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 18 Publications

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

PubMed: 26266980

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

PubMed: 23903655

Hepatology, 2014, 10.1002/hep.27197

PubMed: 24797787

PLoS Pathog, 2015, 11(3):e1004758

PubMed: 25822891

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

PubMed: 26468527

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

PubMed: 25122776

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

PubMed: 22674974

Antiviral Res, 2017, 139:18-24

PubMed: 28025084

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

PubMed: 25845863

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

PubMed: 24982066

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

PubMed: 25385103

Antimicrob Agents Chemother, 2014, 58(1):386-96

PubMed: 24165192
Antimicrob Agents Chemother, 2014, 58(6):3206-16

PubMed: 24663025

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

PubMed: 26070251

Virology, 2014, 476C:168-179

PubMed: 25546252

PLoS One, 2013, 8(12):e82299

PubMed: 24358168

PLoS One, 2013, 8(6):e65273

PubMed: 23755208

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

PubMed: 25796989

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.

Purity & Quality Control

Choose Selective HCV Protease Inhibitors

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	M3\XcWZ2dmO2aX;uJIF{e2G7	Mm\4N{Bl[Xm\|	MmiyRY51cX[rcnHsJIFkfGm4aYT5JIFo[Wmwc4SgTGNXKGenbn;0fZBmKDGkIHnu[oVkfGWmIHnuJIh2dWGwIFj1bFch[2WubIOgZYZ1\XJiMzDkZZl{KGK7IHPlcIwu[mG\|ZXSgdoVxdGmlb36gZZN{[XluIFXDOVA:O2VvME[g{txO	NXj0[IlGOjVzNEixNFA>
human CEM cells	NUPifJFQS3m2b4TvfIlkcXS7IHHzd4F6	Mon5N{Bl[Xm\|	M4fP[GN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGNGVSClZXzsd{Bi\nSncjCzJIRigXNuIFPDOVA:QS54IN88US=>	NFXCWmYzPTF3NEexOC=>
african green monkey Vero cells	MXTDfZRwfG:6aXPpeJkh[XO\|YYm=		NXrN[4o1S3m2b4TvfIlkcXS7IHHnZYlve3RiYX\ybYNidiCpcnXlckBud26tZYmgWoVzdyClZXzsd{whS0N3ME25MlYh\|ryP	M1LD[lI{PDZ4MkOz
human CEM cells	M4rQU2N6fG:2b4jpZ4l1gSCjc4PhfS=>		M2e4dGN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGNGVSClZXzsd{whS0N3ME25MlYh\|ryP	MXKyNlcxPDh6Nx?=
human PBMC cells	NITEdIlEgXSxdH;4bYNqfHliYYPzZZk>		M1TFfmN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJHBDVUNiY3XscJMtKEOFNUC9NVkh\|ryP	MnLsNlI4ODR6OEe=

... 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

Bio Calculators

Molarity Calculator

Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

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

*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and MSDS / COA (available on product pages).

Dilution Calculator

Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

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

This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / COA (available online).

The Serial Dilution Calculator Equation

Serial Dilutions
Concertration (start):
Dilution-folds:

Computed Result

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

Molecular Weight Calculator

Enter the chemical formula of a compound to calculate its molar mass and elemental composition:

Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

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

To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.

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

Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Molarity Calculator

Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2018-11-15)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT03686722	Completed	Diabetes Mellitus Type 2\|Hepatitis C\|Drug Interactions	Mohamed Raslan\|Ain Shams University\|Drug Research Centre Cairo Egypt	September 9 2017	Phase 1
NCT01492504	Completed	Hepatitis C	Bristol-Myers Squibb	February 7 2012	--
NCT02262728	Completed	Hepatitis C Chronic	Janssen Research & Development LLC	September 30 2014	Phase 2
NCT01455090	Completed	Chronic Hepatitis C	Bristol-Myers Squibb	November 30 2011	Phase 2
NCT03247296	Active not recruiting	Hepatitis C	MTI University	February 28 2017	--
NCT03485846	Active not recruiting	Chronic Hepatitis C Genotype 1b	R-Pharm\|Almedis	November 27 2017	Phase 2

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

HCV Protease Signaling Pathway Map

Related HCV Protease Products0

Ledipasvir (GS5885) ^New

Ledipasvir (GS5885) is a HCV NS5A polymerase inhibitor, used for the treatment of hepatitis C virus infection.
Calpeptin ^New

Calpeptin is a potent, cell-permeable calpain inhibitor with ID50 of 52 nM, 34 nM, 138 nM, and 40 nM for Calpain I (porcine erythrocytes), Calpain II (porcine kidney), Papainb, and Calpain I (human platelets), respectively.
Marimastat (BB-2516) ^New

Marimastat (BB-2516) is a broad spectrum matrix metalloprotease (MMP) inhibitor for MMP-9, MMP-1, MMP-2, MMP-14 and MMP-7 with IC50 of 3 nM, 5 nM, 6 nM, 9 nM and 13 nM, respectively. Phase 3.
Danoprevir (ITMN-191)

Danoprevir(ITMN-191) is a peptidomimetic inhibitor of the NS3/4A protease of hepatitis C virus (HCV) with IC50 of 0.2-3.5 nM, inhibition effect for HCV genotypes 1A/1B/4/5/6 is ~10-fold higher than 2B/3A. Phase 2.

Features:A peptidomimetic inhibitor of the NS3/4A protease of hepatitis C virus (HCV).
Lomibuvir (VX-222, VCH-222)

Lomibuvir (VX-222, VCH-222) is a novel, potent and selective inhibitor of HCV polymerase with IC50 of 0.94-1.2 μM, 15.3-fold less effective for mutant M423T, and 108-fold less effective for mutant I482L. Phase 2.

Features:A novel, potent and selective inhibitor of non-nucleoside polymerase, specifically the HCV RNA-dependent RNA polymerase.
Telaprevir (VX-950)

Telaprevir (VX-950) is an HCV NS3-4A serine protease inhibitor with IC50 of 0.35 μM.

Features:Telaprevir is a covalent, reversible inhibitor of the NS3-4A protease (unlike BILN 2061which is a noncovalent inhibitor), with a slow-binding and slow-dissociation mechanism.
MG-132

MG132 is a potent cell-permeable proteasome and calpain inhibitor with IC50s of 0.1 and 1.2 μM for the inhibition of proteasome and calpain, respectively.
Bortezomib (PS-341)

Bortezomib (PS-341) is a potent 20S proteasome inhibitor with K_i of 0.6 nM. It exhibits favorable selectivity towards tumor cells over normal cells.
Carfilzomib (PR-171)

Carfilzomib (PR-171) is an irreversible proteasome inhibitor with IC50 of <5 nM in ANBL-6 cells, displayed preferential in vitro inhibitory potency against the ChT-L activity in the β5 subunit, but little or no effect on the PGPH and T-L activities.
Ixazomib (MLN2238)

MLN2238 inhibits the chymotrypsin-like proteolytic (β5) site of the 20S proteasome with IC50 and K_i of 3.4 nM and 0.93 nM in cell-free assays, respectively, also inhibits the caspase-like (β1) and trypsin-like (β2) proteolytic sites, with IC50 of 31 and 3500 nM. Phase 3.

Features:A first-in-class proteasome inhibitor that has improved pharmacokinetics (PK), pharmacodynamics(PD), and antitumor activity in preclinical studies.

Choose Your Country or Region

By Signaling Pathways

By product type

Daclatasvir (BMS-790052)

Cited by 18 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 2018-11-15)

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 18 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 2018-11-15)

Tech Support

HCV Protease Signaling Pathway Map

Related HCV Protease Products0

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