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Daclatasvir (BMS-790052) HCV Protease inhibitor

Name: Daclatasvir (BMS-790052)
Brand: Selleck Chemicals
SKU: S1482
Rating: 5 (56 reviews)

Cat.No.S1482

Daclatasvir (BMS-790052, EBP883) is a highly selective inhibitor of HCV NS5A with EC50 of 9-50 pM, for a broad range of HCV replicon genotypes and the JFH-1 genotype 2a infectious virus in cell culture. Phase 3.

Chemical Structure

Molecular Weight: 738.88

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Quality Control

Batch: Purity: 99.70%

99.70

Related Targets	HDAC Caspase Proteasome Secretase MMP Cysteine Protease DPP Tyrosinase HIV Protease Serine Protease
Other HCV Protease Inhibitors	Danoprevir Lomibuvir (VX-222) Asunaprevir Tizoxanide PSI-6206 (GS-331007) Mecarbinate Tegobuvir Herba taxilli Extract 2'-C-Methylcytidine

Cell Culture, Treatment & Working Concentration

Cell Lines	Assay Type	Concentration	Incubation Time	Activity Description	PMID
human CEM cells	Cytotoxicity assay		3 days	Cytotoxicity against human CEM cells after 3 days, CC50=9.6 μM	25154714
Huh7	Antiviral assay		3 days	Antiviral activity against HCV genotype 1b infected in human Huh7 cells after 3 days by cell-based replicon assay, EC50=0.000003μM	25148100
Huh-luc/neo-ET replicon	Antiviral assay		48 hrs	Antiviral activity against Hepatitis C virus genotype 1b harboring NS5A L28V mutant gene in Huh-luc/neo-ET replicon cells after 48 hrs by transient replicon mutant-based luciferase assay, EC50=0.000004μM	24568313
HuH7	Antiviral assay			Antiviral activity against HCV genotype 1b infected in human HuH7 cells assessed as reduction in viral RNA replication, EC50=0.000004μM	26099532
HuH7	Antiviral assay			Antiviral activity against HCV1b infected in human HuH7 cells assessed as inhibition of viral replication by RT-PCR analysis, EC50=0.0000066μM	22507961
HuH-Lcu-Neo	Function assay		48 hrs	Inhibition of NS5A in HCV genotype 1b infected in HuH-Lcu-Neo cells assessed as reduction in viral replication incubated for 48 hrs by luciferase reporter gene assay, EC50=0.0000081μM	32202782
Huh-5.2	Antiviral assay		4 days	Antiviral activity against Hepatitis C virus genotype 1b infected in human Huh-5.2 cells assessed as decrease in HCV replicon RNA replication after 4 days by luciferase assay, EC50=0.000009μM	24900811
HuH7	Antiviral assay		3 days	Antiviral activity against HCV genotype 1b Con1 infected in human HuH7 cells assessed as inhibition of viral RNA replication after 3 days by renilla luciferase reporter gene assay, EC50=0.000009μM	24320933
HuH7	Antiviral assay		72 hrs	Antiviral activity against HCV1b infected in human HuH7 cells assessed as inhibition of viral replication after 72 hrs by FRET assay, EC50=0.000009μM	24521299
HuH7	Antiviral assay			Antiviral activity against HCV genotype 1b Con1 infected in human HuH7 cells assessed as inhibition of viral replication, EC50=0.000009μM	26077493
Huh7.5/J6/JFH1/EMCVIRES/hRlucNeo	Function assay		72 hrs	Inhibition of NS5A in HCV genotype 2a infected in human Huh7.5/J6/JFH1/EMCVIRES/hRlucNeo cells assessed as inhibition of replicon levels incubated for 72 hrs by luciferase reporter gene assay, IC50=0.000009μM	31710479
HuH7 replicon	Function assay		2 days	Inhibition of NS5A in HCV genotype 1b infected in human HuH7 replicon cells assessed as reduction in subgenomic viral RNA replication treated for 2 days followed by compound washout and subsequent compound dosing measured after 1 day by SEAP reporter gene, EC50=0.000009μM	30772607
HuH7	Antiviral assay			Antiviral activity against HCV 1b infected in human HuH7 cells by in vitro replicon assay, EC50=0.00001μM	23466233
Huh-luc/neo-ET replicon	Antiviral assay		48 hrs	Antiviral activity against Hepatitis C virus genotype 1b in Huh-luc/neo-ET replicon cells after 48 hrs by replicon-based luciferase assay, EC50=0.00001μM	24568313
HuH7	Function assay			Inhibition of NS5A in HCV genotype-1b infected in human HuH7 cells by luciferase reporter gene assay, EC50=0.000023μM	25453810
HuH7.5/Con1/SG-Neo(I)-hRluc2aUb	Function assay		72 hrs	Inhibition of NS5A in HCV genotype 1b infected in human HuH7.5/Con1/SG-Neo(I)-hRluc2aUb cells assessed as inhibition of replicon levels incubated for 72 hrs by luciferase reporter gene assay, IC50=0.000023μM	31710479
HuH7	Antiviral assay			Antiviral activity against HCV genotype 1b JFH-1 infected in human HuH7 cells assessed as inhibition of viral replication, EC50=0.000028μM	26077493
HuH7	Antiviral assay			Antiviral activity against HCV 1b infected in human HuH7 cells by in vitro replicon assay, EC90=0.00003μM	23466233
HuH-Lcu-Neo	Function assay		48 hrs	Inhibition of NS5A in HCV genotype 1a infected in HuH-Lcu-Neo cells assessed as reduction in viral replication incubated for 48 hrs by luciferase reporter gene assay, EC50=0.0000324μM	32202782
HuH7	Antiviral assay			Antiviral activity against HCV genotype 1b expressing NS5A L31V mutant infected in human HuH7 cells assessed as reduction in viral RNA replication, EC50=0.000035μM	26099532
Huh-luc/neo-ET replicon	Antiviral assay		48 hrs	Antiviral activity against Hepatitis C virus genotype 1a in Huh-luc/neo-ET replicon cells after 48 hrs by replicon-based luciferase assay, EC50=0.0000398μM	24568313
HuH7	Antiviral assay			Antiviral activity against wild type HCV genotype 1b infected in human HuH7 cells assessed as reduction in viral RNA replication, EC50=0.000048μM	26099532
W11.8	Antiviral assay		4 days	Antiviral activity against Hepatitis C virus genotype 1a infected in W11.8 cells assessed as decrease in NS5A expression in replicon cell after 4 days by luminescence based ELISA, EC50=0.00005μM	24900811
HuH7	Antiviral assay		3 days	Antiviral activity against HCV genotype 1a H77 infected in human HuH7 cells assessed as inhibition of viral RNA replication after 3 days by renilla luciferase reporter gene assay, EC50=0.00005μM	24320933
HuH7	Antiviral assay		72 hrs	Antiviral activity against HCV1a infected in human HuH7 cells assessed as inhibition of viral replication after 72 hrs by FRET assay, EC50=0.00005μM	24521299
HuH7	Antiviral assay			Antiviral activity against HCV genotype 5a infected in human HuH7 cells by luciferase reporter gene assay, EC50=0.000051μM	25453811
HuH7	Antiviral assay			Antiviral activity against HCV genotype 1b infected in human HuH7 cells by luciferase reporter gene assay, EC50=0.000073μM	25453811
HuH-Lcu-Neo	Function assay		48 hrs	Inhibition of NS5A in patient-derived HCV genotype 3a infected in HuH-Lcu-Neo cells assessed as reduction in viral replication incubated for 48 hrs by luciferase reporter gene assay, EC50=0.0001145μM	32202782
Huh-luc/neo-ET replicon	Antiviral assay		48 hrs	Antiviral activity against Hepatitis C virus genotype 1b harboring NS5A L31V mutant gene in Huh-luc/neo-ET replicon cells after 48 hrs by transient replicon mutant-based luciferase assay, EC50=0.0001259μM	24568313
HuH7	Function assay			Inhibition of NS5A in HCV genotype-1a infected in human HuH7 cells by luciferase reporter gene assay, EC50=0.00014μM	25453810
HuH7	Antiviral assay			Antiviral activity against HCV genotype 1a infected in human HuH7 cells by luciferase reporter gene assay, EC50=0.00014μM	25453811
HuH7	Antiviral assay			Antiviral activity against HCV genotype 1b expressing NS5A Y93H mutant infected in human HuH7 cells assessed as reduction in viral RNA replication, EC50=0.00018μM	26099532
Huh-luc/neo-ET replicon	Antiviral assay		48 hrs	Antiviral activity against Hepatitis C virus genotype 1b harboring NS5A Y93H mutant gene in Huh-luc/neo-ET replicon cells after 48 hrs by transient replicon mutant-based luciferase assay, EC50=0.0003162μM	24568313
HuH7	Antiviral assay		72 hrs	Antiviral activity against HCV1a infected in human HuH7 cells assessed as inhibition of viral replication after 72 hrs by FRET assay, EC90=0.00038μM	24521299
HuH7	Antiviral assay			Antiviral activity against HCV genotype 4a infected in human HuH7 cells by luciferase reporter gene assay, EC50=0.00041μM	25453811
HuH-Lcu-Neo	Function assay		48 hrs	Inhibition of NS5A in HCV genotype 3a con infected in HuH-Lcu-Neo cells assessed as reduction in viral replication incubated for 48 hrs by luciferase reporter gene assay, EC50=0.0004115μM	32202782
HuH7	Antiviral assay			Antiviral activity against HCV genotype 6a infected in human HuH7 cells by luciferase reporter gene assay, EC50=0.00045μM	25453811
HuH7	Antiviral assay			Antiviral activity against HCV genotype 3a infected in human HuH7 cells by luciferase reporter gene assay, EC50=0.00067μM	25453811
HuH7	Antiviral assay			Antiviral activity against HCV genotype 2a infected in human HuH7 cells by luciferase reporter gene assay, EC50=0.00067μM	25453811
HuH-Lcu-Neo	Function assay		48 hrs	Inhibition of NS5A in patient-derived HCV genotype 2a infected in HuH-Lcu-Neo cells assessed as reduction in viral replication incubated for 48 hrs by luciferase reporter gene assay, EC50=0.0494μM	32202782
HuH-Lcu-Neo	Function assay		48 hrs	Inhibition of NS5A in HCV genotype 2a con infected in HuH-Lcu-Neo cells assessed as reduction in viral replication incubated for 48 hrs by luciferase reporter gene assay, EC50=0.05285μM	32202782
CEM	Cytotoxicity assay		3 days	Cytotoxicity against human CEM cells after 3 days, CC50=9.6μM	22507961
CEM	Cytotoxicity assay			Cytotoxicity against human CEM cells, CC50=9.6μM	22704887
Vero	Cytotoxicity assay			Cytotoxicity against african green monkey Vero cells, CC50=9.6μM	23466233
CEM	Cytotoxicity assay			Cytotoxicity against human CEM cells, CC50=10μM	26099532
PBMC	Cytotoxicity assay			Cytotoxicity against human PBMC cells, CC50=19μM	22704887
Vero	Cytotoxicity assay		3 days	Cytotoxicity against african green monkey Vero cells after 3 days, CC50=21μM	22507961
Vero	Cytotoxicity assay			Cytotoxicity against african green monkey Vero cells, CC50=21μM	22704887
CEM	Cytotoxicity assay			Cytotoxicity against human CEM cells, CC50=21μM	23466233
Vero	Cytotoxicity assay			Cytotoxicity against african green monkey Vero cells, CC50=21μM	26099532
Huh7.5.1	Antiviral assay	100 pM to 1 uM		Antiviral activity against HCV genotype 1b NK/R2AN infected in human Huh7.5.1 cells expressing NS5A L31V mutant assessed as reduction in virus replication at 100 pM to 1 uM by luciferase reporter gene assay	26134551
Huh7.5.1	Antiviral assay	100 pM to 1 uM		Antiviral activity against HCV genotype 1b NK/R2AN infected in human Huh7.5.1 cells expressing NS5A Y93H mutant assessed as reduction in virus replication at 100 pM to 1 uM by luciferase reporter gene assay	26134551
GS4.3	Antiviral assay	0.15 uM	6 days	Antiviral activity against HCV infected in human GS4.3 cells assessed as inhibition of NS3/4A levels at 0.15 uM treated with fresh media containing compound every 2 days measured after 6 days by Western blot method	29232582
GS4.3	Antiviral assay	0.15 uM	6 days	Antiviral activity against HCV infected in human GS4.3 cells assessed as inhibition of viral core protein levels at 0.15 uM treated with fresh media containing compound every 2 days measured after 6 days by Western blot method	29232582
HuH7	Antiviral assay		3 days	Antiviral activity against HCV genotype 1b infected in human HuH7 cells at >= 10 times antiviral EC50 after 3 days by luciferase reporter assay	28430437
HuH7	Antiviral assay		3 days	Antiviral activity against HCV genotype 1b infected in human HuH7 cells co-treated with asunaprevir after 3 days by luciferase reporter assay	28430437
Click to View More Cell Line Experimental Data

Chemical Information, Storage & Stability

Molecular Weight	738.88	Formula	C₄₀H₅₀N₈O₆	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	1009119-64-5	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	EBP883			Smiles	CC(C)C(C(=O)N1CCCC1C2=NC=C(N2)C3=CC=C(C=C3)C4=CC=C(C=C4)C5=CN=C(N5)C6CCCN6C(=O)C(C(C)C)NC(=O)OC)NC(=O)OC

Solubility

In vitro
Batch:

DMSO : 148 mg/mL (200.3 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 148 mg/mL

Water : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
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Dilution Calculator Molecular Weight Calculator

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

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Mechanism of Action

Features	First-in-class, highly selective inhibitor of hepatitis C virus (HCV) NS5A with picomolar EC50 values.
Targets/IC₅₀/Ki	HCV NS5A 9 pM-50 pM(EC50)
In vitro	Daclatasvir (BMS-790052) is one of the most potent inhibitors of HCV replication reported so far. The mean EC50 values of this compound are 50 and 9 pM for HCV genotype 1a and 1b replicons, respectively. It displays a therapeutic index (CC50/EC50) of at least 10⁵ and is inactive towards a panel of 10 RNA and DNA viruses, with EC50 higher than 10 μM. This confirms its specificity for HCV. In Huh7 cells harboring the HCV genotype 1b replicons, it blocks both transient and stable HCV genome replication, with EC50 values ranging from 1-15 pM. At concentrations of 100 pM or 1 nM, it has been shown to alter the subcellular localization and biochemical fractionation of NS5A. This compound inhibits hybrid replicons containing HCV genotype-4 NS5A genes with EC50 of 7-13 pM. Residue 30 of NS5A is an important site for BMS-790052-mediated resistance in the hybrid replicons.
Kinase Assay	FRET assay for HCV NS5A inhibitors
Kinase Assay	This peptide (Ac-Asp-Glu-Asp [EDANS]-Glu-Glu-Abu-[COO] Ala-Ser-Lys [DABCYL]-NH2) contains a fluorescent donor {EDANS, 5-[(2-aminoethyl)amino]naphthalene-1-sulfonic acid} near one end and an acceptor {DABCYL, 4-[(4-dimethylamino)phenyl]azo}benzoic acid} near the other end. Intermolecular resonance energy transfer between the donor and acceptor quenches the peptide's fluorescence, but as the NS3 Protease cleaves the peptide, products are released from resonance energy transfer quenching. The donor's fluorescence increases over time as more substrate is cleaved by NS3 Protease. The detection reagents are: 5× luciferase cell culture lysis reagent diluted with dH₂O to 1×, with NaCl (150 mM) and FRET peptide (20 μM) added. HCV-Huh-7 cells were placed into 96-well plates and allowed to adhere overnight (1×10⁴ cells per well). The next day, Daclatasvir (BMS-790052) was added to the wells, and plates were incubated for 72 hours. Plates were then rinsed with PBS, and FRET assay was performed by adding 30 μL of the aforementioned FRET peptide detection reagent to each well. Signals were acquired using a Cytofluor 4000 instrument, set to 340 nm (excitation)/490 nm (emission) auto mode, run for 20 cycles or less, and reading plates in kinetic mode. Following the FRET assay, 40 μL of luciferase substrate was added to each well, and luciferase activity was measured.
References	[1] https://pubmed.ncbi.nlm.nih.gov/20410884/ [2] https://pubmed.ncbi.nlm.nih.gov/21513964/ [3] https://pubmed.ncbi.nlm.nih.gov/22203595/ [4] https://pubmed.ncbi.nlm.nih.gov/15793110/

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT05992077	Recruiting	HCV Infection	ANRS Emerging Infectious Diseases	August 7 2023	Not Applicable
NCT04852614	Recruiting	Hepatitis C Virus Infection	Ain Shams University	December 1 2020	--
NCT04773756	Completed	Covid19	Alexandria University	November 1 2020	Phase 4
NCT03208322	Withdrawn	Hepatitis C	Bristol-Myers Squibb	November 30 2018	--

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