Journal: RSC Advances

Article Title: Discovery of VEGFR2 inhibitors by integrating naïve Bayesian classification, molecular docking and drug screening approaches †

doi: 10.1039/c7ra12259d

Figure Lengend Snippet: Workflow of the integrated virtual screening and drug screening approaches for VEGFR2 kinase inhibitors.

Article Snippet: Human VEGFR2 (cytoplastic domain expressed as N-terminal GST-fusion protein) was purchased from Carna Biosciences (Kobe, Japan); The HTRF® KinEASETM-TK assay kit (62TK0PEB) was provided by Cisbio Bioassays (Parc Marcel Boiteux, 30200 Codolet, France).

Techniques:

Journal: RSC Advances

Article Title: Discovery of VEGFR2 inhibitors by integrating naïve Bayesian classification, molecular docking and drug screening approaches †

doi: 10.1039/c7ra12259d

Figure Lengend Snippet: Examples of the top 15 good (A) and bad (B) fragments for VEGFR2 inhibition as estimated by NB-c model. The Bayesian score (Score) is given for each fragment.

Article Snippet: Human VEGFR2 (cytoplastic domain expressed as N-terminal GST-fusion protein) was purchased from Carna Biosciences (Kobe, Japan); The HTRF® KinEASETM-TK assay kit (62TK0PEB) was provided by Cisbio Bioassays (Parc Marcel Boiteux, 30200 Codolet, France).

Techniques: Inhibition

Journal: RSC Advances

Article Title: Discovery of VEGFR2 inhibitors by integrating naïve Bayesian classification, molecular docking and drug screening approaches †

doi: 10.1039/c7ra12259d

Figure Lengend Snippet: EstPGood values and LibDock Scores of FDA-approved drugs as predicted by NB-c and LibDock. While the 8 VEGFR2-targeting antiangiogenic agents are represented in red triangles, other drugs are represented in blue squares.

Article Snippet: Human VEGFR2 (cytoplastic domain expressed as N-terminal GST-fusion protein) was purchased from Carna Biosciences (Kobe, Japan); The HTRF® KinEASETM-TK assay kit (62TK0PEB) was provided by Cisbio Bioassays (Parc Marcel Boiteux, 30200 Codolet, France).

Techniques:

Journal: RSC Advances

Article Title: Discovery of VEGFR2 inhibitors by integrating naïve Bayesian classification, molecular docking and drug screening approaches †

doi: 10.1039/c7ra12259d

Figure Lengend Snippet: Inhibitory curves and IC 50 values for the reference compound axitinib (A) and three FDA-approved drugs flubendazole (B), rilpivirine (C), papaverine (D) against VEGFR2.

Article Snippet: Human VEGFR2 (cytoplastic domain expressed as N-terminal GST-fusion protein) was purchased from Carna Biosciences (Kobe, Japan); The HTRF® KinEASETM-TK assay kit (62TK0PEB) was provided by Cisbio Bioassays (Parc Marcel Boiteux, 30200 Codolet, France).

Techniques:

Journal: RSC Advances

Article Title: Discovery of VEGFR2 inhibitors by integrating naïve Bayesian classification, molecular docking and drug screening approaches †

doi: 10.1039/c7ra12259d

Figure Lengend Snippet: The receptor–ligand interactions of the axitinib (A, B), flubendazole (C, D), rilpivirine (E, F), papaverine (G, H) with the active site of VEGFR2.

Article Snippet: Human VEGFR2 (cytoplastic domain expressed as N-terminal GST-fusion protein) was purchased from Carna Biosciences (Kobe, Japan); The HTRF® KinEASETM-TK assay kit (62TK0PEB) was provided by Cisbio Bioassays (Parc Marcel Boiteux, 30200 Codolet, France).

Techniques:

Journal: PLoS ONE

Article Title: Preclinical Activity of ARQ 087, a Novel Inhibitor Targeting FGFR Dysregulation

doi: 10.1371/journal.pone.0162594

Figure Lengend Snippet: (A) ARQ 069. (B) ARQ 087. (C) Enzyme kinetic analysis was performed to determine the mode of inhibition of ARQ 087 with FGFR1 and FGFR2. Concentrations of ATP [ATP] and ARQ 087 [I] are indicated on the graphs. The rate plotted is the AlphaScreen ™ signal obtained from the plate reader with background correction. The experiments were conducted in triplicates and the means and the standard deviations were plotted. The number of parameter ( n p ), the sum of squares rel ( SS rel ), Akaike information criterion ( AIC ), weight of AIC ( w (AIC) ), Bayesian information criterion ( BIC ) and the weight of BIC ( w (BIC) ) for each binding mode were determined by the DynaFit software and are summarized below the plots. The dissociation constant ( K i) of ARQ 087 for FGFR1 and FGFR2 are shown. (D) The effect of ARQ 087 on the activation of FGFR1 and FGFR2 was examined in a continuous autophosphorylation assay.

Article Snippet: Kinase inhibitory activity of ARQ 087 was determined for the recombinant FGFR1 (Cat#08133, Carna BioScience, Kobe, Japan) or FGFR2 proteins (Cat#08134, Carna BioScience, Kobe, Japan), utilizing a biotinylated PYK2 peptide substrate (biotin-AGAGSIESDIYAEIPDETC-NH2, Biopeptide, San Diego, CA), and ATP (Cat#12215226, Roche, Indianapolis, IN), with AlphaScreen ™ technology (PerkinElmer, Waltham, MA).

Techniques: Inhibition, Amplified Luminescent Proximity Homogenous Assay, Binding Assay, Software, Activation Assay

Journal: PLoS ONE

Article Title: Preclinical Activity of ARQ 087, a Novel Inhibitor Targeting FGFR Dysregulation

doi: 10.1371/journal.pone.0162594

Figure Lengend Snippet: ARQ 087 biochemical activity.

Article Snippet: Kinase inhibitory activity of ARQ 087 was determined for the recombinant FGFR1 (Cat#08133, Carna BioScience, Kobe, Japan) or FGFR2 proteins (Cat#08134, Carna BioScience, Kobe, Japan), utilizing a biotinylated PYK2 peptide substrate (biotin-AGAGSIESDIYAEIPDETC-NH2, Biopeptide, San Diego, CA), and ATP (Cat#12215226, Roche, Indianapolis, IN), with AlphaScreen ™ technology (PerkinElmer, Waltham, MA).

Techniques: Activity Assay

Journal: PLoS ONE

Article Title: Preclinical Activity of ARQ 087, a Novel Inhibitor Targeting FGFR Dysregulation

doi: 10.1371/journal.pone.0162594

Figure Lengend Snippet: COS-1 cells ectopically expressing FGFR1, FGFR2, FGFR3 or FGFR4 were treated with the indicated concentrations of ARQ 087 for 2 hours followed by stimulation with 100 pM of FGF1/2/7 for 15 minutes. Total and phospho-FGFR was assessed by Western blot analyses. β-Actin was used as a loading control. The EC 50 values of individual FGFR family members are shown.

Article Snippet: Kinase inhibitory activity of ARQ 087 was determined for the recombinant FGFR1 (Cat#08133, Carna BioScience, Kobe, Japan) or FGFR2 proteins (Cat#08134, Carna BioScience, Kobe, Japan), utilizing a biotinylated PYK2 peptide substrate (biotin-AGAGSIESDIYAEIPDETC-NH2, Biopeptide, San Diego, CA), and ATP (Cat#12215226, Roche, Indianapolis, IN), with AlphaScreen ™ technology (PerkinElmer, Waltham, MA).

Techniques: Expressing, Western Blot

Journal: PLoS ONE

Article Title: Preclinical Activity of ARQ 087, a Novel Inhibitor Targeting FGFR Dysregulation

doi: 10.1371/journal.pone.0162594

Figure Lengend Snippet: ARQ 087 GI 50 in Ba/F3 transfected cell lines.

Article Snippet: Kinase inhibitory activity of ARQ 087 was determined for the recombinant FGFR1 (Cat#08133, Carna BioScience, Kobe, Japan) or FGFR2 proteins (Cat#08134, Carna BioScience, Kobe, Japan), utilizing a biotinylated PYK2 peptide substrate (biotin-AGAGSIESDIYAEIPDETC-NH2, Biopeptide, San Diego, CA), and ATP (Cat#12215226, Roche, Indianapolis, IN), with AlphaScreen ™ technology (PerkinElmer, Waltham, MA).

Techniques: Transfection

Journal: PLoS ONE

Article Title: Preclinical Activity of ARQ 087, a Novel Inhibitor Targeting FGFR Dysregulation

doi: 10.1371/journal.pone.0162594

Figure Lengend Snippet: ARQ 087 activity in FGFR dysregulated cell lines.

Article Snippet: Kinase inhibitory activity of ARQ 087 was determined for the recombinant FGFR1 (Cat#08133, Carna BioScience, Kobe, Japan) or FGFR2 proteins (Cat#08134, Carna BioScience, Kobe, Japan), utilizing a biotinylated PYK2 peptide substrate (biotin-AGAGSIESDIYAEIPDETC-NH2, Biopeptide, San Diego, CA), and ATP (Cat#12215226, Roche, Indianapolis, IN), with AlphaScreen ™ technology (PerkinElmer, Waltham, MA).

Techniques: Activity Assay, Amplification, Over Expression