lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=C(N[C@H]1CC2CCC1C2)c1cnn2ccc(N3CCC[C@@H]3c3cc(F)ccc3F)nc12
InChIKey: INXXEGXCIVUCST-USWJAIAZSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: ELISA Assay: An enzyme-linked immunosorbant assay (ELISA) was used to assess TrkA kinase activity in the presence of inhibitors. Immulon 4HBX 384-well microtiter plates (Thermo part #8755) were coated with a 0.025 mg/mL solution of poly (Glu, Ala, Tyr; 6:3:1; Sigma P3899). Various concentrations of test compound, 2.5 nM TrkA (Invitrogen Corp., histidine-tagged recombinant human TrkA, cytoplasmic domain), and 500 uM ATP were incubated for 25 minutes at ambient temperature in the coated plates while shaking The assay buffer consisted of 25 mM MOPS pH 7.5, 0.005% (v/v) Triton X-100 and 5 mM MgCl2. The reaction mixture was removed from the plate by washing with PBS containing 0.1% (v/v) Tween 20. The phosphorylated reaction product was detected using 0.2 ug/mL of a phosphotyrosine specific monoclonal antibody (clone PY20) conjugated to horseradish peroxidase in conjunction with the TMB Peroxidase Substrate System (KPL).
Measurement: IC50 = 0.6 nM (pChEMBL 9.220000267028809)
Descriptors: MW 437.49, ALogP 4.27, HBA 5, HBD 1, PSA 62.53, QED 0.66
Compound (SMILES): O=C(NC1(CO)CC1)c1cnn2ccc(N3CCC[C@@H]3c3cc(F)ccc3F)nc12
InChIKey: BCFGWXGYMCPFQX-QGZVFWFLSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: ELISA Assay: An enzyme-linked immunosorbant assay (ELISA) was used to assess TrkA kinase activity in the presence of inhibitors. Immulon 4HBX 384-well microtiter plates (Thermo part #8755) were coated with a 0.025 mg/mL solution of poly (Glu, Ala, Tyr; 6:3:1; Sigma P3899). Various concentrations of test compound, 2.5 nM TrkA (Invitrogen Corp., histidine-tagged recombinant human TrkA, cytoplasmic domain), and 500 uM ATP were incubated for 25 minutes at ambient temperature in the coated plates while shaking The assay buffer consisted of 25 mM MOPS pH 7.5, 0.005% (v/v) Triton X-100 and 5 mM MgCl2. The reaction mixture was removed from the plate by washing with PBS containing 0.1% (v/v) Tween 20. The phosphorylated reaction product was detected using 0.2 ug/mL of a phosphotyrosine specific monoclonal antibody (clone PY20) conjugated to horseradish peroxidase in conjunction with the TMB Peroxidase Substrate System (KPL).
Measurement: IC50 = 0.9 nM (pChEMBL 9.050000190734863)
Descriptors: MW 413.43, ALogP 2.6, HBA 6, HBD 2, PSA 82.76, QED 0.67
Compound (SMILES): CC(C)(O)CNC(=O)c1cnn2ccc(N3CCC[C@@H]3c3cc(F)ccc3F)nc12
InChIKey: WUASJGDLFRRAKD-QGZVFWFLSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: ELISA Assay: An enzyme-linked immunosorbant assay (ELISA) was used to assess TrkA kinase activity in the presence of inhibitors. Immulon 4HBX 384-well microtiter plates (Thermo part #8755) were coated with a 0.025 mg/mL solution of poly (Glu, Ala, Tyr; 6:3:1; Sigma P3899). Various concentrations of test compound, 2.5 nM TrkA (Invitrogen Corp., histidine-tagged recombinant human TrkA, cytoplasmic domain), and 500 uM ATP were incubated for 25 minutes at ambient temperature in the coated plates while shaking The assay buffer consisted of 25 mM MOPS pH 7.5, 0.005% (v/v) Triton X-100 and 5 mM MgCl2. The reaction mixture was removed from the plate by washing with PBS containing 0.1% (v/v) Tween 20. The phosphorylated reaction product was detected using 0.2 ug/mL of a phosphotyrosine specific monoclonal antibody (clone PY20) conjugated to horseradish peroxidase in conjunction with the TMB Peroxidase Substrate System (KPL).
Measurement: IC50 = 2.15 nM (pChEMBL 8.670000076293945)
Descriptors: MW 415.44, ALogP 2.85, HBA 6, HBD 2, PSA 82.76, QED 0.67
Compound (SMILES): O=C(c1cnn2ccc(N3CCC[C@@H]3c3cc(F)ccc3F)nc12)N1CC[C@H](O)C1
InChIKey: DSYTUISCOWQTPC-KBXCAEBGSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: ELISA Assay: An enzyme-linked immunosorbant assay (ELISA) was used to assess TrkA kinase activity in the presence of inhibitors. Immulon 4HBX 384-well microtiter plates (Thermo part #8755) were coated with a 0.025 mg/mL solution of poly (Glu, Ala, Tyr; 6:3:1; Sigma P3899). Various concentrations of test compound, 2.5 nM TrkA (Invitrogen Corp., histidine-tagged recombinant human TrkA, cytoplasmic domain), and 500 uM ATP were incubated for 25 minutes at ambient temperature in the coated plates while shaking The assay buffer consisted of 25 mM MOPS pH 7.5, 0.005% (v/v) Triton X-100 and 5 mM MgCl2. The reaction mixture was removed from the plate by washing with PBS containing 0.1% (v/v) Tween 20. The phosphorylated reaction product was detected using 0.2 ug/mL of a phosphotyrosine specific monoclonal antibody (clone PY20) conjugated to horseradish peroxidase in conjunction with the TMB Peroxidase Substrate System (KPL).
Measurement: IC50 = 38.3 nM (pChEMBL 7.420000076293945)
Descriptors: MW 413.43, ALogP 2.56, HBA 6, HBD 1, PSA 73.97, QED 0.71
Compound (SMILES): O=C(c1cnn2ccc(N3CCC[C@@H]3c3cc(F)ccc3F)nc12)N1CC[C@@H](O)C1
InChIKey: DSYTUISCOWQTPC-RDTXWAMCSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Jak2 Inhibition Assay: Compounds of Formula I were screened for their ability to inhibit Jak2 using the general enzyme inhibition assay method, in which the assay mixture contained 500 μM ATP, 10 μM Omnia® Y7 peptide (Catalog # IVGN KNZ3071C, Invitrogen Corporation, Carlsbad, Calif.) and 4 nM Jak2 in a total volume of 20 μL. Human Jak2 kinase domain comprising amino acids 808-1132 was purchased from Invitrogen Corporation, Carlsbad, Calif. (catalog # IVGN PV4210).
Measurement: IC50 = 74.2 nM (pChEMBL 7.130000114440918)
Descriptors: MW 413.43, ALogP 2.56, HBA 6, HBD 1, PSA 73.97, QED 0.71
Compound (SMILES): O=C(NC1CCOCC1)c1cnn2ccc(N3CCC[C@@H]3c3cc(F)ccc3F)nc12
InChIKey: ZXDAOGSITPXTJV-LJQANCHMSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: ELISA Assay: An enzyme-linked immunosorbant assay (ELISA) was used to assess TrkA kinase activity in the presence of inhibitors. Immulon 4HBX 384-well microtiter plates (Thermo part #8755) were coated with a 0.025 mg/mL solution of poly (Glu, Ala, Tyr; 6:3:1; Sigma P3899). Various concentrations of test compound, 2.5 nM TrkA (Invitrogen Corp., histidine-tagged recombinant human TrkA, cytoplasmic domain), and 500 uM ATP were incubated for 25 minutes at ambient temperature in the coated plates while shaking The assay buffer consisted of 25 mM MOPS pH 7.5, 0.005% (v/v) Triton X-100 and 5 mM MgCl2. The reaction mixture was removed from the plate by washing with PBS containing 0.1% (v/v) Tween 20. The phosphorylated reaction product was detected using 0.2 ug/mL of a phosphotyrosine specific monoclonal antibody (clone PY20) conjugated to horseradish peroxidase in conjunction with the TMB Peroxidase Substrate System (KPL).
Measurement: IC50 = 0.6 nM (pChEMBL 9.220000267028809)
Descriptors: MW 427.46, ALogP 3.26, HBA 6, HBD 1, PSA 71.76, QED 0.69
Compound (SMILES): Cn1cnc(CNC(=O)c2cnn3ccc(N4CCC[C@@H]4c4cc(F)ccc4F)nc23)c1
InChIKey: VBDSRXYVIRRJJF-LJQANCHMSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Jak2 Inhibition Assay: Compounds of Formula I were screened for their ability to inhibit Jak2 using the general enzyme inhibition assay method, in which the assay mixture contained 500 μM ATP, 10 μM Omnia® Y7 peptide (Catalog # IVGN KNZ3071C, Invitrogen Corporation, Carlsbad, Calif.) and 4 nM Jak2 in a total volume of 20 μL. Human Jak2 kinase domain comprising amino acids 808-1132 was purchased from Invitrogen Corporation, Carlsbad, Calif. (catalog # IVGN PV4210).
Measurement: IC50 = 2.95 nM (pChEMBL 8.529999732971191)
Descriptors: MW 437.45, ALogP 3.01, HBA 7, HBD 1, PSA 80.35, QED 0.52
Compound (SMILES): Cn1cc(CNC(=O)c2cnn3ccc(N4CCC[C@@H]4c4cc(F)ccc4F)nc23)cn1
InChIKey: WAHDCQYLZWQRBB-LJQANCHMSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: ELISA Assay: An enzyme-linked immunosorbant assay (ELISA) was used to assess TrkA kinase activity in the presence of inhibitors. Immulon 4HBX 384-well microtiter plates (Thermo part #8755) were coated with a 0.025 mg/mL solution of poly (Glu, Ala, Tyr; 6:3:1; Sigma P3899). Various concentrations of test compound, 2.5 nM TrkA (Invitrogen Corp., histidine-tagged recombinant human TrkA, cytoplasmic domain), and 500 uM ATP were incubated for 25 minutes at ambient temperature in the coated plates while shaking The assay buffer consisted of 25 mM MOPS pH 7.5, 0.005% (v/v) Triton X-100 and 5 mM MgCl2. The reaction mixture was removed from the plate by washing with PBS containing 0.1% (v/v) Tween 20. The phosphorylated reaction product was detected using 0.2 ug/mL of a phosphotyrosine specific monoclonal antibody (clone PY20) conjugated to horseradish peroxidase in conjunction with the TMB Peroxidase Substrate System (KPL).
Measurement: IC50 = 2.1 nM (pChEMBL 8.680000305175781)
Descriptors: MW 437.45, ALogP 3.01, HBA 7, HBD 1, PSA 80.35, QED 0.52
Compound (SMILES): Cn1cncc1CCNC(=O)c1cnn2ccc(N3CCC[C@@H]3c3cc(F)ccc3F)nc12
InChIKey: GGJNWRFNZLJBRQ-HXUWFJFHSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: ELISA Assay: An enzyme-linked immunosorbant assay (ELISA) was used to assess TrkA kinase activity in the presence of inhibitors. Immulon 4HBX 384-well microtiter plates (Thermo part #8755) were coated with a 0.025 mg/mL solution of poly (Glu, Ala, Tyr; 6:3:1; Sigma P3899). Various concentrations of test compound, 2.5 nM TrkA (Invitrogen Corp., histidine-tagged recombinant human TrkA, cytoplasmic domain), and 500 uM ATP were incubated for 25 minutes at ambient temperature in the coated plates while shaking The assay buffer consisted of 25 mM MOPS pH 7.5, 0.005% (v/v) Triton X-100 and 5 mM MgCl2. The reaction mixture was removed from the plate by washing with PBS containing 0.1% (v/v) Tween 20. The phosphorylated reaction product was detected using 0.2 ug/mL of a phosphotyrosine specific monoclonal antibody (clone PY20) conjugated to horseradish peroxidase in conjunction with the TMB Peroxidase Substrate System (KPL).
Measurement: IC50 = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 451.48, ALogP 3.06, HBA 7, HBD 1, PSA 80.35, QED 0.49
Compound (SMILES): O=C(NCCN1CCNC1=O)c1cnn2ccc(N3CCC[C@@H]3c3cc(F)ccc3F)nc12
InChIKey: RKUGDCZKRYDCFQ-GOSISDBHSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Jak2 Inhibition Assay: Compounds of Formula I were screened for their ability to inhibit Jak2 using the general enzyme inhibition assay method, in which the assay mixture contained 500 μM ATP, 10 μM Omnia® Y7 peptide (Catalog # IVGN KNZ3071C, Invitrogen Corporation, Carlsbad, Calif.) and 4 nM Jak2 in a total volume of 20 μL. Human Jak2 kinase domain comprising amino acids 808-1132 was purchased from Invitrogen Corporation, Carlsbad, Calif. (catalog # IVGN PV4210).
Measurement: IC50 = 3.6 nM (pChEMBL 8.4399995803833)
Descriptors: MW 455.47, ALogP 2.1, HBA 6, HBD 2, PSA 94.87, QED 0.59
Compound (SMILES): O=C(NCCc1cnc[nH]1)c1cnn2ccc(N3CCC[C@@H]3c3cc(F)ccc3F)nc12
InChIKey: OOFWNPIPNPKKSR-LJQANCHMSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: ELISA Assay: An enzyme-linked immunosorbant assay (ELISA) was used to assess TrkA kinase activity in the presence of inhibitors. Immulon 4HBX 384-well microtiter plates (Thermo part #8755) were coated with a 0.025 mg/mL solution of poly (Glu, Ala, Tyr; 6:3:1; Sigma P3899). Various concentrations of test compound, 2.5 nM TrkA (Invitrogen Corp., histidine-tagged recombinant human TrkA, cytoplasmic domain), and 500 uM ATP were incubated for 25 minutes at ambient temperature in the coated plates while shaking The assay buffer consisted of 25 mM MOPS pH 7.5, 0.005% (v/v) Triton X-100 and 5 mM MgCl2. The reaction mixture was removed from the plate by washing with PBS containing 0.1% (v/v) Tween 20. The phosphorylated reaction product was detected using 0.2 ug/mL of a phosphotyrosine specific monoclonal antibody (clone PY20) conjugated to horseradish peroxidase in conjunction with the TMB Peroxidase Substrate System (KPL).
Measurement: IC50 = 0.4 nM (pChEMBL 9.399999618530273)
Descriptors: MW 437.45, ALogP 3.04, HBA 6, HBD 2, PSA 91.21, QED 0.48
Compound (SMILES): O=C(NC[C@@H](O)CO)c1cnn2ccc(N3CCC[C@@H]3c3cc(F)ccc3F)nc12
InChIKey: GSSDAQWHOJFZRE-CXAGYDPISA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: ELISA Assay: An enzyme-linked immunosorbant assay (ELISA) was used to assess TrkA kinase activity in the presence of inhibitors. Immulon 4HBX 384-well microtiter plates (Thermo part #8755) were coated with a 0.025 mg/mL solution of poly (Glu, Ala, Tyr; 6:3:1; Sigma P3899). Various concentrations of test compound, 2.5 nM TrkA (Invitrogen Corp., histidine-tagged recombinant human TrkA, cytoplasmic domain), and 500 uM ATP were incubated for 25 minutes at ambient temperature in the coated plates while shaking The assay buffer consisted of 25 mM MOPS pH 7.5, 0.005% (v/v) Triton X-100 and 5 mM MgCl2. The reaction mixture was removed from the plate by washing with PBS containing 0.1% (v/v) Tween 20. The phosphorylated reaction product was detected using 0.2 ug/mL of a phosphotyrosine specific monoclonal antibody (clone PY20) conjugated to horseradish peroxidase in conjunction with the TMB Peroxidase Substrate System (KPL).
Measurement: IC50 = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 417.42, ALogP 1.43, HBA 7, HBD 3, PSA 102.99, QED 0.56
Compound (SMILES): CN(C)C(=O)c1cnn2ccc(N3CCC[C@@H]3c3cc(F)ccc3F)nc12
InChIKey: DUJWGLCTYAWISR-MRXNPFEDSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: ELISA Assay: An enzyme-linked immunosorbant assay (ELISA) was used to assess TrkA kinase activity in the presence of inhibitors. Immulon 4HBX 384-well microtiter plates (Thermo part #8755) were coated with a 0.025 mg/mL solution of poly (Glu, Ala, Tyr; 6:3:1; Sigma P3899). Various concentrations of test compound, 2.5 nM TrkA (Invitrogen Corp., histidine-tagged recombinant human TrkA, cytoplasmic domain), and 500 uM ATP were incubated for 25 minutes at ambient temperature in the coated plates while shaking The assay buffer consisted of 25 mM MOPS pH 7.5, 0.005% (v/v) Triton X-100 and 5 mM MgCl2. The reaction mixture was removed from the plate by washing with PBS containing 0.1% (v/v) Tween 20. The phosphorylated reaction product was detected using 0.2 ug/mL of a phosphotyrosine specific monoclonal antibody (clone PY20) conjugated to horseradish peroxidase in conjunction with the TMB Peroxidase Substrate System (KPL).
Measurement: IC50 = 214.5 nM (pChEMBL 6.670000076293945)
Descriptors: MW 371.39, ALogP 3.05, HBA 5, HBD 0, PSA 53.74, QED 0.71
Compound (SMILES): O=C(NCCn1ccnc1)c1cnn2ccc(N3CCC[C@@H]3c3cc(F)ccc3F)nc12
InChIKey: VQFKVNURGWYBCE-LJQANCHMSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: ELISA Assay: An enzyme-linked immunosorbant assay (ELISA) was used to assess TrkA kinase activity in the presence of inhibitors. Immulon 4HBX 384-well microtiter plates (Thermo part #8755) were coated with a 0.025 mg/mL solution of poly (Glu, Ala, Tyr; 6:3:1; Sigma P3899). Various concentrations of test compound, 2.5 nM TrkA (Invitrogen Corp., histidine-tagged recombinant human TrkA, cytoplasmic domain), and 500 uM ATP were incubated for 25 minutes at ambient temperature in the coated plates while shaking The assay buffer consisted of 25 mM MOPS pH 7.5, 0.005% (v/v) Triton X-100 and 5 mM MgCl2. The reaction mixture was removed from the plate by washing with PBS containing 0.1% (v/v) Tween 20. The phosphorylated reaction product was detected using 0.2 ug/mL of a phosphotyrosine specific monoclonal antibody (clone PY20) conjugated to horseradish peroxidase in conjunction with the TMB Peroxidase Substrate System (KPL).
Measurement: IC50 = 2.8 nM (pChEMBL 8.550000190734863)
Descriptors: MW 437.45, ALogP 2.98, HBA 7, HBD 1, PSA 80.35, QED 0.5
Compound (SMILES): O=C(NC[C@H](O)CO)c1cnn2ccc(N3CCC[C@@H]3c3cc(F)ccc3F)nc12
InChIKey: GSSDAQWHOJFZRE-SUMWQHHRSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Jak2 Inhibition Assay: Compounds of Formula I were screened for their ability to inhibit Jak2 using the general enzyme inhibition assay method, in which the assay mixture contained 500 μM ATP, 10 μM Omnia® Y7 peptide (Catalog # IVGN KNZ3071C, Invitrogen Corporation, Carlsbad, Calif.) and 4 nM Jak2 in a total volume of 20 μL. Human Jak2 kinase domain comprising amino acids 808-1132 was purchased from Invitrogen Corporation, Carlsbad, Calif. (catalog # IVGN PV4210).
Measurement: IC50 = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 417.42, ALogP 1.43, HBA 7, HBD 3, PSA 102.99, QED 0.56
Compound (SMILES): COC1COCCC1NC1CC2OCCC2(C(=O)N2CCc3ncc(C(F)(F)F)cc3C2)C1
InChIKey: QOVXPTCADXFNFV-UHFFFAOYSA-N
Target: C-C chemokine receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P41597
Assay: Binding Assay: THP-1 (cells were incubated with 0.5 nM 125I labeled MCP-1 (Perkin-Elmer Life Sciences, Inc. Boston, Mass.) in the presence of varying concentrations of either unlabeled MCP-1 (R & D Systems, Minneapolis, Minn.) or test compound for 2 hours at 30° C. in a 96 well plate. Cells were then harvested onto a filter plate, dried, and 20 μL of Microscint 20 was added to each well. Plates were counted in a TopCount NXT, Microplate Scintillation & Luminescence Counter (Perkin-Elmer Life Sciences, Inc. Boston, Mass.). Blank values (buffer only) were subtracted from all values and drug treated values were compared to vehicle treated values. 1 μM cold MCP-1 was used for nonspecific binding.
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 469.5, ALogP 2.32, HBA 6, HBD 1, PSA 72.92, QED 0.73
Compound (SMILES): C[C@@H](Cc1c(F)c(F)cc(F)c1F)Nc1cc[nH]c(=O)c1-c1nc2cc3c(cc2[nH]1)CN(C1CCN(C)CC1)C3=O
InChIKey: FOLXFWBVNHRGIV-AWEZNQCLSA-N
Target: Activin receptor type-1-like (SINGLE PROTEIN), Homo sapiens
UniProt: P37023
Assay: In Vitro Kinase Activity Assay: Compounds to be tested were dissolved in 100% DMSO in a range of concentrations from 10-8 to 10-3 M including negative control (DMSO), then diluted with Kinase Buffer (50 mM HEPES, pH 7.5, 1 mM EGTA, 10 mM MgCl2, 0.01% Tween-20, and 2 mM DTT, added fresh) to 4x the final concentration. The final curve included 11 concentrations (10-11 to 10-5 M) plus negative control DMSO tested in triplicate.Kinase and ATP concentrations necessary for optimal activity were determined in separate experiments. (Table 2). Briefly, increasing concentrations of kinase were incubated in a fixed concentration of ATP (200 uM) in Kinase Buffer to determine maximal activity at various time points (30-120 min). The concentration of kinase that resulted in maximal activity with the shortest incubation time was then incubated in Kinase Buffer with increasing concentrations of ATP.
Measurement: IC50 = 9.812 nM (pChEMBL 8.010000228881836)
Descriptors: MW 568.58, ALogP 4.57, HBA 5, HBD 3, PSA 97.12, QED 0.23
Compound (SMILES): C[C@@H](Cc1c(F)c(F)cc(F)c1F)Nc1cc[nH]c(=O)c1-c1nc2cc3c(cc2[nH]1)C(=O)N(CCN(C)C)C3=O
InChIKey: DPMQHTABGLRCQK-LBPRGKRZSA-N
Target: Proto-oncogene tyrosine-protein kinase ROS (SINGLE PROTEIN), Homo sapiens
UniProt: P08922
Assay: In Vitro Kinase Activity Assay: Compounds to be tested were dissolved in 100% DMSO in a range of concentrations from 10-8 to 10-3 M including negative control (DMSO), then diluted with Kinase Buffer (50 mM HEPES, pH 7.5, 1 mM EGTA, 10 mM MgCl2, 0.01% Tween-20, and 2 mM DTT, added fresh) to 4x the final concentration. The final curve included 11 concentrations (10-11 to 10-5 M) plus negative control DMSO tested in triplicate.Kinase and ATP concentrations necessary for optimal activity were determined in separate experiments. (Table 2). Briefly, increasing concentrations of kinase were incubated in a fixed concentration of ATP (200 uM) in Kinase Buffer to determine maximal activity at various time points (30-120 min). The concentration of kinase that resulted in maximal activity with the shortest incubation time was then incubated in Kinase Buffer with increasing concentrations of ATP.
Measurement: IC50 = 0.436 nM (pChEMBL 9.359999656677246)
Descriptors: MW 556.52, ALogP 3.68, HBA 6, HBD 3, PSA 114.19, QED 0.17
Compound (SMILES): C[C@@H](Cc1c(F)c(F)cc(F)c1F)Nc1cc[nH]c(=O)c1-c1nc2cc3c(cc2[nH]1)CN(CCN(C)C)C3=O
InChIKey: LRJJEMRURFIKDD-ZDUSSCGKSA-N
Target: NT-3 growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16288
Assay: In Vitro Kinase Activity Assay: Compounds to be tested were dissolved in 100% DMSO in a range of concentrations from 10-8 to 10-3 M including negative control (DMSO), then diluted with Kinase Buffer (50 mM HEPES, pH 7.5, 1 mM EGTA, 10 mM MgCl2, 0.01% Tween-20, and 2 mM DTT, added fresh) to 4x the final concentration. The final curve included 11 concentrations (10-11 to 10-5 M) plus negative control DMSO tested in triplicate.Kinase and ATP concentrations necessary for optimal activity were determined in separate experiments. (Table 2). Briefly, increasing concentrations of kinase were incubated in a fixed concentration of ATP (200 uM) in Kinase Buffer to determine maximal activity at various time points (30-120 min). The concentration of kinase that resulted in maximal activity with the shortest incubation time was then incubated in Kinase Buffer with increasing concentrations of ATP.
Measurement: IC50 = 1.585 nM (pChEMBL 8.800000190734863)
Descriptors: MW 542.54, ALogP 4.04, HBA 5, HBD 3, PSA 97.12, QED 0.23
Compound (SMILES): C[C@@H](Cc1c(F)c(F)cc(F)c1F)Nc1cc[nH]c(=O)c1-c1nc2cc3c(cc2[nH]1)C(=O)N(c1cccnc1)C3=O
InChIKey: WOKJIIMDDCFJJH-LBPRGKRZSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: In Vitro Kinase Activity Assay: Compounds to be tested were dissolved in 100% DMSO in a range of concentrations from 10-8 to 10-3 M including negative control (DMSO), then diluted with Kinase Buffer (50 mM HEPES, pH 7.5, 1 mM EGTA, 10 mM MgCl2, 0.01% Tween-20, and 2 mM DTT, added fresh) to 4x the final concentration. The final curve included 11 concentrations (10-11 to 10-5 M) plus negative control DMSO tested in triplicate.Kinase and ATP concentrations necessary for optimal activity were determined in separate experiments. (Table 2). Briefly, increasing concentrations of kinase were incubated in a fixed concentration of ATP (200 uM) in Kinase Buffer to determine maximal activity at various time points (30-120 min). The concentration of kinase that resulted in maximal activity with the shortest incubation time was then incubated in Kinase Buffer with increasing concentrations of ATP.
Measurement: IC50 = 20.41 nM (pChEMBL 7.690000057220459)
Descriptors: MW 562.48, ALogP 4.71, HBA 6, HBD 3, PSA 123.84, QED 0.16
Compound (SMILES): C[C@@H](Cc1c(F)c(F)cc(F)c1F)Nc1cc[nH]c(=O)c1-c1nc2cc3c(cc2[nH]1)C(O)N(c1cccnc1)C3=O
InChIKey: LKQSELSKVLDVHG-JHQHAWHRSA-N
Target: Activin receptor type-1-like (SINGLE PROTEIN), Homo sapiens
UniProt: P37023
Assay: In Vitro Kinase Activity Assay: Compounds to be tested were dissolved in 100% DMSO in a range of concentrations from 10-8 to 10-3 M including negative control (DMSO), then diluted with Kinase Buffer (50 mM HEPES, pH 7.5, 1 mM EGTA, 10 mM MgCl2, 0.01% Tween-20, and 2 mM DTT, added fresh) to 4x the final concentration. The final curve included 11 concentrations (10-11 to 10-5 M) plus negative control DMSO tested in triplicate.Kinase and ATP concentrations necessary for optimal activity were determined in separate experiments. (Table 2). Briefly, increasing concentrations of kinase were incubated in a fixed concentration of ATP (200 uM) in Kinase Buffer to determine maximal activity at various time points (30-120 min). The concentration of kinase that resulted in maximal activity with the shortest incubation time was then incubated in Kinase Buffer with increasing concentrations of ATP.
Measurement: IC50 = 15.18 nM (pChEMBL 7.820000171661377)
Descriptors: MW 564.5, ALogP 4.56, HBA 6, HBD 4, PSA 127, QED 0.18
Compound (SMILES): COC1c2cc3[nH]c(-c4c(NC(C)Cc5c(F)c(F)cc(F)c5F)cc[nH]c4=O)nc3cc2C(=O)N1c1cccnc1
InChIKey: MSDSJOCXJMWGST-UHFFFAOYSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: In Vitro Kinase Activity Assay: Compounds to be tested were dissolved in 100% DMSO in a range of concentrations from 10-8 to 10-3 M including negative control (DMSO), then diluted with Kinase Buffer (50 mM HEPES, pH 7.5, 1 mM EGTA, 10 mM MgCl2, 0.01% Tween-20, and 2 mM DTT, added fresh) to 4x the final concentration. The final curve included 11 concentrations (10-11 to 10-5 M) plus negative control DMSO tested in triplicate.Kinase and ATP concentrations necessary for optimal activity were determined in separate experiments. (Table 2). Briefly, increasing concentrations of kinase were incubated in a fixed concentration of ATP (200 uM) in Kinase Buffer to determine maximal activity at various time points (30-120 min). The concentration of kinase that resulted in maximal activity with the shortest incubation time was then incubated in Kinase Buffer with increasing concentrations of ATP.
Measurement: IC50 = 41.61 nM (pChEMBL 7.380000114440918)
Descriptors: MW 578.53, ALogP 5.22, HBA 6, HBD 3, PSA 116, QED 0.18
Compound (SMILES): C[C@@H](Cc1c(F)c(F)cc(F)c1F)Nc1cc[nH]c(=O)c1-c1nc2cc3c(cc2[nH]1)C(=O)N(c1ccc(F)nc1)C3=O
InChIKey: ZHMHFNQYAWVRJM-NSHDSACASA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: In Vitro Kinase Activity Assay: Compounds to be tested were dissolved in 100% DMSO in a range of concentrations from 10-8 to 10-3 M including negative control (DMSO), then diluted with Kinase Buffer (50 mM HEPES, pH 7.5, 1 mM EGTA, 10 mM MgCl2, 0.01% Tween-20, and 2 mM DTT, added fresh) to 4x the final concentration. The final curve included 11 concentrations (10-11 to 10-5 M) plus negative control DMSO tested in triplicate.Kinase and ATP concentrations necessary for optimal activity were determined in separate experiments. (Table 2). Briefly, increasing concentrations of kinase were incubated in a fixed concentration of ATP (200 uM) in Kinase Buffer to determine maximal activity at various time points (30-120 min). The concentration of kinase that resulted in maximal activity with the shortest incubation time was then incubated in Kinase Buffer with increasing concentrations of ATP.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 580.47, ALogP 4.85, HBA 6, HBD 3, PSA 123.84, QED 0.11
Compound (SMILES): CC(Cc1cc(F)ccc1F)Nc1cc[nH]c(=O)c1-c1nc2cc3c(cc2[nH]1)C(=O)N(CCN(C)C)C3
InChIKey: BNPMMVDYMYENIM-UHFFFAOYSA-N
Target: Activin receptor type-1-like (SINGLE PROTEIN), Homo sapiens
UniProt: P37023
Assay: In Vitro Kinase Activity Assay: Compounds to be tested were dissolved in 100% DMSO in a range of concentrations from 10-8 to 10-3 M including negative control (DMSO), then diluted with Kinase Buffer (50 mM HEPES, pH 7.5, 1 mM EGTA, 10 mM MgCl2, 0.01% Tween-20, and 2 mM DTT, added fresh) to 4x the final concentration. The final curve included 11 concentrations (10-11 to 10-5 M) plus negative control DMSO tested in triplicate.Kinase and ATP concentrations necessary for optimal activity were determined in separate experiments. (Table 2). Briefly, increasing concentrations of kinase were incubated in a fixed concentration of ATP (200 uM) in Kinase Buffer to determine maximal activity at various time points (30-120 min). The concentration of kinase that resulted in maximal activity with the shortest incubation time was then incubated in Kinase Buffer with increasing concentrations of ATP.
Measurement: IC50 = 9.157 nM (pChEMBL 8.039999961853027)
Descriptors: MW 506.56, ALogP 3.76, HBA 5, HBD 3, PSA 97.12, QED 0.34
Compound (SMILES): Cc1c2c(cc3[nH]c(-c4c(NC(C)Cc5c(F)c(F)cc(F)c5F)cc[nH]c4=O)nc13)C(=O)N(C1CCN(C)CC1)C2
InChIKey: ZUSOUYHYDDCGIC-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase receptor Ret (SINGLE PROTEIN), Homo sapiens
UniProt: P07949
Assay: In Vitro Kinase Activity Assay: Compounds to be tested were dissolved in 100% DMSO in a range of concentrations from 10-8 to 10-3 M including negative control (DMSO), then diluted with Kinase Buffer (50 mM HEPES, pH 7.5, 1 mM EGTA, 10 mM MgCl2, 0.01% Tween-20, and 2 mM DTT, added fresh) to 4x the final concentration. The final curve included 11 concentrations (10-11 to 10-5 M) plus negative control DMSO tested in triplicate.Kinase and ATP concentrations necessary for optimal activity were determined in separate experiments. (Table 2). Briefly, increasing concentrations of kinase were incubated in a fixed concentration of ATP (200 uM) in Kinase Buffer to determine maximal activity at various time points (30-120 min). The concentration of kinase that resulted in maximal activity with the shortest incubation time was then incubated in Kinase Buffer with increasing concentrations of ATP.
Measurement: IC50 = 11.15 nM (pChEMBL 7.949999809265137)
Descriptors: MW 582.6, ALogP 4.88, HBA 5, HBD 3, PSA 97.12, QED 0.22
Compound (SMILES): COc1ccc(S(=O)(=O)[C@@H]2C[C@@H](C(=O)NC3(C#N)CC3)N(C(=O)C3(c4ccc(Cl)cn4)CNC3)C2)c(Cl)c1
InChIKey: FVTJPALETWZNEA-MJGOQNOKSA-N
Target: Procathepsin L (SINGLE PROTEIN), Homo sapiens
UniProt: P07711
Assay: Inhibition of human Cathepsin L
Measurement: IC50 = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 578.48, ALogP 1.85, HBA 8, HBD 2, PSA 141.49, QED 0.51
Compound (SMILES): N#CC1(NC(=O)[C@@H]2C[C@@H](S(=O)(=O)c3ccccc3Cl)CN2C(=O)C2(c3ncc(Br)cc3F)CNC2)CC1
InChIKey: NSNODLMCUTYBRZ-QAPCUYQASA-N
Target: Cathepsin S (SINGLE PROTEIN), Homo sapiens
UniProt: P25774
Assay: Inhibition of Cathepsin S (unknown origin)
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 610.89, ALogP 2.09, HBA 7, HBD 2, PSA 132.26, QED 0.51
Compound (SMILES): CN1CC(C(=O)N2C[C@H](S(=O)(=O)c3ccccc3Cl)C[C@H]2C(=O)NC2(C#N)CC2)(c2ncc(Br)cc2F)C1
InChIKey: MZKPXTUNCMRSJY-APWZRJJASA-N
Target: Procathepsin L (SINGLE PROTEIN), Homo sapiens
UniProt: P07711
Assay: Enzyme Inhibition Assay: Enzyme activity is measured by observing the increase in fluorescence intensity caused by cleavage of a peptide substrate containing a fluorophore whose emission is quenched in the intact peptide.Assay buffer: 100 mM potassium phosphate pH 6.5, EDTA-Na 5 mM, Triton X-100 0.001%, DTT 5 mM.Enzymes (all at 1 nM): human and mouse Cathepsin S, Cat K, Cat B, Cat L.Substrate (20 μM): Z-Val-Val-Arg-AMC, except for Cat K which uses Z-Leu-Arg-AMC (both from Bachem).Z=Benzyloxycarbonyl.AMC=7-Amino-4-Methyl-Coumarin.DTT=dithiothreitol.Final volume: 100 μL.Excitation 360 nm, Emission 465 nm.Enzyme is added to the substance dilutions in 96-well microtitre plates and the reaction is started with substrate. Fluorescence emission is measured over 20 minutes, during which time a linear increase is observed in the absence of inhibitor.
Measurement: IC50 = 12.5 nM (pChEMBL 7.900000095367432)
Descriptors: MW 624.92, ALogP 2.44, HBA 7, HBD 1, PSA 123.47, QED 0.52
Compound (SMILES): CC(C)(C)OC(=O)N1CCC1(C(=O)N1C[C@H](S(=O)(=O)c2ccc(F)cc2Cl)C[C@H]1C(=O)NC1(C#N)CC1)c1ncc(Cl)cc1F
InChIKey: XYMLZPAPBAMTAT-VGEZZCLVSA-N
Target: Procathepsin L (SINGLE PROTEIN), Homo sapiens
UniProt: P07711
Assay: Enzyme Inhibition Assay: Enzyme activity is measured by observing the increase in fluorescence intensity caused by cleavage of a peptide substrate containing a fluorophore whose emission is quenched in the intact peptide.Assay buffer: 100 mM potassium phosphate pH 6.5, EDTA-Na 5 mM, Triton X-100 0.001%, DTT 5 mM.Enzymes (all at 1 nM): human and mouse Cathepsin S, Cat K, Cat B, Cat L.Substrate (20 μM): Z-Val-Val-Arg-AMC, except for Cat K which uses Z-Leu-Arg-AMC (both from Bachem).Z=Benzyloxycarbonyl.AMC=7-Amino-4-Methyl-Coumarin.DTT=dithiothreitol.Final volume: 100 μL.Excitation 360 nm, Emission 465 nm.Enzyme is added to the substance dilutions in 96-well microtitre plates and the reaction is started with substrate. Fluorescence emission is measured over 20 minutes, during which time a linear increase is observed in the absence of inhibitor.
Measurement: IC50 = 922 nM (pChEMBL 6.039999961853027)
Descriptors: MW 684.55, ALogP 4.12, HBA 8, HBD 1, PSA 149.77, QED 0.45
Compound (SMILES): CC(C)(C)OC(=O)N1CCC1(C(=O)N1C[C@H](S(=O)(=O)c2ccc(F)cc2Cl)C[C@H]1C(=O)NC1(C#N)CC1)c1ncc(Br)cc1F
InChIKey: FCADZVXWMPUWJQ-VGEZZCLVSA-N
Target: Procathepsin L (SINGLE PROTEIN), Homo sapiens
UniProt: P07711
Assay: Enzyme Inhibition Assay: Enzyme activity is measured by observing the increase in fluorescence intensity caused by cleavage of a peptide substrate containing a fluorophore whose emission is quenched in the intact peptide.Assay buffer: 100 mM potassium phosphate pH 6.5, EDTA-Na 5 mM, Triton X-100 0.001%, DTT 5 mM.Enzymes (all at 1 nM): human and mouse Cathepsin S, Cat K, Cat B, Cat L.Substrate (20 μM): Z-Val-Val-Arg-AMC, except for Cat K which uses Z-Leu-Arg-AMC (both from Bachem).Z=Benzyloxycarbonyl.AMC=7-Amino-4-Methyl-Coumarin.DTT=dithiothreitol.Final volume: 100 μL.Excitation 360 nm, Emission 465 nm.Enzyme is added to the substance dilutions in 96-well microtitre plates and the reaction is started with substrate. Fluorescence emission is measured over 20 minutes, during which time a linear increase is observed in the absence of inhibitor.
Measurement: IC50 = 2909 nM (pChEMBL 5.539999961853027)
Descriptors: MW 729, ALogP 4.23, HBA 8, HBD 1, PSA 149.77, QED 0.43
Compound (SMILES): C[C@H](Oc1ccc(S(=O)(=O)[C@@H]2C[C@@H](C(=O)NC3(C#N)CC3)N(C(=O)C3(c4ncc(Cl)cc4F)CCN3C(=O)OC(C)(C)C)C2)c(Cl)c1)C(F)(F)F
InChIKey: KLKAVPREINBPNI-UNWPBJHZSA-N
Target: Procathepsin L (SINGLE PROTEIN), Homo sapiens
UniProt: P07711
Assay: Enzyme Inhibition Assay: Enzyme activity is measured by observing the increase in fluorescence intensity caused by cleavage of a peptide substrate containing a fluorophore whose emission is quenched in the intact peptide.Assay buffer: 100 mM potassium phosphate pH 6.5, EDTA-Na 5 mM, Triton X-100 0.001%, DTT 5 mM.Enzymes (all at 1 nM): human and mouse Cathepsin S, Cat K, Cat B, Cat L.Substrate (20 μM): Z-Val-Val-Arg-AMC, except for Cat K which uses Z-Leu-Arg-AMC (both from Bachem).Z=Benzyloxycarbonyl.AMC=7-Amino-4-Methyl-Coumarin.DTT=dithiothreitol.Final volume: 100 μL.Excitation 360 nm, Emission 465 nm.Enzyme is added to the substance dilutions in 96-well microtitre plates and the reaction is started with substrate. Fluorescence emission is measured over 20 minutes, during which time a linear increase is observed in the absence of inhibitor.
Measurement: IC50 = 556.5 nM (pChEMBL 6.25)
Descriptors: MW 778.61, ALogP 5.31, HBA 9, HBD 1, PSA 159, QED 0.35
Compound (SMILES): C[C@H](Oc1ccc(S(=O)(=O)[C@@H]2C[C@@H](C(=O)NC3(C#N)CC3)N(C(=O)C3(c4ncc(Br)cc4F)CCN3C(=O)OC(C)(C)C)C2)c(Cl)c1)C(F)(F)F
InChIKey: ZLUMYEPDTRVKBR-UNWPBJHZSA-N
Target: Procathepsin L (SINGLE PROTEIN), Homo sapiens
UniProt: P07711
Assay: Enzyme Inhibition Assay: Enzyme activity is measured by observing the increase in fluorescence intensity caused by cleavage of a peptide substrate containing a fluorophore whose emission is quenched in the intact peptide.Assay buffer: 100 mM potassium phosphate pH 6.5, EDTA-Na 5 mM, Triton X-100 0.001%, DTT 5 mM.Enzymes (all at 1 nM): human and mouse Cathepsin S, Cat K, Cat B, Cat L.Substrate (20 μM): Z-Val-Val-Arg-AMC, except for Cat K which uses Z-Leu-Arg-AMC (both from Bachem).Z=Benzyloxycarbonyl.AMC=7-Amino-4-Methyl-Coumarin.DTT=dithiothreitol.Final volume: 100 μL.Excitation 360 nm, Emission 465 nm.Enzyme is added to the substance dilutions in 96-well microtitre plates and the reaction is started with substrate. Fluorescence emission is measured over 20 minutes, during which time a linear increase is observed in the absence of inhibitor.
Measurement: IC50 = 1057 nM (pChEMBL 5.980000019073486)
Descriptors: MW 823.06, ALogP 5.42, HBA 9, HBD 1, PSA 159, QED 0.34
Compound (SMILES): N#CC1(NC(=O)[C@@H]2C[C@@H](S(=O)(=O)c3ccc(F)cc3Cl)CN2C(=O)C2(c3ncc(Cl)cc3F)CCN2)CC1
InChIKey: JZLWWEAJMOECOO-YNPWLRABSA-N
Target: Cathepsin S (SINGLE PROTEIN), Homo sapiens
UniProt: P25774
Assay: Enzyme Inhibition Assay: Enzyme activity is measured by observing the increase in fluorescence intensity caused by cleavage of a peptide substrate containing a fluorophore whose emission is quenched in the intact peptide.Assay buffer: 100 mM potassium phosphate pH 6.5, EDTA-Na 5 mM, Triton X-100 0.001%, DTT 5 mM.Enzymes (all at 1 nM): human and mouse Cathepsin S, Cat K, Cat B, Cat L.Substrate (20 μM): Z-Val-Val-Arg-AMC, except for Cat K which uses Z-Leu-Arg-AMC (both from Bachem).Z=Benzyloxycarbonyl.AMC=7-Amino-4-Methyl-Coumarin.DTT=dithiothreitol.Final volume: 100 μL.Excitation 360 nm, Emission 465 nm.Enzyme is added to the substance dilutions in 96-well microtitre plates and the reaction is started with substrate. Fluorescence emission is measured over 20 minutes, during which time a linear increase is observed in the absence of inhibitor.
Measurement: IC50 = 1.574 nM (pChEMBL 8.800000190734863)
Descriptors: MW 584.43, ALogP 2.47, HBA 7, HBD 2, PSA 132.26, QED 0.5
Compound (SMILES): N#CC1(NC(=O)[C@@H]2C[C@@H](S(=O)(=O)c3ccc(F)cc3Cl)CN2C(=O)C2(c3ncc(Br)cc3F)CCN2)CC1
InChIKey: XJKJCKLHFZWKFQ-YNPWLRABSA-N
Target: Procathepsin L (SINGLE PROTEIN), Homo sapiens
UniProt: P07711
Assay: Enzyme Inhibition Assay: Enzyme activity is measured by observing the increase in fluorescence intensity caused by cleavage of a peptide substrate containing a fluorophore whose emission is quenched in the intact peptide.Assay buffer: 100 mM potassium phosphate pH 6.5, EDTA-Na 5 mM, Triton X-100 0.001%, DTT 5 mM.Enzymes (all at 1 nM): human and mouse Cathepsin S, Cat K, Cat B, Cat L.Substrate (20 μM): Z-Val-Val-Arg-AMC, except for Cat K which uses Z-Leu-Arg-AMC (both from Bachem).Z=Benzyloxycarbonyl.AMC=7-Amino-4-Methyl-Coumarin.DTT=dithiothreitol.Final volume: 100 μL.Excitation 360 nm, Emission 465 nm.Enzyme is added to the substance dilutions in 96-well microtitre plates and the reaction is started with substrate. Fluorescence emission is measured over 20 minutes, during which time a linear increase is observed in the absence of inhibitor.
Measurement: IC50 = 48.5 nM (pChEMBL 7.309999942779541)
Descriptors: MW 628.88, ALogP 2.58, HBA 7, HBD 2, PSA 132.26, QED 0.47
Compound (SMILES): C[C@H](Oc1ccc(S(=O)(=O)[C@@H]2C[C@@H](C(=O)NC3(C#N)CC3)N(C(=O)C3(c4ncc(Cl)cc4F)CCN3)C2)c(Cl)c1)C(F)(F)F
InChIKey: LQXJTYUJAKLJDS-JEZVWYIQSA-N
Target: Procathepsin L (SINGLE PROTEIN), Homo sapiens
UniProt: P07711
Assay: Enzyme Inhibition Assay: Enzyme activity is measured by observing the increase in fluorescence intensity caused by cleavage of a peptide substrate containing a fluorophore whose emission is quenched in the intact peptide.Assay buffer: 100 mM potassium phosphate pH 6.5, EDTA-Na 5 mM, Triton X-100 0.001%, DTT 5 mM.Enzymes (all at 1 nM): human and mouse Cathepsin S, Cat K, Cat B, Cat L.Substrate (20 μM): Z-Val-Val-Arg-AMC, except for Cat K which uses Z-Leu-Arg-AMC (both from Bachem).Z=Benzyloxycarbonyl.AMC=7-Amino-4-Methyl-Coumarin.DTT=dithiothreitol.Final volume: 100 μL.Excitation 360 nm, Emission 465 nm.Enzyme is added to the substance dilutions in 96-well microtitre plates and the reaction is started with substrate. Fluorescence emission is measured over 20 minutes, during which time a linear increase is observed in the absence of inhibitor.
Measurement: IC50 = 58.5 nM (pChEMBL 7.230000019073486)
Descriptors: MW 678.49, ALogP 3.66, HBA 8, HBD 2, PSA 141.49, QED 0.4
Compound (SMILES): C=CC(=O)Nc1cc2c(Nc3ccc(Br)cc3F)ncnc2cc1OCCNC(=O)C1CCCN1C
InChIKey: QKEQHMZWPIXXEY-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Tyrosine Kinase Assay: EGFR1 (HER-1) enzyme assay was carried out by using Tyrosine Kinase Assay Kit Green. The entire assay was conducted in accordance with EGFR PTK inhibitor cellular activity test S.O.P.A typical kinase inhibition reaction requires a protein tyrosine kinase, a suitable buffer solution system, a peptide substrate and ATP. In the present EGFR tyrosine kinase assay, a buffer solution system containing 20 mM HEPES (pH 7.4), 5 mM MgCl2 and 2 mM MnCl2; 50 uM Na3VO4; 50 ng/10 ul EGFR (Proquinase); 100 uM ATP; and 10 ng/ml poly(Glu, Tyr) (4:1, Sigma) as a substrate were used.First, 10 ul of EGFR was added to each well of a 96-well plate, 10 ul of the test compounds diluted as described in Test Example 2 (Examples 1 to 173) was added to each well, and the plate was incubated at room temperature for 10 min. The compounds of Test Example 1 were used as control compounds at a concentration of 0.0001 to 10 uM.
Measurement: IC50 = 69 nM (pChEMBL 7.159999847412109)
Descriptors: MW 557.42, ALogP 3.99, HBA 7, HBD 3, PSA 108.48, QED 0.27
Compound (SMILES): Cc1cc(C(=O)N2CCC2)cc2c1-c1ccccc1C2(O)C(F)(F)F
InChIKey: IFSCBPVTGKFEPZ-UHFFFAOYSA-N
Target: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q15119
Assay: Inhibition Assay: The inhibitory action of PDHK activity was indirectly evaluated by performing a kinase reaction in the presence of a test compound and measuring the residual PDH activity. For expression of hPDHK2 activity, Escherichia coli strain BL21(DE3) cells (Novagen) were transformed with the pET17b vector containing modified hPDHK2 cDNA. Escherichia coli were grown to an optical density 0.6 (600 nmol/L) at 30C. Protein expression was induced by the addition of 500 umol/L isopropyl-beta-thiogalactopyranoside. Escherichia coli were cultured at 30 C. for 5 hr and harvested by centrifugation. Resuspension of the Escherichia coli paste was disrupted by a microfluidizer. FLAG-Tagged protein was separated using FLAG affinity gel (Sigma). The gel was washed with 20 mmol/L N-(2-hydroxyethyl)piperazine-N'-2-ethanesulfonic acid-sodium hydroxide (HEPES-NaOH), 500 mmol/L sodium chloride, 1% ethylene glycol, and 0.1% Pluronic F-68 (pH 8.0), and the binding protein was eluted with 20 mmol/L HEPES.
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 347.34, ALogP 3.62, HBA 2, HBD 1, PSA 40.54, QED 0.86
Compound (SMILES): CC1(C)[C@H](Nc2c(C(N)=O)cnn3cc(-c4cccnc4)cc23)CC[C@]1(C)N
InChIKey: MZYWNVPKQJNFLZ-UTKZUKDTSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of GST-tagged JAK2 (unknown origin) after 3 hrs by Caliper assay
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 378.48, ALogP 2.81, HBA 6, HBD 3, PSA 111.33, QED 0.65
Compound (SMILES): Cc1ccncc1-c1cc2c(N[C@@H]3CC[C@](C)(N)C3(C)C)c(C(N)=O)cnn2c1
InChIKey: PNXMWOHTAXWIEX-GCJKJVERSA-N
Target: JAK3/JAK1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P52333
Assay: Inhibition of JAK1/JAK3 in human whole blood assessed as reduction in IL-2 induced IFN-gamma production after 18 hrs by ELISA
Measurement: IC50 = 97 nM (pChEMBL 7.010000228881836)
Descriptors: MW 392.51, ALogP 3.12, HBA 6, HBD 3, PSA 111.33, QED 0.63
Compound (SMILES): Cc1cccc(C(=O)NC23CCCC(NC(=O)c4cccc(Cl)c4)(CC2)C3)n1
InChIKey: IJPARVQEYUOEFX-UHFFFAOYSA-N
Target: N-formyl peptide receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25090
Assay: Radioligand Binding Assay: Binding assays were performed as described in [J. A. O'Brien et al. Mol Pharmacol., 2003, 64, 731-740] with slight modifications, including that a radioligand that binds to the methyl-5-(2-pyridinylethynyl)pyridine (MPEP) binding site was used in place of [3H]-MPEP. Briefly, after thawing, the membrane homogenates were resuspended in 50 mM Tris-HCl and 0.9% NaCl binding buffer at pH 7.4 to a final assay concentration of 20 g protein/well for radioligand filtration binding. Incubations included 5 nM radioligand, membranes and either buffer or varying concentrations of compound. Samples were incubated for 60 min at room temperature with shaking. Non-specific binding was defined with 10 μM cold MPEP when using the radioligand. After incubation, samples were filtered over a GF/C filter (presoaked in 0.25% polyethyleneimine (PEI)) and then washed 4 times using a Tomtec® Harvester 96® Mach III cell harvester (Tomtec, Hamden, Conn.) with 0.5 mL ice-cold 50 mM Tris-HCl (pH 7.4). IC50 values were derived from the inhibition curve and Ki values were calculated according to the Cheng and Prusoff equation of Ki=IC50/(1+[L]/Kd) described in [Y. Cheng and W. H. Prusoff Biochem. Pharmacol. 1973, 22, 3099-3108] where [L] is the concentration of radioligand and Kd is its dissociation constant at the receptor, derived from the saturation isotherm.
Measurement: Ki = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 397.91, ALogP 4.05, HBA 3, HBD 2, PSA 71.09, QED 0.82
Compound (SMILES): Cc1cncc(C(=O)NC23CCCC(NC(=O)c4cccc(F)c4)(CC2)C3)n1
InChIKey: JJSGQCLDNBSOPP-UHFFFAOYSA-N
Target: N-formyl peptide receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25090
Assay: Radioligand Binding Assay: Binding assays were performed as described in [J. A. O'Brien et al. Mol Pharmacol., 2003, 64, 731-740] with slight modifications, including that a radioligand that binds to the methyl-5-(2-pyridinylethynyl)pyridine (MPEP) binding site was used in place of [3H]-MPEP. Briefly, after thawing, the membrane homogenates were resuspended in 50 mM Tris-HCl and 0.9% NaCl binding buffer at pH 7.4 to a final assay concentration of 20 g protein/well for radioligand filtration binding. Incubations included 5 nM radioligand, membranes and either buffer or varying concentrations of compound. Samples were incubated for 60 min at room temperature with shaking. Non-specific binding was defined with 10 μM cold MPEP when using the radioligand. After incubation, samples were filtered over a GF/C filter (presoaked in 0.25% polyethyleneimine (PEI)) and then washed 4 times using a Tomtec® Harvester 96® Mach III cell harvester (Tomtec, Hamden, Conn.) with 0.5 mL ice-cold 50 mM Tris-HCl (pH 7.4). IC50 values were derived from the inhibition curve and Ki values were calculated according to the Cheng and Prusoff equation of Ki=IC50/(1+[L]/Kd) described in [Y. Cheng and W. H. Prusoff Biochem. Pharmacol. 1973, 22, 3099-3108] where [L] is the concentration of radioligand and Kd is its dissociation constant at the receptor, derived from the saturation isotherm.
Measurement: Ki = 78 nM (pChEMBL 7.110000133514404)
Descriptors: MW 382.44, ALogP 2.93, HBA 4, HBD 2, PSA 83.98, QED 0.85
Compound (SMILES): Cc1ncc(C(=O)NC23CCCC(NC(=O)c4cccc(Cl)c4)(CC2)C3)s1
InChIKey: PLUGGALXTRCKCA-UHFFFAOYSA-N
Target: N-formyl peptide receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25090
Assay: Radioligand Binding Assay: Binding assays were performed as described in [J. A. O'Brien et al. Mol Pharmacol., 2003, 64, 731-740] with slight modifications, including that a radioligand that binds to the methyl-5-(2-pyridinylethynyl)pyridine (MPEP) binding site was used in place of [3H]-MPEP. Briefly, after thawing, the membrane homogenates were resuspended in 50 mM Tris-HCl and 0.9% NaCl binding buffer at pH 7.4 to a final assay concentration of 20 g protein/well for radioligand filtration binding. Incubations included 5 nM radioligand, membranes and either buffer or varying concentrations of compound. Samples were incubated for 60 min at room temperature with shaking. Non-specific binding was defined with 10 μM cold MPEP when using the radioligand. After incubation, samples were filtered over a GF/C filter (presoaked in 0.25% polyethyleneimine (PEI)) and then washed 4 times using a Tomtec® Harvester 96® Mach III cell harvester (Tomtec, Hamden, Conn.) with 0.5 mL ice-cold 50 mM Tris-HCl (pH 7.4). IC50 values were derived from the inhibition curve and Ki values were calculated according to the Cheng and Prusoff equation of Ki=IC50/(1+[L]/Kd) described in [Y. Cheng and W. H. Prusoff Biochem. Pharmacol. 1973, 22, 3099-3108] where [L] is the concentration of radioligand and Kd is its dissociation constant at the receptor, derived from the saturation isotherm.
Measurement: Ki = 340 nM (pChEMBL 6.46999979019165)
Descriptors: MW 403.94, ALogP 4.11, HBA 4, HBD 2, PSA 71.09, QED 0.81