ILORASERTIB

/static/temp/default.svg Search structure
Synonyms
Status
Molecule Category UNKNOWN
UNII 6L5D03D975
EPA CompTox DTXSID10153718

Structure

InChI Key WPHKIQPVPYJNAX-UHFFFAOYSA-N
Smiles Nc1ncc(-c2cnn(CCO)c2)c2scc(-c3ccc(NC(=O)Nc4cccc(F)c4)cc3)c12
InChI
InChI=1S/C25H21FN6O2S/c26-17-2-1-3-19(10-17)31-25(34)30-18-6-4-15(5-7-18)21-14-35-23-20(12-28-24(27)22(21)23)16-11-29-32(13-16)8-9-33/h1-7,10-14,33H,8-9H2,(H2,27,28)(H2,30,31,34)

Physicochemical Descriptors

Property Name Value
Molecular Formula C25H21FN6O2S
Molecular Weight 488.55
AlogP 5.18
Hydrogen Bond Acceptor 7.0
Hydrogen Bond Donor 4.0
Number of Rotational Bond 6.0
Polar Surface Area 118.09
Molecular species NEUTRAL
Aromatic Rings 5.0
Heavy Atoms 35.0

Bioactivity

Mechanism of Action Action Reference
Platelet-derived growth factor receptor inhibitor INHIBITOR PubMed
Protein: Platelet-derived growth factor receptor
Description: Platelet-derived growth factor receptor beta
Organism : Homo sapiens
P09619 ENSG00000113721
Protein: Platelet-derived growth factor receptor
Description: Platelet-derived growth factor receptor alpha
Organism : Homo sapiens
P16234 ENSG00000134853
Protein: Vascular endothelial growth factor receptor
Description: Vascular endothelial growth factor receptor 1
Organism : Homo sapiens
P17948 ENSG00000102755
Protein: Vascular endothelial growth factor receptor
Description: Vascular endothelial growth factor receptor 3
Organism : Homo sapiens
P35916 ENSG00000037280
Protein: Vascular endothelial growth factor receptor
Description: Vascular endothelial growth factor receptor 2
Organism : Homo sapiens
P35968 ENSG00000128052
Targets EC50(nM) IC50(nM) Kd(nM) Ki(nM) Inhibition(%)
Enzyme Kinase Protein Kinase AGC protein kinase group AGC protein kinase DMPK family AGC protein kinase ROCK subfamily
- 456 - - -
Enzyme Kinase Protein Kinase Other protein kinase group Other protein kinase AUR family
- 2-12 - - -
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase Abl family
- 12 - - -
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase FGFR family
- 188 - - -
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase InsR family
- 539 - - -
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase PDGFR family
- 16 - 1 -
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase Ret family
- 7 - - -
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase Src family
- 110 - - -
Enzyme Kinase Protein Kinase TK protein kinase group Tyrosine protein kinase VEGFR family
- 2-4 - - -
Enzyme Kinase Protein Kinase TKL protein kinase group TKL protein kinase STKR family TKL protein kinase STKR Type 1 subfamily
- 363 - - -
Ion channel Voltage-gated ion channel Potassium channels Voltage-gated potassium channel
- 1000 - - -
Assay Description Organism Bioactivity Reference
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: MAP4K4 None 50.12 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: MST1R None 10.0 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: CSF1R None 3.162 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: MAP2K2 None 125.89 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: IKBKE None 25.12 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: AXL None 1.585 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: LTK None 39.81 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: FRK None 1.995 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: STK3 None 15.85 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: NTRK3 None 6.31 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: MATK None 39.81 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: RPS6KA3 None 630.96 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: MAP2K1 None 100.0 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: ALK None 199.53 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: PLK4 None 10.0 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: RET None 2.512 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: PRKD2 None 501.19 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: RPS6KB1 None 100.0 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: SYK None 50.12 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: TYRO3 None 63.1 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: STK17A None 794.33 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: LCK None 1.995 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: CHEK2 None 79.43 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: ACVR1 None 398.11 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: ROCK2 None 31.62 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: STK6 None 1.995 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: BTK None 25.12 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: KIT None 15.85 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: FGFR1 None 63.1 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: LYN None 1.995 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: ITK None 12.59 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: TAO1 None 630.96 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: ROS1 None 5.012 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: BLK None 2.512 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: HIPK2 None 158.49 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: MARK3 None 316.23 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: NTRK1 None 63.1 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: INSR None 100.0 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: ZAK None 501.19 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: TYK2 None 794.33 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: EGFR None 501.19 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: SRC None 31.62 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: SRMS None 25.12 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: MAP4K2 None 7.943 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: MET None 3.981 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: ACK1 None 7.943 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: PDGFRB None 0.5012 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: FLT3 None 15.85 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: ERBB2 None 501.19 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: ABL1 None 3.162 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: MKNK2 None 199.53 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: KDR None 1.0 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: EPHA2 None 63.1 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: IGF1R None 199.53 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: MINK None 50.12 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: NEK4 None 199.53 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: PTK2 None 125.89 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: MELK None 251.19 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: PDGFRA None 0.7943 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: LRRK2 None 25.12 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: STK12 None 0.7943 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: FLT4 None 3.162 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: ROCK1 None 158.49 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: FER None 50.12 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: FYN None 63.1 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: HIPK4 None 19.95 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: PDPK1 None 794.33 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: NEK2 None 12.59 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: CDK8 None 158.49 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: FLT1 None 12.59 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: SLK None 7.943 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: FGFR3 None 39.81 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: NTRK2 None 10.0 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: ERBB4 None 199.53 nM
PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: MARK2 None 251.19 nM
Inhibition of KDR using 1 mM ATP by HTRF assay None 2.0 nM
Inhibition of Aurora B using 1 mM ATP by HTRF assay None 7.0 nM
Inhibition of CYP3A4 up to 10 uM None 20.0 %
Inhibition of Aurora A by TR-FRET assay None 12.0 nM
Inhibition of Flt1 by TR-FRET assay None 32.0 nM
Inhibition of PDGFRbeta by TR-FRET assay None 3.0 nM
Inhibition of CSF1R by TR-FRET assay None 16.0 nM
Inhibition of LCK by TR-FRET assay None 3.0 nM
Inhibition of ABL by TR-FRET assay None 12.0 nM
Inhibition of RET by TR-FRET assay None 7.0 nM
Inhibition of FYN by TR-FRET assay None 110.0 nM
Inhibition of FGFR1 by TR-FRET assay None 188.0 nM
Inhibition of ALK by TR-FRET assay None 363.0 nM
Inhibition of ROCK1 by TR-FRET assay None 456.0 nM
Inhibition of IGF1R by TR-FRET assay None 539.0 nM
Inhibition of KDR by TR-FRET assay None 4.0 nM
Inhibition of Aurora B by TR-FRET assay None 2.0 nM
Inhibition of CSF1R Homo sapiens 3.162 nM
Inhibition of PDGFRA Homo sapiens 0.7943 nM
Inhibition of KDR by HTRF analysis in presence of 1 mM ATP Homo sapiens 2.0 nM
Inhibition of Aurora B kinase by HTRF analysis in presence of 1 mM ATP Homo sapiens 7.0 nM
Inhibition of human KDR autophosphorylation expressed in mouse NIH/3T3 cells Homo sapiens 3.0 nM
Enzyme Inhibtion Assay: To determine Aurora B activity of representative compounds of the invention, Active Aurora B enzyme (recombinant residues 1-344) and INCENP (recombinant GST fusion protein (Upstate)) were incubated in wells of a 384 well plate with biotinylted histone H3 peptide residues 1-21 (Upstate), 1 mM ATP, and various concentrations of inhibitors in a HEPES buffer, pH 7.4 containing MgCl2, sodium othrovanadate, and Triton X-100. After 1 hour, the reaction was stopped with EDTA and anti-phospho-histone H3 Europium Cryptate (Cis-Bio) and SA-APC (Phycolink, Prozyme) were added to detect the phosphopeptide. The amount of phosphorylation was determined by the time-resolved fluorescence ratio of signals at 665 nm and 615 nm. Homo sapiens 6.73 nM Enzyme Inhibtion Assay: To determine Aurora B activity of representative compounds of the invention, Active Aurora B enzyme (recombinant residues 1-344) and INCENP (recombinant GST fusion protein (Upstate)) were incubated in wells of a 384 well plate with biotinylted histone H3 peptide residues 1-21 (Upstate), 1 mM ATP, and various concentrations of inhibitors in a HEPES buffer, pH 7.4 containing MgCl2, sodium othrovanadate, and Triton X-100. After 1 hour, the reaction was stopped with EDTA and anti-phospho-histone H3 Europium Cryptate (Cis-Bio) and SA-APC (Phycolink, Prozyme) were added to detect the phosphopeptide. The amount of phosphorylation was determined by the time-resolved fluorescence ratio of signals at 665 nm and 615 nm. Homo sapiens 7.87 nM
Enzyme Inhibtion Assay: To determine Aurora A and C activity of representative compounds of the invention, Active Aurora A or C enzyme was incubated in wells of a 384 well plate with biotinylated STK substrate-2 (Upstate), 1 mM ATP, and various concentrations of inhibitors in a Hepes buffer, pH 7.4 containing MgCl2, sodium othrovanadate, and Triton X-100. After 1 hour, the reaction was stopped with EDTA and anti-phospho-STK antibody Europium Cryptate (Upstate) and SA-XL665 (Upstate) were added to detect the phosphopeptide. The amount of phosphorylation was determined by the time-resolved fluorescence ratio of signals at 665 nm and 615 nm. Homo sapiens 675.42 nM
Homogenous Time-Resolved Fluorescence Assay (HTRF): To determine the activity of the various kinases, a homogenous time-resolved fluorescence (HTRF) in vitro kinase assay was used. (Mathis, G., HTRF(R) Technology. J Biomol Screen, 1999. 4(6): p. 309-314; Alfred J. Kolb, Paul V. Kaplita, David J. Hayes, Young-Whan Park, Christine Pernell, John S. Major and Gerard Mathis, Drug Discovery Today, 1998, 3, 333-342.). For example for KDR, cKIT, FLT1, CSF1R and FTL3, purified enzyme was mixed with 0.5 μM N-biotinylated substrate (Biotin-Ahx-AEEEYFFLA-amide (SEQ. ID. 1)), various concentrations of inhibitor in reaction buffer (50 mM HEPES, pH 7.1, 10 mM MgCl2, 2 mM MnCl2, 0.1% BSA and 1 mM DTT, 40 μL final volume), ATP (1 mM final conc.) in a black 384-well plate. After 60 minutes incubation at room temperature, the reaction was quenched by addition of a buffered EDTA solution. Homo sapiens 2.65 nM Homogenous Time-Resolved Fluorescence Assay (HTRF): To determine the activity of the various kinases, a homogenous time-resolved fluorescence (HTRF) in vitro kinase assay was used. (Mathis, G., HTRF(R) Technology. J Biomol Screen, 1999. 4(6): p. 309-314; Alfred J. Kolb, Paul V. Kaplita, David J. Hayes, Young-Whan Park, Christine Pernell, John S. Major and Gerard Mathis, Drug Discovery Today, 1998, 3, 333-342.). For example for KDR, cKIT, FLT1, CSF1R and FTL3, purified enzyme was mixed with 0.5 μM N-biotinylated substrate (Biotin-Ahx-AEEEYFFLA-amide (SEQ. ID. 1)), various concentrations of inhibitor in reaction buffer (50 mM HEPES, pH 7.1, 10 mM MgCl2, 2 mM MnCl2, 0.1% BSA and 1 mM DTT, 40 μL final volume), ATP (1 mM final conc.) in a black 384-well plate. After 60 minutes incubation at room temperature, the reaction was quenched by addition of a buffered EDTA solution. Homo sapiens 1.59 nM
Homogenous Time-Resolved Fluorescence Assay (HTRF): To determine the activity of the various kinases, a homogenous time-resolved fluorescence (HTRF) in vitro kinase assay was used. (Mathis, G., HTRF(R) Technology. J Biomol Screen, 1999. 4(6): p. 309-314; Alfred J. Kolb, Paul V. Kaplita, David J. Hayes, Young-Whan Park, Christine Pernell, John S. Major and Gerard Mathis, Drug Discovery Today, 1998, 3, 333-342.). For example for KDR, cKIT, FLT1, CSF1R and FTL3, purified enzyme was mixed with 0.5 μM N-biotinylated substrate (Biotin-Ahx-AEEEYFFLA-amide (SEQ. ID. 1)), various concentrations of inhibitor in reaction buffer (50 mM HEPES, pH 7.1, 10 mM MgCl2, 2 mM MnCl2, 0.1% BSA and 1 mM DTT, 40 μL final volume), ATP (1 mM final conc.) in a black 384-well plate. After 60 minutes incubation at room temperature, the reaction was quenched by addition of a buffered EDTA solution. Homo sapiens 19.53 nM Homogenous Time-Resolved Fluorescence Assay (HTRF): To determine the activity of the various kinases, a homogenous time-resolved fluorescence (HTRF) in vitro kinase assay was used. (Mathis, G., HTRF(R) Technology. J Biomol Screen, 1999. 4(6): p. 309-314; Alfred J. Kolb, Paul V. Kaplita, David J. Hayes, Young-Whan Park, Christine Pernell, John S. Major and Gerard Mathis, Drug Discovery Today, 1998, 3, 333-342.). For example for KDR, cKIT, FLT1, CSF1R and FTL3, purified enzyme was mixed with 0.5 μM N-biotinylated substrate (Biotin-Ahx-AEEEYFFLA-amide (SEQ. ID. 1)), various concentrations of inhibitor in reaction buffer (50 mM HEPES, pH 7.1, 10 mM MgCl2, 2 mM MnCl2, 0.1% BSA and 1 mM DTT, 40 μL final volume), ATP (1 mM final conc.) in a black 384-well plate. After 60 minutes incubation at room temperature, the reaction was quenched by addition of a buffered EDTA solution. Homo sapiens 27.27 nM
Homogenous Time-Resolved Fluorescence Assay (HTRF): To determine the activity of the various kinases, a homogenous time-resolved fluorescence (HTRF) in vitro kinase assay was used. (Mathis, G., HTRF(R) Technology. J Biomol Screen, 1999. 4(6): p. 309-314; Alfred J. Kolb, Paul V. Kaplita, David J. Hayes, Young-Whan Park, Christine Pernell, John S. Major and Gerard Mathis, Drug Discovery Today, 1998, 3, 333-342.). For example for KDR, cKIT, FLT1, CSF1R and FTL3, purified enzyme was mixed with 0.5 μM N-biotinylated substrate (Biotin-Ahx-AEEEYFFLA-amide (SEQ. ID. 1)), various concentrations of inhibitor in reaction buffer (50 mM HEPES, pH 7.1, 10 mM MgCl2, 2 mM MnCl2, 0.1% BSA and 1 mM DTT, 40 μL final volume), ATP (1 mM final conc.) in a black 384-well plate. After 60 minutes incubation at room temperature, the reaction was quenched by addition of a buffered EDTA solution. Homo sapiens 2.1 nM Homogenous Time-Resolved Fluorescence Assay (HTRF): To determine the activity of the various kinases, a homogenous time-resolved fluorescence (HTRF) in vitro kinase assay was used. (Mathis, G., HTRF(R) Technology. J Biomol Screen, 1999. 4(6): p. 309-314; Alfred J. Kolb, Paul V. Kaplita, David J. Hayes, Young-Whan Park, Christine Pernell, John S. Major and Gerard Mathis, Drug Discovery Today, 1998, 3, 333-342.). For example for KDR, cKIT, FLT1, CSF1R and FTL3, purified enzyme was mixed with 0.5 μM N-biotinylated substrate (Biotin-Ahx-AEEEYFFLA-amide (SEQ. ID. 1)), various concentrations of inhibitor in reaction buffer (50 mM HEPES, pH 7.1, 10 mM MgCl2, 2 mM MnCl2, 0.1% BSA and 1 mM DTT, 40 μL final volume), ATP (1 mM final conc.) in a black 384-well plate. After 60 minutes incubation at room temperature, the reaction was quenched by addition of a buffered EDTA solution. Homo sapiens 1.25 nM
Homogenous Time-Resolved Fluorescence Assay (HTRF): To determine the activity of the various kinases, a homogenous time-resolved fluorescence (HTRF) in vitro kinase assay was used. (Mathis, G., HTRF(R) Technology. J Biomol Screen, 1999. 4(6): p. 309-314; Alfred J. Kolb, Paul V. Kaplita, David J. Hayes, Young-Whan Park, Christine Pernell, John S. Major and Gerard Mathis, Drug Discovery Today, 1998, 3, 333-342.). For example for KDR, cKIT, FLT1, CSF1R and FTL3, purified enzyme was mixed with 0.5 μM N-biotinylated substrate (Biotin-Ahx-AEEEYFFLA-amide (SEQ. ID. 1)), various concentrations of inhibitor in reaction buffer (50 mM HEPES, pH 7.1, 10 mM MgCl2, 2 mM MnCl2, 0.1% BSA and 1 mM DTT, 40 μL final volume), ATP (1 mM final conc.) in a black 384-well plate. After 60 minutes incubation at room temperature, the reaction was quenched by addition of a buffered EDTA solution. Homo sapiens 1.13 nM Homogenous Time-Resolved Fluorescence Assay (HTRF): To determine the activity of the various kinases, a homogenous time-resolved fluorescence (HTRF) in vitro kinase assay was used. (Mathis, G., HTRF(R) Technology. J Biomol Screen, 1999. 4(6): p. 309-314; Alfred J. Kolb, Paul V. Kaplita, David J. Hayes, Young-Whan Park, Christine Pernell, John S. Major and Gerard Mathis, Drug Discovery Today, 1998, 3, 333-342.). For example for KDR, cKIT, FLT1, CSF1R and FTL3, purified enzyme was mixed with 0.5 μM N-biotinylated substrate (Biotin-Ahx-AEEEYFFLA-amide (SEQ. ID. 1)), various concentrations of inhibitor in reaction buffer (50 mM HEPES, pH 7.1, 10 mM MgCl2, 2 mM MnCl2, 0.1% BSA and 1 mM DTT, 40 μL final volume), ATP (1 mM final conc.) in a black 384-well plate. After 60 minutes incubation at room temperature, the reaction was quenched by addition of a buffered EDTA solution. Homo sapiens 1.3 nM
Homogenous Time-Resolved Fluorescence Assay (HTRF): To determine the activity of the various kinases, a homogenous time-resolved fluorescence (HTRF) in vitro kinase assay was used. (Mathis, G., HTRF(R) Technology. J Biomol Screen, 1999. 4(6): p. 309-314; Alfred J. Kolb, Paul V. Kaplita, David J. Hayes, Young-Whan Park, Christine Pernell, John S. Major and Gerard Mathis, Drug Discovery Today, 1998, 3, 333-342.). For example for KDR, cKIT, FLT1, CSF1R and FTL3, purified enzyme was mixed with 0.5 μM N-biotinylated substrate (Biotin-Ahx-AEEEYFFLA-amide (SEQ. ID. 1)), various concentrations of inhibitor in reaction buffer (50 mM HEPES, pH 7.1, 10 mM MgCl2, 2 mM MnCl2, 0.1% BSA and 1 mM DTT, 40 μL final volume), ATP (1 mM final conc.) in a black 384-well plate. After 60 minutes incubation at room temperature, the reaction was quenched by addition of a buffered EDTA solution. Homo sapiens 3.42 nM Homogenous Time-Resolved Fluorescence Assay (HTRF): To determine the activity of the various kinases, a homogenous time-resolved fluorescence (HTRF) in vitro kinase assay was used. (Mathis, G., HTRF(R) Technology. J Biomol Screen, 1999. 4(6): p. 309-314; Alfred J. Kolb, Paul V. Kaplita, David J. Hayes, Young-Whan Park, Christine Pernell, John S. Major and Gerard Mathis, Drug Discovery Today, 1998, 3, 333-342.). For example for KDR, cKIT, FLT1, CSF1R and FTL3, purified enzyme was mixed with 0.5 μM N-biotinylated substrate (Biotin-Ahx-AEEEYFFLA-amide (SEQ. ID. 1)), various concentrations of inhibitor in reaction buffer (50 mM HEPES, pH 7.1, 10 mM MgCl2, 2 mM MnCl2, 0.1% BSA and 1 mM DTT, 40 μL final volume), ATP (1 mM final conc.) in a black 384-well plate. After 60 minutes incubation at room temperature, the reaction was quenched by addition of a buffered EDTA solution. Homo sapiens 2.22 nM
Inhibition of AuroraA (unknown origin) Homo sapiens 120.0 nM
Inhibition of AuroraC (unknown origin) Homo sapiens 7.0 nM
Inhibition of AuroraB (unknown origin) Homo sapiens 12.0 nM

Cross References

Resources Reference
ChEMBL CHEMBL1980297
DrugBank DB11694
FDA SRS 6L5D03D975
Guide to Pharmacology 9914
PubChem 46207586
SureChEMBL SCHEMBL3381224
ZINC ZINC000063298074
CONTENTS