC/MS/MS analysis CHEMBL4011639
Unchecked Ratio EC50 = 3.2 Ratio of EC50 for HCV genotype 1b replicon NS5B S282T mutant to EC50 for wild type HCV genotype 1b replicon NS5B CHEMBL4011639
Hepatitis C virus NS5B RNA-dependent RNA polymerase EC50 = 366.0 nM Inhibition of NS5B S282T mutant in HCV genotype 1b replicon expressed in human HuH7 cells after 72 hrs by bright Glo-luciferase reporter gene assay CHEMBL4011639
UMP-CMP kinase Drug metabolism Drug metabolism in human HuH7 cells assessed as UMP-CMP kinase-mediated ((2R,3R,4R,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methyl dihydrogen phosphate metabolite formation at 50 uM after 48 hrs by LC/MS/MS analysis CHEMBL4011639
Unchecked Drug metabolism Drug metabolism in human HuH7 cells assessed as nucleoside diphosphate kinase-mediated ((2R,3R,4R,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methyl tetrahydrogen triphosphate metabolite formation at 50 uM after 48 hrs by LC/MS/MS analysis CHEMBL4011639
Mus musculus Activity Subacute toxicity in ICR mouse assessed as alteration in basic levels of SGOT at 100 to 1000 mg/kg, administered once a day via oral gavage for 14 days CHEMBL4011639
Mus musculus Activity Subacute toxicity in ICR mouse assessed as alteration in basic levels of SGPT at 100 to 1000 mg/kg, administered once a day via oral gavage for 14 days CHEMBL4011639
Mus musculus Activity Subacute toxicity in ICR mouse assessed as effect on appearance of hepatocytes at 100 to 1000 mg/kg, administered once a day via oral gavage for 14 days by hematoxylin/eosin-staining based microscopic analysis CHEMBL4011639
Mus musculus Activity Subacute toxicity in ICR mouse assessed as effect on hepatic perilobular vein at 100 to 1000 mg/kg, administered once a day via oral gavage for 14 days by hematoxylin/eosin-staining based microscopic analysis CHEMBL4011639
Mus musculus Activity Subacute toxicity in ICR mouse assessed as effect on renal architecture at 100 to 1000 mg/kg, administered once a day via oral gavage for 14 days by hematoxylin/eosin-staining based microscopic analysis CHEMBL4011639
Mus musculus Activity Subacute toxicity in ICR mouse assessed as effect on glomerulus at 100 to 1000 mg/kg, administered once a day via oral gavage for 14 days by hematoxylin/eosin-staining based microscopic analysis CHEMBL4011639
Mus musculus Activity Subacute toxicity in ICR mouse assessed as effect on tubules at 100 to 1000 mg/kg, administered once a day via oral gavage for 14 days by hematoxylin/eosin-staining based microscopic analysis CHEMBL4011639
Unchecked Drug metabolism Drug metabolism in human HuH7 cells assessed as carboxylesterase-mediated (S)-isopropyl 2-((S)-(((2R,3R,4R,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryloxy)propanoate metabolite formation at 50 uM after 48 hrs by LC/MS/MS analysis CHEMBL4011639
ADMET Drug metabolism Drug metabolism in human HuH7 cells assessed as ((2R,3R,4R,5R)-4-fluoro-3-hydroxy-5-(4-hydroxy-2-oxo-3,4-dihydropyrimidin-1(2H)-yl)-4-methyltetrahydrofuran-2-yl)methyl tetrahydrogen triphosphate metabolite formation at 50 uM after 48 hrs by LC/MS/MS analysis CHEMBL4011639
Mus musculus NOAEL > 1800.0 mg kg-1 Acute toxicity in ICR mouse administered via oral gavage once a day over 14 days CHEMBL4011639
Mus musculus Activity Subacute toxicity in ICR mouse assessed as mortality at 100 to 1000 mg/kg, administered once a day via oral gavage for 14 days CHEMBL4011639