GLECAPREVIR


Synonyms	A-1282576 A-1282576.0 A-12825760 ABT-493 Glecaprevir
Status
Molecule Category	Free-form
UNII	K6BUU8J72P


Active Pharmaceutical Ingredients Bioactive chemicals	Exact Similarity SubStructure	Threshold (%) >= 70

Structure


InChI Key	MLSQGNCUYAMAHD-ITNVBOSISA-N
Smiles	CC(C)(C)[C@@H]1NC(=O)O[C@@H]2CCC[C@H]2OC/C=C/C(F)(F)c2nc3ccccc3nc2O[C@@H]2C[C@@H](C(=O)N[C@]3(C(=O)NS(=O)(=O)C4(C)CC4)C[C@H]3C(F)F)N(C2)C1=O
InChI	InChI=1S/C38H46F4N6O9S/c1-35(2,3)28-32(50)48-19-20(17-24(48)30(49)46-37(18-21(37)29(39)40)33(51)47-58(53,54)36(4)14-15-36)56-31-27(43-22-9-5-6-10-23(22)44-31)38(41,42)13-8-16-55-25-11-7-12-26(25)57-34(52)45-28/h5-6,8-10,13,20-21,24-26,28-29H,7,11-12,14-19H2,1-4H3,(H,45,52)(H,46,49)(H,47,51)/b13-8+/t20-,21+,24+,25-,26-,28-,37-/m1/s1

Physicochemical Descriptors

Property Name	Value
Molecular Formula	C38H46F4N6O9S
Molecular Weight	838.88
AlogP	3.86
Hydrogen Bond Acceptor	11.0
Hydrogen Bond Donor	3.0
Number of Rotational Bond	6.0
Polar Surface Area	195.22
Molecular species	ACID
Aromatic Rings	2.0
Heavy Atoms	58.0

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	-	-	-	-	98
Enzyme Protease Serine protease Serine protease PA clan Serine protease S29 family	-	-	-	-	98

Assay Description	Organism	Bioactivity
Inhibition of HCV NS3/4a protease	Hepatitis C virus	97.5 %
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	0.5 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	0.05 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	90.0 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	230.0 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	0.2 nM
Antiviral activity against HCV genotype 3a infected in human Huh7.5 cells incubated for 72 hrs by luciferase assay	Hepatitis C virus	30.0 nM

Related Entries

Cross References

Resources	Reference
ChEMBL	CHEMBL3545363
DrugBank	DB13879
DrugCentral	5243
FDA SRS	K6BUU8J72P
Guide to Pharmacology	11267
PDB	O31
PubChem	66828839
SureChEMBL	SCHEMBL883097
ZINC	ZINC000164528615

CONTENTS


PREMIER has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 875508. The JU receives support from the EU’s Horizon 2020 research and innovation programme and the European Federation of Pharmaceutical Industries and Associations (EFPIA). The views reflect only the authors’ perspective and the JU is not responsible for any use that may be made of the information this manuscript contains. Elements of the website have been developed under projects PREMIER and the Biocenter Finland Drug Discovery and Chemical Biology network. CSC-IT is thanked for providing computational resources. Content of the website is provided without guarantee for correctness. Data has been collected and integrated from multiple public sources, for the largest: FDA, HUGO Gene Nomenclature Committee, ChEMBL, IUPHAR/BPS guide to pharmacology, Reactome, UniProt, and Ensembl. Credit is given to Ensembl for collecting species images (provided under public domain licences such as Wikimedia and NHGRI).

PREMIER has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 875508. The JU receives support from the EU’s Horizon 2020 research and innovation programme and the European Federation of Pharmaceutical Industries and Associations (EFPIA). The views reflect only the authors’ perspective and the JU is not responsible for any use that may be made of the information this manuscript contains.

Elements of the website have been developed under projects PREMIER and the Biocenter Finland Drug Discovery and Chemical Biology network. CSC-IT is thanked for providing computational resources. Content of the website is provided without guarantee for correctness. Data has been collected and integrated from multiple public sources, for the largest: FDA, HUGO Gene Nomenclature Committee, ChEMBL, IUPHAR/BPS guide to pharmacology, Reactome, UniProt, and Ensembl. Credit is given to Ensembl for collecting species images (provided under public domain licences such as Wikimedia and NHGRI).