lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1cc2ncnc(Oc3cccc(NC(=O)Nc4cc(C(C)(C)F)on4)c3)c2cc1OC
InChIKey: WVLNNTZESMVSCV-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Competition Binding Assay: Competition binding assays used herein were developed, validated and performed as described in Fabian et al., Nature Biotechnology 2005, 23, 329-336. Kinases were produced as fusions to T7 phage (See, Fabian et al. or WO04/015142) or alternatively, the kinases were expressed in HEK-293 cells and subsequently tagged with DNA for PCR detection (See, WO08/005310). For the binding assays, streptavidin-coated magnetic beads were treated with biotinylated affinity ligands for 30 min at room temperature to generate affinity resins. The liganded beads were blocked with excess biotin and washed with blocking buffer (SeaBlock (Pierce), 1% BSA, 0.05% Tween 20, 1 mM DTT) to remove unbound ligand and to reduce non-specific binding. Binding reactions were assembled by combining kinase, liganded affinity beads, and test compounds in 1× binding buffer (20% SeaBlock, 0.17×PBS, 0.05% Tween 20, 6 mM DTT). Test compounds were prepared as 100× stocks in DMSO and rapidly diluted into the aqueous environment. DMSO was added to control assays lacking a test compound. Primary screen interactions were performed in polypropylene 384-well plates in a final volume of 34 μL, while Kd determinations were performed in polystyrene 96-well plates in a final volume of 135 μL. The assay plates were incubated at room temperature with shaking for 1 hour, long enough for binding reactions to reach equilibrium, and the affinity beads were washed extensively with wash buffer (1×PBS, 0.05% Tween 20) to remove unbound protein. The beads were then resuspended in elution buffer (1×PBS, 0.05% Tween 20, 2 μM non-biotinylated affinity ligand) and incubated at room temperature with shaking for 30 min. The kinase concentration in the eluates was measured by quantitative PCR. Each kinase was tested individually against each compound. KdS were determined using eleven serial threefold dilutions.
Measurement: Kd < 250 nM (pChEMBL 6.6020002365112305)
Descriptors: MW 467.46, ALogP 5.28, HBA 8, HBD 2, PSA 120.63, QED 0.38
Compound (SMILES): COc1cc2ncnc(Oc3cccc(NC(=O)Nc4cc(C(C)(CF)CF)on4)c3)c2cc1OC
InChIKey: KJVUAWFWZBUEDN-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Competition Binding Assay: Competition binding assays used herein were developed, validated and performed as described in Fabian et al., Nature Biotechnology 2005, 23, 329-336. Kinases were produced as fusions to T7 phage (See, Fabian et al. or WO04/015142) or alternatively, the kinases were expressed in HEK-293 cells and subsequently tagged with DNA for PCR detection (See, WO08/005310). For the binding assays, streptavidin-coated magnetic beads were treated with biotinylated affinity ligands for 30 min at room temperature to generate affinity resins. The liganded beads were blocked with excess biotin and washed with blocking buffer (SeaBlock (Pierce), 1% BSA, 0.05% Tween 20, 1 mM DTT) to remove unbound ligand and to reduce non-specific binding. Binding reactions were assembled by combining kinase, liganded affinity beads, and test compounds in 1× binding buffer (20% SeaBlock, 0.17×PBS, 0.05% Tween 20, 6 mM DTT). Test compounds were prepared as 100× stocks in DMSO and rapidly diluted into the aqueous environment. DMSO was added to control assays lacking a test compound. Primary screen interactions were performed in polypropylene 384-well plates in a final volume of 34 μL, while Kd determinations were performed in polystyrene 96-well plates in a final volume of 135 μL. The assay plates were incubated at room temperature with shaking for 1 hour, long enough for binding reactions to reach equilibrium, and the affinity beads were washed extensively with wash buffer (1×PBS, 0.05% Tween 20) to remove unbound protein. The beads were then resuspended in elution buffer (1×PBS, 0.05% Tween 20, 2 μM non-biotinylated affinity ligand) and incubated at room temperature with shaking for 30 min. The kinase concentration in the eluates was measured by quantitative PCR. Each kinase was tested individually against each compound. KdS were determined using eleven serial threefold dilutions.
Measurement: Kd < 250 nM (pChEMBL 6.6020002365112305)
Descriptors: MW 499.47, ALogP 5.27, HBA 8, HBD 2, PSA 120.63, QED 0.32
Compound (SMILES): COc1cc2ncnc(Oc3cccc(NC(=O)Nc4cc(C(C)(C)C(F)(F)F)on4)c3)c2cc1OC
InChIKey: DKNUPRMJNUQNHR-UHFFFAOYSA-N
Target: Ephrin type-A receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29317
Assay: Inhibition of EPHA2 in human HEK293 cells after 1 hr by competition binding assay
Measurement: Kd = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 517.46, ALogP 5.91, HBA 8, HBD 2, PSA 120.63, QED 0.31
Compound (SMILES): COc1cc2ncnc(Oc3cccc(NC(=O)Nc4cc(C5(C(F)(F)F)CC5)on4)c3)c2cc1OC
InChIKey: JIUWVCIYTKTSRT-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Competition Binding Assay: Competition binding assays used herein were developed, validated and performed as described in Fabian et al., Nature Biotechnology 2005, 23, 329-336. Kinases were produced as fusions to T7 phage (See, Fabian et al. or WO04/015142) or alternatively, the kinases were expressed in HEK-293 cells and subsequently tagged with DNA for PCR detection (See, WO08/005310). For the binding assays, streptavidin-coated magnetic beads were treated with biotinylated affinity ligands for 30 min at room temperature to generate affinity resins. The liganded beads were blocked with excess biotin and washed with blocking buffer (SeaBlock (Pierce), 1% BSA, 0.05% Tween 20, 1 mM DTT) to remove unbound ligand and to reduce non-specific binding. Binding reactions were assembled by combining kinase, liganded affinity beads, and test compounds in 1× binding buffer (20% SeaBlock, 0.17×PBS, 0.05% Tween 20, 6 mM DTT). Test compounds were prepared as 100× stocks in DMSO and rapidly diluted into the aqueous environment. DMSO was added to control assays lacking a test compound. Primary screen interactions were performed in polypropylene 384-well plates in a final volume of 34 μL, while Kd determinations were performed in polystyrene 96-well plates in a final volume of 135 μL. The assay plates were incubated at room temperature with shaking for 1 hour, long enough for binding reactions to reach equilibrium, and the affinity beads were washed extensively with wash buffer (1×PBS, 0.05% Tween 20) to remove unbound protein. The beads were then resuspended in elution buffer (1×PBS, 0.05% Tween 20, 2 μM non-biotinylated affinity ligand) and incubated at room temperature with shaking for 30 min. The kinase concentration in the eluates was measured by quantitative PCR. Each kinase was tested individually against each compound. KdS were determined using eleven serial threefold dilutions.
Measurement: Kd < 250 nM (pChEMBL 6.6020002365112305)
Descriptors: MW 515.45, ALogP 5.67, HBA 8, HBD 2, PSA 120.63, QED 0.32
Compound (SMILES): COc1cc2ncnc(Sc3cccc(NC(=O)Nc4cc(C(C)(CF)CF)on4)c3)c2cc1OC
InChIKey: VQRAFZJCOZOOMB-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Competition Binding Assay: Competition binding assays used herein were developed, validated and performed as described in Fabian et al., Nature Biotechnology 2005, 23, 329-336. Kinases were produced as fusions to T7 phage (See, Fabian et al. or WO04/015142) or alternatively, the kinases were expressed in HEK-293 cells and subsequently tagged with DNA for PCR detection (See, WO08/005310). For the binding assays, streptavidin-coated magnetic beads were treated with biotinylated affinity ligands for 30 min at room temperature to generate affinity resins. The liganded beads were blocked with excess biotin and washed with blocking buffer (SeaBlock (Pierce), 1% BSA, 0.05% Tween 20, 1 mM DTT) to remove unbound ligand and to reduce non-specific binding. Binding reactions were assembled by combining kinase, liganded affinity beads, and test compounds in 1× binding buffer (20% SeaBlock, 0.17×PBS, 0.05% Tween 20, 6 mM DTT). Test compounds were prepared as 100× stocks in DMSO and rapidly diluted into the aqueous environment. DMSO was added to control assays lacking a test compound. Primary screen interactions were performed in polypropylene 384-well plates in a final volume of 34 μL, while Kd determinations were performed in polystyrene 96-well plates in a final volume of 135 μL. The assay plates were incubated at room temperature with shaking for 1 hour, long enough for binding reactions to reach equilibrium, and the affinity beads were washed extensively with wash buffer (1×PBS, 0.05% Tween 20) to remove unbound protein. The beads were then resuspended in elution buffer (1×PBS, 0.05% Tween 20, 2 μM non-biotinylated affinity ligand) and incubated at room temperature with shaking for 30 min. The kinase concentration in the eluates was measured by quantitative PCR. Each kinase was tested individually against each compound. KdS were determined using eleven serial threefold dilutions.
Measurement: Kd < 250 nM (pChEMBL 6.6020002365112305)
Descriptors: MW 515.54, ALogP 5.63, HBA 8, HBD 2, PSA 111.4, QED 0.28
Compound (SMILES): COc1cc2ncnc(Sc3cccc(NC(=O)Nc4cc(C5(C(F)(F)F)CC5)on4)c3)c2cc1OC
InChIKey: WKWHUIXJXMGBLU-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Competition Binding Assay: Competition binding assays used herein were developed, validated and performed as described in Fabian et al., Nature Biotechnology 2005, 23, 329-336. Kinases were produced as fusions to T7 phage (See, Fabian et al. or WO04/015142) or alternatively, the kinases were expressed in HEK-293 cells and subsequently tagged with DNA for PCR detection (See, WO08/005310). For the binding assays, streptavidin-coated magnetic beads were treated with biotinylated affinity ligands for 30 min at room temperature to generate affinity resins. The liganded beads were blocked with excess biotin and washed with blocking buffer (SeaBlock (Pierce), 1% BSA, 0.05% Tween 20, 1 mM DTT) to remove unbound ligand and to reduce non-specific binding. Binding reactions were assembled by combining kinase, liganded affinity beads, and test compounds in 1× binding buffer (20% SeaBlock, 0.17×PBS, 0.05% Tween 20, 6 mM DTT). Test compounds were prepared as 100× stocks in DMSO and rapidly diluted into the aqueous environment. DMSO was added to control assays lacking a test compound. Primary screen interactions were performed in polypropylene 384-well plates in a final volume of 34 μL, while Kd determinations were performed in polystyrene 96-well plates in a final volume of 135 μL. The assay plates were incubated at room temperature with shaking for 1 hour, long enough for binding reactions to reach equilibrium, and the affinity beads were washed extensively with wash buffer (1×PBS, 0.05% Tween 20) to remove unbound protein. The beads were then resuspended in elution buffer (1×PBS, 0.05% Tween 20, 2 μM non-biotinylated affinity ligand) and incubated at room temperature with shaking for 30 min. The kinase concentration in the eluates was measured by quantitative PCR. Each kinase was tested individually against each compound. KdS were determined using eleven serial threefold dilutions.
Measurement: Kd < 250 nM (pChEMBL 6.6020002365112305)
Descriptors: MW 531.52, ALogP 6.02, HBA 8, HBD 2, PSA 111.4, QED 0.28
Compound (SMILES): COc1cc2ncnc(Sc3cccc(NC(=O)Nc4cc(C(C)(C)F)no4)c3)c2cc1OC
InChIKey: UCNNCXUHEWXYRD-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Competition Binding Assay: Competition binding assays used herein were developed, validated and performed as described in Fabian et al., Nature Biotechnology 2005, 23, 329-336. Kinases were produced as fusions to T7 phage (See, Fabian et al. or WO04/015142) or alternatively, the kinases were expressed in HEK-293 cells and subsequently tagged with DNA for PCR detection (See, WO08/005310). For the binding assays, streptavidin-coated magnetic beads were treated with biotinylated affinity ligands for 30 min at room temperature to generate affinity resins. The liganded beads were blocked with excess biotin and washed with blocking buffer (SeaBlock (Pierce), 1% BSA, 0.05% Tween 20, 1 mM DTT) to remove unbound ligand and to reduce non-specific binding. Binding reactions were assembled by combining kinase, liganded affinity beads, and test compounds in 1× binding buffer (20% SeaBlock, 0.17×PBS, 0.05% Tween 20, 6 mM DTT). Test compounds were prepared as 100× stocks in DMSO and rapidly diluted into the aqueous environment. DMSO was added to control assays lacking a test compound. Primary screen interactions were performed in polypropylene 384-well plates in a final volume of 34 μL, while Kd determinations were performed in polystyrene 96-well plates in a final volume of 135 μL. The assay plates were incubated at room temperature with shaking for 1 hour, long enough for binding reactions to reach equilibrium, and the affinity beads were washed extensively with wash buffer (1×PBS, 0.05% Tween 20) to remove unbound protein. The beads were then resuspended in elution buffer (1×PBS, 0.05% Tween 20, 2 μM non-biotinylated affinity ligand) and incubated at room temperature with shaking for 30 min. The kinase concentration in the eluates was measured by quantitative PCR. Each kinase was tested individually against each compound. KdS were determined using eleven serial threefold dilutions.
Measurement: Kd < 250 nM (pChEMBL 6.6020002365112305)
Descriptors: MW 483.53, ALogP 5.63, HBA 8, HBD 2, PSA 111.4, QED 0.33
Compound (SMILES): COc1cc2ncnc(Oc3cccc(NC(=O)Nc4cc(C(C)(C)C)nn4C(C)C)c3)c2cc1OC
InChIKey: YIVXZTLMJYYLEW-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Competition Binding Assay: Competition binding assays used herein were developed, validated and performed as described in Fabian et al., Nature Biotechnology 2005, 23, 329-336. Kinases were produced as fusions to T7 phage (See, Fabian et al. or WO04/015142) or alternatively, the kinases were expressed in HEK-293 cells and subsequently tagged with DNA for PCR detection (See, WO08/005310). For the binding assays, streptavidin-coated magnetic beads were treated with biotinylated affinity ligands for 30 min at room temperature to generate affinity resins. The liganded beads were blocked with excess biotin and washed with blocking buffer (SeaBlock (Pierce), 1% BSA, 0.05% Tween 20, 1 mM DTT) to remove unbound ligand and to reduce non-specific binding. Binding reactions were assembled by combining kinase, liganded affinity beads, and test compounds in 1× binding buffer (20% SeaBlock, 0.17×PBS, 0.05% Tween 20, 6 mM DTT). Test compounds were prepared as 100× stocks in DMSO and rapidly diluted into the aqueous environment. DMSO was added to control assays lacking a test compound. Primary screen interactions were performed in polypropylene 384-well plates in a final volume of 34 μL, while Kd determinations were performed in polystyrene 96-well plates in a final volume of 135 μL. The assay plates were incubated at room temperature with shaking for 1 hour, long enough for binding reactions to reach equilibrium, and the affinity beads were washed extensively with wash buffer (1×PBS, 0.05% Tween 20) to remove unbound protein. The beads were then resuspended in elution buffer (1×PBS, 0.05% Tween 20, 2 μM non-biotinylated affinity ligand) and incubated at room temperature with shaking for 30 min. The kinase concentration in the eluates was measured by quantitative PCR. Each kinase was tested individually against each compound. KdS were determined using eleven serial threefold dilutions.
Measurement: Kd < 250 nM (pChEMBL 6.6020002365112305)
Descriptors: MW 504.59, ALogP 6.16, HBA 8, HBD 2, PSA 112.42, QED 0.31
Compound (SMILES): COc1cc2ncnc(Oc3cccc(NC(=O)Nc4cc(C(C)(C)C)nn4CC(C)C)c3)c2cc1OC
InChIKey: VCWAPASQOFBPCX-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Competition Binding Assay: Competition binding assays used herein were developed, validated and performed as described in Fabian et al., Nature Biotechnology 2005, 23, 329-336. Kinases were produced as fusions to T7 phage (See, Fabian et al. or WO04/015142) or alternatively, the kinases were expressed in HEK-293 cells and subsequently tagged with DNA for PCR detection (See, WO08/005310). For the binding assays, streptavidin-coated magnetic beads were treated with biotinylated affinity ligands for 30 min at room temperature to generate affinity resins. The liganded beads were blocked with excess biotin and washed with blocking buffer (SeaBlock (Pierce), 1% BSA, 0.05% Tween 20, 1 mM DTT) to remove unbound ligand and to reduce non-specific binding. Binding reactions were assembled by combining kinase, liganded affinity beads, and test compounds in 1× binding buffer (20% SeaBlock, 0.17×PBS, 0.05% Tween 20, 6 mM DTT). Test compounds were prepared as 100× stocks in DMSO and rapidly diluted into the aqueous environment. DMSO was added to control assays lacking a test compound. Primary screen interactions were performed in polypropylene 384-well plates in a final volume of 34 μL, while Kd determinations were performed in polystyrene 96-well plates in a final volume of 135 μL. The assay plates were incubated at room temperature with shaking for 1 hour, long enough for binding reactions to reach equilibrium, and the affinity beads were washed extensively with wash buffer (1×PBS, 0.05% Tween 20) to remove unbound protein. The beads were then resuspended in elution buffer (1×PBS, 0.05% Tween 20, 2 μM non-biotinylated affinity ligand) and incubated at room temperature with shaking for 30 min. The kinase concentration in the eluates was measured by quantitative PCR. Each kinase was tested individually against each compound. KdS were determined using eleven serial threefold dilutions.
Measurement: Kd < 250 nM (pChEMBL 6.6020002365112305)
Descriptors: MW 518.62, ALogP 6.23, HBA 8, HBD 2, PSA 112.42, QED 0.28
Compound (SMILES): COc1cc2ncnc(Oc3cccc(NC(=O)Nc4cc(C(C)(C)C)nn4C4CCCCC4)c3)c2cc1OC
InChIKey: JXASCTLUTOLAIV-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Competition Binding Assay: Competition binding assays used herein were developed, validated and performed as described in Fabian et al., Nature Biotechnology 2005, 23, 329-336. Kinases were produced as fusions to T7 phage (See, Fabian et al. or WO04/015142) or alternatively, the kinases were expressed in HEK-293 cells and subsequently tagged with DNA for PCR detection (See, WO08/005310). For the binding assays, streptavidin-coated magnetic beads were treated with biotinylated affinity ligands for 30 min at room temperature to generate affinity resins. The liganded beads were blocked with excess biotin and washed with blocking buffer (SeaBlock (Pierce), 1% BSA, 0.05% Tween 20, 1 mM DTT) to remove unbound ligand and to reduce non-specific binding. Binding reactions were assembled by combining kinase, liganded affinity beads, and test compounds in 1× binding buffer (20% SeaBlock, 0.17×PBS, 0.05% Tween 20, 6 mM DTT). Test compounds were prepared as 100× stocks in DMSO and rapidly diluted into the aqueous environment. DMSO was added to control assays lacking a test compound. Primary screen interactions were performed in polypropylene 384-well plates in a final volume of 34 μL, while Kd determinations were performed in polystyrene 96-well plates in a final volume of 135 μL. The assay plates were incubated at room temperature with shaking for 1 hour, long enough for binding reactions to reach equilibrium, and the affinity beads were washed extensively with wash buffer (1×PBS, 0.05% Tween 20) to remove unbound protein. The beads were then resuspended in elution buffer (1×PBS, 0.05% Tween 20, 2 μM non-biotinylated affinity ligand) and incubated at room temperature with shaking for 30 min. The kinase concentration in the eluates was measured by quantitative PCR. Each kinase was tested individually against each compound. KdS were determined using eleven serial threefold dilutions.
Measurement: Kd < 250 nM (pChEMBL 6.6020002365112305)
Descriptors: MW 544.66, ALogP 7.08, HBA 8, HBD 2, PSA 112.42, QED 0.26
Compound (SMILES): COc1cc2ncnc(Oc3cccc(NC(=O)Nc4cc(C(C)(C)C)nn4-c4ccccc4)c3)c2cc1OC
InChIKey: HFYIZLRRKJSQDC-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Competition Binding Assay: Competition binding assays used herein were developed, validated and performed as described in Fabian et al., Nature Biotechnology 2005, 23, 329-336. Kinases were produced as fusions to T7 phage (See, Fabian et al. or WO04/015142) or alternatively, the kinases were expressed in HEK-293 cells and subsequently tagged with DNA for PCR detection (See, WO08/005310). For the binding assays, streptavidin-coated magnetic beads were treated with biotinylated affinity ligands for 30 min at room temperature to generate affinity resins. The liganded beads were blocked with excess biotin and washed with blocking buffer (SeaBlock (Pierce), 1% BSA, 0.05% Tween 20, 1 mM DTT) to remove unbound ligand and to reduce non-specific binding. Binding reactions were assembled by combining kinase, liganded affinity beads, and test compounds in 1× binding buffer (20% SeaBlock, 0.17×PBS, 0.05% Tween 20, 6 mM DTT). Test compounds were prepared as 100× stocks in DMSO and rapidly diluted into the aqueous environment. DMSO was added to control assays lacking a test compound. Primary screen interactions were performed in polypropylene 384-well plates in a final volume of 34 μL, while Kd determinations were performed in polystyrene 96-well plates in a final volume of 135 μL. The assay plates were incubated at room temperature with shaking for 1 hour, long enough for binding reactions to reach equilibrium, and the affinity beads were washed extensively with wash buffer (1×PBS, 0.05% Tween 20) to remove unbound protein. The beads were then resuspended in elution buffer (1×PBS, 0.05% Tween 20, 2 μM non-biotinylated affinity ligand) and incubated at room temperature with shaking for 30 min. The kinase concentration in the eluates was measured by quantitative PCR. Each kinase was tested individually against each compound. KdS were determined using eleven serial threefold dilutions.
Measurement: Kd = 750 nM (pChEMBL 6.119999885559082)
Descriptors: MW 538.61, ALogP 6.57, HBA 8, HBD 2, PSA 112.42, QED 0.24
Compound (SMILES): COc1cc2ncnc(Oc3cccc(NC(=O)Nc4cc(C(C)(C)C)nn4Cc4ccccc4)c3)c2cc1OC
InChIKey: WNGRZHJFZIEVKD-UHFFFAOYSA-N
Target: RAF proto-oncogene serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P04049
Assay: Competition Binding Assay: Competition binding assays used herein were developed, validated and performed as described in Fabian et al., Nature Biotechnology 2005, 23, 329-336. Kinases were produced as fusions to T7 phage (See, Fabian et al. or WO04/015142) or alternatively, the kinases were expressed in HEK-293 cells and subsequently tagged with DNA for PCR detection (See, WO08/005310). For the binding assays, streptavidin-coated magnetic beads were treated with biotinylated affinity ligands for 30 min at room temperature to generate affinity resins. The liganded beads were blocked with excess biotin and washed with blocking buffer (SeaBlock (Pierce), 1% BSA, 0.05% Tween 20, 1 mM DTT) to remove unbound ligand and to reduce non-specific binding. Binding reactions were assembled by combining kinase, liganded affinity beads, and test compounds in 1× binding buffer (20% SeaBlock, 0.17×PBS, 0.05% Tween 20, 6 mM DTT). Test compounds were prepared as 100× stocks in DMSO and rapidly diluted into the aqueous environment. DMSO was added to control assays lacking a test compound. Primary screen interactions were performed in polypropylene 384-well plates in a final volume of 34 μL, while Kd determinations were performed in polystyrene 96-well plates in a final volume of 135 μL. The assay plates were incubated at room temperature with shaking for 1 hour, long enough for binding reactions to reach equilibrium, and the affinity beads were washed extensively with wash buffer (1×PBS, 0.05% Tween 20) to remove unbound protein. The beads were then resuspended in elution buffer (1×PBS, 0.05% Tween 20, 2 μM non-biotinylated affinity ligand) and incubated at room temperature with shaking for 30 min. The kinase concentration in the eluates was measured by quantitative PCR. Each kinase was tested individually against each compound. KdS were determined using eleven serial threefold dilutions.
Measurement: Kd > 1000 nM (pChEMBL 6)
Descriptors: MW 552.64, ALogP 6.63, HBA 8, HBD 2, PSA 112.42, QED 0.22
Compound (SMILES): CN(C)S(=O)(=O)c1ccc(NC(=S)N2CCC(C(O)(c3ccccc3)c3ccccc3)CC2)cc1
InChIKey: VAUKHARIAMDAGF-UHFFFAOYSA-N
Target: Beta-3 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P13945
Assay: PDSP Secondary Binding target: ADRB3 - 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 = 3496.23 nM (pChEMBL 5.460000038146973)
Descriptors: MW 509.7, ALogP 4.28, HBA 4, HBD 2, PSA 72.88, QED 0.48
Compound (SMILES): CCCS(=O)(=O)Nc1ccc(F)c(C(=O)Nc2cnc3ccccc3c2)c1F
InChIKey: DODKKMVEACMFCI-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of B-Raf (unknown origin)
Measurement: IC50 <= 10000 nM (pChEMBL 5)
Descriptors: MW 405.43, ALogP 3.92, HBA 4, HBD 2, PSA 88.16, QED 0.65
Compound (SMILES): CCCS(=O)(=O)Nc1ccc(F)c(C(=O)Nc2cnc3cc(-c4ccccc4)nn3c2)c1F
InChIKey: ZMQCXSYWTICDLW-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of B-Raf V600E mutant in human Malme-3M cells assessed as basal ERK phosphorylation
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 471.49, ALogP 4.08, HBA 6, HBD 2, PSA 105.46, QED 0.42
Compound (SMILES): O=C(O)CSc1cc(NS(=O)(=O)c2cccs2)c2ccccc2c1O
InChIKey: GVAXUAIZKLJWSB-UHFFFAOYSA-N
Target: Bcl-2-related protein A1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16548
Assay: Displacement of Flu-BID/FAM-BID from His-tagged A1-BFL-1 (1 to 151) (unknown origin) expressed in Escherichia coli BL21(DE3) after 3 hrs by fluorescence polarization assay
Measurement: Ki = 6140 nM (pChEMBL 5.210000038146973)
Descriptors: MW 395.48, ALogP 3.58, HBA 6, HBD 3, PSA 103.7, QED 0.44
Compound (SMILES): O=S(=O)(Nc1cc(Sc2ncn[nH]2)c(O)c2ccccc12)c1ccc2ccccc2c1
InChIKey: UGODIOOKONOGOI-UHFFFAOYSA-N
Target: Histone acetyltransferase RTT109 (SINGLE PROTEIN), Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
UniProt: Q07794
Assay: Inhibition of Vps75-stimulated recombinant Saccharomyces cerevisiae histone acetyltransferase Rtt109 using Asf1-dH3-H4 as substrate assessed as coenzyme A production after 45 mins by CPM based HTS assay
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 448.53, ALogP 4.77, HBA 6, HBD 3, PSA 107.97, QED 0.33
Compound (SMILES): O=c1[nH]cnc2c1oc1ccc(Br)cc12
InChIKey: LCWIMYAVOHBYBI-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: Inhibition of PIM1
Measurement: IC50 = 526 nM (pChEMBL 6.28000020980835)
Descriptors: MW 265.07, ALogP 2.43, HBA 3, HBD 1, PSA 58.89, QED 0.68
Compound (SMILES): O=c1[nH]c(CN2CC[C@H](O)C2)nc2c1oc1ccc(Br)cc12
InChIKey: FRRLLRQAGKSVMU-VIFPVBQESA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: Inhibition of N-terminus His-tagged human PIM1 expressed in Escherichia coli using AKRRRLSA as substrate after 1 to 2 hrs by chemiluminescence assay
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 364.2, ALogP 2, HBA 5, HBD 2, PSA 82.36, QED 0.73
Compound (SMILES): O=c1[nH]c(CN2CC[C@@H](O)C2)nc2c1oc1ccc(Br)cc12
InChIKey: FRRLLRQAGKSVMU-SECBINFHSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: Inhibition of N-terminus His-tagged human PIM1 expressed in Escherichia coli using AKRRRLSA as substrate after 1 to 2 hrs by chemiluminescence assay
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 364.2, ALogP 2, HBA 5, HBD 2, PSA 82.36, QED 0.73
Compound (SMILES): N[C@H]1CCN(Cc2nc3c(oc4ccc(Br)cc43)c(=O)[nH]2)C1
InChIKey: HNIDDGUBRPIXPG-VIFPVBQESA-N
Target: Serine/threonine-protein kinase pim-3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86V86
Assay: Inhibition of N-terminal His-tagged human PIM3 expressed in Escherichia coli using AKRRRLSA as substrate after 1 to 2 hrs by luciferasse-luciferin-coupled chemiluminescence assay
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 363.22, ALogP 1.96, HBA 5, HBD 2, PSA 88.15, QED 0.73
Compound (SMILES): N[C@@H]1CCN(Cc2nc3c(oc4ccc(Br)cc43)c(=O)[nH]2)C1
InChIKey: HNIDDGUBRPIXPG-SECBINFHSA-N
Target: Casein kinase II alpha'/ beta (PROTEIN COMPLEX), Homo sapiens
UniProt: P67870
Assay: Inhibition of N-terminal MBP-tagged human alpha2beta2 CK2 expressed in Escherichia coli using casein as substrate after 1 to 2 hrs by luciferasse-luciferin-coupled chemiluminescence assay
Measurement: IC50 = 535 nM (pChEMBL 6.269999980926514)
Descriptors: MW 363.22, ALogP 1.96, HBA 5, HBD 2, PSA 88.15, QED 0.73
Compound (SMILES): O=c1[nH]c(CN2CCCC2)nc2c1oc1ccc(Br)cc12
InChIKey: WSZGOCPQOSHGAF-UHFFFAOYSA-N
Target: Casein kinase II alpha'/ beta (PROTEIN COMPLEX), Homo sapiens
UniProt: P67870
Assay: Inhibition of N-terminal MBP-tagged human alpha2beta2 CK2 expressed in Escherichia coli using casein as substrate after 1 to 2 hrs by luciferasse-luciferin-coupled chemiluminescence assay
Measurement: IC50 = 92 nM (pChEMBL 7.039999961853027)
Descriptors: MW 348.2, ALogP 3.03, HBA 4, HBD 1, PSA 62.13, QED 0.77
Compound (SMILES): CO[C@H]1CCN(Cc2nc3c(oc4ccc(Br)cc43)c(=O)[nH]2)C1
InChIKey: YANNSWWYRMATEM-JTQLQIEISA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: Inhibition of N-terminus His-tagged human PIM1 expressed in Escherichia coli using AKRRRLSA as substrate after 1 to 2 hrs by chemiluminescence assay
Measurement: IC50 = 77 nM (pChEMBL 7.110000133514404)
Descriptors: MW 378.23, ALogP 2.65, HBA 5, HBD 1, PSA 71.36, QED 0.76
Compound (SMILES): O=C(O)C1CCN(Cc2nc3c(oc4ccc(Br)cc43)c(=O)[nH]2)C1
InChIKey: XQEZXMGUDOPHOF-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: Inhibition of N-terminus His-tagged human PIM1 expressed in Escherichia coli using AKRRRLSA as substrate after 1 to 2 hrs by chemiluminescence assay
Measurement: IC50 = 142 nM (pChEMBL 6.849999904632568)
Descriptors: MW 392.21, ALogP 2.34, HBA 5, HBD 2, PSA 99.43, QED 0.71
Compound (SMILES): O=c1[nH]c(C2CNC2)nc2c1oc1ccc(Br)cc12
InChIKey: VYHCLYDDXNTHAU-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: Inhibition of N-terminus His-tagged human PIM1 expressed in Escherichia coli using AKRRRLSA as substrate after 1 to 2 hrs by chemiluminescence assay
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 320.15, ALogP 2.12, HBA 4, HBD 2, PSA 70.92, QED 0.72
Compound (SMILES): O=c1[nH]c([C@@H]2CCCN2)nc2c1oc1ccc(Br)cc12
InChIKey: IFSZNNCMCGMAHD-VIFPVBQESA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: Inhibition of N-terminus His-tagged human PIM1 expressed in Escherichia coli using AKRRRLSA as substrate after 1 to 2 hrs by chemiluminescence assay
Measurement: IC50 = 31 nM (pChEMBL 7.510000228881836)
Descriptors: MW 334.17, ALogP 2.86, HBA 4, HBD 2, PSA 70.92, QED 0.72
Compound (SMILES): O=c1[nH]c([C@H]2CCCN2)nc2c1oc1ccc(Br)cc12
InChIKey: IFSZNNCMCGMAHD-SECBINFHSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: Inhibition of N-terminus His-tagged human PIM1 expressed in Escherichia coli using AKRRRLSA as substrate after 1 to 2 hrs by chemiluminescence assay
Measurement: IC50 = 104 nM (pChEMBL 6.980000019073486)
Descriptors: MW 334.17, ALogP 2.86, HBA 4, HBD 2, PSA 70.92, QED 0.72
Compound (SMILES): O=c1[nH]c(C2CCCNC2)nc2c1oc1ccc(Br)cc12
InChIKey: XODCTWLLGVOGFI-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: Inhibition of N-terminus His-tagged human PIM1 expressed in Escherichia coli using AKRRRLSA as substrate after 1 to 2 hrs by chemiluminescence assay
Measurement: IC50 = 39 nM (pChEMBL 7.409999847412109)
Descriptors: MW 348.2, ALogP 2.9, HBA 4, HBD 2, PSA 70.92, QED 0.71
Compound (SMILES): O=c1[nH]c(C2CCNCC2)nc2c1oc1ccc(Br)cc12
InChIKey: GVUXAQWOKREQBF-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: Inhibition of N-terminus His-tagged human PIM1 expressed in Escherichia coli using AKRRRLSA as substrate after 1 to 2 hrs by chemiluminescence assay
Measurement: IC50 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 348.2, ALogP 2.9, HBA 4, HBD 2, PSA 70.92, QED 0.71
Compound (SMILES): CC(N)c1nc2c(oc3ccc(Br)cc32)c(=O)[nH]1
InChIKey: LGRJHSGKEBRDHI-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: Inhibition of N-terminus His-tagged human PIM1 expressed in Escherichia coli using AKRRRLSA as substrate after 1 to 2 hrs by chemiluminescence assay
Measurement: IC50 = 72 nM (pChEMBL 7.139999866485596)
Descriptors: MW 308.14, ALogP 2.45, HBA 4, HBD 2, PSA 84.91, QED 0.72
Compound (SMILES): CN1CCC[C@H]1c1nc2c(oc3ccc(Br)cc32)c(=O)[nH]1
InChIKey: BNLHKRKGCKUVHA-JTQLQIEISA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: Inhibition of N-terminus His-tagged human PIM1 expressed in Escherichia coli using AKRRRLSA as substrate after 1 to 2 hrs by chemiluminescence assay
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 348.2, ALogP 3.2, HBA 4, HBD 1, PSA 62.13, QED 0.73
Compound (SMILES): O=c1[nH]c([C@@H]2C[C@@H](O)CN2)nc2c1oc1ccc(Br)cc12
InChIKey: CNVDRXITZNMNTP-APPZFPTMSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: Inhibition of N-terminus His-tagged human PIM1 expressed in Escherichia coli using AKRRRLSA as substrate after 1 to 2 hrs by chemiluminescence assay
Measurement: IC50 = 73 nM (pChEMBL 7.139999866485596)
Descriptors: MW 350.17, ALogP 1.83, HBA 5, HBD 3, PSA 91.15, QED 0.62
Compound (SMILES): O=c1[nH]c([C@@H]2C[C@@H](F)CN2)nc2c1oc1ccc(Br)cc12
InChIKey: SCHVVSMHPGRYLE-APPZFPTMSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: Inhibition of N-terminus His-tagged human PIM1 expressed in Escherichia coli using AKRRRLSA as substrate after 1 to 2 hrs by chemiluminescence assay
Measurement: IC50 = 46 nM (pChEMBL 7.340000152587891)
Descriptors: MW 352.16, ALogP 2.8, HBA 4, HBD 2, PSA 70.92, QED 0.71
Compound (SMILES): O=c1[nH]c([C@@H]2C[C@H](F)CN2)nc2c1oc1ccc(Br)cc12
InChIKey: SCHVVSMHPGRYLE-CBAPKCEASA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: Inhibition of N-terminus His-tagged human PIM1 expressed in Escherichia coli using AKRRRLSA as substrate after 1 to 2 hrs by chemiluminescence assay
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 352.16, ALogP 2.8, HBA 4, HBD 2, PSA 70.92, QED 0.71
Compound (SMILES): O=c1[nH]c([C@@H]2CCCN2)nc2c1oc1ccc(Cl)cc12
InChIKey: JJWLXRKVUJDJKG-VIFPVBQESA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: Inhibition of N-terminus His-tagged human PIM1 expressed in Escherichia coli using AKRRRLSA as substrate after 1 to 2 hrs by chemiluminescence assay
Measurement: IC50 = 42 nM (pChEMBL 7.380000114440918)
Descriptors: MW 289.72, ALogP 2.75, HBA 4, HBD 2, PSA 70.92, QED 0.72
Compound (SMILES): COc1ccc2oc3c(=O)[nH]c([C@@H]4CCCN4)nc3c2c1
InChIKey: PSJHTNRKPOXZIN-JTQLQIEISA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: Inhibition of N-terminus His-tagged human PIM1 expressed in Escherichia coli using AKRRRLSA as substrate after 1 to 2 hrs by chemiluminescence assay
Measurement: IC50 = 77 nM (pChEMBL 7.110000133514404)
Descriptors: MW 285.3, ALogP 2.1, HBA 5, HBD 2, PSA 80.15, QED 0.75
Compound (SMILES): O=c1[nH]c([C@@H]2C[C@@H](F)CN2)nc2c1oc1ccc(Cl)cc12
InChIKey: ONHQPZWMSNCSPQ-APPZFPTMSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: Inhibition of N-terminus His-tagged human PIM1 expressed in Escherichia coli using AKRRRLSA as substrate after 1 to 2 hrs by chemiluminescence assay
Measurement: IC50 = 65 nM (pChEMBL 7.190000057220459)
Descriptors: MW 307.71, ALogP 2.7, HBA 4, HBD 2, PSA 70.92, QED 0.72
Compound (SMILES): COc1ccc2oc3c(=O)[nH]c([C@@H]4C[C@@H](F)CN4)nc3c2c1
InChIKey: FZIXDSBXXBDCIU-XCBNKYQSSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: Inhibition of N-terminus His-tagged human PIM1 expressed in Escherichia coli using AKRRRLSA as substrate after 1 to 2 hrs by chemiluminescence assay
Measurement: IC50 = 102 nM (pChEMBL 6.989999771118164)
Descriptors: MW 303.29, ALogP 2.05, HBA 5, HBD 2, PSA 80.15, QED 0.76
Compound (SMILES): CS(=O)(=O)Cc1cc(N2CCOCC2)nc(-c2ccc3[nH]ccc3c2)n1
InChIKey: CGCKKFFDYBVAMW-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of human recombinant PI3Kalpha expressed in baculovirus system using PI(4,5)P2 as substrate after 20 mins
Measurement: IC50 = 26300 nM (pChEMBL 4.579999923706055)
Descriptors: MW 372.45, ALogP 2.01, HBA 6, HBD 1, PSA 88.18, QED 0.75
Compound (SMILES): CS(=O)(=O)Cc1cc(N2CCOCC2)nc(-c2cccc3[nH]ccc23)n1
InChIKey: YXULRTVZRGHXHN-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Inhibition of recombinant FLAG-tagged mTOR kinase expressed in HEK293 cells using Biotin-Ahx-Lys-Lys-Ala-Asn-Gln-Val-Phe-Leu-Gly-Phe-Thr-Tyr-Val-Ala-Pro-Ser-Val-Leu-Glu-Ser-Val-Lys-Glu-NH2 as substrate after 90 mins
Measurement: IC50 = 1460 nM (pChEMBL 5.840000152587891)
Descriptors: MW 372.45, ALogP 2.01, HBA 6, HBD 1, PSA 88.18, QED 0.75
Compound (SMILES): CS(=O)(=O)Cc1cc(N2CCOCC2)nc(-c2ccc3[nH]cnc3c2)n1
InChIKey: FQGJJMJBPHPEQO-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Inhibition of recombinant FLAG-tagged mTOR kinase expressed in HEK293 cells using Biotin-Ahx-Lys-Lys-Ala-Asn-Gln-Val-Phe-Leu-Gly-Phe-Thr-Tyr-Val-Ala-Pro-Ser-Val-Leu-Glu-Ser-Val-Lys-Glu-NH2 as substrate after 90 mins
Measurement: IC50 = 285 nM (pChEMBL 6.539999961853027)
Descriptors: MW 373.44, ALogP 1.4, HBA 7, HBD 1, PSA 101.07, QED 0.74
Compound (SMILES): CS(=O)(=O)Cc1cc(N2CCOCC2)nc(-c2cnc3[nH]ccc3c2)n1
InChIKey: ZQAXZFDFIFNDJG-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Inhibition of recombinant FLAG-tagged mTOR kinase expressed in HEK293 cells using Biotin-Ahx-Lys-Lys-Ala-Asn-Gln-Val-Phe-Leu-Gly-Phe-Thr-Tyr-Val-Ala-Pro-Ser-Val-Leu-Glu-Ser-Val-Lys-Glu-NH2 as substrate after 90 mins
Measurement: IC50 = 262 nM (pChEMBL 6.579999923706055)
Descriptors: MW 373.44, ALogP 1.4, HBA 7, HBD 1, PSA 101.07, QED 0.74
Compound (SMILES): C[C@H]1COCCN1c1cc(CS(C)(=O)=O)nc(-c2ccc3[nH]ccc3c2)n1
InChIKey: XMHSFTLIAYTIQQ-ZDUSSCGKSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Inhibition of recombinant FLAG-tagged mTOR kinase expressed in HEK293 cells using Biotin-Ahx-Lys-Lys-Ala-Asn-Gln-Val-Phe-Leu-Gly-Phe-Thr-Tyr-Val-Ala-Pro-Ser-Val-Leu-Glu-Ser-Val-Lys-Glu-NH2 as substrate after 90 mins
Measurement: IC50 = 303 nM (pChEMBL 6.519999980926514)
Descriptors: MW 386.48, ALogP 2.39, HBA 6, HBD 1, PSA 88.18, QED 0.74
Compound (SMILES): CS(=O)(=O)Cc1cc(N2CC3CCC(C2)O3)nc(-c2ccc3[nH]ccc3c2)n1
InChIKey: WLUUEQZPBDKNPQ-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Inhibition of recombinant FLAG-tagged mTOR kinase expressed in HEK293 cells using Biotin-Ahx-Lys-Lys-Ala-Asn-Gln-Val-Phe-Leu-Gly-Phe-Thr-Tyr-Val-Ala-Pro-Ser-Val-Leu-Glu-Ser-Val-Lys-Glu-NH2 as substrate after 90 mins
Measurement: IC50 = 252 nM (pChEMBL 6.599999904632568)
Descriptors: MW 398.49, ALogP 2.54, HBA 6, HBD 1, PSA 88.18, QED 0.73
Compound (SMILES): CS(=O)(=O)Cc1cc(N2CCOCC2)nc(-c2ccc(NS(C)(=O)=O)cc2)n1
InChIKey: KDOUDNKSTLGXTR-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Inhibition of recombinant FLAG-tagged mTOR kinase expressed in HEK293 cells using Biotin-Ahx-Lys-Lys-Ala-Asn-Gln-Val-Phe-Leu-Gly-Phe-Thr-Tyr-Val-Ala-Pro-Ser-Val-Leu-Glu-Ser-Val-Lys-Glu-NH2 as substrate after 90 mins
Measurement: IC50 = 2600 nM (pChEMBL 5.579999923706055)
Descriptors: MW 426.52, ALogP 0.9, HBA 8, HBD 1, PSA 118.56, QED 0.72
Compound (SMILES): CS(=O)(=O)Cc1cc(N2CCOCC2)nc(NC(=O)c2ccno2)n1
InChIKey: PDUSMTDBBDWQRB-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Inhibition of recombinant FLAG-tagged mTOR kinase expressed in HEK293 cells using Biotin-Ahx-Lys-Lys-Ala-Asn-Gln-Val-Phe-Leu-Gly-Phe-Thr-Tyr-Val-Ala-Pro-Ser-Val-Leu-Glu-Ser-Val-Lys-Glu-NH2 as substrate after 90 mins
Measurement: IC50 = 37 nM (pChEMBL 7.429999828338623)
Descriptors: MW 367.39, ALogP 0.1, HBA 9, HBD 1, PSA 127.52, QED 0.78
Compound (SMILES): CS(=O)(=O)Cc1cc(N2CCOCC2)nc(-c2ccc(NC(=O)Nc3ccc(F)cc3)cc2)n1
InChIKey: CTTXJIASTBIXRL-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Inhibition of recombinant FLAG-tagged mTOR kinase expressed in HEK293 cells using Biotin-Ahx-Lys-Lys-Ala-Asn-Gln-Val-Phe-Leu-Gly-Phe-Thr-Tyr-Val-Ala-Pro-Ser-Val-Leu-Glu-Ser-Val-Lys-Glu-NH2 as substrate after 90 mins
Measurement: IC50 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 485.54, ALogP 3.31, HBA 7, HBD 2, PSA 113.52, QED 0.55
Compound (SMILES): CN1CCN(c2ccc(/C=C(\C#N)c3ccccc3Br)cc2)CC1
InChIKey: ZJMDTBBCNMGFMS-SAPNQHFASA-N
Target: Peroxisome proliferator-activated receptor delta (SINGLE PROTEIN), Homo sapiens
UniProt: Q03181
Assay: Binding affinity to GST-PPAR-beta/delta LBP (unknown origin) after 20 mins by TR-FRET assay
Measurement: IC50 = 29 nM (pChEMBL 7.539999961853027)
Descriptors: MW 382.31, ALogP 4.27, HBA 3, HBD 0, PSA 30.27, QED 0.59
Compound (SMILES): COc1ccc2cc(-c3nn(CC4CCNCC4)c4ncnc(N)c34)ccc2c1
InChIKey: MBHHJCMRPHUOAD-UHFFFAOYSA-N
Target: Calmodulin-domain protein kinase 1 (SINGLE PROTEIN), Toxoplasma gondii
UniProt: Q9BJF5
Assay: Biological Assay: Most known kinase inhibitors bind in the ATP-binding pocket of the active site19,20. These inhibitors exploit many of the same hydrophobic contacts as the purine ring of ATP and make at least one conserved hydrogen bond to the hinge region. Potent inhibitors also occupy at least one hydrophobic pocket adjacent to the ATP-binding site. These additional hydrophobic interactions increase both binding affinity and target selectivity of the inhibitor because there is substantial heterogeneity among different kinases in these regions. Examination of the TgCDPK1 sequence in the vicinity of the ATP-binding pocket (FIG. 2b ) shows that it contains a glycine residue at a position that has been termed the gatekeeper residue because it constrains access to the ATP-binding site21-23. The glycine at this position in TgCDPK1 (Gly128) is expected to create a much larger pocket off the ATP-binding site than is typically seen in protein kinases and comparison of the TgCDPK1 structure with other kinases shows that this is indeed the case. This difference in the active site architectures can be exploited for design of selective inhibitors against TgCDPK1.
Measurement: IC50 = 4.9 nM (pChEMBL 8.3100004196167)
Descriptors: MW 388.48, ALogP 3.24, HBA 7, HBD 2, PSA 90.88, QED 0.56
Compound (SMILES): CCOc1ccc2cc(-c3nn(CC4CCNCC4)c4ncnc(N)c34)ccc2c1
InChIKey: DLMBMHOJKBPKLK-UHFFFAOYSA-N
Target: Calcium-dependent protein kinase 4 (SINGLE PROTEIN), Plasmodium falciparum (isolate 3D7)
UniProt: Q8IBS5
Assay: Inhibition of CDPK4 in Plasmodium falciparum 3D7 microgametes
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 402.5, ALogP 3.63, HBA 7, HBD 2, PSA 90.88, QED 0.53
Compound (SMILES): Nc1ncnc2c1c(-c1cnc3ccccc3c1)nn2CC1CCNCC1
InChIKey: JSONRPFPVGYCOB-UHFFFAOYSA-N
Target: Calmodulin-domain protein kinase 1 (SINGLE PROTEIN), Toxoplasma gondii
UniProt: Q9BJF5
Assay: Biological Assay: Most known kinase inhibitors bind in the ATP-binding pocket of the active site19,20. These inhibitors exploit many of the same hydrophobic contacts as the purine ring of ATP and make at least one conserved hydrogen bond to the hinge region. Potent inhibitors also occupy at least one hydrophobic pocket adjacent to the ATP-binding site. These additional hydrophobic interactions increase both binding affinity and target selectivity of the inhibitor because there is substantial heterogeneity among different kinases in these regions. Examination of the TgCDPK1 sequence in the vicinity of the ATP-binding pocket (FIG. 2b ) shows that it contains a glycine residue at a position that has been termed the gatekeeper residue because it constrains access to the ATP-binding site21-23. The glycine at this position in TgCDPK1 (Gly128) is expected to create a much larger pocket off the ATP-binding site than is typically seen in protein kinases and comparison of the TgCDPK1 structure with other kinases shows that this is indeed the case. This difference in the active site architectures can be exploited for design of selective inhibitors against TgCDPK1.
Measurement: IC50 = 114 nM (pChEMBL 6.940000057220459)
Descriptors: MW 359.44, ALogP 2.62, HBA 7, HBD 2, PSA 94.54, QED 0.58
Compound (SMILES): CC(C)n1nc(-c2cc3c(Cl)cccc3[nH]2)c2c(N)ncnc21
InChIKey: XVLBYYUDKFJBBH-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: In vitro kinase assay: This assay is relatively simple, reasonably sensitive, and the peptide substrate can be adjusted both in terms of sequence and concentration to meet the assay requirements. Other exemplary kinase assays are detailed in U.S. Pat. No. 5,759,787 and U.S. application Ser. No. 12/728,926, both of which are incorporated herein by reference.
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 326.79, ALogP 3.79, HBA 5, HBD 2, PSA 85.41, QED 0.59
Compound (SMILES): COc1ccc(-c2nn(CC3CCNCC3)c3ncnc(N)c23)cc1C
InChIKey: MQULVMDBNSSIMR-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase Src (SINGLE PROTEIN), Homo sapiens
UniProt: P12931
Assay: Inhibition Assay: Inhibition of human tyrosine kinases.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 352.44, ALogP 2.39, HBA 7, HBD 2, PSA 90.88, QED 0.75
Compound (SMILES): Nc1ncnc2c1cnn2CC1CCNCC1
InChIKey: WIWYTHZSXOQVGK-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase Src (SINGLE PROTEIN), Homo sapiens
UniProt: P12931
Assay: Inhibition Assay: Inhibition of human tyrosine kinases.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 232.29, ALogP 0.41, HBA 6, HBD 2, PSA 81.65, QED 0.78
Compound (SMILES): Nc1nc2ccc(C(=O)c3ccccc3)cc2[nH]1
InChIKey: GPMHHSJZGVOEFS-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Inhibition of human ABL
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 237.26, ALogP 2.38, HBA 3, HBD 2, PSA 71.77, QED 0.67