lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CCNC(=O)Nc1ccc2ncc(Nc3ccc(F)cc3)nc2n1
InChIKey: FIHFDFLGUOPQCN-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 326.34, ALogP 3.05, HBA 5, HBD 3, PSA 91.83, QED 0.69
Compound (SMILES): COc1cc(-c2cnc3ccc(NC(=O)NCCCCO)nc3n2)ccc1O
InChIKey: DCTSFNQDKNOVNW-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 383.41, ALogP 2.3, HBA 7, HBD 4, PSA 129.49, QED 0.46
Compound (SMILES): CCNC(=O)Nc1ccc2ncc(-c3ccc(O)cc3Cl)nc2n1
InChIKey: MWVGADULZNNNBD-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 > 31600 nM (pChEMBL 4.5)
Descriptors: MW 343.77, ALogP 3.19, HBA 5, HBD 3, PSA 100.03, QED 0.68
Compound (SMILES): CCNC(=O)Nc1ccc2ncc(-c3ccc(Cl)cc3OC)nc2n1
InChIKey: FEWYNEPNJCINKR-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 357.8, ALogP 3.5, HBA 5, HBD 2, PSA 89.03, QED 0.75
Compound (SMILES): CCNC(=O)Nc1ccc2ncc(-c3c(C)n[nH]c3C)nc2n1
InChIKey: QNCYYKDYYZCTLG-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 311.35, ALogP 2.17, HBA 5, HBD 3, PSA 108.48, QED 0.69
Compound (SMILES): CCNC(=O)Nc1ccc2ncc(-c3cnn(C)c3)nc2n1
InChIKey: XJIYEGGCGUIRCS-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 297.32, ALogP 1.57, HBA 6, HBD 2, PSA 97.62, QED 0.76
Compound (SMILES): CCNC(=O)Nc1ccc2ncc(-c3ccc(C#N)s3)nc2n1
InChIKey: RWXDBJGWZRCTGV-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 > 31600 nM (pChEMBL 4.5)
Descriptors: MW 324.37, ALogP 2.77, HBA 6, HBD 2, PSA 103.59, QED 0.77
Compound (SMILES): CCNC(=O)Nc1ccc2ncc(Nc3ccc(OC)c(Cl)c3)nc2n1
InChIKey: KJGDMGQFNHYEJL-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 372.82, ALogP 3.57, HBA 6, HBD 3, PSA 101.06, QED 0.63
Compound (SMILES): CCNC(=O)Nc1ccc2ncc(Nc3cnc4ccccc4c3)nc2n1
InChIKey: GTXHPXZGOMSYCS-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 359.39, ALogP 3.46, HBA 6, HBD 3, PSA 104.72, QED 0.52
Compound (SMILES): CCNC(=O)Nc1ccc2ncc(Nc3cc(OC)cc(OC)c3)nc2n1
InChIKey: ZOQMIVJPGLELME-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 368.4, ALogP 2.93, HBA 7, HBD 3, PSA 110.29, QED 0.61
Compound (SMILES): CCNC(=O)Nc1ccc2ncc(Nc3cnccn3)nc2n1
InChIKey: PKTVDIKAWBOBHE-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 310.32, ALogP 1.7, HBA 7, HBD 3, PSA 117.61, QED 0.67
Compound (SMILES): CCNC(=O)Nc1ccc2ncc(Nc3cccc(OC(C)C)c3)nc2n1
InChIKey: QMIOTVIVFHJLRE-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 366.43, ALogP 3.7, HBA 6, HBD 3, PSA 101.06, QED 0.61
Compound (SMILES): CCNC(=O)Nc1ccc2ncc(-c3ccc(OS(=O)(=O)c4ccc(C)cc4)c(OC)c3)nc2n1
InChIKey: JADAOPXXHHTXCZ-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 493.55, ALogP 3.92, HBA 8, HBD 2, PSA 132.4, QED 0.37
Compound (SMILES): CCNC(=O)Nc1ccc2ncc(Nc3ccnc(Cl)c3)nc2n1
InChIKey: YSHFKPDXFMRJNK-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 343.78, ALogP 2.96, HBA 6, HBD 3, PSA 104.72, QED 0.63
Compound (SMILES): CCNC(=O)Nc1ccc2ncc(Nc3cc(Cl)c(O)c(Cl)c3)nc2n1
InChIKey: AZVLCPRJRHUTLO-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 393.23, ALogP 3.92, HBA 6, HBD 4, PSA 112.06, QED 0.5
Compound (SMILES): CCNC(=O)Nc1ccc2ncc(-c3cc(Cl)c(O)c(Cl)c3)nc2n1
InChIKey: CXBHFFRYCQDYJB-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 378.22, ALogP 3.85, HBA 5, HBD 3, PSA 100.03, QED 0.64
Compound (SMILES): CCNC(=O)Nc1ccc2ncc(Nc3ccc(OC)c(OC)c3)nc2n1
InChIKey: DRWFTIUSLYCJRC-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 > 31600 nM (pChEMBL 4.5)
Descriptors: MW 368.4, ALogP 2.93, HBA 7, HBD 3, PSA 110.29, QED 0.61
Compound (SMILES): CCNC(=O)Nc1ccc2ncc(Nc3ccc(C)c(O)c3)nc2n1
InChIKey: MSCFAGPRQLSBAA-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 338.37, ALogP 2.92, HBA 6, HBD 4, PSA 112.06, QED 0.58
Compound (SMILES): CCNC(=O)Nc1ccc2ncc(Nc3cc(C(=O)O)cc(C(F)(F)F)c3)nc2n1
InChIKey: MCCZLWHAVAVRTO-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 420.35, ALogP 3.63, HBA 6, HBD 4, PSA 129.13, QED 0.5
Compound (SMILES): CCNC(=O)Nc1ccc2ncc(Nc3ccc(OC)nc3)nc2n1
InChIKey: JKSSXRZOJWLBOS-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 339.36, ALogP 2.31, HBA 7, HBD 3, PSA 113.95, QED 0.65
Compound (SMILES): CCNC(=O)Nc1ccc2ncc(Nc3ccc(C#N)cc3)nc2n1
InChIKey: PBZPXOYARLLVNE-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 333.36, ALogP 2.78, HBA 6, HBD 3, PSA 115.62, QED 0.68
Compound (SMILES): CCNC(=O)Nc1ccc2ncc(-c3cccc(O)c3)nc2n1
InChIKey: NPDDZRHJDIJGFY-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 309.33, ALogP 2.54, HBA 5, HBD 3, PSA 100.03, QED 0.69
Compound (SMILES): CCNC(=O)Nc1ccc2ncc(Nc3cccc(C)c3)nc2n1
InChIKey: XJSUNTWILGRFNF-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 322.37, ALogP 3.22, HBA 5, HBD 3, PSA 91.83, QED 0.69
Compound (SMILES): CCNC(=O)Nc1ccc2ncc(Nc3ccccc3C)nc2n1
InChIKey: LQWYBBIRQIJRMB-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 > 31600 nM (pChEMBL 4.5)
Descriptors: MW 322.37, ALogP 3.22, HBA 5, HBD 3, PSA 91.83, QED 0.69
Compound (SMILES): CCNC(=O)Nc1ccc2ncc(-c3ccc(OP(=O)(O)O)c(OC)c3)nc2n1
InChIKey: NYHXXAIWIWSJLZ-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 419.33, ALogP 2.31, HBA 7, HBD 4, PSA 155.79, QED 0.44
Compound (SMILES): CCNC(=O)Nc1ccc2ncc(-c3cc(Cl)c(O)c(OC)c3)nc2n1
InChIKey: CJANMZPZNNYAPL-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 373.8, ALogP 3.2, HBA 6, HBD 3, PSA 109.26, QED 0.65
Compound (SMILES): CCNC(=O)Nc1ccc2ncc(Nc3ccc4ccccc4c3)nc2n1
InChIKey: FGXVXHYSQPGYKL-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 > 31600 nM (pChEMBL 4.5)
Descriptors: MW 358.41, ALogP 4.06, HBA 5, HBD 3, PSA 91.83, QED 0.51
Compound (SMILES): CCNC(=O)Nc1ccc2ncc(-c3ccc(O)c(OC)c3)nc2n1
InChIKey: OVGNDEJGXTVQKL-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 339.36, ALogP 2.55, HBA 6, HBD 3, PSA 109.26, QED 0.67
Compound (SMILES): NC(=O)CN1C[C@H]2[C@H]3Cc4ccc(O)cc4[C@@]2(CCN3CC2CC2)CC1=O
InChIKey: LYLWKMFSKRHION-WAOWUJCRSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Radioligand Dose-Displacement Binding Assay: Radioligand dose-displacement binding assays for u-opioid receptors used 0.3 nM [3H]-diprenorphine (Perkin Elmer, Shelton, Conn.), with 5 mg membrane protein/well in a final volume of 500 ul binding buffer (10 mM MgCl2, 1 mM EDTA, 5% DMSO, 50 mM HEPES, pH 7.4). Reactions were carried out in the absence or presence of increasing concentrations of unlabeled naloxone. All reactions were conducted in 96-deep well polypropylene plates for 2 hours at room temperature. Binding reactions were terminated by rapid filtration onto 96-well Unifilter GF/C filter plates (Perkin Elmer, Shelton, Conn.), presoaked in 0.5% polyethylenimine using a 96-well tissue harvester (Perkin Elmer, Shelton, Conn.) followed by performing three filtration washes with 500 ul of ice-cold binding buffer. Filter plates were subsequently dried at 50 C. for 2-3 hours. BetaScint scintillation cocktail (Perkin Elmer, Shelton, Conn.) was added (50 ul/well), and plates were counted using a Packard Top-Counter.
Measurement: Ki = 24.41 nM (pChEMBL 7.610000133514404)
Descriptors: MW 369.47, ALogP 1, HBA 4, HBD 2, PSA 86.87, QED 0.83
Compound (SMILES): O=C1C[C@]23CCN(CC4CC4)[C@H](Cc4ccc(O)cc42)[C@@H]3CN1Cc1ccc(O)cc1
InChIKey: UYSYZXYBTLVRLE-BFLUCZKCSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Radioligand Dose-Displacement Binding Assay: Radioligand dose-displacement binding assays for u-opioid receptors used 0.3 nM [3H]-diprenorphine (Perkin Elmer, Shelton, Conn.), with 5 mg membrane protein/well in a final volume of 500 ul binding buffer (10 mM MgCl2, 1 mM EDTA, 5% DMSO, 50 mM HEPES, pH 7.4). Reactions were carried out in the absence or presence of increasing concentrations of unlabeled naloxone. All reactions were conducted in 96-deep well polypropylene plates for 2 hours at room temperature. Binding reactions were terminated by rapid filtration onto 96-well Unifilter GF/C filter plates (Perkin Elmer, Shelton, Conn.), presoaked in 0.5% polyethylenimine using a 96-well tissue harvester (Perkin Elmer, Shelton, Conn.) followed by performing three filtration washes with 500 ul of ice-cold binding buffer. Filter plates were subsequently dried at 50 C. for 2-3 hours. BetaScint scintillation cocktail (Perkin Elmer, Shelton, Conn.) was added (50 ul/well), and plates were counted using a Packard Top-Counter.
Measurement: Ki = 22.92 nM (pChEMBL 7.639999866485596)
Descriptors: MW 418.54, ALogP 3.42, HBA 4, HBD 2, PSA 64.01, QED 0.8
Compound (SMILES): O=C1C[C@]23CCN(CC4CC4)[C@H](Cc4ccc(O)cc42)[C@@H]3CN1
InChIKey: XYEIPZFSMVUKKD-YQVWRLOYSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Radioligand Dose-Displacement Binding Assay: Radioligand dose-displacement binding assays for u-opioid receptors used 0.3 nM [3H]-diprenorphine (Perkin Elmer, Shelton, Conn.), with 5 mg membrane protein/well in a final volume of 500 ul binding buffer (10 mM MgCl2, 1 mM EDTA, 5% DMSO, 50 mM HEPES, pH 7.4). Reactions were carried out in the absence or presence of increasing concentrations of unlabeled naloxone. All reactions were conducted in 96-deep well polypropylene plates for 2 hours at room temperature. Binding reactions were terminated by rapid filtration onto 96-well Unifilter GF/C filter plates (Perkin Elmer, Shelton, Conn.), presoaked in 0.5% polyethylenimine using a 96-well tissue harvester (Perkin Elmer, Shelton, Conn.) followed by performing three filtration washes with 500 ul of ice-cold binding buffer. Filter plates were subsequently dried at 50 C. for 2-3 hours. BetaScint scintillation cocktail (Perkin Elmer, Shelton, Conn.) was added (50 ul/well), and plates were counted using a Packard Top-Counter.
Measurement: Ki = 5.61 nM (pChEMBL 8.25)
Descriptors: MW 312.41, ALogP 1.81, HBA 3, HBD 2, PSA 52.57, QED 0.88
Compound (SMILES): O=C(O)CN1C[C@H]2[C@H]3Cc4ccc(O)cc4[C@@]2(CCN3CC2CC2)CC1=O
InChIKey: OEEAMJRZEPDTTK-WAOWUJCRSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Radioligand Dose-Displacement Binding Assay: Radioligand dose-displacement binding assays for u-opioid receptors used 0.3 nM [3H]-diprenorphine (Perkin Elmer, Shelton, Conn.), with 5 mg membrane protein/well in a final volume of 500 ul binding buffer (10 mM MgCl2, 1 mM EDTA, 5% DMSO, 50 mM HEPES, pH 7.4). Reactions were carried out in the absence or presence of increasing concentrations of unlabeled naloxone. All reactions were conducted in 96-deep well polypropylene plates for 2 hours at room temperature. Binding reactions were terminated by rapid filtration onto 96-well Unifilter GF/C filter plates (Perkin Elmer, Shelton, Conn.), presoaked in 0.5% polyethylenimine using a 96-well tissue harvester (Perkin Elmer, Shelton, Conn.) followed by performing three filtration washes with 500 ul of ice-cold binding buffer. Filter plates were subsequently dried at 50 C. for 2-3 hours. BetaScint scintillation cocktail (Perkin Elmer, Shelton, Conn.) was added (50 ul/well), and plates were counted using a Packard Top-Counter.
Measurement: Ki = 4.03 nM (pChEMBL 8.390000343322754)
Descriptors: MW 370.45, ALogP 1.6, HBA 4, HBD 2, PSA 81.08, QED 0.84
Compound (SMILES): Oc1ccc2c(c1)[C@@]13CCNC[C@H]1[C@@H](C2)N(CC1CC1)CC3
InChIKey: NAYWQSXUMUNQOO-OTWHNJEPSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Radioligand Dose-Displacement Binding Assay: Radioligand dose-displacement binding assays for u-opioid receptors used 0.3 nM [3H]-diprenorphine (Perkin Elmer, Shelton, Conn.), with 5 mg membrane protein/well in a final volume of 500 ul binding buffer (10 mM MgCl2, 1 mM EDTA, 5% DMSO, 50 mM HEPES, pH 7.4). Reactions were carried out in the absence or presence of increasing concentrations of unlabeled naloxone. All reactions were conducted in 96-deep well polypropylene plates for 2 hours at room temperature. Binding reactions were terminated by rapid filtration onto 96-well Unifilter GF/C filter plates (Perkin Elmer, Shelton, Conn.), presoaked in 0.5% polyethylenimine using a 96-well tissue harvester (Perkin Elmer, Shelton, Conn.) followed by performing three filtration washes with 500 ul of ice-cold binding buffer. Filter plates were subsequently dried at 50 C. for 2-3 hours. BetaScint scintillation cocktail (Perkin Elmer, Shelton, Conn.) was added (50 ul/well), and plates were counted using a Packard Top-Counter.
Measurement: Ki = 50.42 nM (pChEMBL 7.300000190734863)
Descriptors: MW 298.43, ALogP 2.28, HBA 3, HBD 2, PSA 35.5, QED 0.88
Compound (SMILES): Cn1cc(CNc2cc(OC[C@H]3C[C@@H]3c3ccccn3)nc3ccnn23)cn1
InChIKey: YLPZTDCVMOWRPZ-CVEARBPZSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Inhibition of PDE10A (unknown origin) by IMAP assay
Measurement: Ki = 0.23 nM (pChEMBL 9.640000343322754)
Descriptors: MW 375.44, ALogP 2.65, HBA 8, HBD 1, PSA 82.16, QED 0.53
Compound (SMILES): Cc1c(C)n(Cc2ccc(-c3ccccc3C(=O)O)cc2)c2ccc(C(=O)N[C@H](C)c3ccc(Br)cc3)cc12
InChIKey: HBMXDCXJXYASGW-OAQYLSRUSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Transactivation of human PPARgamma in HEK293T cells after 18 hrs by luciferase reporter gene assay
Measurement: EC50 = 129 nM (pChEMBL 6.889999866485596)
Descriptors: MW 581.51, ALogP 7.93, HBA 3, HBD 2, PSA 71.33, QED 0.21
Compound (SMILES): COc1ccc([C@@H](C)NC(=O)c2ccc3c(c2)c(C)c(C)n3Cc2ccc(-c3ccccc3C(=O)O)cc2)cc1
InChIKey: QNANVKGUWWFSIH-JOCHJYFZSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Lanthascreen Competitive Binding Assay: The assay was performed according to manufacturer protocol. A mixture of nM GST-PPARG-LBD, 5 nM Tb-GST-antibody, 5 nM Fluormone Pan-PPAR Green, and serial dilutions of the experimental compound, beginning at 10 μM downwards, was added to wells of black 384-well low-volume plates (Greiner) to a total volume of 18 μL. All dilutions were made in TR-FRET assay buffer C. DMSO at 2% final concentration was used as a no-ligand control. Experiment was performed in triplicate, and incubated for 2 hours in the dark prior to assay read in Perkin Elmer ViewLux ultra HTS microplate reader. FRET signal was measured by excitation at 340 nm and emission at 520 nm for fluorescein and 490 nm for terbium. Fold change over DMSO was calculated using GraphPad Prism Software (La Jolla, Calif.) by calculating 520 nm/490 nm ratio. Graphs were plotted as fold change of FRET signal for compound treatment over DMSO-only control.
Measurement: IC50 = 0.5 nM (pChEMBL 9.300000190734863)
Descriptors: MW 532.64, ALogP 7.17, HBA 4, HBD 2, PSA 80.56, QED 0.22
Compound (SMILES): Cc1c(C)n(Cc2ccc(-c3ccccc3C(=O)O)cc2)c2ccc(C(=O)NCc3ccc4c(c3)OCO4)cc12
InChIKey: XCYTZHNEBZAPSP-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Displacement of fluormone PPAR green tracer ligand from recombinant GST-tagged PPARgamma ligand binding domain (unknown origin) incubated for 4 hrs by competitive fluorescence polarization binding assay
Measurement: Ki = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 532.6, ALogP 6.33, HBA 5, HBD 2, PSA 89.79, QED 0.26
Compound (SMILES): CC[C@@H](NC(=O)c1ccc2c(c1)c(C)c(C)n2Cc1ccc(-c2ccccc2C(=O)O)cc1)c1ccccc1
InChIKey: GAGNYMUXGIUCTR-WJOKGBTCSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Transactivation of human PPARgamma in HEK293T cells after 18 hrs by luciferase reporter gene assay
Measurement: EC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 516.64, ALogP 7.55, HBA 3, HBD 2, PSA 71.33, QED 0.22
Compound (SMILES): COc1cc(-c2cc3ncccc3c(O[C@H](C)[C@H]3CNC(=O)C3)n2)ccc1OC(F)(F)F
InChIKey: IWADCUQKACLNKJ-TZMCWYRMSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: FLT3 Kinase Assay: FLT3 is obtained from Invitrogen in 50 mM Tris (pH7.5); 100 mM NaCl; 0.05 mM EDTA, 0.05% NP-40, 2 mM DTT; 50% Glycerol # PV3182; Lot 286671; sequence see below). The enzyme is diluted to 720 nM (35 μg/ml) in enzyme dilution buffer and 10 μl aliquots are stored at −80° C.The activity of FLT3 is measured using the Z′-LYTETM assay technology from Invitrogen (#PV3191)
Measurement: IC50 = 633 nM (pChEMBL 6.199999809265137)
Descriptors: MW 447.41, ALogP 4.11, HBA 6, HBD 1, PSA 82.57, QED 0.61
Compound (SMILES): COc1ccc(-c2cc3ncccc3c(OC[C@H]3CNC(=O)C3)n2)cc1OC
InChIKey: YSFVSZHFOYRRJX-CYBMUJFWSA-N
Target: Tyrosine-protein kinase SYK (SINGLE PROTEIN), Homo sapiens
UniProt: P43405
Assay: Kinase Glo Luminescence Kinase Assay: Recombinant human Syk (amino acids 342-635) was expressed as a fusion protein with an N-terminal GST tag, affinity-purified and deep-frozen at a concentration of approx. 50 - 100 uM in test buffer (25 mM HEPES pH7.5; 25 mM MgCI2;5 mM MnCI2; 50 mM KCI; 0.2% BSA; 0.01 % CHAPS; 100 uM Na3V04; 0.5 mM DTT) and 10% glycerol at -80 C until use.The catalytic activity of the GST-Syk kinase fusion protein was determined using the Kinase Glo Luminescence Kinase test (Promega; V6712). In this homogeneous test the amount of ATP remaining after the kinase reaction is quantified by a luciferin-luciferase reaction using luminescence. The luminescence signal obtained correlates with the amount of ATP still present and thus correlates inversely with the activity of the protein kinase. Method:The test compounds were dissolved in 100 % DMSO at a concentration of 10 mM and diluted in DMSO to a concentration of 1 mM.
Measurement: IC50 = 4.1 nM (pChEMBL 8.390000343322754)
Descriptors: MW 379.42, ALogP 2.83, HBA 6, HBD 1, PSA 82.57, QED 0.71
Compound (SMILES): Cc1cc2ncccc2c(OC[C@H]2CNC(=O)C2)n1
InChIKey: LGLTUBADVDGOPY-SNVBAGLBSA-N
Target: Tyrosine-protein kinase SYK (SINGLE PROTEIN), Homo sapiens
UniProt: P43405
Assay: Kinase Glo Luminescence Kinase Assay: Recombinant human Syk (amino acids 342-635) was expressed as a fusion protein with an N-terminal GST tag, affinity-purified and deep-frozen at a concentration of approx. 50 - 100 uM in test buffer (25 mM HEPES pH7.5; 25 mM MgCI2;5 mM MnCI2; 50 mM KCI; 0.2% BSA; 0.01 % CHAPS; 100 uM Na3V04; 0.5 mM DTT) and 10% glycerol at -80 C until use.The catalytic activity of the GST-Syk kinase fusion protein was determined using the Kinase Glo Luminescence Kinase test (Promega; V6712). In this homogeneous test the amount of ATP remaining after the kinase reaction is quantified by a luciferin-luciferase reaction using luminescence. The luminescence signal obtained correlates with the amount of ATP still present and thus correlates inversely with the activity of the protein kinase. Method:The test compounds were dissolved in 100 % DMSO at a concentration of 10 mM and diluted in DMSO to a concentration of 1 mM.
Measurement: IC50 = 2.1 nM (pChEMBL 8.680000305175781)
Descriptors: MW 257.29, ALogP 1.45, HBA 4, HBD 1, PSA 64.11, QED 0.9
Compound (SMILES): NC(=O)c1c(-c2ccc([NH2+][O-])cc2)nsc1NC(=O)NCCCN1CCOCC1
InChIKey: JHIDXHNBKLDKNG-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Kinase Assay: Biochemical PDGFRbeta kinase assays were performed in 96 well microtiter plates that were coated overnight with 75 ug of poly-Glu-Tyr (4:1) in 10 mM Phosphate Buffered Saline (PBS), pH 7.4. The coated plates were washed with 2 mls per well PBS+0.05% Tween-20 (PBS-T), blocked by incubation with PBS containing 1% BSA, then washed with 2 mls per well PBS-T prior to starting the reaction. Reactions were carried out in 100 uL reaction volumes containing 36 uM ATP in kinase buffer (50 mM Hepes buffer pH 7.4, 20 mM MgCl2, 0.1 mM MnCl2 and 0.2 mM Na3VO4). Test compounds were reconstituted in 100% DMSO and added to the reaction to give a final DMSO concentration of 5%. Reactions were initiated by the addition 20 ul per well of kinase buffer containing 200-300 ng purified cytoplasmic domain PDGFR-b protein (Millipore). Following a 60 minute incubation at 30 C., the reactions were washed 2 mls per well PBS-T.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 420.5, ALogP 0.45, HBA 7, HBD 4, PSA 149.25, QED 0.28