Daclatasvir (BMS-790052)

Catalog No.S1482 Synonyms: EBP883

Molecular Weight(MW): 738.88

Daclatasvir (BMS-790052) 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.

Cited by 19 Publications

Nature, 2015, 524(7566):471-5

PubMed: 26266980 ( click the link to review the publication )

Cell Rep, 2018, 25(4):833-840

PubMed: 30355490 ( click the link to review the publication )

Nature, 2013, 501(7466):237-41

PubMed: 23903655 ( click the link to review the publication )

Hepatology, 2014, 10.1002/hep.27197

PubMed: 24797787 ( click the link to review the publication )

PLoS Pathog, 2015, 11(3):e1004758

PubMed: 25822891 ( click the link to review the publication )

J Virol, 2015, 90(1):254-65

PubMed: 26468527 ( click the link to review the publication )

J Virol, 2014, 88(20):12098-111

PubMed: 25122776 ( click the link to review the publication )

J Virol, 2012, 86(16):8581-91

PubMed: 22674974 ( click the link to review the publication )

Antiviral Res, 2017, 139:18-24

PubMed: 28025084 ( click the link to review the publication )

Antimicrob Agents Chemother, 2015, 10.1128/AAC.00223-15

PubMed: 25845863 ( click the link to review the publication )

Antimicrob Agents Chemother, 2014, 58(9):5386-94

PubMed: 24982066 ( click the link to review the publication )

Antimicrob Agents Chemother, 2014, 59(1):599-608

PubMed: 25385103 ( click the link to review the publication )
Antimicrob Agents Chemother, 2014, 58(1):386-96

PubMed: 24165192 ( click the link to review the publication )

Antimicrob Agents Chemother, 2014, 58(6):3206-16

PubMed: 24663025 ( click the link to review the publication )

Biochem Pharmacol, 2015, 96(3):190-201

PubMed: 26070251 ( click the link to review the publication )

Virology, 2014, 476C:168-179

PubMed: 25546252 ( click the link to review the publication )

PLoS One, 2013, 8(12):e82299

PubMed: 24358168 ( click the link to review the publication )

PLoS One, 2013, 8(6):e65273

PubMed: 23755208 ( click the link to review the publication )

J Virol Methods, 2015, 10.1016/j.jviromet.2015.03.009

PubMed: 25796989 ( click the link to review the publication )

4 Customer Reviews

Sensitivity of PR63cc to the combinatory treatment with asunaprevir and daclatasvir. Huh7.5.1 cells infected with PR63cc or JFH1 at an MOI of 0.05 for 3 days were treated with either asunaprevir, daclatasvir or in combination for another 3 days. 40 nM asunaprevir and 0.05 nM daclatasvir, approximately the EC50 concentration of the each inhibitor for JFH1, were used. The antiviral efficiency of each compound was evaluated by quantifying the intracellular HCV RNA by RT-qPCR. Data were expressed as the percentage of mock treatment control. The error bars were calculated from two independent experiments. ns, P > 0.05. *, P < 0.05.

Antiviral Res, 2017, 139:18-24. Daclatasvir (BMS-790052) purchased from Selleck.

The toxicity of BMS-790052 (BMS) and Telaprevir (TPV) was measured by seeding 96-well plates to 70% confluence and exposing the cells to up to 50 μM of compound for 72 hours. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] was added to each well at a final concentration of 500 μg/ml 4 h before dissolving crystals in 100 μl of DMSO and measuring at 550 nm UV wavelengths. The 50% cytotoxic concentration (CC50) was then calculation using the OD550 value and the following formula: log CC50=log concentration of HPP-[(HPP-50)/(HPP-LPP)×log d HPP: highest protective percentage closest to 50% LPP: Lowest protective percentage closest to 50% d: dilution factor

2011 Dr. Julie Sheldon,Dr Esteban Domingo and Dr Celia Perales. Daclatasvir (BMS-790052) purchased from Selleck.
Huh7.5 cells were infected with JFH-1 (2a) strain. Once the cells reached 80% infectivity they were treated with pMconcentration of BMS790052 for two different time points. Cells were collected in SDS sample loading buffer and probed for NS5A and GAPDH. After 16hrs hyperphosphorylated NS5A disappeared with increasing concentration of the drug. 40hrs of treatment resulted complete disappearance of NS5A. GAPDH is internal control.

2011 Dr. Anita Nag of Florida State University. Daclatasvir (BMS-790052) purchased from Selleck.

80% infected HCV JFH-1 cells were treated with several concentrations of BMS790052 in pMrange. Cells were fixed after 16hrs and NS5A was probed.Cells treated with BMS790052 shows NS5A present in clusters compared to an even cytoplasmic distribution in untreated cells.

2011 Dr. Anita Nag of Florida State University. Daclatasvir (BMS-790052) purchased from Selleck.

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Biological Activity

Description

Features

First-in-class, highly selective inhibitor of hepatitis C virus (HCV) NS5A with picomolar EC50 values.

Targets

HCV NS5A ^[1]

9 pM-50 pM(EC50)

In vitro

BMS-790052 is one of the most potent inhibitors of HCV replication reported so far. The mean EC50 valuses of BMS-790052 are 50 and 9 pM for HCV genotype 1a and 1b replicons, respectively. BMS-790052 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 BMS-790052's specificity for HCV. ^[1] In Huh7 cells harboring the HCV genotype 1b replicons, BMS-790052 blocks both transient and stable HCV genome replication, with EC50 values raging from 1-15 pM. BMS-790052 (100 pM or 1 nM) has been shown to alter the subcellular localization and biochemical fractionation of NS5A. ^[2] BMS-790052 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. ^[3]

Cell Data

Cell Lines	Assay Type	Incubation Time	Activity Description	PMID
human Huh7 cells	NVywdXlwTnWwY4Tpc44h[XO\|YYm=	Mk\SN{Bl[Xm\|	M17QdWFvfGm4aYLhcEBi[3Srdnn0fUBi\2GrboP0JGhEXiCpZX7veJlx\SBzYjDpcoZm[3SnZDDpckBpfW2jbjDIeYg4KGOnbHzzJIFnfGW{IEOg[IF6eyCkeTDj[YxtNWKjc3XkJJJmeGyrY3;uJIF{e2G7LDDFR\|UxRTOnLUC2JO69VQ>?	M3G4V\|I2OTR6MUCw
human CEM cells	MoHWR5l1d3SxeHnjbZR6KGG\|c3H5	NEXjUWU{KGSjeYO=	NH3kWXdEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBETU1iY3XscJMh[W[2ZYKgN{Bl[Xm\|LDDDR\|UxRTlwNjFOwG0>	MkDQNlUyPTR5MUS=
african green monkey Vero cells	MWrDfZRwfG:6aXPpeJkh[XO\|YYm=		M3\rbGN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGGocnnjZY4h\3KnZX6gcY9vc2W7IG\ldo8h[2WubIOsJGNEPTB;OT62JO69VQ>?	NGX4b\|UzOzR4NkKzNy=>
human CEM cells	MlfPR5l1d3SxeHnjbZR6KGG\|c3H5		MYfDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDDSW0h[2WubIOsJGNEPTB;OT62JO69VQ>?	MYmyNlcxPDh6Nx?=
human PBMC cells	MV7DfZRwfG:6aXPpeJkh[XO\|YYm=		NH3ldXBEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBRSk2FIHPlcIx{NCCFQ{WwQVE6KM7:TR?=	MYeyNlcxPDh6Nx?=

... Click to View More Cell Line Experimental Data

Protocol

Kinase Assay:^[4]	+ Expand FRET assay for HCV NS5A inhibitors: The peptide (Ac-Asp-Glu-Asp [EDANS]-Glu-Glu-Abu-[COO] Ala-Ser-Lys [DABCYL]-NH2) contains a fluorescence donor {EDANS, 5-[(2-aminoethyl)amino]naphthalene-1-sulfonic acid} near one end of the peptide and an acceptor {DABCYL, 4-[(4-dimethylamino)phenyl]azo)benzoic acid} near the other end. Intermolecular resonance energy transfer between the donor and the acceptor quenches the fluorescence of the peptide, but as the NS3 protease cleaves the peptide, the products are released from resonance energy transfer quenching. The fluorescence of the donor increases over time as more substrate is cleaved by the NS3 protease. The assay reagent is: 5× luciferase cell culture lysis reagent diluted to 1× with dH₂O, NaCl (150 mM), the FRET peptide (20 μM). HCV-Huh-7 cells are placed in a 96-well plate, and allowed to attach overnight (1×10⁴ cells per well). The next day, BMS-790052 is added to the wells and the plate is incubated for 72 hours. The plate is then rinsed with PBS and used for the FRET assay by the addition of 30 μL of the FRET peptide assay reagent (described above) per well. Signals are obtained using the Cytofluor 4000 instrument, which has been set to 340 nm (excitation)/490 nm (emission) automatic mode, for 20 cycles or less, with the plate being read in the kinetic mode. Following FRET, 40 μL of luciferase substrate is added to each well and the luciferase is measured.
Cell Research:^[1]	+ Expand Cell lines: HCV replicon cells (Huh7) Concentrations: 0.1 pM - 50 μM, dissolved in DMSO (the final concentration of DMSO is 0.5%) Incubation Time: 72 hours Method: BMS-790052 is added to 96-well plates containing HCV replicon cells seeded approximately 12 hours before in 200 µL media.The cell plates are tested for replication activity and cytotoxicity after 72 hours of incubation. Cytotoxicity is measured with CellTiter-Blue, after which the media and dye are removed, plates are inverted and the remaining liquid is blotted with paper towels. Replication activity of the HCV genotype 1a cell lines is quantified using Renilla luciferase. 1× Renilla luciferase lysis buffer (30 µL) is added to each well and plates are incubated with gentle shaking for 15 min. Renilla luciferase substrate (40 µL) is then added and the signals are detected using a Top Count luminometer set for light emission quantification. One hundred per cent activity is calculated for each cell line for the DMSO-only wells; percentage activity is calculated for each concentration of the inhibitor by dividing the average value for wells containing compound by the average value for wells containing DMSO. (Only for Reference)

Kinase Assay:^[4]

+ Expand

FRET assay for HCV NS5A inhibitors:

The peptide (Ac-Asp-Glu-Asp [EDANS]-Glu-Glu-Abu-[COO] Ala-Ser-Lys [DABCYL]-NH2) contains a fluorescence donor {EDANS, 5-[(2-aminoethyl)amino]naphthalene-1-sulfonic acid} near one end of the peptide and an acceptor {DABCYL, 4-[(4-dimethylamino)phenyl]azo)benzoic acid} near the other end. Intermolecular resonance energy transfer between the donor and the acceptor quenches the fluorescence of the peptide, but as the NS3 protease cleaves the peptide, the products are released from resonance energy transfer quenching. The fluorescence of the donor increases over time as more substrate is cleaved by the NS3 protease. The assay reagent is: 5× luciferase cell culture lysis reagent diluted to 1× with dH₂O, NaCl (150 mM), the FRET peptide (20 μM). HCV-Huh-7 cells are placed in a 96-well plate, and allowed to attach overnight (1×10⁴ cells per well). The next day, BMS-790052 is added to the wells and the plate is incubated for 72 hours. The plate is then rinsed with PBS and used for the FRET assay by the addition of 30 μL of the FRET peptide assay reagent (described above) per well. Signals are obtained using the Cytofluor 4000 instrument, which has been set to 340 nm (excitation)/490 nm (emission) automatic mode, for 20 cycles or less, with the plate being read in the kinetic mode. Following FRET, 40 μL of luciferase substrate is added to each well and the luciferase is measured.

Cell Research:^[1]

+ Expand

Cell lines: HCV replicon cells (Huh7)
Concentrations: 0.1 pM - 50 μM, dissolved in DMSO (the final concentration of DMSO is 0.5%)
Incubation Time: 72 hours
Method: BMS-790052 is added to 96-well plates containing HCV replicon cells seeded approximately 12 hours before in 200 µL media.The cell plates are tested for replication activity and cytotoxicity after 72 hours of incubation. Cytotoxicity is measured with CellTiter-Blue, after which the media and dye are removed, plates are inverted and the remaining liquid is blotted with paper towels. Replication activity of the HCV genotype 1a cell lines is quantified using Renilla luciferase. 1× Renilla luciferase lysis buffer (30 µL) is added to each well and plates are incubated with gentle shaking for 15 min. Renilla luciferase substrate (40 µL) is then added and the signals are detected using a Top Count luminometer set for light emission quantification. One hundred per cent activity is calculated for each cell line for the DMSO-only wells; percentage activity is calculated for each concentration of the inhibitor by dividing the average value for wells containing compound by the average value for wells containing DMSO.
(Only for Reference)

References

[4] O'Boyle DR 2nd, et al. Antimicrob Agents Chemother, 2005, 49(4), 1346-1353.

+ Expand

Solubility (25°C)

In vitro	DMSO	148 mg/mL (200.3 mM)
	Ethanol	148 mg/mL (200.3 mM)
	Water	Insoluble

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information Download Daclatasvir (BMS-790052) SDF

Molecular Weight	738.88
Formula	C₄₀H₅₀N₈O₆
CAS No.	1009119-64-5
Storage	3 years -20°C powder
Storage	2 years -80°C in solvent
Synonyms	EBP883

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Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2019-03-27)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT03882307	Not yet recruiting	Hepatitis C Chronic	Assiut University	May 1 2019	Early Phase 1
NCT03882307	Not yet recruiting	Hepatitis C Chronic	Assiut University	May 1 2019	Early Phase 1
NCT03883698	Recruiting	Kidney Failure Chronic\|Hepatitis C	Sanjay Gandhi Postgraduate Institute of Medical Sciences	March 15 2019	Phase 3
NCT03883698	Recruiting	Kidney Failure Chronic\|Hepatitis C	Sanjay Gandhi Postgraduate Institute of Medical Sciences	March 15 2019	Phase 3
NCT03748745	Active not recruiting	Drug Interactions	Nanjing Sanhome Pharmaceutical Co. Ltd.	November 19 2018	Phase 1
NCT03537196	Enrolling by invitation	Hepatitis C\|Drug Use\|Viral Hepatitis C	French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)	November 13 2018	Phase 4

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HCV Protease Signaling Pathway Map

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Daclatasvir (BMS-790052)

Cited by 19 Publications

4 Customer Reviews

Purity & Quality Control

Choose Selective HCV Protease Inhibitors

Biological Activity

Protocol

References

Solubility (25°C)

Chemical Information Download Daclatasvir (BMS-790052) SDF

Bio Calculators

Molarity Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Dilution Calculator

Concentration _(start) x Volume _(start) = Concentration _(final) x Volume _(final)

The Serial Dilution Calculator Equation

Serial Dilutions

Computed Result

Molecular Weight Calculator

Total Molecular Weight: g/mol

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Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molarity Calculator

Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2019-03-27)

Tech Support

HCV Protease Signaling Pathway Map

Related HCV Protease Products0

Choose Your Country or Region

By Signaling Pathways

By product type

Daclatasvir (BMS-790052)

Cited by 19 Publications

4 Customer Reviews

Purity & Quality Control

Choose Selective HCV Protease Inhibitors

Biological Activity

Protocol

References

Solubility (25°C)

Chemical Information Download Daclatasvir (BMS-790052) SDF

Bio Calculators

Molarity Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Dilution Calculator

Concentration (start) x Volume (start) = Concentration (final) x Volume (final)

The Serial Dilution Calculator Equation

Serial Dilutions

Computed Result

Molecular Weight Calculator

Total Molecular Weight: g/mol

Instructions to calculate molar mass (molecular weight) of a chemical compound:

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molarity Calculator

Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2019-03-27)

Tech Support

HCV Protease Signaling Pathway Map

Related HCV Protease Products0

Concentration _(start) x Volume _(start) = Concentration _(final) x Volume _(final)