lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): C=CC(=O)Nc1cccc(-n2c(=O)cnc3cnc(Nc4ccc(Cl)cc4)nc32)c1
InChIKey: NPYHVKHWRDSLAV-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: EGFR kinase assay: In vitro enzyme activity assay: wild-type and various mutants (T790M, L858R, L861Q, L858 R/T790M) EGFR, Z′-Lyte Kinase Assay Kit were purchased from Invitrogen. 10 concentration gradients, from 5.1×10−11 mol/L to 1.0×10−6 mol/L, were set for all of the compounds to be tested. Concentrations of different kinases were determined based on the optimization of experiment, and the corresponding concentrations were: EGFR (PV3872, Invitrogen) 0.287 μg/μL, EGFR-T790M (PV4803, Invitrogen) 0.174 μg/μL, EGFR-L858R (PV4128, Invitrogen) 0.054 μg/μL, EGFR-L858R/T790M (PV4879, Invitrogen) 0.055 μg/μL. Compounds were diluted for 3 times in DMSO from 5.1×10−9 M to 1×10−4 M. 4 μL of compound was dissolved in 96 μL of water, to give a 4× compound solution. 40 μM ATP was dissolved in 1.33× kinase buffer, and a kinase/peptide mixture comprising 2× kinase, 4 μM tyrosine and four peptides was prepared for use. 10 μL of kinase reaction system comprised 2.5 μL of compound solution, 5 μL of Kinase/peptide mixture, and 2.5 μL of ATP solution. 5 μL of phosphopeptide solution was used in place of kinase/peptide mixture as 100% phosphorylation control. 2.5 μL of 1.33× kinase buffer was used to replace ATP solution as 100% inhibition control, and 2.5 μL of 4% DMSO solution was used to replace compound solution as 0% inhibition control. After thoroughly mixing the solution within the plate, the plate was incubated at room temperature for 1.5 hours. 5 μL of DevelopmentSolution was added into each well, and then the plate was incubated at room temperature for another 1 hour, and non-phosphorylated peptide was cleaved within this period. Finally, the reaction was quenched by adding 5 μL of Stop Reagent. The Plate was measured with EnVision Multilabel Reader (Perkin Elmer). Experimental data were calculated by using GraphPad Prism version 4.0.
Measurement: IC50 = 2825 nM (pChEMBL 5.550000190734863)
Descriptors: MW 418.84, ALogP 3.7, HBA 7, HBD 2, PSA 101.8, QED 0.48
Compound (SMILES): C=CC(=O)Nc1ccc(-n2c(=O)cnc3cnc(Nc4ccc(N5CCOCC5)cc4)nc32)cc1
InChIKey: CHFSRPYBDAIBQR-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: EGFR kinase assay: In vitro enzyme activity assay: wild-type and various mutants (T790M, L858R, L861Q, L858 R/T790M) EGFR, Z′-Lyte Kinase Assay Kit were purchased from Invitrogen. 10 concentration gradients, from 5.1×10−11 mol/L to 1.0×10−6 mol/L, were set for all of the compounds to be tested. Concentrations of different kinases were determined based on the optimization of experiment, and the corresponding concentrations were: EGFR (PV3872, Invitrogen) 0.287 μg/μL, EGFR-T790M (PV4803, Invitrogen) 0.174 μg/μL, EGFR-L858R (PV4128, Invitrogen) 0.054 μg/μL, EGFR-L858R/T790M (PV4879, Invitrogen) 0.055 μg/μL. Compounds were diluted for 3 times in DMSO from 5.1×10−9 M to 1×10−4 M. 4 μL of compound was dissolved in 96 μL of water, to give a 4× compound solution. 40 μM ATP was dissolved in 1.33× kinase buffer, and a kinase/peptide mixture comprising 2× kinase, 4 μM tyrosine and four peptides was prepared for use. 10 μL of kinase reaction system comprised 2.5 μL of compound solution, 5 μL of Kinase/peptide mixture, and 2.5 μL of ATP solution. 5 μL of phosphopeptide solution was used in place of kinase/peptide mixture as 100% phosphorylation control. 2.5 μL of 1.33× kinase buffer was used to replace ATP solution as 100% inhibition control, and 2.5 μL of 4% DMSO solution was used to replace compound solution as 0% inhibition control. After thoroughly mixing the solution within the plate, the plate was incubated at room temperature for 1.5 hours. 5 μL of DevelopmentSolution was added into each well, and then the plate was incubated at room temperature for another 1 hour, and non-phosphorylated peptide was cleaved within this period. Finally, the reaction was quenched by adding 5 μL of Stop Reagent. The Plate was measured with EnVision Multilabel Reader (Perkin Elmer). Experimental data were calculated by using GraphPad Prism version 4.0.
Measurement: IC50 = 3297 nM (pChEMBL 5.480000019073486)
Descriptors: MW 469.51, ALogP 2.88, HBA 9, HBD 2, PSA 114.27, QED 0.41
Compound (SMILES): C=CC(=O)Nc1cccc(-n2c(=O)cnc3cnc(Nc4ccc(N5CCOCC5)cc4)nc32)c1
InChIKey: NXZQKEJXOSVRFZ-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: EGFR kinase assay: In vitro enzyme activity assay: wild-type and various mutants (T790M, L858R, L861Q, L858 R/T790M) EGFR, Z′-Lyte Kinase Assay Kit were purchased from Invitrogen. 10 concentration gradients, from 5.1×10−11 mol/L to 1.0×10−6 mol/L, were set for all of the compounds to be tested. Concentrations of different kinases were determined based on the optimization of experiment, and the corresponding concentrations were: EGFR (PV3872, Invitrogen) 0.287 μg/μL, EGFR-T790M (PV4803, Invitrogen) 0.174 μg/μL, EGFR-L858R (PV4128, Invitrogen) 0.054 μg/μL, EGFR-L858R/T790M (PV4879, Invitrogen) 0.055 μg/μL. Compounds were diluted for 3 times in DMSO from 5.1×10−9 M to 1×10−4 M. 4 μL of compound was dissolved in 96 μL of water, to give a 4× compound solution. 40 μM ATP was dissolved in 1.33× kinase buffer, and a kinase/peptide mixture comprising 2× kinase, 4 μM tyrosine and four peptides was prepared for use. 10 μL of kinase reaction system comprised 2.5 μL of compound solution, 5 μL of Kinase/peptide mixture, and 2.5 μL of ATP solution. 5 μL of phosphopeptide solution was used in place of kinase/peptide mixture as 100% phosphorylation control. 2.5 μL of 1.33× kinase buffer was used to replace ATP solution as 100% inhibition control, and 2.5 μL of 4% DMSO solution was used to replace compound solution as 0% inhibition control. After thoroughly mixing the solution within the plate, the plate was incubated at room temperature for 1.5 hours. 5 μL of DevelopmentSolution was added into each well, and then the plate was incubated at room temperature for another 1 hour, and non-phosphorylated peptide was cleaved within this period. Finally, the reaction was quenched by adding 5 μL of Stop Reagent. The Plate was measured with EnVision Multilabel Reader (Perkin Elmer). Experimental data were calculated by using GraphPad Prism version 4.0.
Measurement: IC50 = 798 nM (pChEMBL 6.099999904632568)
Descriptors: MW 469.51, ALogP 2.88, HBA 9, HBD 2, PSA 114.27, QED 0.41
Compound (SMILES): C=CC(=O)Nc1ccc(-n2c(=O)cnc3cnc(Nc4ccc(N5CCN(C)CC5)cc4)nc32)cc1
InChIKey: DRGNKFXIAXKCCX-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: EGFR kinase assay: In vitro enzyme activity assay: wild-type and various mutants (T790M, L858R, L861Q, L858 R/T790M) EGFR, Z′-Lyte Kinase Assay Kit were purchased from Invitrogen. 10 concentration gradients, from 5.1×10−11 mol/L to 1.0×10−6 mol/L, were set for all of the compounds to be tested. Concentrations of different kinases were determined based on the optimization of experiment, and the corresponding concentrations were: EGFR (PV3872, Invitrogen) 0.287 μg/μL, EGFR-T790M (PV4803, Invitrogen) 0.174 μg/μL, EGFR-L858R (PV4128, Invitrogen) 0.054 μg/μL, EGFR-L858R/T790M (PV4879, Invitrogen) 0.055 μg/μL. Compounds were diluted for 3 times in DMSO from 5.1×10−9 M to 1×10−4 M. 4 μL of compound was dissolved in 96 μL of water, to give a 4× compound solution. 40 μM ATP was dissolved in 1.33× kinase buffer, and a kinase/peptide mixture comprising 2× kinase, 4 μM tyrosine and four peptides was prepared for use. 10 μL of kinase reaction system comprised 2.5 μL of compound solution, 5 μL of Kinase/peptide mixture, and 2.5 μL of ATP solution. 5 μL of phosphopeptide solution was used in place of kinase/peptide mixture as 100% phosphorylation control. 2.5 μL of 1.33× kinase buffer was used to replace ATP solution as 100% inhibition control, and 2.5 μL of 4% DMSO solution was used to replace compound solution as 0% inhibition control. After thoroughly mixing the solution within the plate, the plate was incubated at room temperature for 1.5 hours. 5 μL of DevelopmentSolution was added into each well, and then the plate was incubated at room temperature for another 1 hour, and non-phosphorylated peptide was cleaved within this period. Finally, the reaction was quenched by adding 5 μL of Stop Reagent. The Plate was measured with EnVision Multilabel Reader (Perkin Elmer). Experimental data were calculated by using GraphPad Prism version 4.0.
Measurement: IC50 = 51 nM (pChEMBL 7.289999961853027)
Descriptors: MW 482.55, ALogP 2.8, HBA 9, HBD 2, PSA 108.28, QED 0.4
Compound (SMILES): C=CC(=O)Nc1cccc(-n2c(=O)cnc3cnc(Nc4ccc(N5CCCCC5)cc4)nc32)c1
InChIKey: VJFSMDWEMFOWDK-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: EGFR kinase assay: In vitro enzyme activity assay: wild-type and various mutants (T790M, L858R, L861Q, L858 R/T790M) EGFR, Z′-Lyte Kinase Assay Kit were purchased from Invitrogen. 10 concentration gradients, from 5.1×10−11 mol/L to 1.0×10−6 mol/L, were set for all of the compounds to be tested. Concentrations of different kinases were determined based on the optimization of experiment, and the corresponding concentrations were: EGFR (PV3872, Invitrogen) 0.287 μg/μL, EGFR-T790M (PV4803, Invitrogen) 0.174 μg/μL, EGFR-L858R (PV4128, Invitrogen) 0.054 μg/μL, EGFR-L858R/T790M (PV4879, Invitrogen) 0.055 μg/μL. Compounds were diluted for 3 times in DMSO from 5.1×10−9 M to 1×10−4 M. 4 μL of compound was dissolved in 96 μL of water, to give a 4× compound solution. 40 μM ATP was dissolved in 1.33× kinase buffer, and a kinase/peptide mixture comprising 2× kinase, 4 μM tyrosine and four peptides was prepared for use. 10 μL of kinase reaction system comprised 2.5 μL of compound solution, 5 μL of Kinase/peptide mixture, and 2.5 μL of ATP solution. 5 μL of phosphopeptide solution was used in place of kinase/peptide mixture as 100% phosphorylation control. 2.5 μL of 1.33× kinase buffer was used to replace ATP solution as 100% inhibition control, and 2.5 μL of 4% DMSO solution was used to replace compound solution as 0% inhibition control. After thoroughly mixing the solution within the plate, the plate was incubated at room temperature for 1.5 hours. 5 μL of DevelopmentSolution was added into each well, and then the plate was incubated at room temperature for another 1 hour, and non-phosphorylated peptide was cleaved within this period. Finally, the reaction was quenched by adding 5 μL of Stop Reagent. The Plate was measured with EnVision Multilabel Reader (Perkin Elmer). Experimental data were calculated by using GraphPad Prism version 4.0.
Measurement: IC50 = 878 nM (pChEMBL 6.059999942779541)
Descriptors: MW 467.53, ALogP 4.03, HBA 8, HBD 2, PSA 105.04, QED 0.41
Compound (SMILES): C=CC(=O)Nc1cccc(-n2c(=O)cnc3cnc(Nc4ccc(N(CC)CC)cc4)nc32)c1
InChIKey: BIUVCZQWTOSTRS-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: EGFR kinase assay: In vitro enzyme activity assay: wild-type and various mutants (T790M, L858R, L861Q, L858 R/T790M) EGFR, Z′-Lyte Kinase Assay Kit were purchased from Invitrogen. 10 concentration gradients, from 5.1×10−11 mol/L to 1.0×10−6 mol/L, were set for all of the compounds to be tested. Concentrations of different kinases were determined based on the optimization of experiment, and the corresponding concentrations were: EGFR (PV3872, Invitrogen) 0.287 μg/μL, EGFR-T790M (PV4803, Invitrogen) 0.174 μg/μL, EGFR-L858R (PV4128, Invitrogen) 0.054 μg/μL, EGFR-L858R/T790M (PV4879, Invitrogen) 0.055 μg/μL. Compounds were diluted for 3 times in DMSO from 5.1×10−9 M to 1×10−4 M. 4 μL of compound was dissolved in 96 μL of water, to give a 4× compound solution. 40 μM ATP was dissolved in 1.33× kinase buffer, and a kinase/peptide mixture comprising 2× kinase, 4 μM tyrosine and four peptides was prepared for use. 10 μL of kinase reaction system comprised 2.5 μL of compound solution, 5 μL of Kinase/peptide mixture, and 2.5 μL of ATP solution. 5 μL of phosphopeptide solution was used in place of kinase/peptide mixture as 100% phosphorylation control. 2.5 μL of 1.33× kinase buffer was used to replace ATP solution as 100% inhibition control, and 2.5 μL of 4% DMSO solution was used to replace compound solution as 0% inhibition control. After thoroughly mixing the solution within the plate, the plate was incubated at room temperature for 1.5 hours. 5 μL of DevelopmentSolution was added into each well, and then the plate was incubated at room temperature for another 1 hour, and non-phosphorylated peptide was cleaved within this period. Finally, the reaction was quenched by adding 5 μL of Stop Reagent. The Plate was measured with EnVision Multilabel Reader (Perkin Elmer). Experimental data were calculated by using GraphPad Prism version 4.0.
Measurement: IC50 = 1757 nM (pChEMBL 5.75)
Descriptors: MW 455.52, ALogP 3.89, HBA 8, HBD 2, PSA 105.04, QED 0.39
Compound (SMILES): C=CC(=O)Nc1ccc(-n2c(=O)cnc3cnc(Nc4ccc(N5CCN(C)CC5)cc4OC)nc32)cc1
InChIKey: BMYBPXJXNNXUJF-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: EGFR kinase assay: In vitro enzyme activity assay: wild-type and various mutants (T790M, L858R, L861Q, L858 R/T790M) EGFR, Z′-Lyte Kinase Assay Kit were purchased from Invitrogen. 10 concentration gradients, from 5.1×10−11 mol/L to 1.0×10−6 mol/L, were set for all of the compounds to be tested. Concentrations of different kinases were determined based on the optimization of experiment, and the corresponding concentrations were: EGFR (PV3872, Invitrogen) 0.287 μg/μL, EGFR-T790M (PV4803, Invitrogen) 0.174 μg/μL, EGFR-L858R (PV4128, Invitrogen) 0.054 μg/μL, EGFR-L858R/T790M (PV4879, Invitrogen) 0.055 μg/μL. Compounds were diluted for 3 times in DMSO from 5.1×10−9 M to 1×10−4 M. 4 μL of compound was dissolved in 96 μL of water, to give a 4× compound solution. 40 μM ATP was dissolved in 1.33× kinase buffer, and a kinase/peptide mixture comprising 2× kinase, 4 μM tyrosine and four peptides was prepared for use. 10 μL of kinase reaction system comprised 2.5 μL of compound solution, 5 μL of Kinase/peptide mixture, and 2.5 μL of ATP solution. 5 μL of phosphopeptide solution was used in place of kinase/peptide mixture as 100% phosphorylation control. 2.5 μL of 1.33× kinase buffer was used to replace ATP solution as 100% inhibition control, and 2.5 μL of 4% DMSO solution was used to replace compound solution as 0% inhibition control. After thoroughly mixing the solution within the plate, the plate was incubated at room temperature for 1.5 hours. 5 μL of DevelopmentSolution was added into each well, and then the plate was incubated at room temperature for another 1 hour, and non-phosphorylated peptide was cleaved within this period. Finally, the reaction was quenched by adding 5 μL of Stop Reagent. The Plate was measured with EnVision Multilabel Reader (Perkin Elmer). Experimental data were calculated by using GraphPad Prism version 4.0.
Measurement: IC50 = 229 nM (pChEMBL 6.639999866485596)
Descriptors: MW 512.57, ALogP 2.8, HBA 10, HBD 2, PSA 117.51, QED 0.36
Compound (SMILES): C=CC(=O)Nc1cccc(-n2c(=O)c(C)nc3cnc(Nc4ccc(OC)cc4)nc32)c1
InChIKey: FGPPXNCHKYRZCI-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: EGFR kinase assay: In vitro enzyme activity assay: wild-type and various mutants (T790M, L858R, L861Q, L858 R/T790M) EGFR, Z′-Lyte Kinase Assay Kit were purchased from Invitrogen. 10 concentration gradients, from 5.1×10−11 mol/L to 1.0×10−6 mol/L, were set for all of the compounds to be tested. Concentrations of different kinases were determined based on the optimization of experiment, and the corresponding concentrations were: EGFR (PV3872, Invitrogen) 0.287 μg/μL, EGFR-T790M (PV4803, Invitrogen) 0.174 μg/μL, EGFR-L858R (PV4128, Invitrogen) 0.054 μg/μL, EGFR-L858R/T790M (PV4879, Invitrogen) 0.055 μg/μL. Compounds were diluted for 3 times in DMSO from 5.1×10−9 M to 1×10−4 M. 4 μL of compound was dissolved in 96 μL of water, to give a 4× compound solution. 40 μM ATP was dissolved in 1.33× kinase buffer, and a kinase/peptide mixture comprising 2× kinase, 4 μM tyrosine and four peptides was prepared for use. 10 μL of kinase reaction system comprised 2.5 μL of compound solution, 5 μL of Kinase/peptide mixture, and 2.5 μL of ATP solution. 5 μL of phosphopeptide solution was used in place of kinase/peptide mixture as 100% phosphorylation control. 2.5 μL of 1.33× kinase buffer was used to replace ATP solution as 100% inhibition control, and 2.5 μL of 4% DMSO solution was used to replace compound solution as 0% inhibition control. After thoroughly mixing the solution within the plate, the plate was incubated at room temperature for 1.5 hours. 5 μL of DevelopmentSolution was added into each well, and then the plate was incubated at room temperature for another 1 hour, and non-phosphorylated peptide was cleaved within this period. Finally, the reaction was quenched by adding 5 μL of Stop Reagent. The Plate was measured with EnVision Multilabel Reader (Perkin Elmer). Experimental data were calculated by using GraphPad Prism version 4.0.
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 428.45, ALogP 3.36, HBA 8, HBD 2, PSA 111.03, QED 0.45
Compound (SMILES): COc1ccc(Nc2ncc3ncc(=O)n(-c4cccc(N)c4)c3n2)cc1
InChIKey: QKANEQHLFOWQRR-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: EGFR kinase assay: In vitro enzyme activity assay: wild-type and various mutants (T790M, L858R, L861Q, L858 R/T790M) EGFR, Z′-Lyte Kinase Assay Kit were purchased from Invitrogen. 10 concentration gradients, from 5.1×10−11 mol/L to 1.0×10−6 mol/L, were set for all of the compounds to be tested. Concentrations of different kinases were determined based on the optimization of experiment, and the corresponding concentrations were: EGFR (PV3872, Invitrogen) 0.287 μg/μL, EGFR-T790M (PV4803, Invitrogen) 0.174 μg/μL, EGFR-L858R (PV4128, Invitrogen) 0.054 μg/μL, EGFR-L858R/T790M (PV4879, Invitrogen) 0.055 μg/μL. Compounds were diluted for 3 times in DMSO from 5.1×10−9 M to 1×10−4 M. 4 μL of compound was dissolved in 96 μL of water, to give a 4× compound solution. 40 μM ATP was dissolved in 1.33× kinase buffer, and a kinase/peptide mixture comprising 2× kinase, 4 μM tyrosine and four peptides was prepared for use. 10 μL of kinase reaction system comprised 2.5 μL of compound solution, 5 μL of Kinase/peptide mixture, and 2.5 μL of ATP solution. 5 μL of phosphopeptide solution was used in place of kinase/peptide mixture as 100% phosphorylation control. 2.5 μL of 1.33× kinase buffer was used to replace ATP solution as 100% inhibition control, and 2.5 μL of 4% DMSO solution was used to replace compound solution as 0% inhibition control. After thoroughly mixing the solution within the plate, the plate was incubated at room temperature for 1.5 hours. 5 μL of DevelopmentSolution was added into each well, and then the plate was incubated at room temperature for another 1 hour, and non-phosphorylated peptide was cleaved within this period. Finally, the reaction was quenched by adding 5 μL of Stop Reagent. The Plate was measured with EnVision Multilabel Reader (Perkin Elmer). Experimental data were calculated by using GraphPad Prism version 4.0.
Measurement: IC50 = 87159 nM (pChEMBL 4.059999942779541)
Descriptors: MW 360.38, ALogP 2.51, HBA 8, HBD 2, PSA 107.95, QED 0.54
Compound (SMILES): C=CC(=O)Nc1ccc(-n2c(=O)cnc3cnc(Nc4ccc(OC)cc4)nc32)cc1
InChIKey: BPENWXBDNSHEHD-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Blk (SINGLE PROTEIN), Homo sapiens
UniProt: P51451
Assay: EGFR kinase assay: In vitro enzyme activity assay: wild-type and various mutants (T790M, L858R, L861Q, L858 R/T790M) EGFR, Z′-Lyte Kinase Assay Kit were purchased from Invitrogen. 10 concentration gradients, from 5.1×10−11 mol/L to 1.0×10−6 mol/L, were set for all of the compounds to be tested. Concentrations of different kinases were determined based on the optimization of experiment, and the corresponding concentrations were: EGFR (PV3872, Invitrogen) 0.287 μg/μL, EGFR-T790M (PV4803, Invitrogen) 0.174 μg/μL, EGFR-L858R (PV4128, Invitrogen) 0.054 μg/μL, EGFR-L858R/T790M (PV4879, Invitrogen) 0.055 μg/μL. Compounds were diluted for 3 times in DMSO from 5.1×10−9 M to 1×10−4 M. 4 μL of compound was dissolved in 96 μL of water, to give a 4× compound solution. 40 μM ATP was dissolved in 1.33× kinase buffer, and a kinase/peptide mixture comprising 2× kinase, 4 μM tyrosine and four peptides was prepared for use. 10 μL of kinase reaction system comprised 2.5 μL of compound solution, 5 μL of Kinase/peptide mixture, and 2.5 μL of ATP solution. 5 μL of phosphopeptide solution was used in place of kinase/peptide mixture as 100% phosphorylation control. 2.5 μL of 1.33× kinase buffer was used to replace ATP solution as 100% inhibition control, and 2.5 μL of 4% DMSO solution was used to replace compound solution as 0% inhibition control. After thoroughly mixing the solution within the plate, the plate was incubated at room temperature for 1.5 hours. 5 μL of DevelopmentSolution was added into each well, and then the plate was incubated at room temperature for another 1 hour, and non-phosphorylated peptide was cleaved within this period. Finally, the reaction was quenched by adding 5 μL of Stop Reagent. The Plate was measured with EnVision Multilabel Reader (Perkin Elmer). Experimental data were calculated by using GraphPad Prism version 4.0.
Measurement: IC50 = 3037 nM (pChEMBL 5.519999980926514)
Descriptors: MW 414.43, ALogP 3.05, HBA 8, HBD 2, PSA 111.03, QED 0.47
Compound (SMILES): C=CC(=O)Nc1cccc(-n2c(=O)cnc3cnc(Nc4ccc(OC)cc4)nc32)c1
InChIKey: BLWDOLCMBQDSMT-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of human BTK using poly-Glu-Tyr (4:1) as substrate incubated for 1 hr by ELISA
Measurement: IC50 = 1.8 nM (pChEMBL 8.739999771118164)
Descriptors: MW 414.43, ALogP 3.05, HBA 8, HBD 2, PSA 111.03, QED 0.47
Compound (SMILES): COc1ccc(Nc2ncc3ncc(=O)n(-c4ccc(NC(=O)/C=C/CN(C)C)cc4)c3n2)cc1
InChIKey: ZVPLRCNYKVNOMV-SNAWJCMRSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: EGFR kinase assay: In vitro enzyme activity assay: wild-type and various mutants (T790M, L858R, L861Q, L858 R/T790M) EGFR, Z′-Lyte Kinase Assay Kit were purchased from Invitrogen. 10 concentration gradients, from 5.1×10−11 mol/L to 1.0×10−6 mol/L, were set for all of the compounds to be tested. Concentrations of different kinases were determined based on the optimization of experiment, and the corresponding concentrations were: EGFR (PV3872, Invitrogen) 0.287 μg/μL, EGFR-T790M (PV4803, Invitrogen) 0.174 μg/μL, EGFR-L858R (PV4128, Invitrogen) 0.054 μg/μL, EGFR-L858R/T790M (PV4879, Invitrogen) 0.055 μg/μL. Compounds were diluted for 3 times in DMSO from 5.1×10−9 M to 1×10−4 M. 4 μL of compound was dissolved in 96 μL of water, to give a 4× compound solution. 40 μM ATP was dissolved in 1.33× kinase buffer, and a kinase/peptide mixture comprising 2× kinase, 4 μM tyrosine and four peptides was prepared for use. 10 μL of kinase reaction system comprised 2.5 μL of compound solution, 5 μL of Kinase/peptide mixture, and 2.5 μL of ATP solution. 5 μL of phosphopeptide solution was used in place of kinase/peptide mixture as 100% phosphorylation control. 2.5 μL of 1.33× kinase buffer was used to replace ATP solution as 100% inhibition control, and 2.5 μL of 4% DMSO solution was used to replace compound solution as 0% inhibition control. After thoroughly mixing the solution within the plate, the plate was incubated at room temperature for 1.5 hours. 5 μL of DevelopmentSolution was added into each well, and then the plate was incubated at room temperature for another 1 hour, and non-phosphorylated peptide was cleaved within this period. Finally, the reaction was quenched by adding 5 μL of Stop Reagent. The Plate was measured with EnVision Multilabel Reader (Perkin Elmer). Experimental data were calculated by using GraphPad Prism version 4.0.
Measurement: IC50 = 152 nM (pChEMBL 6.820000171661377)
Descriptors: MW 471.52, ALogP 2.98, HBA 9, HBD 2, PSA 114.27, QED 0.38
Compound (SMILES): COc1ccc(Nc2ncc3ncc(=O)n(-c4cccc(NC(=O)/C=C/CN(C)C)c4)c3n2)cc1
InChIKey: SJMNSZVROFACMM-VMPITWQZSA-N
Target: Tyrosine-protein kinase Blk (SINGLE PROTEIN), Homo sapiens
UniProt: P51451
Assay: EGFR kinase assay: In vitro enzyme activity assay: wild-type and various mutants (T790M, L858R, L861Q, L858 R/T790M) EGFR, Z′-Lyte Kinase Assay Kit were purchased from Invitrogen. 10 concentration gradients, from 5.1×10−11 mol/L to 1.0×10−6 mol/L, were set for all of the compounds to be tested. Concentrations of different kinases were determined based on the optimization of experiment, and the corresponding concentrations were: EGFR (PV3872, Invitrogen) 0.287 μg/μL, EGFR-T790M (PV4803, Invitrogen) 0.174 μg/μL, EGFR-L858R (PV4128, Invitrogen) 0.054 μg/μL, EGFR-L858R/T790M (PV4879, Invitrogen) 0.055 μg/μL. Compounds were diluted for 3 times in DMSO from 5.1×10−9 M to 1×10−4 M. 4 μL of compound was dissolved in 96 μL of water, to give a 4× compound solution. 40 μM ATP was dissolved in 1.33× kinase buffer, and a kinase/peptide mixture comprising 2× kinase, 4 μM tyrosine and four peptides was prepared for use. 10 μL of kinase reaction system comprised 2.5 μL of compound solution, 5 μL of Kinase/peptide mixture, and 2.5 μL of ATP solution. 5 μL of phosphopeptide solution was used in place of kinase/peptide mixture as 100% phosphorylation control. 2.5 μL of 1.33× kinase buffer was used to replace ATP solution as 100% inhibition control, and 2.5 μL of 4% DMSO solution was used to replace compound solution as 0% inhibition control. After thoroughly mixing the solution within the plate, the plate was incubated at room temperature for 1.5 hours. 5 μL of DevelopmentSolution was added into each well, and then the plate was incubated at room temperature for another 1 hour, and non-phosphorylated peptide was cleaved within this period. Finally, the reaction was quenched by adding 5 μL of Stop Reagent. The Plate was measured with EnVision Multilabel Reader (Perkin Elmer). Experimental data were calculated by using GraphPad Prism version 4.0.
Measurement: IC50 = 106 nM (pChEMBL 6.96999979019165)
Descriptors: MW 471.52, ALogP 2.98, HBA 9, HBD 2, PSA 114.27, QED 0.38
Compound (SMILES): C=CC(=O)Nc1cccc(-n2c(=O)cnc3cnc(Nc4ccccc4)nc32)c1
InChIKey: CMZKQVFPFYPHOD-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: EGFR kinase assay: In vitro enzyme activity assay: wild-type and various mutants (T790M, L858R, L861Q, L858 R/T790M) EGFR, Z′-Lyte Kinase Assay Kit were purchased from Invitrogen. 10 concentration gradients, from 5.1×10−11 mol/L to 1.0×10−6 mol/L, were set for all of the compounds to be tested. Concentrations of different kinases were determined based on the optimization of experiment, and the corresponding concentrations were: EGFR (PV3872, Invitrogen) 0.287 μg/μL, EGFR-T790M (PV4803, Invitrogen) 0.174 μg/μL, EGFR-L858R (PV4128, Invitrogen) 0.054 μg/μL, EGFR-L858R/T790M (PV4879, Invitrogen) 0.055 μg/μL. Compounds were diluted for 3 times in DMSO from 5.1×10−9 M to 1×10−4 M. 4 μL of compound was dissolved in 96 μL of water, to give a 4× compound solution. 40 μM ATP was dissolved in 1.33× kinase buffer, and a kinase/peptide mixture comprising 2× kinase, 4 μM tyrosine and four peptides was prepared for use. 10 μL of kinase reaction system comprised 2.5 μL of compound solution, 5 μL of Kinase/peptide mixture, and 2.5 μL of ATP solution. 5 μL of phosphopeptide solution was used in place of kinase/peptide mixture as 100% phosphorylation control. 2.5 μL of 1.33× kinase buffer was used to replace ATP solution as 100% inhibition control, and 2.5 μL of 4% DMSO solution was used to replace compound solution as 0% inhibition control. After thoroughly mixing the solution within the plate, the plate was incubated at room temperature for 1.5 hours. 5 μL of DevelopmentSolution was added into each well, and then the plate was incubated at room temperature for another 1 hour, and non-phosphorylated peptide was cleaved within this period. Finally, the reaction was quenched by adding 5 μL of Stop Reagent. The Plate was measured with EnVision Multilabel Reader (Perkin Elmer). Experimental data were calculated by using GraphPad Prism version 4.0.
Measurement: IC50 = 1859 nM (pChEMBL 5.730000019073486)
Descriptors: MW 384.4, ALogP 3.04, HBA 7, HBD 2, PSA 101.8, QED 0.51
Compound (SMILES): O=P(O)(O)C(Nc1cccc2ccccc12)P(=O)(O)O
InChIKey: MDQNHUVXMAEAFD-UHFFFAOYSA-N
Target: Carbonic anhydrase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9ULX7
Assay: Inhibition of human recombinant carbonic anhydrase 14 preincubated for 15 mins by stopped flow CO2 hydration method
Measurement: IC50 = 319 nM (pChEMBL 6.5)
Descriptors: MW 317.17, ALogP 1.89, HBA 3, HBD 5, PSA 127.09, QED 0.54
Compound (SMILES): O=P(O)(O)C(Nc1ccc(Oc2ccccc2)cc1)P(=O)(O)O
InChIKey: GPHBFHLZRQMFLJ-UHFFFAOYSA-N
Target: 72 kDa type IV collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P08253
Assay: Inhibition of APMA-activated recombinant human MMP2 using Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 as substrate incubated for 30 mins prior to substrate addition measured after 2 to 4 hrs by fluorometric assay
Measurement: IC50 = 2800 nM (pChEMBL 5.550000190734863)
Descriptors: MW 359.21, ALogP 2.53, HBA 4, HBD 5, PSA 136.32, QED 0.5
Compound (SMILES): O=P(O)(O)C(Nc1ccc(Oc2ccc(Cl)cc2)cc1)P(=O)(O)O
InChIKey: VRCNSKZUURJQAN-UHFFFAOYSA-N
Target: 72 kDa type IV collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P08253
Assay: Inhibition of APMA-activated recombinant human MMP2 using Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 as substrate incubated for 30 mins prior to substrate addition measured after 2 to 4 hrs by fluorometric assay
Measurement: IC50 = 2100 nM (pChEMBL 5.679999828338623)
Descriptors: MW 393.66, ALogP 3.18, HBA 4, HBD 5, PSA 136.32, QED 0.47
Compound (SMILES): O=P(O)(O)C(Nc1ccc(Oc2ccc(Br)cc2)cc1)P(=O)(O)O
InChIKey: ZSBBJNVNCGRSOS-UHFFFAOYSA-N
Target: 72 kDa type IV collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P08253
Assay: Inhibition of APMA-activated recombinant human MMP2 using Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 as substrate incubated for 30 mins prior to substrate addition measured after 2 to 4 hrs by fluorometric assay
Measurement: IC50 = 2800 nM (pChEMBL 5.550000190734863)
Descriptors: MW 438.11, ALogP 3.29, HBA 4, HBD 5, PSA 136.32, QED 0.43
Compound (SMILES): O=P(O)(O)C(Nc1ccc(Cl)c(Cl)c1)P(=O)(O)O
InChIKey: ADHSWFUIIRWNHD-UHFFFAOYSA-N
Target: Carbonic anhydrase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9ULX7
Assay: Inhibition of human recombinant carbonic anhydrase 14 preincubated for 15 mins by stopped flow CO2 hydration method
Measurement: IC50 = 7837 nM (pChEMBL 5.110000133514404)
Descriptors: MW 336, ALogP 2.04, HBA 3, HBD 5, PSA 127.09, QED 0.53
Compound (SMILES): O=[N+]([O-])c1cc(NC(P(=O)(O)O)P(=O)(O)O)ccc1F
InChIKey: GSMGLRFAXIPFLS-UHFFFAOYSA-N
Target: Carbonic anhydrase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9ULX7
Assay: Inhibition of human recombinant carbonic anhydrase 14 preincubated for 15 mins by stopped flow CO2 hydration method
Measurement: IC50 = 8807 nM (pChEMBL 5.050000190734863)
Descriptors: MW 330.1, ALogP 0.78, HBA 5, HBD 5, PSA 170.23, QED 0.3
Compound (SMILES): O=P(O)(O)C(Nc1cccc(C(F)(F)F)c1)P(=O)(O)O
InChIKey: SENUMOHBDKDZCG-UHFFFAOYSA-N
Target: Carbonic anhydrase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9ULX7
Assay: Inhibition of human recombinant carbonic anhydrase 14 preincubated for 15 mins by stopped flow CO2 hydration method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 335.11, ALogP 1.76, HBA 3, HBD 5, PSA 127.09, QED 0.53
Compound (SMILES): O=P(O)(O)C(Nc1cccc(F)c1)P(=O)(O)O
InChIKey: SCLGFWTXZFUITP-UHFFFAOYSA-N
Target: 72 kDa type IV collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P08253
Assay: Inhibition of APMA-activated recombinant human MMP2 using Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 as substrate incubated for 30 mins prior to substrate addition measured after 2 to 4 hrs by fluorometric assay
Measurement: IC50 = 42000 nM (pChEMBL 4.380000114440918)
Descriptors: MW 285.1, ALogP 0.88, HBA 3, HBD 5, PSA 127.09, QED 0.52
Compound (SMILES): O=P(O)(O)C(Nc1ccc(O)cc1)P(=O)(O)O
InChIKey: XQVNOYYFZWUDCV-UHFFFAOYSA-N
Target: Carbonic anhydrase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9ULX7
Assay: Inhibition of human recombinant carbonic anhydrase 14 preincubated for 15 mins by stopped flow CO2 hydration method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 283.11, ALogP 0.44, HBA 4, HBD 6, PSA 147.32, QED 0.34
Compound (SMILES): Cc1ccc(NC(P(=O)(O)O)P(=O)(O)O)cc1
InChIKey: FVJHDPVFVSTFKH-UHFFFAOYSA-N
Target: 72 kDa type IV collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P08253
Assay: Inhibition of APMA-activated recombinant human MMP2 using Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 as substrate incubated for 30 mins prior to substrate addition measured after 2 to 4 hrs by fluorometric assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 281.14, ALogP 1.05, HBA 3, HBD 5, PSA 127.09, QED 0.52
Compound (SMILES): O=P(O)(O)C(Nc1ccc(C(F)(F)F)cc1)P(=O)(O)O
InChIKey: RBHODZPTKHWXDX-UHFFFAOYSA-N
Target: 72 kDa type IV collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P08253
Assay: Inhibition of APMA-activated recombinant human MMP2 using Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 as substrate incubated for 30 mins prior to substrate addition measured after 2 to 4 hrs by fluorometric assay
Measurement: IC50 = 15000 nM (pChEMBL 4.820000171661377)
Descriptors: MW 335.11, ALogP 1.76, HBA 3, HBD 5, PSA 127.09, QED 0.53
Compound (SMILES): O=P(O)(O)C(Nc1ccc(Br)cc1)P(=O)(O)O
InChIKey: AXIAQHKDCQVIKV-UHFFFAOYSA-N
Target: Carbonic anhydrase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9ULX7
Assay: Inhibition of human recombinant carbonic anhydrase 14 preincubated for 15 mins by stopped flow CO2 hydration method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 346.01, ALogP 1.5, HBA 3, HBD 5, PSA 127.09, QED 0.52
Compound (SMILES): O=[N+]([O-])c1ccc(NC(P(=O)(O)O)P(=O)(O)O)cc1
InChIKey: HTWBLJFKBSZUAN-UHFFFAOYSA-N
Target: Carbonic anhydrase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9ULX7
Assay: Inhibition of human recombinant carbonic anhydrase 14 preincubated for 15 mins by stopped flow CO2 hydration method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 312.11, ALogP 0.65, HBA 5, HBD 5, PSA 170.23, QED 0.3
Compound (SMILES): O=P(O)(O)C(Nc1ccccc1)P(=O)(O)O
InChIKey: XVNZXEWQQDCZSM-UHFFFAOYSA-N
Target: 72 kDa type IV collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P08253
Assay: Inhibition of APMA-activated recombinant human MMP2 using Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 as substrate incubated for 30 mins prior to substrate addition measured after 2 to 4 hrs by fluorometric assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 267.11, ALogP 0.74, HBA 3, HBD 5, PSA 127.09, QED 0.51
Compound (SMILES): O=P(O)(O)C(Nc1ccc(F)cc1)P(=O)(O)O
InChIKey: CXOBNZQSLVRTMZ-UHFFFAOYSA-N
Target: 72 kDa type IV collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P08253
Assay: Inhibition of APMA-activated recombinant human MMP2 using Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 as substrate incubated for 30 mins prior to substrate addition measured after 2 to 4 hrs by fluorometric assay
Measurement: IC50 = 28200 nM (pChEMBL 4.550000190734863)
Descriptors: MW 285.1, ALogP 0.88, HBA 3, HBD 5, PSA 127.09, QED 0.52
Compound (SMILES): Cc1csc(NC(=O)c2cc(F)cc(Oc3cncnc3)c2)n1
InChIKey: AXVLPJHYYFHCHK-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: PDSP Secondary Binding target: DRD3 - Compounds are tested at 10 uM concentration, plate are incubated at room temperature in the dark for 90 minutes. Reaction are stopped by vacuum filtration onto 0.3% polyethyleneimine soaked filter mats using Filtermate harvester. Scintillation cocktail is then melted onto microwave-dried filters on a hot plate and the radio activity is counted in Microbia counter. Compounds showing a minimum of 50% inhibition at 10 uM concentration are carried forward in this secondary binding assay to determine equilibrium binding affinity.
Measurement: Ki = 2144.62 nM (pChEMBL 5.670000076293945)
Descriptors: MW 330.34, ALogP 3.43, HBA 6, HBD 1, PSA 77, QED 0.79
Compound (SMILES): COc1cc2c(NC3CCN(C(C)C)CC3)nc(N3CCC(F)(F)CC3)nc2cc1OCCCN1CCCC1
InChIKey: RNAMYOYQYRYFQY-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase EHMT1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H9B1
Assay: Inhibition of lysine methyltransferase GLP (unknown origin) using [3H]-SAM as substrate after 0.25 hrs by scintillation proximity assay
Measurement: IC50 < 2.5 nM (pChEMBL 8.60200023651123)
Descriptors: MW 546.71, ALogP 5.02, HBA 8, HBD 1, PSA 65.99, QED 0.42
Compound (SMILES): CCc1ccc2nc(Nc3cc(Cc4ccccc4)nc(N[C@H]4CC[C@H](O)CC4)n3)sc2c1
InChIKey: DPRNXTSMYVCYLJ-XUTJKUGGSA-N
Target: Cytoplasmic tyrosine-protein kinase BMX (SINGLE PROTEIN), Homo sapiens
UniProt: P51813
Assay: Inhibition of Bmx (unknown origin)
Measurement: IC50 = 158.49 nM (pChEMBL 6.800000190734863)
Descriptors: MW 459.62, ALogP 5.7, HBA 7, HBD 3, PSA 82.96, QED 0.33
Compound (SMILES): Cc1cccc(CC(=O)N2CCc3c2ccc(-c2cn(C)c4ncnc(N)c24)c3F)n1
InChIKey: PRWSIEBRGXYXAJ-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes using diclofenac as substrate after 5 to 60 mins by LC-MS/MS analysis
Measurement: IC50 = 24700 nM (pChEMBL 4.610000133514404)
Descriptors: MW 416.46, ALogP 3.19, HBA 6, HBD 1, PSA 89.93, QED 0.55
Compound (SMILES): Cn1cc(-c2ccc3c(c2F)CCN3C(=O)Cc2cccc(C(F)(F)F)n2)c2c(N)ncnc21
InChIKey: QAEKSWBVYBVLNO-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes using diclofenac as substrate after 5 to 60 mins by LC-MS/MS analysis
Measurement: IC50 = 19200 nM (pChEMBL 4.71999979019165)
Descriptors: MW 470.43, ALogP 3.9, HBA 6, HBD 1, PSA 89.93, QED 0.46
Compound (SMILES): Cc1cc(C)n(CC(=O)N2CCc3c2ccc(-c2cn(C)c4ncnc(N)c24)c3F)n1
InChIKey: HFOKVVVCWLIUBP-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes using phenacetin as substrate after 5 to 60 mins by LC-MS/MS analysis
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 419.46, ALogP 2.76, HBA 7, HBD 1, PSA 94.86, QED 0.55
Compound (SMILES): O=C1OCc2cc(CCN3CCN(C(=O)Cc4ccc(-n5cnnn5)cc4)CC3)ccc21
InChIKey: LKLRNYYBQWYHND-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by electrophysiology assay
Measurement: IC50 = 4500 nM (pChEMBL 5.349999904632568)
Descriptors: MW 432.48, ALogP 1.26, HBA 8, HBD 0, PSA 93.45, QED 0.54
Compound (SMILES): CCc1nc(N[C@@H]2CCC[C@@H]2C#N)c2cc[nH]c(=O)c2n1
InChIKey: OUAYPLUHINPFJL-MWLCHTKSSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of JAK1 (unknown origin)
Measurement: Ki = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 283.34, ALogP 1.98, HBA 5, HBD 2, PSA 94.46, QED 0.9
Compound (SMILES): CN1CCN(Cc2ccc(-c3cnc4[nH]cc(-c5ccc6[nH]ccc6c5)c4c3)cc2)CC1
InChIKey: QKKIWEILHCXECO-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P06493
Assay: Inhibition of wild type human CDK1 by high throughput ATP-[33P] radiolabeled assay
Measurement: IC50 = 1125 nM (pChEMBL 5.949999809265137)
Descriptors: MW 421.55, ALogP 5.13, HBA 3, HBD 2, PSA 50.95, QED 0.42
Compound (SMILES): O=C(COc1ccc(Cl)cc1)NNC(=S)NCCCCC1CCCCC1
InChIKey: JRAYHZWPXHIVJI-UHFFFAOYSA-N
Target: A disintegrin and metalloproteinase with thrombospondin motifs 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O75173
Assay: Inhibition of human recombinant ADAMTS-4 using QTVTWPDMELPLPRNITEGEARGSVIL-TVKPIFEVSPSPL(biotinyl)K as substrate incubated for 10 mins prior to substrate addition measured after 3 hrs by spectrophotometry
Measurement: IC50 = 630 nM (pChEMBL 6.199999809265137)
Descriptors: MW 397.97, ALogP 3.96, HBA 3, HBD 3, PSA 62.39, QED 0.35
Compound (SMILES): C=CC(=O)Nc1ccc(-n2c(=O)cnc3cnc(Nc4ccc(OC)cc4)nc32)cc1
InChIKey: BPENWXBDNSHEHD-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: EGFR kinase assay: In vitro enzyme activity assay: wild-type and various mutants (T790M, L858R, L861Q, L858 R/T790M) EGFR, Z′-Lyte Kinase Assay Kit were purchased from Invitrogen. 10 concentration gradients, from 5.1×10−11 mol/L to 1.0×10−6 mol/L, were set for all of the compounds to be tested. Concentrations of different kinases were determined based on the optimization of experiment, and the corresponding concentrations were: EGFR (PV3872, Invitrogen) 0.287 μg/μL, EGFR-T790M (PV4803, Invitrogen) 0.174 μg/μL, EGFR-L858R (PV4128, Invitrogen) 0.054 μg/μL, EGFR-L858R/T790M (PV4879, Invitrogen) 0.055 μg/μL. Compounds were diluted for 3 times in DMSO from 5.1×10−9 M to 1×10−4 M. 4 μL of compound was dissolved in 96 μL of water, to give a 4× compound solution. 40 μM ATP was dissolved in 1.33× kinase buffer, and a kinase/peptide mixture comprising 2× kinase, 4 μM tyrosine and four peptides was prepared for use. 10 μL of kinase reaction system comprised 2.5 μL of compound solution, 5 μL of Kinase/peptide mixture, and 2.5 μL of ATP solution. 5 μL of phosphopeptide solution was used in place of kinase/peptide mixture as 100% phosphorylation control. 2.5 μL of 1.33× kinase buffer was used to replace ATP solution as 100% inhibition control, and 2.5 μL of 4% DMSO solution was used to replace compound solution as 0% inhibition control. After thoroughly mixing the solution within the plate, the plate was incubated at room temperature for 1.5 hours. 5 μL of DevelopmentSolution was added into each well, and then the plate was incubated at room temperature for another 1 hour, and non-phosphorylated peptide was cleaved within this period. Finally, the reaction was quenched by adding 5 μL of Stop Reagent. The Plate was measured with EnVision Multilabel Reader (Perkin Elmer). Experimental data were calculated by using GraphPad Prism version 4.0.
Measurement: IC50 = 128 nM (pChEMBL 6.889999866485596)
Descriptors: MW 414.43, ALogP 3.05, HBA 8, HBD 2, PSA 111.03, QED 0.47
Compound (SMILES): C=CC(=O)Nc1cccc(-n2c(=O)cnc3cnc(Nc4ccc(OC)cc4)nc32)c1
InChIKey: BLWDOLCMBQDSMT-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Blk (SINGLE PROTEIN), Homo sapiens
UniProt: P51451
Assay: EGFR kinase assay: In vitro enzyme activity assay: wild-type and various mutants (T790M, L858R, L861Q, L858 R/T790M) EGFR, Z′-Lyte Kinase Assay Kit were purchased from Invitrogen. 10 concentration gradients, from 5.1×10−11 mol/L to 1.0×10−6 mol/L, were set for all of the compounds to be tested. Concentrations of different kinases were determined based on the optimization of experiment, and the corresponding concentrations were: EGFR (PV3872, Invitrogen) 0.287 μg/μL, EGFR-T790M (PV4803, Invitrogen) 0.174 μg/μL, EGFR-L858R (PV4128, Invitrogen) 0.054 μg/μL, EGFR-L858R/T790M (PV4879, Invitrogen) 0.055 μg/μL. Compounds were diluted for 3 times in DMSO from 5.1×10−9 M to 1×10−4 M. 4 μL of compound was dissolved in 96 μL of water, to give a 4× compound solution. 40 μM ATP was dissolved in 1.33× kinase buffer, and a kinase/peptide mixture comprising 2× kinase, 4 μM tyrosine and four peptides was prepared for use. 10 μL of kinase reaction system comprised 2.5 μL of compound solution, 5 μL of Kinase/peptide mixture, and 2.5 μL of ATP solution. 5 μL of phosphopeptide solution was used in place of kinase/peptide mixture as 100% phosphorylation control. 2.5 μL of 1.33× kinase buffer was used to replace ATP solution as 100% inhibition control, and 2.5 μL of 4% DMSO solution was used to replace compound solution as 0% inhibition control. After thoroughly mixing the solution within the plate, the plate was incubated at room temperature for 1.5 hours. 5 μL of DevelopmentSolution was added into each well, and then the plate was incubated at room temperature for another 1 hour, and non-phosphorylated peptide was cleaved within this period. Finally, the reaction was quenched by adding 5 μL of Stop Reagent. The Plate was measured with EnVision Multilabel Reader (Perkin Elmer). Experimental data were calculated by using GraphPad Prism version 4.0.
Measurement: IC50 = 69 nM (pChEMBL 7.159999847412109)
Descriptors: MW 414.43, ALogP 3.05, HBA 8, HBD 2, PSA 111.03, QED 0.47
Compound (SMILES): O=P(O)(O)C(Nc1ccc(Cl)c(Cl)c1)P(=O)(O)O
InChIKey: ADHSWFUIIRWNHD-UHFFFAOYSA-N
Target: Glutamine synthetase, chloroplastic (SINGLE PROTEIN), Zea mays
UniProt: P25462
Assay: Inhibition of Zea mays cv. Jeff (maize) leaf glutamine synthetase using L-glutamate as substrate assessed as inorganic phosphate production after 20 min by malachite green assay relative to control
Measurement: IC50 = 31915.38 nM (pChEMBL 4.5)
Descriptors: MW 336, ALogP 2.04, HBA 3, HBD 5, PSA 127.09, QED 0.53
Compound (SMILES): Cc1csc(NC(=O)c2cc(F)cc(Oc3cncnc3)c2)n1
InChIKey: AXVLPJHYYFHCHK-UHFFFAOYSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q01959
Assay: PDSP Secondary Binding target: SLC6A3 - Compounds are tested at 10 uM concentration, plate are incubated at room temperature in the dark for 90 minutes. Reaction are stopped by vacuum filtration onto 0.3% polyethyleneimine soaked filter mats using Filtermate harvester. Scintillation cocktail is then melted onto microwave-dried filters on a hot plate and the radio activity is counted in Microbia counter. Compounds showing a minimum of 50% inhibition at 10 uM concentration are carried forward in this secondary binding assay to determine equilibrium binding affinity.
Measurement: Ki = 2989.86 nM (pChEMBL 5.519999980926514)
Descriptors: MW 330.34, ALogP 3.43, HBA 6, HBD 1, PSA 77, QED 0.79
Compound (SMILES): COc1cc2c(NC3CCN(C(C)C)CC3)nc(N3CCC(F)(F)CC3)nc2cc1OCCCN1CCCC1
InChIKey: RNAMYOYQYRYFQY-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase EHMT2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96KQ7
Assay: Non-competitive inhibition of lysine methyltransferase G9a (unknown origin) using SAM as substrate by Michaelis-Menten kinetic assay
Measurement: Ki = 3.7 nM (pChEMBL 8.430000305175781)
Descriptors: MW 546.71, ALogP 5.02, HBA 8, HBD 1, PSA 65.99, QED 0.42
Compound (SMILES): CCc1ccc2nc(Nc3cc(Cc4ccccc4)nc(N[C@H]4CC[C@H](O)CC4)n3)sc2c1
InChIKey: DPRNXTSMYVCYLJ-XUTJKUGGSA-N
Target: Tyrosine-protein kinase TXK (SINGLE PROTEIN), Homo sapiens
UniProt: P42681
Assay: Inhibition of TXK (unknown origin)
Measurement: IC50 = 79.43 nM (pChEMBL 7.099999904632568)
Descriptors: MW 459.62, ALogP 5.7, HBA 7, HBD 3, PSA 82.96, QED 0.33
Compound (SMILES): Cc1cccc(CC(=O)N2CCc3c2ccc(-c2cn(C)c4ncnc(N)c24)c3F)n1
InChIKey: PRWSIEBRGXYXAJ-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes using phenacetin as substrate after 5 to 60 mins by LC-MS/MS analysis
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 416.46, ALogP 3.19, HBA 6, HBD 1, PSA 89.93, QED 0.55
Compound (SMILES): Cn1cc(-c2ccc3c(c2F)CCN3C(=O)Cc2cccc(C(F)(F)F)n2)c2c(N)ncnc21
InChIKey: QAEKSWBVYBVLNO-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes using phenacetin as substrate after 5 to 60 mins by LC-MS/MS analysis
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 470.43, ALogP 3.9, HBA 6, HBD 1, PSA 89.93, QED 0.46
Compound (SMILES): Cc1cc(C)n(CC(=O)N2CCc3c2ccc(-c2cn(C)c4ncnc(N)c24)c3F)n1
InChIKey: HFOKVVVCWLIUBP-UHFFFAOYSA-N
Target: Eukaryotic translation initiation factor 2-alpha kinase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NZJ5
Assay: Inhibition of thapsigargin-induced autophosphorylation of PERK in human A549 cells preincubated for 1 hr followed by thapsigargin-induction measured after 1 hr by Western blotting analysis
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 419.46, ALogP 2.76, HBA 7, HBD 1, PSA 94.86, QED 0.55