lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=C(C1CCN(c2nccc(C(F)(F)F)n2)CC1)N1CC[C@H](N[C@H]2CC[C@@](O)(c3ccc(-c4ncccn4)cn3)CC2)C1
InChIKey: SPIFANYBQBPTEP-BOSRLCDASA-N
Target: C-C chemokine receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P41597
Assay: Antagonist activity at CCR2 receptor in human PBMC assessed as inhibition of MCP1-mediated leukocyte chemotaxis after 30 mins by microscopy
Measurement: IC50 = 4.3 nM (pChEMBL 8.369999885559082)
Descriptors: MW 596.66, ALogP 3.58, HBA 9, HBD 2, PSA 120.26, QED 0.44
Compound (SMILES): O=C(C1CCN(c2cc(C(F)(F)F)ncn2)CC1)N1CC[C@H](N[C@H]2CC[C@@](O)(c3ccc(-c4ncccn4)cn3)CC2)C1
InChIKey: SHJGPNCQJMRRNB-BOSRLCDASA-N
Target: C-C chemokine receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P41597
Assay: Displacement of [125I]MCP1 from human CCR2 in PBMC after 30 mins by gamma counting
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 596.66, ALogP 3.58, HBA 9, HBD 2, PSA 120.26, QED 0.44
Compound (SMILES): N#Cc1ccnc(N2CCC(C(=O)N3CC[C@H](N[C@H]4CC[C@@](O)(c5ccc(-c6ncccn6)cn5)CC4)C3)CC2)c1
InChIKey: IOTAVZSKYWFPSG-LNFMTQTQSA-N
Target: C-C chemokine receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P41597
Assay: Antagonist activity at CCR2 receptor in human PBMC assessed as inhibition of MCP1-mediated leukocyte chemotaxis after 30 mins by microscopy
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 552.68, ALogP 3.04, HBA 9, HBD 2, PSA 131.16, QED 0.47
Compound (SMILES): O=C(N1CC[C@H](N[C@H]2CC[C@@](O)(c3ccc(-c4ncccn4)cn3)CC2)C1)C1(O)CCN(c2cc(C(F)(F)F)ccn2)CC1
InChIKey: GGMJCJBGFPYRGS-MOMDTQCHSA-N
Target: C-C chemokine receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P41597
Assay: Antagonist activity at CCR2 receptor in human PBMC assessed as inhibition of MCP1-mediated leukocyte chemotaxis after 30 mins by microscopy
Measurement: IC50 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 611.67, ALogP 3.3, HBA 9, HBD 3, PSA 127.6, QED 0.38
Compound (SMILES): CN1CCCC[C@@H]1c1c(O)cc(O)c2c(=O)cc(-c3ccccc3)oc12
InChIKey: BBZGOLNDVQZCIH-CQSZACIVSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q63470
Assay: Inhibition of GST-tagged rat recombinant DYRK1A expressed in Escherichia coli using KKISGRLSPIMTEQ as substrate
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 351.4, ALogP 4.03, HBA 5, HBD 2, PSA 73.91, QED 0.73
Compound (SMILES): CN1CCCC[C@H]1c1c(O)cc(O)c2c(=O)cc(-c3ccccc3)oc12
InChIKey: BBZGOLNDVQZCIH-AWEZNQCLSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q63470
Assay: Inhibition of GST-tagged rat recombinant DYRK1A expressed in Escherichia coli using KKISGRLSPIMTEQ as substrate
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 351.4, ALogP 4.03, HBA 5, HBD 2, PSA 73.91, QED 0.73
Compound (SMILES): COc1cc(O)c(C2CCCCN2)c2oc(-c3ccccc3)cc(=O)c12
InChIKey: NCKUKESTUWVGFY-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q63470
Assay: Inhibition of GST-tagged rat recombinant DYRK1A expressed in Escherichia coli using KKISGRLSPIMTEQ as substrate
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 351.4, ALogP 3.99, HBA 5, HBD 2, PSA 71.7, QED 0.75
Compound (SMILES): CN1CCCC1c1c(O)cc(O)c2c(=O)cc(-c3ccccc3)oc12
InChIKey: YTRPTVLTUWVLKO-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q63470
Assay: Inhibition of GST-tagged rat recombinant DYRK1A expressed in Escherichia coli using KKISGRLSPIMTEQ as substrate
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 337.38, ALogP 3.64, HBA 5, HBD 2, PSA 73.91, QED 0.75
Compound (SMILES): CN1CCC[C@@H]1c1c(O)cc(O)c2c(=O)cc(-c3ccccc3)oc12
InChIKey: YTRPTVLTUWVLKO-CYBMUJFWSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q63470
Assay: Inhibition of GST-tagged rat recombinant DYRK1A expressed in Escherichia coli using KKISGRLSPIMTEQ as substrate
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 337.38, ALogP 3.64, HBA 5, HBD 2, PSA 73.91, QED 0.75
Compound (SMILES): CN1CCC[C@H]1c1c(O)cc(O)c2c(=O)cc(-c3ccccc3)oc12
InChIKey: YTRPTVLTUWVLKO-ZDUSSCGKSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q63470
Assay: Inhibition of GST-tagged rat recombinant DYRK1A expressed in Escherichia coli using KKISGRLSPIMTEQ as substrate
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 337.38, ALogP 3.64, HBA 5, HBD 2, PSA 73.91, QED 0.75
Compound (SMILES): O=c1cc(-c2ccccc2)oc2c(C3CCCN3)c(O)cc(O)c12
InChIKey: QFAVABBJYSVONF-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q63470
Assay: Inhibition of GST-tagged rat recombinant DYRK1A expressed in Escherichia coli using KKISGRLSPIMTEQ as substrate
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 323.35, ALogP 3.3, HBA 5, HBD 3, PSA 82.7, QED 0.67
Compound (SMILES): CCCCCC(NC)c1c(O)cc(O)c2c(=O)cc(-c3ccccc3)oc12
InChIKey: NUPCRABGLYUOME-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q63470
Assay: Inhibition of GST-tagged rat recombinant DYRK1A expressed in Escherichia coli using KKISGRLSPIMTEQ as substrate
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 367.45, ALogP 4.71, HBA 5, HBD 3, PSA 82.7, QED 0.53
Compound (SMILES): CCCCC[C@@H](NC)c1c(O)cc(O)c2c(=O)cc(-c3ccccc3)oc12
InChIKey: NUPCRABGLYUOME-OAHLLOKOSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q63470
Assay: Inhibition of GST-tagged rat recombinant DYRK1A expressed in Escherichia coli using KKISGRLSPIMTEQ as substrate
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 367.45, ALogP 4.71, HBA 5, HBD 3, PSA 82.7, QED 0.53
Compound (SMILES): CCCCC[C@H](NC)c1c(O)cc(O)c2c(=O)cc(-c3ccccc3)oc12
InChIKey: NUPCRABGLYUOME-HNNXBMFYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q63470
Assay: Inhibition of GST-tagged rat recombinant DYRK1A expressed in Escherichia coli using KKISGRLSPIMTEQ as substrate
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 367.45, ALogP 4.71, HBA 5, HBD 3, PSA 82.7, QED 0.53
Compound (SMILES): COCCOc1cnc2ccc([C@H](C)n3nnc4ccn(-c5cc(C)ns5)c(=O)c43)cc2c1
InChIKey: ACDVIHRBYWUYPZ-HNNXBMFYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) in absence of NADPH
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 462.54, ALogP 3.53, HBA 10, HBD 0, PSA 96.95, QED 0.34
Compound (SMILES): CN(CCCC(=O)NC1CC1)C(=O)c1ccc2c(c1)c1c(n2C)CCC(C2CCOCC2)C1
InChIKey: FLWYTHWMIDUSGM-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 > 33000 nM (pChEMBL 4.480999946594238)
Descriptors: MW 451.61, ALogP 3.84, HBA 4, HBD 1, PSA 63.57, QED 0.7
Compound (SMILES): CCN(CCCC(=O)NC1CC1)C(=O)c1ccc2c(c1)c1c(n2C)CCC(C2CCOCC2)C1
InChIKey: DNVTUOZKJXLMMC-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 > 33000 nM (pChEMBL 4.480999946594238)
Descriptors: MW 465.64, ALogP 4.23, HBA 4, HBD 1, PSA 63.57, QED 0.63
Compound (SMILES): CN(CC(=O)NC1CC1)C(=O)c1ccc2c(c1)c1c(n2C)CCC(C2CCOCC2)C1
InChIKey: LBJXQEHAPRESNJ-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Displacement of [3H]CP55940 from human CB1 receptor expressed in HEK293 cells
Measurement: Ki = 44.5 nM (pChEMBL 7.349999904632568)
Descriptors: MW 423.56, ALogP 3.06, HBA 4, HBD 1, PSA 63.57, QED 0.8
Compound (SMILES): CCN(CC(=O)NC1CC1)C(=O)c1ccc2c(c1)c1c(n2C)CCC(C2CCOCC2)C1
InChIKey: MAAGUWONZDCLSO-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 > 33000 nM (pChEMBL 4.480999946594238)
Descriptors: MW 437.58, ALogP 3.45, HBA 4, HBD 1, PSA 63.57, QED 0.75
Compound (SMILES): CNC(=O)CCCN(C)C(=O)c1ccc2c(c1)c1c(n2C)CCC(C2CCOCC2)C1
InChIKey: LYYAOAAEQUTERQ-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 > 33000 nM (pChEMBL 4.480999946594238)
Descriptors: MW 425.57, ALogP 3.31, HBA 4, HBD 1, PSA 63.57, QED 0.77
Compound (SMILES): CN(CC(=O)NC1CC1)C(=O)c1ccc2c(c1)c1c(n2C)CC[C@@H](C2CCOCC2)C1
InChIKey: LBJXQEHAPRESNJ-QGZVFWFLSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Displacement of [3H]CP55940 from human CB1 receptor expressed in HEK293 cells
Measurement: Ki = 24.5 nM (pChEMBL 7.610000133514404)
Descriptors: MW 423.56, ALogP 3.06, HBA 4, HBD 1, PSA 63.57, QED 0.8
Compound (SMILES): CN(CC(=O)NC1CC1)C(=O)c1ccc2c(c1)c1c(n2C)CC[C@H](C2CCOCC2)C1
InChIKey: LBJXQEHAPRESNJ-KRWDZBQOSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Displacement of [3H]CP55940 from human CB1 receptor expressed in HEK293 cells
Measurement: Ki = 177 nM (pChEMBL 6.75)
Descriptors: MW 423.56, ALogP 3.06, HBA 4, HBD 1, PSA 63.57, QED 0.8
Compound (SMILES): CNC(=O)CCCN(C)C(=O)c1ccc2c(c1)c1c(n2C)CC[C@@H](C2CCOCC2)C1
InChIKey: LYYAOAAEQUTERQ-GOSISDBHSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Agonist activity at human CB1 receptor expressed in HEK293 cells assessed as [35S]GTPgamma binding
Measurement: EC50 = 51.4 nM (pChEMBL 7.289999961853027)
Descriptors: MW 425.57, ALogP 3.31, HBA 4, HBD 1, PSA 63.57, QED 0.77
Compound (SMILES): COc1ccc(/C=C2\SC(c3ccc4ccccc4c3)=NC2=O)cc1
InChIKey: JQWPSUIXKSIMCL-UNOMPAQXSA-N
Target: Polyunsaturated fatty acid 5-lipoxygenase (SINGLE PROTEIN), Rattus norvegicus
UniProt: P12527
Assay: Inhibition of rat 5-LOX expressed in insect sf21 cells preincubated for 4 mins followed by Arachidonic acid addition and measured after 4 mins by FOX assay
Measurement: IC50 = 127 nM (pChEMBL 6.900000095367432)
Descriptors: MW 345.42, ALogP 4.91, HBA 3, HBD 0, PSA 38.66, QED 0.63
Compound (SMILES): COc1ccc(/C(C)=C2\SC(c3ccc(C)cc3)=NC2=O)cc1
InChIKey: YKGPOYMRORJVEM-LGMDPLHJSA-N
Target: Polyunsaturated fatty acid 5-lipoxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P09917
Assay: Inhibition of 5-LO in human PMNL S100 extract using arachidonic acid as substrate incubated for 15 mins prior to substrate addition measured after 10 mins by HPLC analysis
Measurement: IC50 = 1970 nM (pChEMBL 5.710000038146973)
Descriptors: MW 323.42, ALogP 4.45, HBA 3, HBD 0, PSA 38.66, QED 0.78
Compound (SMILES): CN1CCN(C(=O)c2cc(Nc3ncc4cc(/C=N/O)n(C5CCCC5)c4n3)cn2C)CC1
InChIKey: FGLDVWQEBUVALV-AFUMVMLFSA-N
Target: Cyclin-dependent kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P06493
Assay: Inhibition of CDK1
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 450.55, ALogP 2.82, HBA 9, HBD 2, PSA 103.81, QED 0.35
Compound (SMILES): CN1CCN(C(=O)c2cc(Nc3ncc4cc(C#N)n(C5CCCC5)c4n3)cn2C)CC1
InChIKey: QJOLFMLQXIPTTF-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P06493
Assay: Inhibition of CDK1
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 432.53, ALogP 2.89, HBA 8, HBD 1, PSA 95.01, QED 0.68
Compound (SMILES): CN1CCN(C(=O)c2cc(Nc3ncc4ccn(C5CCCC5)c4n3)cn2C)CC1
InChIKey: CGEOTWGXFRJZLW-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P06493
Assay: Inhibition of CDK1
Measurement: IC50 = 240 nM (pChEMBL 6.619999885559082)
Descriptors: MW 407.52, ALogP 3.02, HBA 7, HBD 1, PSA 71.22, QED 0.72
Compound (SMILES): CN1CCN(C(=O)c2cc(Nc3ncc4cc(C(N)=O)n(C5CCCC5)c4n3)cn2C)CC1
InChIKey: CXCXNZWXDOVZBA-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P06493
Assay: Inhibition of CDK1
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 450.55, ALogP 2.12, HBA 8, HBD 2, PSA 114.31, QED 0.62
Compound (SMILES): CNCc1cc2cnc(Nc3cc(C(=O)N4CCN(C)CC4)n(C)c3)nc2n1C1CCCC1
InChIKey: VCLDLBGMMXCQJL-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P06493
Assay: Inhibition of CDK1
Measurement: IC50 = 700 nM (pChEMBL 6.159999847412109)
Descriptors: MW 450.59, ALogP 2.74, HBA 8, HBD 2, PSA 83.25, QED 0.6
Compound (SMILES): CC(O)c1cc2cnc(Nc3cc(C(=O)N4CCN(C)CC4)n(C)c3)nc2n1C1CCCC1
InChIKey: JZAIDLUIAGRFMY-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P06493
Assay: Inhibition of CDK1
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 451.58, ALogP 3.07, HBA 8, HBD 2, PSA 91.45, QED 0.62
Compound (SMILES): CN1CCN(C(=O)c2cc(Nc3ncc4cc(CO)n(C5CCCC5)c4n3)cn2C)CC1
InChIKey: FGBBAYDBFFBOCR-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P06493
Assay: Inhibition of CDK1
Measurement: IC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 437.55, ALogP 2.51, HBA 8, HBD 2, PSA 91.45, QED 0.64
Compound (SMILES): CN1CCN(C(=O)c2cc(Nc3ncc4cc(C(=O)O)n(C5CCCC5)c4n3)cn2C)CC1
InChIKey: RRNINKNJSOMCSD-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P06493
Assay: Inhibition of CDK1
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 451.53, ALogP 2.71, HBA 8, HBD 2, PSA 108.52, QED 0.61
Compound (SMILES): CN1CCN(C(=O)c2cc(Nc3ncc4cc(-c5cnco5)n(C5CCCC5)c4n3)cn2C)CC1
InChIKey: PSWIPMICOQJHRP-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P06493
Assay: Inhibition of CDK1
Measurement: IC50 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 474.57, ALogP 3.67, HBA 9, HBD 1, PSA 97.25, QED 0.47
Compound (SMILES): CN1CCN(C(=O)c2cc(Nc3ncc4cc(-c5cnn(C)c5)n(C5CCCC5)c4n3)cn2C)CC1
InChIKey: WKKLEERAKHQFTN-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P06493
Assay: Inhibition of CDK1
Measurement: IC50 = 180 nM (pChEMBL 6.75)
Descriptors: MW 487.61, ALogP 3.42, HBA 9, HBD 1, PSA 89.04, QED 0.46
Compound (SMILES): CN1CCN(C(=O)c2cc(Nc3ncc4cc(-c5cncn5C)n(C5CCCC5)c4n3)cn2C)CC1
InChIKey: SYZBPKURKLVKGY-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P06493
Assay: Inhibition of CDK1
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 487.61, ALogP 3.42, HBA 9, HBD 1, PSA 89.04, QED 0.46
Compound (SMILES): Cc1c(-c2cc3cnc(Nc4cc(C(=O)N5CCN(C)CC5)n(C)c4)nc3n2C2CCCC2)cnn1C
InChIKey: HCDXOVUMIOIELK-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P06493
Assay: Inhibition of CDK1
Measurement: IC50 = 330 nM (pChEMBL 6.480000019073486)
Descriptors: MW 501.64, ALogP 3.73, HBA 9, HBD 1, PSA 89.04, QED 0.45
Compound (SMILES): CC(C)CCn1cc(-c2cc3cnc(Nc4cc(C(=O)N5CCN(C)CC5)n(C)c4)nc3n2C2CCCC2)cn1
InChIKey: LLSACPYCBRAUIJ-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P06493
Assay: Inhibition of CDK1
Measurement: IC50 = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 543.72, ALogP 4.93, HBA 9, HBD 1, PSA 89.04, QED 0.34
Compound (SMILES): CN1CCN(C(=O)c2cc(Nc3ncc4cc(-c5ccnn5C)n(C5CCCC5)c4n3)cn2C)CC1
InChIKey: NDJAPUTXCKBOMQ-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P06493
Assay: Inhibition of CDK1
Measurement: IC50 = 1700 nM (pChEMBL 5.769999980926514)
Descriptors: MW 487.61, ALogP 3.42, HBA 9, HBD 1, PSA 89.04, QED 0.46
Compound (SMILES): CN1CCN(C(=O)c2cc(Nc3ncc4cc(-c5cnn(Cc6ccccc6)c5)n(C5CCCC5)c4n3)cn2C)CC1
InChIKey: ZNZJOKVVRNTGRH-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P06493
Assay: Inhibition of CDK1
Measurement: IC50 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 563.71, ALogP 4.93, HBA 9, HBD 1, PSA 89.04, QED 0.3
Compound (SMILES): COc1cc2ncnc(Oc3cccc(NC(=O)Nc4cnn(C(C)(C)C)c4)c3)c2cc1OC
InChIKey: IFXAOWUQOMSUJO-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 = 375 nM (pChEMBL 6.429999828338623)
Descriptors: MW 462.51, ALogP 5.03, HBA 8, HBD 2, PSA 112.42, QED 0.41
Compound (SMILES): COc1cc2ncnc(Oc3cccc(NC(=O)Nc4cc(C(C)(C)C)nn4C)c3)c2cc1OC
InChIKey: PKTRVWCEEGNMJB-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 476.54, ALogP 5.11, HBA 8, HBD 2, PSA 112.42, QED 0.4
Compound (SMILES): COc1cc2ncnc(Oc3cccc(NC(=O)Nc4cc(C(C)C)on4)c3)c2cc1OC
InChIKey: YYHBORBBLVUAAA-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 449.47, ALogP 5.19, HBA 8, HBD 2, PSA 120.63, QED 0.4
Compound (SMILES): COc1cc2ncnc(Oc3cccc(NC(=O)Nc4cc(C5CCCC5)on4)c3)c2cc1OC
InChIKey: WHQDMUQAOKWQGJ-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 475.51, ALogP 5.73, HBA 8, HBD 2, PSA 120.63, QED 0.35
Compound (SMILES): COc1cc2ncnc(Oc3cccc(NC(=O)Nc4cc(-c5ccccc5)on4)c3)c2cc1OC
InChIKey: LAMMEOXIKPNJPT-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 = 375 nM (pChEMBL 6.429999828338623)
Descriptors: MW 483.48, ALogP 5.74, HBA 8, HBD 2, PSA 120.63, QED 0.3
Compound (SMILES): COc1cc2ncnc(Oc3cccc(NC(=O)Nc4cc(C(C)C)no4)c3)c2cc1OC
InChIKey: IJFYJRITYUFHIZ-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 449.47, ALogP 5.19, HBA 8, HBD 2, PSA 120.63, QED 0.4
Compound (SMILES): COc1cc2ncnc(Oc3cccc(NC(=O)Nc4cc(C5CCCC5)no4)c3)c2cc1OC
InChIKey: BZQXAZQNWLIEIY-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 = 375 nM (pChEMBL 6.429999828338623)
Descriptors: MW 475.51, ALogP 5.73, HBA 8, HBD 2, PSA 120.63, QED 0.35
Compound (SMILES): COc1cc2ncnc(Oc3cccc(NC(=O)Nc4cc(C(C)(C)CO)on4)c3)c2cc1OC
InChIKey: IAGGRHWCYNZTRO-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 479.49, ALogP 4.34, HBA 9, HBD 3, PSA 140.86, QED 0.34
Compound (SMILES): COCC(C)(C)c1cc(NC(=O)Nc2cccc(Oc3ncnc4cc(OC)c(OC)cc34)c2)no1
InChIKey: TXDAURYRIAGJTB-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 = 375 nM (pChEMBL 6.429999828338623)
Descriptors: MW 493.52, ALogP 5, HBA 9, HBD 2, PSA 129.86, QED 0.33
Compound (SMILES): COc1cc2ncnc(Oc3cccc(NC(=O)Nc4cc(C(F)(F)F)no4)c3)c2cc1OC
InChIKey: YHZIGQSQXNNOCU-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 475.38, ALogP 5.09, HBA 8, HBD 2, PSA 120.63, QED 0.4
Compound (SMILES): COc1cc2ncnc(Oc3cccc(NC(=O)Nc4cc(C(C)(F)F)no4)c3)c2cc1OC
InChIKey: JBERXKFWRMHYGJ-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 471.42, ALogP 5.18, HBA 8, HBD 2, PSA 120.63, QED 0.38
Compound (SMILES): COc1cc2ncnc(Oc3cccc(NC(=O)Nc4cc(C(C)(CF)CF)no4)c3)c2cc1OC
InChIKey: GWKRUFQUNYAAIW-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 = 375 nM (pChEMBL 6.429999828338623)
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)no4)c3)c2cc1OC
InChIKey: XBOWKGDSLPGIEK-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 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)CCC5)no4)c3)c2cc1OC
InChIKey: BRQZEGWSBNNJQR-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 = 375 nM (pChEMBL 6.429999828338623)
Descriptors: MW 529.48, ALogP 6.06, HBA 8, HBD 2, PSA 120.63, QED 0.3