lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CCNC(=O)Nc1cccc(-c2cnc3cc(C#Cc4cncn4C)ccn23)c1
InChIKey: XDINCDPCSFTXGX-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: In Vitro Kinase Inhibition Assay: Enzymes (from Upstate) were prepared at 2× final concentration in 1× kinase assay buffer (Table 1). Enzymes were then incubated with test compounds, biotinylated Flt3 substrate (biotin −DNEYFYV) (Cell Signalling Technology Inc.) and ATP. The reaction was allowed to proceed for 3 hours (FGFR3) or 2.5 hrs (PDGFR-beta) at room temperature on a plate shaker at 900 rpm before being stopped with 20 μl of 35 mM EDTA, pH 8 (FGFR3) or 55 mM EDTA, pH 8 (PDGFR-beta). Twenty pl of 5× detection mix (50 mM HEPES pH 7.5, 0.1% BSA, 2 nM Eu-anti-pY (PY20) (PerkinElmer) 15 nM SA-XL665 (Cisbio) for FGFR3 and 50 mM HEPES, pH 7.5, 0.5 M KF, 0.1% BSA, 11.34 nM Eu-anti-pY (PT66) (PerkinElmer), 94 nM SA-XL665 (Cisbio) for PDGFR-beta) was then added to each well and the plate sealed and incubated at room temperature for one hour on a plate shaker at 900 rpm. The plate was then read on a Packard Fusion plate reader in TRF mode. Kinase Assay buffers were:A: 50 mM HEPES pH 7.5, 6 mM MnCl2, 1 mM DTT, 0.
Measurement: IC50 = 28.8 nM (pChEMBL 7.539999961853027)
Descriptors: MW 384.44, ALogP 3.28, HBA 5, HBD 2, PSA 76.25, QED 0.53
Compound (SMILES): Cn1cncc1C#Cc1ccn2c(-c3cncc(NC(=O)NCC(F)(F)F)c3)cnc2c1
InChIKey: CFBREHDGIOQZPT-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: In Vitro Kinase Inhibition Assay: Enzymes (from Upstate) were prepared at 2× final concentration in 1× kinase assay buffer (Table 1). Enzymes were then incubated with test compounds, biotinylated Flt3 substrate (biotin −DNEYFYV) (Cell Signalling Technology Inc.) and ATP. The reaction was allowed to proceed for 3 hours (FGFR3) or 2.5 hrs (PDGFR-beta) at room temperature on a plate shaker at 900 rpm before being stopped with 20 μl of 35 mM EDTA, pH 8 (FGFR3) or 55 mM EDTA, pH 8 (PDGFR-beta). Twenty pl of 5× detection mix (50 mM HEPES pH 7.5, 0.1% BSA, 2 nM Eu-anti-pY (PY20) (PerkinElmer) 15 nM SA-XL665 (Cisbio) for FGFR3 and 50 mM HEPES, pH 7.5, 0.5 M KF, 0.1% BSA, 11.34 nM Eu-anti-pY (PT66) (PerkinElmer), 94 nM SA-XL665 (Cisbio) for PDGFR-beta) was then added to each well and the plate sealed and incubated at room temperature for one hour on a plate shaker at 900 rpm. The plate was then read on a Packard Fusion plate reader in TRF mode. Kinase Assay buffers were:A: 50 mM HEPES pH 7.5, 6 mM MnCl2, 1 mM DTT, 0.
Measurement: IC50 = 4100 nM (pChEMBL 5.389999866485596)
Descriptors: MW 439.4, ALogP 3.21, HBA 6, HBD 2, PSA 89.14, QED 0.48
Compound (SMILES): CC(C)n1ccnc1C#Cc1ccn2c(-c3cccc(NC(=O)NCC(F)(F)F)c3)cnc2c1
InChIKey: FTHYPURQIWLRDH-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: In Vitro Kinase Inhibition Assay: Enzymes (from Upstate) were prepared at 2× final concentration in 1× kinase assay buffer (Table 1). Enzymes were then incubated with test compounds, biotinylated Flt3 substrate (biotin −DNEYFYV) (Cell Signalling Technology Inc.) and ATP. The reaction was allowed to proceed for 3 hours (FGFR3) or 2.5 hrs (PDGFR-beta) at room temperature on a plate shaker at 900 rpm before being stopped with 20 μl of 35 mM EDTA, pH 8 (FGFR3) or 55 mM EDTA, pH 8 (PDGFR-beta). Twenty pl of 5× detection mix (50 mM HEPES pH 7.5, 0.1% BSA, 2 nM Eu-anti-pY (PY20) (PerkinElmer) 15 nM SA-XL665 (Cisbio) for FGFR3 and 50 mM HEPES, pH 7.5, 0.5 M KF, 0.1% BSA, 11.34 nM Eu-anti-pY (PT66) (PerkinElmer), 94 nM SA-XL665 (Cisbio) for PDGFR-beta) was then added to each well and the plate sealed and incubated at room temperature for one hour on a plate shaker at 900 rpm. The plate was then read on a Packard Fusion plate reader in TRF mode. Kinase Assay buffers were:A: 50 mM HEPES pH 7.5, 6 mM MnCl2, 1 mM DTT, 0.
Measurement: IC50 = 8.66 nM (pChEMBL 8.0600004196167)
Descriptors: MW 466.47, ALogP 4.86, HBA 5, HBD 2, PSA 76.25, QED 0.42
Compound (SMILES): Cn1cncc1C#Cc1ccn2c(-c3cccc(NC(N)=O)c3)cnc2c1
InChIKey: JYWWZJSNCJTSQO-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: In Vitro Kinase Inhibition Assay: Enzymes (from Upstate) were prepared at 2× final concentration in 1× kinase assay buffer (Table 1). Enzymes were then incubated with test compounds, biotinylated Flt3 substrate (biotin −DNEYFYV) (Cell Signalling Technology Inc.) and ATP. The reaction was allowed to proceed for 3 hours (FGFR3) or 2.5 hrs (PDGFR-beta) at room temperature on a plate shaker at 900 rpm before being stopped with 20 μl of 35 mM EDTA, pH 8 (FGFR3) or 55 mM EDTA, pH 8 (PDGFR-beta). Twenty pl of 5× detection mix (50 mM HEPES pH 7.5, 0.1% BSA, 2 nM Eu-anti-pY (PY20) (PerkinElmer) 15 nM SA-XL665 (Cisbio) for FGFR3 and 50 mM HEPES, pH 7.5, 0.5 M KF, 0.1% BSA, 11.34 nM Eu-anti-pY (PT66) (PerkinElmer), 94 nM SA-XL665 (Cisbio) for PDGFR-beta) was then added to each well and the plate sealed and incubated at room temperature for one hour on a plate shaker at 900 rpm. The plate was then read on a Packard Fusion plate reader in TRF mode. Kinase Assay buffers were:A: 50 mM HEPES pH 7.5, 6 mM MnCl2, 1 mM DTT, 0.
Measurement: IC50 = 9.65 nM (pChEMBL 8.020000457763672)
Descriptors: MW 356.39, ALogP 2.63, HBA 5, HBD 2, PSA 90.24, QED 0.54
Compound (SMILES): NC(=O)Nc1cccc(-c2cnc3cc(-c4nncs4)ccn23)c1
InChIKey: MBJSTRUZPYRLFI-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: In Vitro Kinase Inhibition Assay: Enzymes (from Upstate) were prepared at 2× final concentration in 1× kinase assay buffer (Table 1). Enzymes were then incubated with test compounds, biotinylated Flt3 substrate (biotin −DNEYFYV) (Cell Signalling Technology Inc.) and ATP. The reaction was allowed to proceed for 3 hours (FGFR3) or 2.5 hrs (PDGFR-beta) at room temperature on a plate shaker at 900 rpm before being stopped with 20 μl of 35 mM EDTA, pH 8 (FGFR3) or 55 mM EDTA, pH 8 (PDGFR-beta). Twenty pl of 5× detection mix (50 mM HEPES pH 7.5, 0.1% BSA, 2 nM Eu-anti-pY (PY20) (PerkinElmer) 15 nM SA-XL665 (Cisbio) for FGFR3 and 50 mM HEPES, pH 7.5, 0.5 M KF, 0.1% BSA, 11.34 nM Eu-anti-pY (PT66) (PerkinElmer), 94 nM SA-XL665 (Cisbio) for PDGFR-beta) was then added to each well and the plate sealed and incubated at room temperature for one hour on a plate shaker at 900 rpm. The plate was then read on a Packard Fusion plate reader in TRF mode. Kinase Assay buffers were:A: 50 mM HEPES pH 7.5, 6 mM MnCl2, 1 mM DTT, 0.
Measurement: IC50 = 4.89 nM (pChEMBL 8.3100004196167)
Descriptors: MW 336.38, ALogP 3.01, HBA 6, HBD 2, PSA 98.2, QED 0.6
Compound (SMILES): O=C(NCC(F)(F)F)Nc1cccc(-c2cnc3cc(-c4nccc(N5CCNCC5)n4)ccn23)c1
InChIKey: LBTOQVUEHUHPPN-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: In Vitro Kinase Inhibition Assay: Enzymes (from Upstate) were prepared at 2× final concentration in 1× kinase assay buffer (Table 1). Enzymes were then incubated with test compounds, biotinylated Flt3 substrate (biotin −DNEYFYV) (Cell Signalling Technology Inc.) and ATP. The reaction was allowed to proceed for 3 hours (FGFR3) or 2.5 hrs (PDGFR-beta) at room temperature on a plate shaker at 900 rpm before being stopped with 20 μl of 35 mM EDTA, pH 8 (FGFR3) or 55 mM EDTA, pH 8 (PDGFR-beta). Twenty pl of 5× detection mix (50 mM HEPES pH 7.5, 0.1% BSA, 2 nM Eu-anti-pY (PY20) (PerkinElmer) 15 nM SA-XL665 (Cisbio) for FGFR3 and 50 mM HEPES, pH 7.5, 0.5 M KF, 0.1% BSA, 11.34 nM Eu-anti-pY (PT66) (PerkinElmer), 94 nM SA-XL665 (Cisbio) for PDGFR-beta) was then added to each well and the plate sealed and incubated at room temperature for one hour on a plate shaker at 900 rpm. The plate was then read on a Packard Fusion plate reader in TRF mode. Kinase Assay buffers were:A: 50 mM HEPES pH 7.5, 6 mM MnCl2, 1 mM DTT, 0.
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 496.5, ALogP 3.55, HBA 7, HBD 3, PSA 99.48, QED 0.39
Compound (SMILES): O=C(NCC(F)(F)F)Nc1cccc(-c2cnc3cc(-c4nccc(N5CCN(CCO)CC5)n4)ccn23)c1
InChIKey: MSEJMQBBJYYONO-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: In Vitro Kinase Inhibition Assay: Enzymes (from Upstate) were prepared at 2× final concentration in 1× kinase assay buffer (Table 1). Enzymes were then incubated with test compounds, biotinylated Flt3 substrate (biotin −DNEYFYV) (Cell Signalling Technology Inc.) and ATP. The reaction was allowed to proceed for 3 hours (FGFR3) or 2.5 hrs (PDGFR-beta) at room temperature on a plate shaker at 900 rpm before being stopped with 20 μl of 35 mM EDTA, pH 8 (FGFR3) or 55 mM EDTA, pH 8 (PDGFR-beta). Twenty pl of 5× detection mix (50 mM HEPES pH 7.5, 0.1% BSA, 2 nM Eu-anti-pY (PY20) (PerkinElmer) 15 nM SA-XL665 (Cisbio) for FGFR3 and 50 mM HEPES, pH 7.5, 0.5 M KF, 0.1% BSA, 11.34 nM Eu-anti-pY (PT66) (PerkinElmer), 94 nM SA-XL665 (Cisbio) for PDGFR-beta) was then added to each well and the plate sealed and incubated at room temperature for one hour on a plate shaker at 900 rpm. The plate was then read on a Packard Fusion plate reader in TRF mode. Kinase Assay buffers were:A: 50 mM HEPES pH 7.5, 6 mM MnCl2, 1 mM DTT, 0.
Measurement: IC50 = 9.1 nM (pChEMBL 8.039999961853027)
Descriptors: MW 540.55, ALogP 3.26, HBA 8, HBD 3, PSA 110.92, QED 0.33
Compound (SMILES): NCC1CCN(c2ccc(-c3ccn4c(-c5cccc(NC(=O)NCC(F)(F)F)c5)cnc4c3)cn2)CC1
InChIKey: PVQIXAPQDZSQLL-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: In Vitro Kinase Inhibition Assay: VEGFR2 (from Upstate), prepared at 2x final concentration, was incubated with test compounds, biotinylated Flt3 substrate (biotin-VASSDNEYFYVDF) (Cell Signalling Technology Inc.) and ATP in the appropriate assay buffer (Table 1). The reaction was allowed to proceed for 1 hour at room temperature on a plate shaker at 700 rpm before being stopped with 35 mM EDTA, pH 8 (VEGFR2). 5x detection mix (50 mM HEPES, pH 7.5, 0.1% BSA, 11.34 nM Eu-anti-pY (PY20), 187.5 nM SA-XL665) was then added to each well and the plate sealed and incubated at room temperature for one hour on a plate shaker at 700 rpm. The plate was then read on a Packard Fusion plate reader or a BMG Pherastar both in TRF mode. Kinase Assay buffers were: 50 mM HEPES pH 7.5, 6 mM MnCl2, 1 mM DTT, 0.01% TritonX-100, 0.1 mM Sodium orthovanadate.
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 523.56, ALogP 4.92, HBA 6, HBD 3, PSA 100.58, QED 0.33
Compound (SMILES): CN(C)S(=O)(=O)NCC1CCN(c2ccc(-c3ccn4c(-c5cccc(NC(=O)NCC(F)(F)F)c5)cnc4c3)cn2)CC1
InChIKey: ZFGCJOPEEZQSLP-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: In Vitro Kinase Inhibition Assay: VEGFR2 (from Upstate), prepared at 2x final concentration, was incubated with test compounds, biotinylated Flt3 substrate (biotin-VASSDNEYFYVDF) (Cell Signalling Technology Inc.) and ATP in the appropriate assay buffer (Table 1). The reaction was allowed to proceed for 1 hour at room temperature on a plate shaker at 700 rpm before being stopped with 35 mM EDTA, pH 8 (VEGFR2). 5x detection mix (50 mM HEPES, pH 7.5, 0.1% BSA, 11.34 nM Eu-anti-pY (PY20), 187.5 nM SA-XL665) was then added to each well and the plate sealed and incubated at room temperature for one hour on a plate shaker at 700 rpm. The plate was then read on a Packard Fusion plate reader or a BMG Pherastar both in TRF mode. Kinase Assay buffers were: 50 mM HEPES pH 7.5, 6 mM MnCl2, 1 mM DTT, 0.01% TritonX-100, 0.1 mM Sodium orthovanadate.
Measurement: IC50 = 35 nM (pChEMBL 7.460000038146973)
Descriptors: MW 630.7, ALogP 4.36, HBA 7, HBD 3, PSA 123.97, QED 0.25
Compound (SMILES): CC(C)COC(=O)Nc1nc(-c2ccn3c(-c4cccc(NC(=O)NCC(F)(F)F)c4)cnc3c2)ncc1F
InChIKey: VCMCSGGIBKJGPQ-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: In Vitro Kinase Inhibition Assay: Enzymes (from Upstate) were prepared at 2× final concentration in 1× kinase assay buffer (Table 1). Enzymes were then incubated with test compounds, biotinylated Flt3 substrate (biotin −DNEYFYV) (Cell Signalling Technology Inc.) and ATP. The reaction was allowed to proceed for 3 hours (FGFR3) or 2.5 hrs (PDGFR-beta) at room temperature on a plate shaker at 900 rpm before being stopped with 20 μl of 35 mM EDTA, pH 8 (FGFR3) or 55 mM EDTA, pH 8 (PDGFR-beta). Twenty pl of 5× detection mix (50 mM HEPES pH 7.5, 0.1% BSA, 2 nM Eu-anti-pY (PY20) (PerkinElmer) 15 nM SA-XL665 (Cisbio) for FGFR3 and 50 mM HEPES, pH 7.5, 0.5 M KF, 0.1% BSA, 11.34 nM Eu-anti-pY (PT66) (PerkinElmer), 94 nM SA-XL665 (Cisbio) for PDGFR-beta) was then added to each well and the plate sealed and incubated at room temperature for one hour on a plate shaker at 900 rpm. The plate was then read on a Packard Fusion plate reader in TRF mode. Kinase Assay buffers were:A: 50 mM HEPES pH 7.5, 6 mM MnCl2, 1 mM DTT, 0.
Measurement: IC50 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 545.5, ALogP 5.49, HBA 7, HBD 3, PSA 122.54, QED 0.26
Compound (SMILES): NCc1cc(NC(=O)NCC(F)(F)F)cc(-c2cnc3cc(-c4ccnc(C(F)(F)F)n4)ccn23)c1
InChIKey: WYVWWVCLAZRGJB-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: In Vitro Kinase Inhibition Assay: Enzymes (from Upstate) were prepared at 2× final concentration in 1× kinase assay buffer (Table 1). Enzymes were then incubated with test compounds, biotinylated Flt3 substrate (biotin −DNEYFYV) (Cell Signalling Technology Inc.) and ATP. The reaction was allowed to proceed for 3 hours (FGFR3) or 2.5 hrs (PDGFR-beta) at room temperature on a plate shaker at 900 rpm before being stopped with 20 μl of 35 mM EDTA, pH 8 (FGFR3) or 55 mM EDTA, pH 8 (PDGFR-beta). Twenty pl of 5× detection mix (50 mM HEPES pH 7.5, 0.1% BSA, 2 nM Eu-anti-pY (PY20) (PerkinElmer) 15 nM SA-XL665 (Cisbio) for FGFR3 and 50 mM HEPES, pH 7.5, 0.5 M KF, 0.1% BSA, 11.34 nM Eu-anti-pY (PT66) (PerkinElmer), 94 nM SA-XL665 (Cisbio) for PDGFR-beta) was then added to each well and the plate sealed and incubated at room temperature for one hour on a plate shaker at 900 rpm. The plate was then read on a Packard Fusion plate reader in TRF mode. Kinase Assay buffers were:A: 50 mM HEPES pH 7.5, 6 mM MnCl2, 1 mM DTT, 0.
Measurement: IC50 = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 509.41, ALogP 4.62, HBA 6, HBD 3, PSA 110.23, QED 0.34
Compound (SMILES): O=C(NCC(F)(F)F)Nc1cccc(-c2cnc3cc(-c4ncc(CO)cn4)ccn23)c1
InChIKey: ZMFFVTZRQUAWJV-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: In Vitro Kinase Inhibition Assay: Enzymes (from Upstate) were prepared at 2× final concentration in 1× kinase assay buffer (Table 1). Enzymes were then incubated with test compounds, biotinylated Flt3 substrate (biotin −DNEYFYV) (Cell Signalling Technology Inc.) and ATP. The reaction was allowed to proceed for 3 hours (FGFR3) or 2.5 hrs (PDGFR-beta) at room temperature on a plate shaker at 900 rpm before being stopped with 20 μl of 35 mM EDTA, pH 8 (FGFR3) or 55 mM EDTA, pH 8 (PDGFR-beta). Twenty pl of 5× detection mix (50 mM HEPES pH 7.5, 0.1% BSA, 2 nM Eu-anti-pY (PY20) (PerkinElmer) 15 nM SA-XL665 (Cisbio) for FGFR3 and 50 mM HEPES, pH 7.5, 0.5 M KF, 0.1% BSA, 11.34 nM Eu-anti-pY (PT66) (PerkinElmer), 94 nM SA-XL665 (Cisbio) for PDGFR-beta) was then added to each well and the plate sealed and incubated at room temperature for one hour on a plate shaker at 900 rpm. The plate was then read on a Packard Fusion plate reader in TRF mode. Kinase Assay buffers were:A: 50 mM HEPES pH 7.5, 6 mM MnCl2, 1 mM DTT, 0.
Measurement: IC50 = 9.4 nM (pChEMBL 8.029999732971191)
Descriptors: MW 442.4, ALogP 3.63, HBA 6, HBD 3, PSA 104.44, QED 0.44
Compound (SMILES): Nc1nc(-c2ccn3c(-c4cccc(NC(=O)NCC(F)(F)F)c4)cnc3c2)ncc1C(=O)O
InChIKey: WNJVGIPJSLLBIX-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: In Vitro Kinase Inhibition Assay: Enzymes (from Upstate) were prepared at 2× final concentration in 1× kinase assay buffer (Table 1). Enzymes were then incubated with test compounds, biotinylated Flt3 substrate (biotin −DNEYFYV) (Cell Signalling Technology Inc.) and ATP. The reaction was allowed to proceed for 3 hours (FGFR3) or 2.5 hrs (PDGFR-beta) at room temperature on a plate shaker at 900 rpm before being stopped with 20 μl of 35 mM EDTA, pH 8 (FGFR3) or 55 mM EDTA, pH 8 (PDGFR-beta). Twenty pl of 5× detection mix (50 mM HEPES pH 7.5, 0.1% BSA, 2 nM Eu-anti-pY (PY20) (PerkinElmer) 15 nM SA-XL665 (Cisbio) for FGFR3 and 50 mM HEPES, pH 7.5, 0.5 M KF, 0.1% BSA, 11.34 nM Eu-anti-pY (PT66) (PerkinElmer), 94 nM SA-XL665 (Cisbio) for PDGFR-beta) was then added to each well and the plate sealed and incubated at room temperature for one hour on a plate shaker at 900 rpm. The plate was then read on a Packard Fusion plate reader in TRF mode. Kinase Assay buffers were:A: 50 mM HEPES pH 7.5, 6 mM MnCl2, 1 mM DTT, 0.
Measurement: IC50 = 2.6 nM (pChEMBL 8.59000015258789)
Descriptors: MW 471.4, ALogP 3.42, HBA 7, HBD 4, PSA 147.53, QED 0.35
Compound (SMILES): CC(O)c1cnc(-c2ccn3c(-c4cccc(NC(=O)NCC(F)(F)F)c4)cnc3c2)nc1
InChIKey: HGUINYREMXETNK-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: In Vitro Kinase Inhibition Assay: Enzymes (from Upstate) were prepared at 2× final concentration in 1× kinase assay buffer (Table 1). Enzymes were then incubated with test compounds, biotinylated Flt3 substrate (biotin −DNEYFYV) (Cell Signalling Technology Inc.) and ATP. The reaction was allowed to proceed for 3 hours (FGFR3) or 2.5 hrs (PDGFR-beta) at room temperature on a plate shaker at 900 rpm before being stopped with 20 μl of 35 mM EDTA, pH 8 (FGFR3) or 55 mM EDTA, pH 8 (PDGFR-beta). Twenty pl of 5× detection mix (50 mM HEPES pH 7.5, 0.1% BSA, 2 nM Eu-anti-pY (PY20) (PerkinElmer) 15 nM SA-XL665 (Cisbio) for FGFR3 and 50 mM HEPES, pH 7.5, 0.5 M KF, 0.1% BSA, 11.34 nM Eu-anti-pY (PT66) (PerkinElmer), 94 nM SA-XL665 (Cisbio) for PDGFR-beta) was then added to each well and the plate sealed and incubated at room temperature for one hour on a plate shaker at 900 rpm. The plate was then read on a Packard Fusion plate reader in TRF mode. Kinase Assay buffers were:A: 50 mM HEPES pH 7.5, 6 mM MnCl2, 1 mM DTT, 0.
Measurement: IC50 = 3.8 nM (pChEMBL 8.420000076293945)
Descriptors: MW 456.43, ALogP 4.2, HBA 6, HBD 3, PSA 104.44, QED 0.42
Compound (SMILES): CS(=O)(=O)Nc1nc(-c2ccn3c(-c4cccc(NC(=O)NCC(F)(F)F)c4)cnc3c2)ncc1F
InChIKey: UECMCQUYFRUDBW-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: In Vitro Kinase Inhibition Assay: Enzymes (from Upstate) were prepared at 2× final concentration in 1× kinase assay buffer (Table 1). Enzymes were then incubated with test compounds, biotinylated Flt3 substrate (biotin −DNEYFYV) (Cell Signalling Technology Inc.) and ATP. The reaction was allowed to proceed for 3 hours (FGFR3) or 2.5 hrs (PDGFR-beta) at room temperature on a plate shaker at 900 rpm before being stopped with 20 μl of 35 mM EDTA, pH 8 (FGFR3) or 55 mM EDTA, pH 8 (PDGFR-beta). Twenty pl of 5× detection mix (50 mM HEPES pH 7.5, 0.1% BSA, 2 nM Eu-anti-pY (PY20) (PerkinElmer) 15 nM SA-XL665 (Cisbio) for FGFR3 and 50 mM HEPES, pH 7.5, 0.5 M KF, 0.1% BSA, 11.34 nM Eu-anti-pY (PT66) (PerkinElmer), 94 nM SA-XL665 (Cisbio) for PDGFR-beta) was then added to each well and the plate sealed and incubated at room temperature for one hour on a plate shaker at 900 rpm. The plate was then read on a Packard Fusion plate reader in TRF mode. Kinase Assay buffers were:A: 50 mM HEPES pH 7.5, 6 mM MnCl2, 1 mM DTT, 0.
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 523.47, ALogP 3.65, HBA 7, HBD 3, PSA 130.38, QED 0.33
Compound (SMILES): CCNC(=O)Nc1cccc(-c2cnc3cc(-c4ncccn4)ccn23)c1
InChIKey: VFMZSECBZUUMQD-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: In Vitro Kinase Inhibition Assay: Enzymes (from Upstate) were prepared at 2× final concentration in 1× kinase assay buffer (Table 1). Enzymes were then incubated with test compounds, biotinylated Flt3 substrate (biotin −DNEYFYV) (Cell Signalling Technology Inc.) and ATP. The reaction was allowed to proceed for 3 hours (FGFR3) or 2.5 hrs (PDGFR-beta) at room temperature on a plate shaker at 900 rpm before being stopped with 20 μl of 35 mM EDTA, pH 8 (FGFR3) or 55 mM EDTA, pH 8 (PDGFR-beta). Twenty pl of 5× detection mix (50 mM HEPES pH 7.5, 0.1% BSA, 2 nM Eu-anti-pY (PY20) (PerkinElmer) 15 nM SA-XL665 (Cisbio) for FGFR3 and 50 mM HEPES, pH 7.5, 0.5 M KF, 0.1% BSA, 11.34 nM Eu-anti-pY (PT66) (PerkinElmer), 94 nM SA-XL665 (Cisbio) for PDGFR-beta) was then added to each well and the plate sealed and incubated at room temperature for one hour on a plate shaker at 900 rpm. The plate was then read on a Packard Fusion plate reader in TRF mode. Kinase Assay buffers were:A: 50 mM HEPES pH 7.5, 6 mM MnCl2, 1 mM DTT, 0.
Measurement: IC50 = 97.3 nM (pChEMBL 7.010000228881836)
Descriptors: MW 358.41, ALogP 3.6, HBA 5, HBD 2, PSA 84.21, QED 0.58
Compound (SMILES): Nc1nc(-c2ccn3c(-c4cc(NC(=O)NCC(F)(F)F)cc(OC5CCCC5)c4)cnc3c2)ncc1F
InChIKey: VGDOBUQFOYJAMM-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: In Vitro Kinase Inhibition Assay: VEGFR2 (from Upstate), prepared at 2x final concentration, was incubated with test compounds, biotinylated Flt3 substrate (biotin-VASSDNEYFYVDF) (Cell Signalling Technology Inc.) and ATP in the appropriate assay buffer (Table 1). The reaction was allowed to proceed for 1 hour at room temperature on a plate shaker at 700 rpm before being stopped with 35 mM EDTA, pH 8 (VEGFR2). 5x detection mix (50 mM HEPES, pH 7.5, 0.1% BSA, 11.34 nM Eu-anti-pY (PY20), 187.5 nM SA-XL665) was then added to each well and the plate sealed and incubated at room temperature for one hour on a plate shaker at 700 rpm. The plate was then read on a Packard Fusion plate reader or a BMG Pherastar both in TRF mode. Kinase Assay buffers were: 50 mM HEPES pH 7.5, 6 mM MnCl2, 1 mM DTT, 0.01% TritonX-100, 0.1 mM Sodium orthovanadate.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 529.5, ALogP 5.18, HBA 7, HBD 3, PSA 119.46, QED 0.3
Compound (SMILES): Cn1ccnc1C#Cc1ccn2c(-c3cccc(NC(=O)NCC(F)(F)F)c3)cnc2c1
InChIKey: VDVHTIUPAJLKPX-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: In Vitro Kinase Inhibition Assay: Enzymes (from Upstate) were prepared at 2× final concentration in 1× kinase assay buffer (Table 1). Enzymes were then incubated with test compounds, biotinylated Flt3 substrate (biotin −DNEYFYV) (Cell Signalling Technology Inc.) and ATP. The reaction was allowed to proceed for 3 hours (FGFR3) or 2.5 hrs (PDGFR-beta) at room temperature on a plate shaker at 900 rpm before being stopped with 20 μl of 35 mM EDTA, pH 8 (FGFR3) or 55 mM EDTA, pH 8 (PDGFR-beta). Twenty pl of 5× detection mix (50 mM HEPES pH 7.5, 0.1% BSA, 2 nM Eu-anti-pY (PY20) (PerkinElmer) 15 nM SA-XL665 (Cisbio) for FGFR3 and 50 mM HEPES, pH 7.5, 0.5 M KF, 0.1% BSA, 11.34 nM Eu-anti-pY (PT66) (PerkinElmer), 94 nM SA-XL665 (Cisbio) for PDGFR-beta) was then added to each well and the plate sealed and incubated at room temperature for one hour on a plate shaker at 900 rpm. The plate was then read on a Packard Fusion plate reader in TRF mode. Kinase Assay buffers were:A: 50 mM HEPES pH 7.5, 6 mM MnCl2, 1 mM DTT, 0.
Measurement: IC50 = 4.8 nM (pChEMBL 8.319999694824219)
Descriptors: MW 438.41, ALogP 3.82, HBA 5, HBD 2, PSA 76.25, QED 0.48
Compound (SMILES): Cc1ccc(NC(=O)NCC(F)(F)F)cc1-c1cnc2cc(-c3ncc(F)c(N)n3)ccn12
InChIKey: DTUYOXYPYKBHJA-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: In Vitro Kinase Inhibition Assay: Enzymes (from Upstate) were prepared at 2× final concentration in 1× kinase assay buffer (Table 1). Enzymes were then incubated with test compounds, biotinylated Flt3 substrate (biotin −DNEYFYV) (Cell Signalling Technology Inc.) and ATP. The reaction was allowed to proceed for 3 hours (FGFR3) or 2.5 hrs (PDGFR-beta) at room temperature on a plate shaker at 900 rpm before being stopped with 20 μl of 35 mM EDTA, pH 8 (FGFR3) or 55 mM EDTA, pH 8 (PDGFR-beta). Twenty pl of 5× detection mix (50 mM HEPES pH 7.5, 0.1% BSA, 2 nM Eu-anti-pY (PY20) (PerkinElmer) 15 nM SA-XL665 (Cisbio) for FGFR3 and 50 mM HEPES, pH 7.5, 0.5 M KF, 0.1% BSA, 11.34 nM Eu-anti-pY (PT66) (PerkinElmer), 94 nM SA-XL665 (Cisbio) for PDGFR-beta) was then added to each well and the plate sealed and incubated at room temperature for one hour on a plate shaker at 900 rpm. The plate was then read on a Packard Fusion plate reader in TRF mode. Kinase Assay buffers were:A: 50 mM HEPES pH 7.5, 6 mM MnCl2, 1 mM DTT, 0.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 459.41, ALogP 4.17, HBA 6, HBD 3, PSA 110.23, QED 0.4
Compound (SMILES): O=C(NCC(F)(F)F)Nc1cc(OC2CCCC2)cc(-c2cnc3cc(-c4ncccn4)ccn23)c1
InChIKey: FGRBOLXVKFYATN-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: In Vitro Kinase Inhibition Assay: Enzymes (from Upstate) were prepared at 2× final concentration in 1× kinase assay buffer (Table 1). Enzymes were then incubated with test compounds, biotinylated Flt3 substrate (biotin −DNEYFYV) (Cell Signalling Technology Inc.) and ATP. The reaction was allowed to proceed for 3 hours (FGFR3) or 2.5 hrs (PDGFR-beta) at room temperature on a plate shaker at 900 rpm before being stopped with 20 μl of 35 mM EDTA, pH 8 (FGFR3) or 55 mM EDTA, pH 8 (PDGFR-beta). Twenty pl of 5× detection mix (50 mM HEPES pH 7.5, 0.1% BSA, 2 nM Eu-anti-pY (PY20) (PerkinElmer) 15 nM SA-XL665 (Cisbio) for FGFR3 and 50 mM HEPES, pH 7.5, 0.5 M KF, 0.1% BSA, 11.34 nM Eu-anti-pY (PT66) (PerkinElmer), 94 nM SA-XL665 (Cisbio) for PDGFR-beta) was then added to each well and the plate sealed and incubated at room temperature for one hour on a plate shaker at 900 rpm. The plate was then read on a Packard Fusion plate reader in TRF mode. Kinase Assay buffers were:A: 50 mM HEPES pH 7.5, 6 mM MnCl2, 1 mM DTT, 0.
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 496.49, ALogP 5.46, HBA 6, HBD 2, PSA 93.44, QED 0.37
Compound (SMILES): COCCOc1cc(NC(=O)NCC(F)(F)F)cc(-c2cnc3cc(-c4ncc(F)c(N)n4)ccn23)c1
InChIKey: INZWQYHHQXPVDZ-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: In Vitro Kinase Inhibition Assay: Enzymes (from Upstate) were prepared at 2× final concentration in 1× kinase assay buffer (Table 1). Enzymes were then incubated with test compounds, biotinylated Flt3 substrate (biotin −DNEYFYV) (Cell Signalling Technology Inc.) and ATP. The reaction was allowed to proceed for 3 hours (FGFR3) or 2.5 hrs (PDGFR-beta) at room temperature on a plate shaker at 900 rpm before being stopped with 20 μl of 35 mM EDTA, pH 8 (FGFR3) or 55 mM EDTA, pH 8 (PDGFR-beta). Twenty pl of 5× detection mix (50 mM HEPES pH 7.5, 0.1% BSA, 2 nM Eu-anti-pY (PY20) (PerkinElmer) 15 nM SA-XL665 (Cisbio) for FGFR3 and 50 mM HEPES, pH 7.5, 0.5 M KF, 0.1% BSA, 11.34 nM Eu-anti-pY (PT66) (PerkinElmer), 94 nM SA-XL665 (Cisbio) for PDGFR-beta) was then added to each well and the plate sealed and incubated at room temperature for one hour on a plate shaker at 900 rpm. The plate was then read on a Packard Fusion plate reader in TRF mode. Kinase Assay buffers were:A: 50 mM HEPES pH 7.5, 6 mM MnCl2, 1 mM DTT, 0.
Measurement: IC50 = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 519.46, ALogP 3.89, HBA 8, HBD 3, PSA 128.69, QED 0.24
Compound (SMILES): CCNc1nnc(-c2ccn3c(-c4cccc(NC(=O)NCC(F)(F)F)c4)cnc3c2)s1
InChIKey: PNXIXQODPQFYIU-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: In Vitro Kinase Inhibition Assay: VEGFR2 (from Upstate), prepared at 2x final concentration, was incubated with test compounds, biotinylated Flt3 substrate (biotin-VASSDNEYFYVDF) (Cell Signalling Technology Inc.) and ATP in the appropriate assay buffer (Table 1). The reaction was allowed to proceed for 1 hour at room temperature on a plate shaker at 700 rpm before being stopped with 35 mM EDTA, pH 8 (VEGFR2). 5x detection mix (50 mM HEPES, pH 7.5, 0.1% BSA, 11.34 nM Eu-anti-pY (PY20), 187.5 nM SA-XL665) was then added to each well and the plate sealed and incubated at room temperature for one hour on a plate shaker at 700 rpm. The plate was then read on a Packard Fusion plate reader or a BMG Pherastar both in TRF mode. Kinase Assay buffers were: 50 mM HEPES pH 7.5, 6 mM MnCl2, 1 mM DTT, 0.01% TritonX-100, 0.1 mM Sodium orthovanadate.
Measurement: IC50 = 8.5 nM (pChEMBL 8.069999694824219)
Descriptors: MW 461.47, ALogP 4.64, HBA 7, HBD 3, PSA 96.24, QED 0.39
Compound (SMILES): CCOC(=O)c1cnc(-c2ccn3c(-c4cccc(NC(=O)NCC(F)(F)F)c4)cnc3c2)nc1N
InChIKey: KJBNGJWFSNGUGW-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: In Vitro Kinase Inhibition Assay: Enzymes (from Upstate) were prepared at 2× final concentration in 1× kinase assay buffer (Table 1). Enzymes were then incubated with test compounds, biotinylated Flt3 substrate (biotin −DNEYFYV) (Cell Signalling Technology Inc.) and ATP. The reaction was allowed to proceed for 3 hours (FGFR3) or 2.5 hrs (PDGFR-beta) at room temperature on a plate shaker at 900 rpm before being stopped with 20 μl of 35 mM EDTA, pH 8 (FGFR3) or 55 mM EDTA, pH 8 (PDGFR-beta). Twenty pl of 5× detection mix (50 mM HEPES pH 7.5, 0.1% BSA, 2 nM Eu-anti-pY (PY20) (PerkinElmer) 15 nM SA-XL665 (Cisbio) for FGFR3 and 50 mM HEPES, pH 7.5, 0.5 M KF, 0.1% BSA, 11.34 nM Eu-anti-pY (PT66) (PerkinElmer), 94 nM SA-XL665 (Cisbio) for PDGFR-beta) was then added to each well and the plate sealed and incubated at room temperature for one hour on a plate shaker at 900 rpm. The plate was then read on a Packard Fusion plate reader in TRF mode. Kinase Assay buffers were:A: 50 mM HEPES pH 7.5, 6 mM MnCl2, 1 mM DTT, 0.
Measurement: IC50 = 4.6 nM (pChEMBL 8.34000015258789)
Descriptors: MW 499.45, ALogP 3.9, HBA 8, HBD 3, PSA 136.53, QED 0.34
Compound (SMILES): COCCNc1nnc(-c2ccn3c(-c4cccc(NC(=O)NCC(F)(F)F)c4)cnc3c2)s1
InChIKey: ZQZJPSOCPROOHD-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: In Vitro Kinase Inhibition Assay: VEGFR2 (from Upstate), prepared at 2x final concentration, was incubated with test compounds, biotinylated Flt3 substrate (biotin-VASSDNEYFYVDF) (Cell Signalling Technology Inc.) and ATP in the appropriate assay buffer (Table 1). The reaction was allowed to proceed for 1 hour at room temperature on a plate shaker at 700 rpm before being stopped with 35 mM EDTA, pH 8 (VEGFR2). 5x detection mix (50 mM HEPES, pH 7.5, 0.1% BSA, 11.34 nM Eu-anti-pY (PY20), 187.5 nM SA-XL665) was then added to each well and the plate sealed and incubated at room temperature for one hour on a plate shaker at 700 rpm. The plate was then read on a Packard Fusion plate reader or a BMG Pherastar both in TRF mode. Kinase Assay buffers were: 50 mM HEPES pH 7.5, 6 mM MnCl2, 1 mM DTT, 0.01% TritonX-100, 0.1 mM Sodium orthovanadate.
Measurement: IC50 = 9.3 nM (pChEMBL 8.029999732971191)
Descriptors: MW 491.5, ALogP 4.26, HBA 8, HBD 3, PSA 105.47, QED 0.32
Compound (SMILES): O=C(NCC(F)(F)F)Nc1cccc(-c2cnc3cc(-c4nnc(Nc5cccnc5)s4)ccn23)c1
InChIKey: BPAJYHCGDYVNDI-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: In Vitro Kinase Inhibition Assay: Enzymes (from Upstate) were prepared at 2× final concentration in 1× kinase assay buffer (Table 1). Enzymes were then incubated with test compounds, biotinylated Flt3 substrate (biotin −DNEYFYV) (Cell Signalling Technology Inc.) and ATP. The reaction was allowed to proceed for 3 hours (FGFR3) or 2.5 hrs (PDGFR-beta) at room temperature on a plate shaker at 900 rpm before being stopped with 20 μl of 35 mM EDTA, pH 8 (FGFR3) or 55 mM EDTA, pH 8 (PDGFR-beta). Twenty pl of 5× detection mix (50 mM HEPES pH 7.5, 0.1% BSA, 2 nM Eu-anti-pY (PY20) (PerkinElmer) 15 nM SA-XL665 (Cisbio) for FGFR3 and 50 mM HEPES, pH 7.5, 0.5 M KF, 0.1% BSA, 11.34 nM Eu-anti-pY (PT66) (PerkinElmer), 94 nM SA-XL665 (Cisbio) for PDGFR-beta) was then added to each well and the plate sealed and incubated at room temperature for one hour on a plate shaker at 900 rpm. The plate was then read on a Packard Fusion plate reader in TRF mode. Kinase Assay buffers were:A: 50 mM HEPES pH 7.5, 6 mM MnCl2, 1 mM DTT, 0.
Measurement: IC50 = 0.99 nM (pChEMBL 9)
Descriptors: MW 510.51, ALogP 5.34, HBA 8, HBD 3, PSA 109.13, QED 0.28
Compound (SMILES): COC(=O)c1cnc(-c2ccn3c(-c4cccc(NC(=O)NCC(F)(F)F)c4)cnc3c2)nc1
InChIKey: BVLAXQYVLQGRTE-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: In Vitro Kinase Inhibition Assay: Enzymes (from Upstate) were prepared at 2× final concentration in 1× kinase assay buffer (Table 1). Enzymes were then incubated with test compounds, biotinylated Flt3 substrate (biotin −DNEYFYV) (Cell Signalling Technology Inc.) and ATP. The reaction was allowed to proceed for 3 hours (FGFR3) or 2.5 hrs (PDGFR-beta) at room temperature on a plate shaker at 900 rpm before being stopped with 20 μl of 35 mM EDTA, pH 8 (FGFR3) or 55 mM EDTA, pH 8 (PDGFR-beta). Twenty pl of 5× detection mix (50 mM HEPES pH 7.5, 0.1% BSA, 2 nM Eu-anti-pY (PY20) (PerkinElmer) 15 nM SA-XL665 (Cisbio) for FGFR3 and 50 mM HEPES, pH 7.5, 0.5 M KF, 0.1% BSA, 11.34 nM Eu-anti-pY (PT66) (PerkinElmer), 94 nM SA-XL665 (Cisbio) for PDGFR-beta) was then added to each well and the plate sealed and incubated at room temperature for one hour on a plate shaker at 900 rpm. The plate was then read on a Packard Fusion plate reader in TRF mode. Kinase Assay buffers were:A: 50 mM HEPES pH 7.5, 6 mM MnCl2, 1 mM DTT, 0.
Measurement: IC50 = 8.5 nM (pChEMBL 8.069999694824219)
Descriptors: MW 470.41, ALogP 3.93, HBA 7, HBD 2, PSA 110.51, QED 0.43
Compound (SMILES): Cc1cc(NC(=O)NCC(F)(F)F)cc(-c2cnc3cc(-c4ncc(F)c(N)n4)ccn23)c1
InChIKey: YCZYZKUTEYPMTA-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: In Vitro Kinase Inhibition Assay: Enzymes (from Upstate) were prepared at 2× final concentration in 1× kinase assay buffer (Table 1). Enzymes were then incubated with test compounds, biotinylated Flt3 substrate (biotin −DNEYFYV) (Cell Signalling Technology Inc.) and ATP. The reaction was allowed to proceed for 3 hours (FGFR3) or 2.5 hrs (PDGFR-beta) at room temperature on a plate shaker at 900 rpm before being stopped with 20 μl of 35 mM EDTA, pH 8 (FGFR3) or 55 mM EDTA, pH 8 (PDGFR-beta). Twenty pl of 5× detection mix (50 mM HEPES pH 7.5, 0.1% BSA, 2 nM Eu-anti-pY (PY20) (PerkinElmer) 15 nM SA-XL665 (Cisbio) for FGFR3 and 50 mM HEPES, pH 7.5, 0.5 M KF, 0.1% BSA, 11.34 nM Eu-anti-pY (PT66) (PerkinElmer), 94 nM SA-XL665 (Cisbio) for PDGFR-beta) was then added to each well and the plate sealed and incubated at room temperature for one hour on a plate shaker at 900 rpm. The plate was then read on a Packard Fusion plate reader in TRF mode. Kinase Assay buffers were:A: 50 mM HEPES pH 7.5, 6 mM MnCl2, 1 mM DTT, 0.
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 459.41, ALogP 4.17, HBA 6, HBD 3, PSA 110.23, QED 0.4
Compound (SMILES): CC(=O)c1cnc(-c2ccn3c(-c4cccc(NC(=O)NCC(F)(F)F)c4)cnc3c2)nc1
InChIKey: JRPMJPQLBARUEQ-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: In Vitro Kinase Inhibition Assay: Enzymes (from Upstate) were prepared at 2× final concentration in 1× kinase assay buffer (Table 1). Enzymes were then incubated with test compounds, biotinylated Flt3 substrate (biotin −DNEYFYV) (Cell Signalling Technology Inc.) and ATP. The reaction was allowed to proceed for 3 hours (FGFR3) or 2.5 hrs (PDGFR-beta) at room temperature on a plate shaker at 900 rpm before being stopped with 20 μl of 35 mM EDTA, pH 8 (FGFR3) or 55 mM EDTA, pH 8 (PDGFR-beta). Twenty pl of 5× detection mix (50 mM HEPES pH 7.5, 0.1% BSA, 2 nM Eu-anti-pY (PY20) (PerkinElmer) 15 nM SA-XL665 (Cisbio) for FGFR3 and 50 mM HEPES, pH 7.5, 0.5 M KF, 0.1% BSA, 11.34 nM Eu-anti-pY (PT66) (PerkinElmer), 94 nM SA-XL665 (Cisbio) for PDGFR-beta) was then added to each well and the plate sealed and incubated at room temperature for one hour on a plate shaker at 900 rpm. The plate was then read on a Packard Fusion plate reader in TRF mode. Kinase Assay buffers were:A: 50 mM HEPES pH 7.5, 6 mM MnCl2, 1 mM DTT, 0.
Measurement: IC50 = 5.2 nM (pChEMBL 8.279999732971191)
Descriptors: MW 454.41, ALogP 4.34, HBA 6, HBD 2, PSA 101.28, QED 0.44
Compound (SMILES): CC(F)(F)c1cnc(-c2ccn3c(-c4cccc(NC(=O)NCC(F)(F)F)c4)cnc3c2)nc1
InChIKey: BROOSVBOLOJDTF-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: In Vitro Kinase Inhibition Assay: Enzymes (from Upstate) were prepared at 2× final concentration in 1× kinase assay buffer (Table 1). Enzymes were then incubated with test compounds, biotinylated Flt3 substrate (biotin −DNEYFYV) (Cell Signalling Technology Inc.) and ATP. The reaction was allowed to proceed for 3 hours (FGFR3) or 2.5 hrs (PDGFR-beta) at room temperature on a plate shaker at 900 rpm before being stopped with 20 μl of 35 mM EDTA, pH 8 (FGFR3) or 55 mM EDTA, pH 8 (PDGFR-beta). Twenty pl of 5× detection mix (50 mM HEPES pH 7.5, 0.1% BSA, 2 nM Eu-anti-pY (PY20) (PerkinElmer) 15 nM SA-XL665 (Cisbio) for FGFR3 and 50 mM HEPES, pH 7.5, 0.5 M KF, 0.1% BSA, 11.34 nM Eu-anti-pY (PT66) (PerkinElmer), 94 nM SA-XL665 (Cisbio) for PDGFR-beta) was then added to each well and the plate sealed and incubated at room temperature for one hour on a plate shaker at 900 rpm. The plate was then read on a Packard Fusion plate reader in TRF mode. Kinase Assay buffers were:A: 50 mM HEPES pH 7.5, 6 mM MnCl2, 1 mM DTT, 0.
Measurement: IC50 = 3.7 nM (pChEMBL 8.430000305175781)
Descriptors: MW 476.41, ALogP 5.25, HBA 5, HBD 2, PSA 84.21, QED 0.39
Compound (SMILES): O=C(NCC(F)(F)F)Nc1cc(Br)cc(-c2cnc3cc(-c4ccnc(C(F)(F)F)n4)ccn23)c1
InChIKey: NSOPAAHEWFDMGX-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: In Vitro Kinase Inhibition Assay: Enzymes (from Upstate) were prepared at 2× final concentration in 1× kinase assay buffer (Table 1). Enzymes were then incubated with test compounds, biotinylated Flt3 substrate (biotin −DNEYFYV) (Cell Signalling Technology Inc.) and ATP. The reaction was allowed to proceed for 3 hours (FGFR3) or 2.5 hrs (PDGFR-beta) at room temperature on a plate shaker at 900 rpm before being stopped with 20 μl of 35 mM EDTA, pH 8 (FGFR3) or 55 mM EDTA, pH 8 (PDGFR-beta). Twenty pl of 5× detection mix (50 mM HEPES pH 7.5, 0.1% BSA, 2 nM Eu-anti-pY (PY20) (PerkinElmer) 15 nM SA-XL665 (Cisbio) for FGFR3 and 50 mM HEPES, pH 7.5, 0.5 M KF, 0.1% BSA, 11.34 nM Eu-anti-pY (PT66) (PerkinElmer), 94 nM SA-XL665 (Cisbio) for PDGFR-beta) was then added to each well and the plate sealed and incubated at room temperature for one hour on a plate shaker at 900 rpm. The plate was then read on a Packard Fusion plate reader in TRF mode. Kinase Assay buffers were:A: 50 mM HEPES pH 7.5, 6 mM MnCl2, 1 mM DTT, 0.
Measurement: IC50 = 39 nM (pChEMBL 7.409999847412109)
Descriptors: MW 559.27, ALogP 5.92, HBA 5, HBD 2, PSA 84.21, QED 0.3
Compound (SMILES): O=C(NCC(F)(F)F)Nc1cc(CO)cc(-c2cnc3cc(-c4ccnc(C(F)(F)F)n4)ccn23)c1
InChIKey: ATXXDEHFKKXQLH-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: In Vitro Kinase Inhibition Assay: Enzymes (from Upstate) were prepared at 2× final concentration in 1× kinase assay buffer (Table 1). Enzymes were then incubated with test compounds, biotinylated Flt3 substrate (biotin −DNEYFYV) (Cell Signalling Technology Inc.) and ATP. The reaction was allowed to proceed for 3 hours (FGFR3) or 2.5 hrs (PDGFR-beta) at room temperature on a plate shaker at 900 rpm before being stopped with 20 μl of 35 mM EDTA, pH 8 (FGFR3) or 55 mM EDTA, pH 8 (PDGFR-beta). Twenty pl of 5× detection mix (50 mM HEPES pH 7.5, 0.1% BSA, 2 nM Eu-anti-pY (PY20) (PerkinElmer) 15 nM SA-XL665 (Cisbio) for FGFR3 and 50 mM HEPES, pH 7.5, 0.5 M KF, 0.1% BSA, 11.34 nM Eu-anti-pY (PT66) (PerkinElmer), 94 nM SA-XL665 (Cisbio) for PDGFR-beta) was then added to each well and the plate sealed and incubated at room temperature for one hour on a plate shaker at 900 rpm. The plate was then read on a Packard Fusion plate reader in TRF mode. Kinase Assay buffers were:A: 50 mM HEPES pH 7.5, 6 mM MnCl2, 1 mM DTT, 0.
Measurement: IC50 = 78 nM (pChEMBL 7.110000133514404)
Descriptors: MW 510.4, ALogP 4.65, HBA 6, HBD 3, PSA 104.44, QED 0.34
Compound (SMILES): O=C(NCC(F)(F)F)Nc1cc(-c2cnc3cc(-c4ccnc(C(F)(F)F)n4)ccn23)cc(C(F)(F)F)c1
InChIKey: FGXQLECJGRJKMH-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: In Vitro Kinase Inhibition Assay: Enzymes (from Upstate) were prepared at 2× final concentration in 1× kinase assay buffer (Table 1). Enzymes were then incubated with test compounds, biotinylated Flt3 substrate (biotin −DNEYFYV) (Cell Signalling Technology Inc.) and ATP. The reaction was allowed to proceed for 3 hours (FGFR3) or 2.5 hrs (PDGFR-beta) at room temperature on a plate shaker at 900 rpm before being stopped with 20 μl of 35 mM EDTA, pH 8 (FGFR3) or 55 mM EDTA, pH 8 (PDGFR-beta). Twenty pl of 5× detection mix (50 mM HEPES pH 7.5, 0.1% BSA, 2 nM Eu-anti-pY (PY20) (PerkinElmer) 15 nM SA-XL665 (Cisbio) for FGFR3 and 50 mM HEPES, pH 7.5, 0.5 M KF, 0.1% BSA, 11.34 nM Eu-anti-pY (PT66) (PerkinElmer), 94 nM SA-XL665 (Cisbio) for PDGFR-beta) was then added to each well and the plate sealed and incubated at room temperature for one hour on a plate shaker at 900 rpm. The plate was then read on a Packard Fusion plate reader in TRF mode. Kinase Assay buffers were:A: 50 mM HEPES pH 7.5, 6 mM MnCl2, 1 mM DTT, 0.
Measurement: IC50 = 270 nM (pChEMBL 6.570000171661377)
Descriptors: MW 548.37, ALogP 6.18, HBA 5, HBD 2, PSA 84.21, QED 0.3
Compound (SMILES): O=C(NCC(F)(F)F)Nc1cc(Cl)cc(-c2cnc3cc(-c4ccnc(C(F)(F)F)n4)ccn23)c1
InChIKey: WNCQEKLGKYUWQO-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: In Vitro Kinase Inhibition Assay: Enzymes (from Upstate) were prepared at 2× final concentration in 1× kinase assay buffer (Table 1). Enzymes were then incubated with test compounds, biotinylated Flt3 substrate (biotin −DNEYFYV) (Cell Signalling Technology Inc.) and ATP. The reaction was allowed to proceed for 3 hours (FGFR3) or 2.5 hrs (PDGFR-beta) at room temperature on a plate shaker at 900 rpm before being stopped with 20 μl of 35 mM EDTA, pH 8 (FGFR3) or 55 mM EDTA, pH 8 (PDGFR-beta). Twenty pl of 5× detection mix (50 mM HEPES pH 7.5, 0.1% BSA, 2 nM Eu-anti-pY (PY20) (PerkinElmer) 15 nM SA-XL665 (Cisbio) for FGFR3 and 50 mM HEPES, pH 7.5, 0.5 M KF, 0.1% BSA, 11.34 nM Eu-anti-pY (PT66) (PerkinElmer), 94 nM SA-XL665 (Cisbio) for PDGFR-beta) was then added to each well and the plate sealed and incubated at room temperature for one hour on a plate shaker at 900 rpm. The plate was then read on a Packard Fusion plate reader in TRF mode. Kinase Assay buffers were:A: 50 mM HEPES pH 7.5, 6 mM MnCl2, 1 mM DTT, 0.
Measurement: IC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 514.82, ALogP 5.81, HBA 5, HBD 2, PSA 84.21, QED 0.34
Compound (SMILES): COc1cc(NC(=O)NCC(F)(F)F)cc(-c2cnc3cc(-c4ccnc(C(F)(F)F)n4)ccn23)c1
InChIKey: WZCXHBXCIDFPEP-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: In Vitro Kinase Inhibition Assay: Enzymes (from Upstate) were prepared at 2× final concentration in 1× kinase assay buffer (Table 1). Enzymes were then incubated with test compounds, biotinylated Flt3 substrate (biotin −DNEYFYV) (Cell Signalling Technology Inc.) and ATP. The reaction was allowed to proceed for 3 hours (FGFR3) or 2.5 hrs (PDGFR-beta) at room temperature on a plate shaker at 900 rpm before being stopped with 20 μl of 35 mM EDTA, pH 8 (FGFR3) or 55 mM EDTA, pH 8 (PDGFR-beta). Twenty pl of 5× detection mix (50 mM HEPES pH 7.5, 0.1% BSA, 2 nM Eu-anti-pY (PY20) (PerkinElmer) 15 nM SA-XL665 (Cisbio) for FGFR3 and 50 mM HEPES, pH 7.5, 0.5 M KF, 0.1% BSA, 11.34 nM Eu-anti-pY (PT66) (PerkinElmer), 94 nM SA-XL665 (Cisbio) for PDGFR-beta) was then added to each well and the plate sealed and incubated at room temperature for one hour on a plate shaker at 900 rpm. The plate was then read on a Packard Fusion plate reader in TRF mode. Kinase Assay buffers were:A: 50 mM HEPES pH 7.5, 6 mM MnCl2, 1 mM DTT, 0.
Measurement: IC50 = 93 nM (pChEMBL 7.03000020980835)
Descriptors: MW 510.4, ALogP 5.17, HBA 6, HBD 2, PSA 93.44, QED 0.36
Compound (SMILES): N#Cc1cc(NC(=O)NCC(F)(F)F)cc(-c2cnc3cc(-c4ccnc(C(F)(F)F)n4)ccn23)c1
InChIKey: YTDZNWZGUHQNSK-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: In Vitro Kinase Inhibition Assay: Enzymes (from Upstate) were prepared at 2× final concentration in 1× kinase assay buffer (Table 1). Enzymes were then incubated with test compounds, biotinylated Flt3 substrate (biotin −DNEYFYV) (Cell Signalling Technology Inc.) and ATP. The reaction was allowed to proceed for 3 hours (FGFR3) or 2.5 hrs (PDGFR-beta) at room temperature on a plate shaker at 900 rpm before being stopped with 20 μl of 35 mM EDTA, pH 8 (FGFR3) or 55 mM EDTA, pH 8 (PDGFR-beta). Twenty pl of 5× detection mix (50 mM HEPES pH 7.5, 0.1% BSA, 2 nM Eu-anti-pY (PY20) (PerkinElmer) 15 nM SA-XL665 (Cisbio) for FGFR3 and 50 mM HEPES, pH 7.5, 0.5 M KF, 0.1% BSA, 11.34 nM Eu-anti-pY (PT66) (PerkinElmer), 94 nM SA-XL665 (Cisbio) for PDGFR-beta) was then added to each well and the plate sealed and incubated at room temperature for one hour on a plate shaker at 900 rpm. The plate was then read on a Packard Fusion plate reader in TRF mode. Kinase Assay buffers were:A: 50 mM HEPES pH 7.5, 6 mM MnCl2, 1 mM DTT, 0.
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 505.38, ALogP 5.03, HBA 6, HBD 2, PSA 108, QED 0.38
Compound (SMILES): Nc1nc(-c2ccn3c(-c4cc(Cl)cc(NC(=O)NCC(F)(F)F)c4)cnc3c2)ncc1F
InChIKey: QYNBIMXPCRURFE-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: In Vitro Kinase Inhibition Assay: Enzymes (from Upstate) were prepared at 2× final concentration in 1× kinase assay buffer (Table 1). Enzymes were then incubated with test compounds, biotinylated Flt3 substrate (biotin −DNEYFYV) (Cell Signalling Technology Inc.) and ATP. The reaction was allowed to proceed for 3 hours (FGFR3) or 2.5 hrs (PDGFR-beta) at room temperature on a plate shaker at 900 rpm before being stopped with 20 μl of 35 mM EDTA, pH 8 (FGFR3) or 55 mM EDTA, pH 8 (PDGFR-beta). Twenty pl of 5× detection mix (50 mM HEPES pH 7.5, 0.1% BSA, 2 nM Eu-anti-pY (PY20) (PerkinElmer) 15 nM SA-XL665 (Cisbio) for FGFR3 and 50 mM HEPES, pH 7.5, 0.5 M KF, 0.1% BSA, 11.34 nM Eu-anti-pY (PT66) (PerkinElmer), 94 nM SA-XL665 (Cisbio) for PDGFR-beta) was then added to each well and the plate sealed and incubated at room temperature for one hour on a plate shaker at 900 rpm. The plate was then read on a Packard Fusion plate reader in TRF mode. Kinase Assay buffers were:A: 50 mM HEPES pH 7.5, 6 mM MnCl2, 1 mM DTT, 0.
Measurement: IC50 = 5.5 nM (pChEMBL 8.260000228881836)
Descriptors: MW 479.83, ALogP 4.52, HBA 6, HBD 3, PSA 110.23, QED 0.37