GRAZOPREVIR

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Synonyms
Status
Molecule Category Mixture
ATC J05AP11
UNII 8YE81R1X1J
EPA CompTox DTXSID50159234

Structure

InChI Key OBMNJSNZOWALQB-NCQNOWPTSA-N
Smiles C=C[C@@H]1C[C@]1(NC(=O)[C@@H]1C[C@@H]2CN1C(=O)[C@H](C(C)(C)C)NC(=O)O[C@@H]1C[C@H]1CCCCCc1nc3ccc(OC)cc3nc1O2)C(=O)NS(=O)(=O)C1CC1
InChI
InChI=1S/C38H50N6O9S/c1-6-22-19-38(22,35(47)43-54(49,50)25-13-14-25)42-32(45)29-18-24-20-44(29)34(46)31(37(2,3)4)41-36(48)53-30-16-21(30)10-8-7-9-11-27-33(52-24)40-28-17-23(51-5)12-15-26(28)39-27/h6,12,15,17,21-22,24-25,29-31H,1,7-11,13-14,16,18-20H2,2-5H3,(H,41,48)(H,42,45)(H,43,47)/t21-,22-,24-,29+,30-,31-,38-/m1/s1

Physicochemical Descriptors

Property Name Value
Molecular Formula C38H52N6O10S
Molecular Weight 784.93
AlogP 3.3
Hydrogen Bond Acceptor 11.0
Hydrogen Bond Donor 3.0
Number of Rotational Bond 7.0
Polar Surface Area 195.22
Molecular species ACID
Aromatic Rings 2.0
Heavy Atoms 54.0

Bioactivity

Mechanism of Action Action Reference
Hepatitis C virus serine protease, NS3/NS4A inhibitor INHIBITOR FDA
Targets EC50(nM) IC50(nM) Kd(nM) Ki(nM) Inhibition(%)
Enzyme Protease Serine protease Serine protease PA clan Serine protease S29 family Serine protease S29 regulatory subfamily
- 0-2 - 0 99
Enzyme Protease Serine protease Serine protease PA clan Serine protease S29 family
- 0-2 - 0 99
Enzyme Protease Serine protease
- 0-12 - 0 99
Unclassified protein
- - - 0-12 -
Assay Description Organism Bioactivity Reference
Inhibition of Hepatitis C virus (isolate BK) genotype 1b NS3/4a protease expressed in Escherichia coli by time-resolved fluorescence analysis Hepatitis C virus (isolate BK) 0.02 nM
Inhibition of Hepatitis C virus (isolate NZL1) genotype 3a NS3/4a protease expressed in Escherichia coli by time-resolved fluorescence analysis Hepatitis C virus (isolate NZL1) 0.7 nM
Inhibition of Hepatitis C virus (isolate BK) genotype 1b NS3/4a protease R155K mutant expressed in Escherichia coli by time-resolved fluorescence analysis Hepatitis C virus (isolate BK) 0.07 nM
Inhibition of Hepatitis C virus (isolate BK) genotype 1b NS3/4a protease A156T mutant expressed in Escherichia coli by time-resolved fluorescence analysis Hepatitis C virus (isolate BK) 5.3 nM
Inhibition of Hepatitis C virus (isolate BK) genotype 1b NS3/4a protease A156V mutant expressed in Escherichia coli by time-resolved fluorescence analysis Hepatitis C virus (isolate BK) 12.0 nM
Inhibition of Hepatitis C virus (isolate BK) genotype 1b NS3/4a protease D168V mutant expressed in Escherichia coli by time-resolved fluorescence analysis Hepatitis C virus (isolate BK) 0.14 nM
Antiviral activity against Hepatitis C virus (isolate Con1) genotype 1b infected in human HuH7 cells assessed as inhibition of viral replication after 24 hrs in presence of 50% NHS Hepatitis C virus (isolate Con1) 7.4 nM
Antiviral activity against Hepatitis C virus genotype 1a infected in human HuH7 cells assessed as inhibition of viral replication after 24 hrs presence of 40% NHS Hepatitis C virus subtype 1a 7.0 nM
Inhibition of Hepatitis C virus genotype 1b NS3/4A protease D168Y mutant assessed as substrate cleavage using Ac-C(Eu)DDMEEAbu(COO)ASK(QSY7)-amide as substrate incubated for 30 mins prior to substrate addition by time-resolved fluorescence assay Hepatitis C virus subtype 1b 0.14 nM
Inhibition of Hepatitis C virus genotype 1b NS3/4A protease A156V mutant assessed as substrate cleavage using Ac-C(Eu)DDMEEAbu(COO)ASK(QSY7)-amide as substrate incubated for 30 mins prior to substrate addition by time-resolved fluorescence assay Hepatitis C virus subtype 1b 12.0 nM
Inhibition of Hepatitis C virus genotype 1b NS3/4A protease A156T mutant assessed as substrate cleavage using Ac-C(Eu)DDMEEAbu(COO)ASK(QSY7)-amide as substrate incubated for 30 mins prior to substrate addition by time-resolved fluorescence assay Hepatitis C virus subtype 1b 5.3 nM
Inhibition of Hepatitis C virus genotype 1b NS3/4A protease R155K mutant assessed as substrate cleavage using Ac-C(Eu)DDMEEAbu(COO)ASK(QSY7)-amide as substrate incubated for 30 mins prior to substrate addition by time-resolved fluorescence assay Hepatitis C virus subtype 1b 0.07 nM
Antiviral activity against Hepatitis C virus genotype 3a infected in HuH7 cells assessed as reduction in replicon RNA level after 72 hrs by TaqMan-based RT-PCR analysis in presence of 10% FBS Hepatitis C virus subtype 3a 13.0 nM
Antiviral activity against Hepatitis C virus genotype 1b infected in HuH7 cells assessed as reduction in replicon RNA level after 72 hrs by TaqMan-based RT-PCR analysis in presence of 10% FBS Hepatitis C virus subtype 1b 1.5 nM
Inhibition of Hepatitis C virus genotype 3a NS3/4A protease assessed as substrate cleavage using Ac-C(Eu)DDMEEAbu(COO)ASK(QSY7)-amide as substrate incubated for 30 mins prior to substrate addition by time-resolved fluorescence assay Hepatitis C virus subtype 3a 0.7 nM
Inhibition of Hepatitis C virus genotype 1b NS3/4A protease assessed as substrate cleavage using Ac-C(Eu)DDMEEAbu(COO)ASK(QSY7)-amide as substrate incubated for 30 mins prior to substrate addition by time-resolved fluorescence assay Hepatitis C virus subtype 1b 0.02 nM
Antiviral activity against HCV genotype 1a infected in human HuH7 cells assessed as inhibition of viral replication after 72 hrs by RT-PCR method Hepatitis C virus subtype 1a 0.3 nM
Inhibition of HCV genotype 1b full length NS3/4A protease using Ac-C(Eu)DDMEEAbu[COO]ASK(QSY7)-amide as substrate preincubated for 30 mins followed by substrate addition measured after 2.5 hrs by TRF assay Hepatitis C virus subtype 1b 0.004 nM
Inhibition of HCV genotype 3a full length NS3/4A protease using Ac-C(Eu)DDMEEAbu[COO]ASK(QSY7)-amide as substrate preincubated for 30 mins followed by substrate addition measured after 2.5 hrs by TRF assay Hepatitis C virus subtype 3a 0.69 nM
Inhibition of HCV genotype 1b NS3/4A protease R155K mutant using Ac-C(Eu)DDMEEAbu[COO]ASK(QSY7)-amide as substrate preincubated for 30 mins followed by substrate addition measured after 2.5 hrs by TRF assay Hepatitis C virus subtype 1b 0.021 nM
Inhibition of HCV genotype 1b NS3/4A protease A156T mutant using Ac-C(Eu)DDMEEAbu[COO]ASK(QSY7)-amide as substrate preincubated for 30 mins followed by substrate addition measured after 2.5 hrs by TRF assay Hepatitis C virus subtype 1b 3.917 nM
Inhibition of HCV genotype 1b NS3/4A protease A156V mutant using Ac-C(Eu)DDMEEAbu[COO]ASK(QSY7)-amide as substrate preincubated for 30 mins followed by substrate addition measured after 2.5 hrs by TRF assay Hepatitis C virus subtype 1b 5.511 nM
Inhibition of HCV genotype 1b NS3/4A protease D168Y mutant using Ac-C(Eu)DDMEEAbu[COO]ASK(QSY7)-amide as substrate preincubated for 30 mins followed by substrate addition measured after 2.5 hrs by TRF assay Hepatitis C virus subtype 1b 0.105 nM
Inhibition of HCV genotype 1a NS3/4A protease using Ac-C(Eu)DDMEEAbu[COO]ASK(QSY7)-amide as substrate preincubated for 30 mins followed by substrate addition measured after 2.5 hrs by TRF assay Hepatitis C virus subtype 1a 0.007 nM
Antiviral activity against HCV genotype 1b infected in human HuH7 cells assessed as inhibition of viral replication after 72 hrs by RT-PCR method Hepatitis C virus subtype 1b 0.3 nM
Antiviral activity against HCV genotype 2a infected in human HuH7 cells assessed as inhibition of viral replication after 72 hrs by RT-PCR method Hepatitis C virus subtype 2a 1.2 nM
Antiviral activity against HCV genotype 2b infected in human HuH7 cells assessed as inhibition of viral replication after 72 hrs by RT-PCR method Hepatitis C virus subtype 2b 5.0 nM
Antiviral activity against HCV genotype 3a infected in human HuH7 cells assessed as inhibition of viral replication after 72 hrs by RT-PCR method Hepatitis C virus subtype 3a 7.2 nM
Inhibition of HCV genotype 1a NS3/4A protease assessed as substrate cleavage using Ac-C(Eu)DDMEEAbu(COO)ASK(QSY7)-amide as substrate incubated for 30 mins prior to substrate addition measured after 2.5 hrs by time-resolved fluorescence assay Hepatitis C virus subtype 1a 0.02 nM
Inhibition of HCV genotype 1b NS3/4A protease assessed as substrate cleavage using Ac-C(Eu)DDMEEAbu(COO)ASK(QSY7)-amide as substrate incubated for 30 mins prior to substrate addition measured after 2.5 hrs by time-resolved fluorescence assay Hepatitis C virus subtype 1b 0.01 nM
Inhibition of HCV genotype 2a NS3/4A protease assessed as substrate cleavage using Ac-C(Eu)DDMEEAbu(COO)ASK(QSY7)-amide as substrate incubated for 30 mins prior to substrate addition measured after 2.5 hrs by time-resolved fluorescence assay Hepatitis C virus subtype 2a 0.14 nM
Inhibition of HCV genotype 3a NS3/4A protease assessed as substrate cleavage using Ac-C(Eu)DDMEEAbu(COO)ASK(QSY7)-amide as substrate incubated for 30 mins prior to substrate addition measured after 2.5 hrs by time-resolved fluorescence assay Hepatitis C virus subtype 3a 0.75 nM
Inhibition of HCV genotype 1b NS3/4A protease R155K mutant assessed as substrate cleavage using Ac-C(Eu)DDMEEAbu(COO)ASK(QSY7)-amide as substrate incubated for 30 mins prior to substrate addition measured after 2.5 hrs by time-resolved fluorescence assay Hepatitis C virus subtype 1b 0.06 nM
Inhibition of HCV genotype 1b NS3/4A protease A156V mutant assessed as substrate cleavage using Ac-C(Eu)DDMEEAbu(COO)ASK(QSY7)-amide as substrate incubated for 30 mins prior to substrate addition measured after 2.5 hrs by time-resolved fluorescence assay Hepatitis C virus subtype 1b 6.09 nM
Inhibition of HCV genotype 1b NS3/4A protease A156T mutant assessed as substrate cleavage using Ac-C(Eu)DDMEEAbu(COO)ASK(QSY7)-amide as substrate incubated for 30 mins prior to substrate addition measured after 2.5 hrs by time-resolved fluorescence assay Hepatitis C virus subtype 1b 3.82 nM
Inhibition of HCV genotype 1b NS3/4A protease D168Y mutant assessed as substrate cleavage using Ac-C(Eu)DDMEEAbu(COO)ASK(QSY7)-amide as substrate incubated for 30 mins prior to substrate addition measured after 2.5 hrs by time-resolved fluorescence assay Hepatitis C virus subtype 1b 0.22 nM
Antiviral activity against HCV genotype 1a infected in human HuH7 cells assessed as reduction viral RNA level after 72 hrs by RT-PCR method Hepatitis C virus subtype 1a 0.6 nM
Antiviral activity against HCV genotype 1b infected in human HuH7 cells assessed as reduction viral RNA level after 72 hrs by RT-PCR method Hepatitis C virus subtype 1b 0.6 nM
Antiviral activity against HCV genotype 2a infected in human HuH7 cells assessed as reduction viral RNA level after 72 hrs by RT-PCR method Hepatitis C virus subtype 2a 5.4 nM
Antiviral activity against HCV genotype 3a infected in human HuH7 cells assessed as reduction viral RNA level after 72 hrs by RT-PCR method Hepatitis C virus subtype 3a 7.2 nM
Inhibition of HCV NS3 protease pre-incubated for 30 mins before TRF peptide substrate addition and measured after 1 hr by time resolved fluorescence assay Hepatitis C virus 0.016 nM
Antiviral activity against Hepatitis C virus subtype 1b infected in HBI10A cells harboring HCV subgenomic bicistronic replicon assessed as reduction in viral replication Hepatitis C virus subtype 1b 2.0 nM
Inhibition of HCV subtype 1b NS3 protease D168T mutant pre-incubated for 30 mins before TRF peptide substrate addition and measured after 1 hr by time resolved fluorescence assay Hepatitis C virus subtype 1b 0.18 nM
Inhibition of HCV subtype 1b NS3 protease D168A mutant pre-incubated for 30 mins before TRF peptide substrate addition and measured after 1 hr by time resolved fluorescence assay Hepatitis C virus subtype 1b 0.43 nM
Inhibition of HCV subtype 1b NS3 protease D168E mutant pre-incubated for 30 mins before TRF peptide substrate addition and measured after 1 hr by time resolved fluorescence assay Hepatitis C virus subtype 1b 0.04 nM
Inhibition of HCV subtype 1b NS3 protease D168G mutant pre-incubated for 30 mins before TRF peptide substrate addition and measured after 1 hr by time resolved fluorescence assay Hepatitis C virus subtype 1b 0.08 nM
Inhibition of HCV subtype 1b NS3 protease D168V mutant pre-incubated for 30 mins before TRF peptide substrate addition and measured after 1 hr by time resolved fluorescence assay Hepatitis C virus subtype 1b 0.14 nM
Inhibition of HCV subtype 1b NS3 protease D168Y mutant pre-incubated for 30 mins before TRF peptide substrate addition and measured after 1 hr by time resolved fluorescence assay Hepatitis C virus subtype 1b 0.22 nM
Inhibition of HCV subtype 1b NS3 protease D168Q mutant pre-incubated for 30 mins before TRF peptide substrate addition and measured after 1 hr by time resolved fluorescence assay Hepatitis C virus subtype 1b 0.12 nM
Inhibition of HCV subtype 1b NS3 protease A156S mutant pre-incubated for 30 mins before TRF peptide substrate addition and measured after 1 hr by time resolved fluorescence assay Hepatitis C virus subtype 1b 0.05 nM
Inhibition of HCV subtype 1b NS3 protease A156T mutant pre-incubated for 30 mins before TRF peptide substrate addition and measured after 1 hr by time resolved fluorescence assay Hepatitis C virus subtype 1b 5.2 nM
Inhibition of HCV subtype 1b NS3 protease A156V mutant pre-incubated for 30 mins before TRF peptide substrate addition and measured after 1 hr by time resolved fluorescence assay Hepatitis C virus subtype 1b 11.0 nM
Inhibition of HCV subtype 1b NS3 protease R155K mutant pre-incubated for 30 mins before TRF peptide substrate addition and measured after 1 hr by time resolved fluorescence assay Hepatitis C virus subtype 1b 0.07 nM
Inhibition of HCV subtype 1b NS3 protease R155Q mutant pre-incubated for 30 mins before TRF peptide substrate addition and measured after 1 hr by time resolved fluorescence assay Hepatitis C virus subtype 1b 0.43 nM
Inhibition of HCV subtype 1b NS3 protease R155G mutant pre-incubated for 30 mins before TRF peptide substrate addition and measured after 1 hr by time resolved fluorescence assay Hepatitis C virus subtype 1b 0.63 nM
Inhibition of HCV subtype 1b NS3 protease R155N mutant pre-incubated for 30 mins before TRF peptide substrate addition and measured after 1 hr by time resolved fluorescence assay Hepatitis C virus subtype 1b 0.13 nM
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells at 10 uM after 48 hours by high content imaging Homo sapiens -4.15 %
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 -61.53 % SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 -57.5 % SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 -18.42 %
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus 0.0 % Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus -0.09 % Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus -0.08 % Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus -0.09 % Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus 0.0 % Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus -0.08 %
Inhibition of HCV NS3/4a protease using Ac-DE-Dap(QXL520)-EE-Abu-shi-[COO]AS-C(5-FAMsp)-NH2 as substrate after 15 mins Hepatitis C virus 2.0 nM
Antiviral activity against HCV Hepatitis C virus 9.5 nM
Inhibition of HCV NS3/4a protease Hepatitis C virus 98.8 %
Inhibition of HCV GT-3a NS3/4a protease using Ac-DE-D(Edans)-EE-Abu-c-[COO]-AS-K(Dabcy1)-NH2 preincubated for 1 hr followed by substrate addition Hepatitis C virus subtype 3a 30.0 nM
Inhibition of HCV GT-1a NS3/4a protease using Ac-DE-D(Edans)-EE-Abu-c-[COO]-AS-K(Dabcy1)-NH2 preincubated for 1 hr followed by substrate addition Hepatitis C virus subtype 3a 0.2 nM
Inhibition of HCV NS3/4a protease D168A mutant using Ac-DE-D(Edans)-EE-Abu-c-[COO]-AS-K(Dabcy1)-NH2 preincubated for 1 hr followed by substrate addition Hepatitis C virus 49.0 nM
Antiviral activity against HCV genotype 1b infected in human Huh7 cells incubated for 96 hrs by luciferase assay Hepatitis C virus 0.2 nM
Antiviral activity against HCV genotype 1b harboring A156T mutant infected in human Huh7 cells incubated for 96 hrs by luciferase assay Hepatitis C virus 261.0 nM
Antiviral activity against HCV genotype 1b harboring D168A mutant infected in human Huh7 cells incubated for 96 hrs by luciferase assay Hepatitis C virus 12.0 nM
Antiviral activity against HCV genotype 3a infected in human Huh7.5 cells incubated for 72 hrs by luciferase assay Hepatitis C virus 65.0 nM

Cross References

Resources Reference
ChEBI 132975
ChEMBL CHEMBL2063090
DrugBank DB11575
DrugCentral 5081
FDA SRS 8YE81R1X1J
PDB SUE
PharmGKB PA166163437
PubChem 71576667
SureChEMBL SCHEMBL2175313
ZINC ZINC000095551509
ChEMBL CHEMBL3039533
FDA SRS 4O2AB118LA
PubChem 71576667
SureChEMBL SCHEMBL18259662
CONTENTS