lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1cccnc1-c1cc(N2CCN(c3ncc(Br)cn3)CC2)ncc1Cl
InChIKey: WWYGCCZDPROVMS-UHFFFAOYSA-N
Target: Protein smoothened (SINGLE PROTEIN), Homo sapiens
UniProt: Q99835
Assay: Radioligand Competition Binding Assay: For the binding competition assay, 100 μL of Assay Buffer was added to all the wells of a 96 well GF/B filter plate (Millipore MultiScreen-HTS-FB cat# MSFBN6B50) for 10 minutes to pre-wet the filter prior to evacuation of the buffer (8 inches Hg for 8 seconds). To the pre-wet wells is added: 20 μL of Assay Buffer, 10 μL diluted test agent, 20 μL of a tritiated Smo antagonist (15 nM stock solution), and 50 μL of membrane preparation (40 μg total protein per well). The plates are sealed and mixed at room temperature for 5 min, incubated at room temperature for 2 hours, then washed 5 times with 100 μL/each of wash buffer and vacuum dried for 8 seconds at 8 inches Hg. The plate is then dried for one hour in a 60° C. oven prior to the addition of 45 μL of Microscint 20 (Packard, #6013621) to each well and incubation at RT for 30 minutes to 1 hour. The plate is counted in a TopCount scintillation counter (Perkin Elmer).
Measurement: IC50 = 40.3 nM (pChEMBL 7.389999866485596)
Descriptors: MW 445.75, ALogP 3.98, HBA 6, HBD 0, PSA 58.04, QED 0.61
Compound (SMILES): Cc1cccnc1-c1cc(N2CCN(C(=O)CC(C)(C)O)CC2)ncc1Cl
InChIKey: XTXSAWMGFAKDAH-UHFFFAOYSA-N
Target: Protein smoothened (SINGLE PROTEIN), Homo sapiens
UniProt: Q99835
Assay: Radioligand Competition Binding Assay: For the binding competition assay, 100 μL of Assay Buffer was added to all the wells of a 96 well GF/B filter plate (Millipore MultiScreen-HTS-FB cat# MSFBN6B50) for 10 minutes to pre-wet the filter prior to evacuation of the buffer (8 inches Hg for 8 seconds). To the pre-wet wells is added: 20 μL of Assay Buffer, 10 μL diluted test agent, 20 μL of a tritiated Smo antagonist (15 nM stock solution), and 50 μL of membrane preparation (40 μg total protein per well). The plates are sealed and mixed at room temperature for 5 min, incubated at room temperature for 2 hours, then washed 5 times with 100 μL/each of wash buffer and vacuum dried for 8 seconds at 8 inches Hg. The plate is then dried for one hour in a 60° C. oven prior to the addition of 45 μL of Microscint 20 (Packard, #6013621) to each well and incubation at RT for 30 minutes to 1 hour. The plate is counted in a TopCount scintillation counter (Perkin Elmer).
Measurement: IC50 = 21.7 nM (pChEMBL 7.659999847412109)
Descriptors: MW 388.9, ALogP 2.92, HBA 5, HBD 1, PSA 69.56, QED 0.87
Compound (SMILES): Cc1cccnc1-c1cc(N2CCC(CNS(C)(=O)=O)CC2)ncc1Cl
InChIKey: NAFXJLDKWAEQQL-UHFFFAOYSA-N
Target: Protein smoothened (SINGLE PROTEIN), Homo sapiens
UniProt: Q99835
Assay: Radioligand Competition Binding Assay: For the binding competition assay, 100 μL of Assay Buffer was added to all the wells of a 96 well GF/B filter plate (Millipore MultiScreen-HTS-FB cat# MSFBN6B50) for 10 minutes to pre-wet the filter prior to evacuation of the buffer (8 inches Hg for 8 seconds). To the pre-wet wells is added: 20 μL of Assay Buffer, 10 μL diluted test agent, 20 μL of a tritiated Smo antagonist (15 nM stock solution), and 50 μL of membrane preparation (40 μg total protein per well). The plates are sealed and mixed at room temperature for 5 min, incubated at room temperature for 2 hours, then washed 5 times with 100 μL/each of wash buffer and vacuum dried for 8 seconds at 8 inches Hg. The plate is then dried for one hour in a 60° C. oven prior to the addition of 45 μL of Microscint 20 (Packard, #6013621) to each well and incubation at RT for 30 minutes to 1 hour. The plate is counted in a TopCount scintillation counter (Perkin Elmer).
Measurement: IC50 = 57 nM (pChEMBL 7.239999771118164)
Descriptors: MW 394.93, ALogP 2.87, HBA 5, HBD 1, PSA 75.19, QED 0.84
Compound (SMILES): Cc1cccnc1-c1cc(N2CCC(NCCS(C)(=O)=O)CC2)ncc1Cl
InChIKey: WTYLXWLLVMSWMV-UHFFFAOYSA-N
Target: Protein smoothened (SINGLE PROTEIN), Homo sapiens
UniProt: Q99835
Assay: Radioligand Competition Binding Assay: For the binding competition assay, 100 μL of Assay Buffer was added to all the wells of a 96 well GF/B filter plate (Millipore MultiScreen-HTS-FB cat# MSFBN6B50) for 10 minutes to pre-wet the filter prior to evacuation of the buffer (8 inches Hg for 8 seconds). To the pre-wet wells is added: 20 μL of Assay Buffer, 10 μL diluted test agent, 20 μL of a tritiated Smo antagonist (15 nM stock solution), and 50 μL of membrane preparation (40 μg total protein per well). The plates are sealed and mixed at room temperature for 5 min, incubated at room temperature for 2 hours, then washed 5 times with 100 μL/each of wash buffer and vacuum dried for 8 seconds at 8 inches Hg. The plate is then dried for one hour in a 60° C. oven prior to the addition of 45 μL of Microscint 20 (Packard, #6013621) to each well and incubation at RT for 30 minutes to 1 hour. The plate is counted in a TopCount scintillation counter (Perkin Elmer).
Measurement: IC50 = 39 nM (pChEMBL 7.409999847412109)
Descriptors: MW 408.96, ALogP 2.71, HBA 6, HBD 1, PSA 75.19, QED 0.79
Compound (SMILES): Cc1cccnc1-c1ccnc(N2CCC(NS(C)(=O)=O)CC2)n1
InChIKey: SJAARYOXUDOCTO-UHFFFAOYSA-N
Target: Protein smoothened (SINGLE PROTEIN), Homo sapiens
UniProt: Q99835
Assay: Radioligand Competition Binding Assay: For the binding competition assay, 100 μL of Assay Buffer was added to all the wells of a 96 well GF/B filter plate (Millipore MultiScreen-HTS-FB cat# MSFBN6B50) for 10 minutes to pre-wet the filter prior to evacuation of the buffer (8 inches Hg for 8 seconds). To the pre-wet wells is added: 20 μL of Assay Buffer, 10 μL diluted test agent, 20 μL of a tritiated Smo antagonist (15 nM stock solution), and 50 μL of membrane preparation (40 μg total protein per well). The plates are sealed and mixed at room temperature for 5 min, incubated at room temperature for 2 hours, then washed 5 times with 100 μL/each of wash buffer and vacuum dried for 8 seconds at 8 inches Hg. The plate is then dried for one hour in a 60° C. oven prior to the addition of 45 μL of Microscint 20 (Packard, #6013621) to each well and incubation at RT for 30 minutes to 1 hour. The plate is counted in a TopCount scintillation counter (Perkin Elmer).
Measurement: IC50 = 17.7 nM (pChEMBL 7.75)
Descriptors: MW 347.44, ALogP 1.37, HBA 6, HBD 1, PSA 88.08, QED 0.9
Compound (SMILES): Cc1cccnc1-c1cc(N2CCC(CS(C)(=O)=O)CC2)ncc1Cl
InChIKey: RSLWOZPBZRENDK-UHFFFAOYSA-N
Target: Protein smoothened (SINGLE PROTEIN), Homo sapiens
UniProt: Q99835
Assay: Radioligand Competition Binding Assay: For the binding competition assay, 100 μL of Assay Buffer was added to all the wells of a 96 well GF/B filter plate (Millipore MultiScreen-HTS-FB cat# MSFBN6B50) for 10 minutes to pre-wet the filter prior to evacuation of the buffer (8 inches Hg for 8 seconds). To the pre-wet wells is added: 20 μL of Assay Buffer, 10 μL diluted test agent, 20 μL of a tritiated Smo antagonist (15 nM stock solution), and 50 μL of membrane preparation (40 μg total protein per well). The plates are sealed and mixed at room temperature for 5 min, incubated at room temperature for 2 hours, then washed 5 times with 100 μL/each of wash buffer and vacuum dried for 8 seconds at 8 inches Hg. The plate is then dried for one hour in a 60° C. oven prior to the addition of 45 μL of Microscint 20 (Packard, #6013621) to each well and incubation at RT for 30 minutes to 1 hour. The plate is counted in a TopCount scintillation counter (Perkin Elmer).
Measurement: IC50 = 35.8 nM (pChEMBL 7.449999809265137)
Descriptors: MW 379.91, ALogP 3.37, HBA 5, HBD 0, PSA 63.16, QED 0.81
Compound (SMILES): Cc1cccnc1-c1cc(N2CCC(NC(=O)CC(C)(C)O)CC2)ncc1Cl
InChIKey: PHCUCPUPPNSWKD-UHFFFAOYSA-N
Target: Protein smoothened (SINGLE PROTEIN), Homo sapiens
UniProt: Q99835
Assay: Radioligand Competition Binding Assay: For the binding competition assay, 100 μL of Assay Buffer was added to all the wells of a 96 well GF/B filter plate (Millipore MultiScreen-HTS-FB cat# MSFBN6B50) for 10 minutes to pre-wet the filter prior to evacuation of the buffer (8 inches Hg for 8 seconds). To the pre-wet wells is added: 20 μL of Assay Buffer, 10 μL diluted test agent, 20 μL of a tritiated Smo antagonist (15 nM stock solution), and 50 μL of membrane preparation (40 μg total protein per well). The plates are sealed and mixed at room temperature for 5 min, incubated at room temperature for 2 hours, then washed 5 times with 100 μL/each of wash buffer and vacuum dried for 8 seconds at 8 inches Hg. The plate is then dried for one hour in a 60° C. oven prior to the addition of 45 μL of Microscint 20 (Packard, #6013621) to each well and incubation at RT for 30 minutes to 1 hour. The plate is counted in a TopCount scintillation counter (Perkin Elmer).
Measurement: IC50 = 54.3 nM (pChEMBL 7.260000228881836)
Descriptors: MW 402.93, ALogP 3.35, HBA 5, HBD 2, PSA 78.35, QED 0.8
Compound (SMILES): CS(=O)(=O)CC1CCN(c2ccc(Cl)c(-c3ccccn3)n2)CC1
InChIKey: SGUFMILVUPZIQG-UHFFFAOYSA-N
Target: Protein smoothened (SINGLE PROTEIN), Homo sapiens
UniProt: Q99835
Assay: Radioligand Competition Binding Assay: For the binding competition assay, 100 μL of Assay Buffer was added to all the wells of a 96 well GF/B filter plate (Millipore MultiScreen-HTS-FB cat# MSFBN6B50) for 10 minutes to pre-wet the filter prior to evacuation of the buffer (8 inches Hg for 8 seconds). To the pre-wet wells is added: 20 μL of Assay Buffer, 10 μL diluted test agent, 20 μL of a tritiated Smo antagonist (15 nM stock solution), and 50 μL of membrane preparation (40 μg total protein per well). The plates are sealed and mixed at room temperature for 5 min, incubated at room temperature for 2 hours, then washed 5 times with 100 μL/each of wash buffer and vacuum dried for 8 seconds at 8 inches Hg. The plate is then dried for one hour in a 60° C. oven prior to the addition of 45 μL of Microscint 20 (Packard, #6013621) to each well and incubation at RT for 30 minutes to 1 hour. The plate is counted in a TopCount scintillation counter (Perkin Elmer).
Measurement: IC50 = 38.2 nM (pChEMBL 7.420000076293945)
Descriptors: MW 365.89, ALogP 3.06, HBA 5, HBD 0, PSA 63.16, QED 0.83
Compound (SMILES): Cc1cccnc1-c1cc(N2CCC(C(=O)NCc3ncc[nH]3)CC2)ncc1Cl
InChIKey: GDZLWILLTGAIOB-UHFFFAOYSA-N
Target: Protein smoothened (SINGLE PROTEIN), Homo sapiens
UniProt: Q99835
Assay: Radioligand Competition Binding Assay: For the binding competition assay, 100 μL of Assay Buffer was added to all the wells of a 96 well GF/B filter plate (Millipore MultiScreen-HTS-FB cat# MSFBN6B50) for 10 minutes to pre-wet the filter prior to evacuation of the buffer (8 inches Hg for 8 seconds). To the pre-wet wells is added: 20 μL of Assay Buffer, 10 μL diluted test agent, 20 μL of a tritiated Smo antagonist (15 nM stock solution), and 50 μL of membrane preparation (40 μg total protein per well). The plates are sealed and mixed at room temperature for 5 min, incubated at room temperature for 2 hours, then washed 5 times with 100 μL/each of wash buffer and vacuum dried for 8 seconds at 8 inches Hg. The plate is then dried for one hour in a 60° C. oven prior to the addition of 45 μL of Microscint 20 (Packard, #6013621) to each well and incubation at RT for 30 minutes to 1 hour. The plate is counted in a TopCount scintillation counter (Perkin Elmer).
Measurement: IC50 = 64.9 nM (pChEMBL 7.190000057220459)
Descriptors: MW 410.91, ALogP 3.36, HBA 5, HBD 2, PSA 86.8, QED 0.67
Compound (SMILES): Cc1cccnc1-c1cc(N2CCC(C(=O)NC3(c4ccccn4)CC3)CC2)ncc1Cl
InChIKey: LOCCNPPVUUHKJF-UHFFFAOYSA-N
Target: Protein smoothened (SINGLE PROTEIN), Homo sapiens
UniProt: Q99835
Assay: Radioligand Competition Binding Assay: For the binding competition assay, 100 μL of Assay Buffer was added to all the wells of a 96 well GF/B filter plate (Millipore MultiScreen-HTS-FB cat# MSFBN6B50) for 10 minutes to pre-wet the filter prior to evacuation of the buffer (8 inches Hg for 8 seconds). To the pre-wet wells is added: 20 μL of Assay Buffer, 10 μL diluted test agent, 20 μL of a tritiated Smo antagonist (15 nM stock solution), and 50 μL of membrane preparation (40 μg total protein per well). The plates are sealed and mixed at room temperature for 5 min, incubated at room temperature for 2 hours, then washed 5 times with 100 μL/each of wash buffer and vacuum dried for 8 seconds at 8 inches Hg. The plate is then dried for one hour in a 60° C. oven prior to the addition of 45 μL of Microscint 20 (Packard, #6013621) to each well and incubation at RT for 30 minutes to 1 hour. The plate is counted in a TopCount scintillation counter (Perkin Elmer).
Measurement: IC50 = 63.3 nM (pChEMBL 7.199999809265137)
Descriptors: MW 447.97, ALogP 4.52, HBA 5, HBD 1, PSA 71.01, QED 0.62
Compound (SMILES): Cc1cccnc1-c1cc(N2CCC(C(=O)N3CCC(Nc4ccccn4)CC3)CC2)ncc1Cl
InChIKey: OZHLHIAQQGTEDR-UHFFFAOYSA-N
Target: Protein smoothened (SINGLE PROTEIN), Homo sapiens
UniProt: Q99835
Assay: Radioligand Competition Binding Assay: For the binding competition assay, 100 μL of Assay Buffer was added to all the wells of a 96 well GF/B filter plate (Millipore MultiScreen-HTS-FB cat# MSFBN6B50) for 10 minutes to pre-wet the filter prior to evacuation of the buffer (8 inches Hg for 8 seconds). To the pre-wet wells is added: 20 μL of Assay Buffer, 10 μL diluted test agent, 20 μL of a tritiated Smo antagonist (15 nM stock solution), and 50 μL of membrane preparation (40 μg total protein per well). The plates are sealed and mixed at room temperature for 5 min, incubated at room temperature for 2 hours, then washed 5 times with 100 μL/each of wash buffer and vacuum dried for 8 seconds at 8 inches Hg. The plate is then dried for one hour in a 60° C. oven prior to the addition of 45 μL of Microscint 20 (Packard, #6013621) to each well and incubation at RT for 30 minutes to 1 hour. The plate is counted in a TopCount scintillation counter (Perkin Elmer).
Measurement: IC50 = 106 nM (pChEMBL 6.96999979019165)
Descriptors: MW 491.04, ALogP 4.82, HBA 6, HBD 1, PSA 74.25, QED 0.55
Compound (SMILES): Cc1cccnc1-c1cc(N2CCC(C(=O)N[C@@H]3CCN(S(C)(=O)=O)C3)CC2)ncc1Cl
InChIKey: ZVCUWAZEOPIHAB-QGZVFWFLSA-N
Target: Protein smoothened (SINGLE PROTEIN), Homo sapiens
UniProt: Q99835
Assay: Radioligand Competition Binding Assay: For the binding competition assay, 100 μL of Assay Buffer was added to all the wells of a 96 well GF/B filter plate (Millipore MultiScreen-HTS-FB cat# MSFBN6B50) for 10 minutes to pre-wet the filter prior to evacuation of the buffer (8 inches Hg for 8 seconds). To the pre-wet wells is added: 20 μL of Assay Buffer, 10 μL diluted test agent, 20 μL of a tritiated Smo antagonist (15 nM stock solution), and 50 μL of membrane preparation (40 μg total protein per well). The plates are sealed and mixed at room temperature for 5 min, incubated at room temperature for 2 hours, then washed 5 times with 100 μL/each of wash buffer and vacuum dried for 8 seconds at 8 inches Hg. The plate is then dried for one hour in a 60° C. oven prior to the addition of 45 μL of Microscint 20 (Packard, #6013621) to each well and incubation at RT for 30 minutes to 1 hour. The plate is counted in a TopCount scintillation counter (Perkin Elmer).
Measurement: IC50 = 90.7 nM (pChEMBL 7.039999961853027)
Descriptors: MW 478.02, ALogP 2.47, HBA 6, HBD 1, PSA 95.5, QED 0.71
Compound (SMILES): Cc1cccnc1-c1cc(N2CCC(C(=O)N[C@@H]3c4ccccc4C[C@@H]3O)CC2)ncc1Cl
InChIKey: AIOBCPALFXAIAP-WIOPSUGQSA-N
Target: Protein smoothened (SINGLE PROTEIN), Homo sapiens
UniProt: Q99835
Assay: Radioligand Competition Binding Assay: For the binding competition assay, 100 μL of Assay Buffer was added to all the wells of a 96 well GF/B filter plate (Millipore MultiScreen-HTS-FB cat# MSFBN6B50) for 10 minutes to pre-wet the filter prior to evacuation of the buffer (8 inches Hg for 8 seconds). To the pre-wet wells is added: 20 μL of Assay Buffer, 10 μL diluted test agent, 20 μL of a tritiated Smo antagonist (15 nM stock solution), and 50 μL of membrane preparation (40 μg total protein per well). The plates are sealed and mixed at room temperature for 5 min, incubated at room temperature for 2 hours, then washed 5 times with 100 μL/each of wash buffer and vacuum dried for 8 seconds at 8 inches Hg. The plate is then dried for one hour in a 60° C. oven prior to the addition of 45 μL of Microscint 20 (Packard, #6013621) to each well and incubation at RT for 30 minutes to 1 hour. The plate is counted in a TopCount scintillation counter (Perkin Elmer).
Measurement: IC50 = 184 nM (pChEMBL 6.739999771118164)
Descriptors: MW 462.98, ALogP 4.1, HBA 5, HBD 2, PSA 78.35, QED 0.61
Compound (SMILES): COc1cnc(NC(=O)C2CCN(c3cc(-c4ncccc4C)c(Cl)cn3)CC2)cn1
InChIKey: FSGGUYJSHRKIGF-UHFFFAOYSA-N
Target: Protein smoothened (SINGLE PROTEIN), Homo sapiens
UniProt: Q99835
Assay: Radioligand Competition Binding Assay: For the binding competition assay, 100 μL of Assay Buffer was added to all the wells of a 96 well GF/B filter plate (Millipore MultiScreen-HTS-FB cat# MSFBN6B50) for 10 minutes to pre-wet the filter prior to evacuation of the buffer (8 inches Hg for 8 seconds). To the pre-wet wells is added: 20 μL of Assay Buffer, 10 μL diluted test agent, 20 μL of a tritiated Smo antagonist (15 nM stock solution), and 50 μL of membrane preparation (40 μg total protein per well). The plates are sealed and mixed at room temperature for 5 min, incubated at room temperature for 2 hours, then washed 5 times with 100 μL/each of wash buffer and vacuum dried for 8 seconds at 8 inches Hg. The plate is then dried for one hour in a 60° C. oven prior to the addition of 45 μL of Microscint 20 (Packard, #6013621) to each well and incubation at RT for 30 minutes to 1 hour. The plate is counted in a TopCount scintillation counter (Perkin Elmer).
Measurement: IC50 = 71.4 nM (pChEMBL 7.150000095367432)
Descriptors: MW 438.92, ALogP 3.76, HBA 7, HBD 1, PSA 93.13, QED 0.65
Compound (SMILES): Cc1cccnc1-c1cc(N2CCC(C(=O)N[C@H]3CCN(S(C)(=O)=O)C3)CC2)ncc1Cl
InChIKey: ZVCUWAZEOPIHAB-KRWDZBQOSA-N
Target: Protein smoothened (SINGLE PROTEIN), Homo sapiens
UniProt: Q99835
Assay: Radioligand Competition Binding Assay: For the binding competition assay, 100 μL of Assay Buffer was added to all the wells of a 96 well GF/B filter plate (Millipore MultiScreen-HTS-FB cat# MSFBN6B50) for 10 minutes to pre-wet the filter prior to evacuation of the buffer (8 inches Hg for 8 seconds). To the pre-wet wells is added: 20 μL of Assay Buffer, 10 μL diluted test agent, 20 μL of a tritiated Smo antagonist (15 nM stock solution), and 50 μL of membrane preparation (40 μg total protein per well). The plates are sealed and mixed at room temperature for 5 min, incubated at room temperature for 2 hours, then washed 5 times with 100 μL/each of wash buffer and vacuum dried for 8 seconds at 8 inches Hg. The plate is then dried for one hour in a 60° C. oven prior to the addition of 45 μL of Microscint 20 (Packard, #6013621) to each well and incubation at RT for 30 minutes to 1 hour. The plate is counted in a TopCount scintillation counter (Perkin Elmer).
Measurement: IC50 = 67 nM (pChEMBL 7.170000076293945)
Descriptors: MW 478.02, ALogP 2.47, HBA 6, HBD 1, PSA 95.5, QED 0.71
Compound (SMILES): Cc1cccnc1-c1cc(N2CCC(C(=O)NCCC3C(=O)Nc4ccccc43)CC2)ncc1Cl
InChIKey: CLPWZBZTSOALRY-UHFFFAOYSA-N
Target: Protein smoothened (SINGLE PROTEIN), Homo sapiens
UniProt: Q99835
Assay: Radioligand Competition Binding Assay: For the binding competition assay, 100 μL of Assay Buffer was added to all the wells of a 96 well GF/B filter plate (Millipore MultiScreen-HTS-FB cat# MSFBN6B50) for 10 minutes to pre-wet the filter prior to evacuation of the buffer (8 inches Hg for 8 seconds). To the pre-wet wells is added: 20 μL of Assay Buffer, 10 μL diluted test agent, 20 μL of a tritiated Smo antagonist (15 nM stock solution), and 50 μL of membrane preparation (40 μg total protein per well). The plates are sealed and mixed at room temperature for 5 min, incubated at room temperature for 2 hours, then washed 5 times with 100 μL/each of wash buffer and vacuum dried for 8 seconds at 8 inches Hg. The plate is then dried for one hour in a 60° C. oven prior to the addition of 45 μL of Microscint 20 (Packard, #6013621) to each well and incubation at RT for 30 minutes to 1 hour. The plate is counted in a TopCount scintillation counter (Perkin Elmer).
Measurement: IC50 = 40.9 nM (pChEMBL 7.389999866485596)
Descriptors: MW 490.01, ALogP 4.56, HBA 5, HBD 2, PSA 87.22, QED 0.53
Compound (SMILES): Cc1cccnc1-c1cc(N2CCC(C(=O)N3CC(S(=O)(=O)CC4CC4)C3)CC2)ncc1Cl
InChIKey: KVQJOXYYYNDLNJ-UHFFFAOYSA-N
Target: Protein smoothened (SINGLE PROTEIN), Homo sapiens
UniProt: Q99835
Assay: Radioligand Competition Binding Assay: For the binding competition assay, 100 μL of Assay Buffer was added to all the wells of a 96 well GF/B filter plate (Millipore MultiScreen-HTS-FB cat# MSFBN6B50) for 10 minutes to pre-wet the filter prior to evacuation of the buffer (8 inches Hg for 8 seconds). To the pre-wet wells is added: 20 μL of Assay Buffer, 10 μL diluted test agent, 20 μL of a tritiated Smo antagonist (15 nM stock solution), and 50 μL of membrane preparation (40 μg total protein per well). The plates are sealed and mixed at room temperature for 5 min, incubated at room temperature for 2 hours, then washed 5 times with 100 μL/each of wash buffer and vacuum dried for 8 seconds at 8 inches Hg. The plate is then dried for one hour in a 60° C. oven prior to the addition of 45 μL of Microscint 20 (Packard, #6013621) to each well and incubation at RT for 30 minutes to 1 hour. The plate is counted in a TopCount scintillation counter (Perkin Elmer).
Measurement: IC50 = 234 nM (pChEMBL 6.630000114440918)
Descriptors: MW 489.04, ALogP 3.36, HBA 6, HBD 0, PSA 83.47, QED 0.62
Compound (SMILES): Cc1cccnc1-c1cc(N2CCC(C(=O)NC[C@H]3CCCO3)CC2)ncc1Cl
InChIKey: BZNDFZAVUBXGOV-QGZVFWFLSA-N
Target: Protein smoothened (SINGLE PROTEIN), Homo sapiens
UniProt: Q99835
Assay: Radioligand Competition Binding Assay: For the binding competition assay, 100 μL of Assay Buffer was added to all the wells of a 96 well GF/B filter plate (Millipore MultiScreen-HTS-FB cat# MSFBN6B50) for 10 minutes to pre-wet the filter prior to evacuation of the buffer (8 inches Hg for 8 seconds). To the pre-wet wells is added: 20 μL of Assay Buffer, 10 μL diluted test agent, 20 μL of a tritiated Smo antagonist (15 nM stock solution), and 50 μL of membrane preparation (40 μg total protein per well). The plates are sealed and mixed at room temperature for 5 min, incubated at room temperature for 2 hours, then washed 5 times with 100 μL/each of wash buffer and vacuum dried for 8 seconds at 8 inches Hg. The plate is then dried for one hour in a 60° C. oven prior to the addition of 45 μL of Microscint 20 (Packard, #6013621) to each well and incubation at RT for 30 minutes to 1 hour. The plate is counted in a TopCount scintillation counter (Perkin Elmer).
Measurement: IC50 = 137 nM (pChEMBL 6.860000133514404)
Descriptors: MW 414.94, ALogP 3.62, HBA 5, HBD 1, PSA 67.35, QED 0.81
Compound (SMILES): Cc1cccnc1-c1cc(N2CCC(C(=O)NCC3(O)CCC3)CC2)ncc1Cl
InChIKey: SUZRODZAHZGKMX-UHFFFAOYSA-N
Target: Protein smoothened (SINGLE PROTEIN), Homo sapiens
UniProt: Q99835
Assay: Radioligand Competition Binding Assay: For the binding competition assay, 100 μL of Assay Buffer was added to all the wells of a 96 well GF/B filter plate (Millipore MultiScreen-HTS-FB cat# MSFBN6B50) for 10 minutes to pre-wet the filter prior to evacuation of the buffer (8 inches Hg for 8 seconds). To the pre-wet wells is added: 20 μL of Assay Buffer, 10 μL diluted test agent, 20 μL of a tritiated Smo antagonist (15 nM stock solution), and 50 μL of membrane preparation (40 μg total protein per well). The plates are sealed and mixed at room temperature for 5 min, incubated at room temperature for 2 hours, then washed 5 times with 100 μL/each of wash buffer and vacuum dried for 8 seconds at 8 inches Hg. The plate is then dried for one hour in a 60° C. oven prior to the addition of 45 μL of Microscint 20 (Packard, #6013621) to each well and incubation at RT for 30 minutes to 1 hour. The plate is counted in a TopCount scintillation counter (Perkin Elmer).
Measurement: IC50 = 157 nM (pChEMBL 6.800000190734863)
Descriptors: MW 414.94, ALogP 3.35, HBA 5, HBD 2, PSA 78.35, QED 0.78
Compound (SMILES): Cc1cccnc1-c1cc(N2CCC(C(=O)N3CCc4c(c(C(C)C)nn4C)C3)CC2)ncc1Cl
InChIKey: IGUKANISNAZKPA-UHFFFAOYSA-N
Target: Protein smoothened (SINGLE PROTEIN), Homo sapiens
UniProt: Q99835
Assay: Radioligand Competition Binding Assay: For the binding competition assay, 100 μL of Assay Buffer was added to all the wells of a 96 well GF/B filter plate (Millipore MultiScreen-HTS-FB cat# MSFBN6B50) for 10 minutes to pre-wet the filter prior to evacuation of the buffer (8 inches Hg for 8 seconds). To the pre-wet wells is added: 20 μL of Assay Buffer, 10 μL diluted test agent, 20 μL of a tritiated Smo antagonist (15 nM stock solution), and 50 μL of membrane preparation (40 μg total protein per well). The plates are sealed and mixed at room temperature for 5 min, incubated at room temperature for 2 hours, then washed 5 times with 100 μL/each of wash buffer and vacuum dried for 8 seconds at 8 inches Hg. The plate is then dried for one hour in a 60° C. oven prior to the addition of 45 μL of Microscint 20 (Packard, #6013621) to each well and incubation at RT for 30 minutes to 1 hour. The plate is counted in a TopCount scintillation counter (Perkin Elmer).
Measurement: IC50 = 145 nM (pChEMBL 6.840000152587891)
Descriptors: MW 493.06, ALogP 4.76, HBA 6, HBD 0, PSA 67.15, QED 0.52
Compound (SMILES): Cc1cccnc1-c1cc(N2CCC(C(=O)N[C@@H]3CC[C@@H](O)C3)CC2)ncc1Cl
InChIKey: WCLLDRLJFCQECL-IAGOWNOFSA-N
Target: Protein smoothened (SINGLE PROTEIN), Homo sapiens
UniProt: Q99835
Assay: Radioligand Competition Binding Assay: For the binding competition assay, 100 μL of Assay Buffer was added to all the wells of a 96 well GF/B filter plate (Millipore MultiScreen-HTS-FB cat# MSFBN6B50) for 10 minutes to pre-wet the filter prior to evacuation of the buffer (8 inches Hg for 8 seconds). To the pre-wet wells is added: 20 μL of Assay Buffer, 10 μL diluted test agent, 20 μL of a tritiated Smo antagonist (15 nM stock solution), and 50 μL of membrane preparation (40 μg total protein per well). The plates are sealed and mixed at room temperature for 5 min, incubated at room temperature for 2 hours, then washed 5 times with 100 μL/each of wash buffer and vacuum dried for 8 seconds at 8 inches Hg. The plate is then dried for one hour in a 60° C. oven prior to the addition of 45 μL of Microscint 20 (Packard, #6013621) to each well and incubation at RT for 30 minutes to 1 hour. The plate is counted in a TopCount scintillation counter (Perkin Elmer).
Measurement: IC50 = 162 nM (pChEMBL 6.789999961853027)
Descriptors: MW 414.94, ALogP 3.35, HBA 5, HBD 2, PSA 78.35, QED 0.8
Compound (SMILES): Cc1cccnc1-c1cc(N2CCC(C(=O)NCCS(C)(=O)=O)CC2)ncc1Cl
InChIKey: KQZSNWSGGOQJAF-UHFFFAOYSA-N
Target: Protein smoothened (SINGLE PROTEIN), Homo sapiens
UniProt: Q99835
Assay: Radioligand Competition Binding Assay: For the binding competition assay, 100 μL of Assay Buffer was added to all the wells of a 96 well GF/B filter plate (Millipore MultiScreen-HTS-FB cat# MSFBN6B50) for 10 minutes to pre-wet the filter prior to evacuation of the buffer (8 inches Hg for 8 seconds). To the pre-wet wells is added: 20 μL of Assay Buffer, 10 μL diluted test agent, 20 μL of a tritiated Smo antagonist (15 nM stock solution), and 50 μL of membrane preparation (40 μg total protein per well). The plates are sealed and mixed at room temperature for 5 min, incubated at room temperature for 2 hours, then washed 5 times with 100 μL/each of wash buffer and vacuum dried for 8 seconds at 8 inches Hg. The plate is then dried for one hour in a 60° C. oven prior to the addition of 45 μL of Microscint 20 (Packard, #6013621) to each well and incubation at RT for 30 minutes to 1 hour. The plate is counted in a TopCount scintillation counter (Perkin Elmer).
Measurement: IC50 = 217 nM (pChEMBL 6.659999847412109)
Descriptors: MW 436.97, ALogP 2.48, HBA 6, HBD 1, PSA 92.26, QED 0.75
Compound (SMILES): Cc1cccnc1-c1cc(N2CCC(C(=O)N[C@@H]3CS(=O)(=O)C[C@H]3O)CC2)ncc1Cl
InChIKey: ZXKPYYNXJBOKHX-QZTJIDSGSA-N
Target: Protein smoothened (SINGLE PROTEIN), Homo sapiens
UniProt: Q99835
Assay: Radioligand Competition Binding Assay: For the binding competition assay, 100 μL of Assay Buffer was added to all the wells of a 96 well GF/B filter plate (Millipore MultiScreen-HTS-FB cat# MSFBN6B50) for 10 minutes to pre-wet the filter prior to evacuation of the buffer (8 inches Hg for 8 seconds). To the pre-wet wells is added: 20 μL of Assay Buffer, 10 μL diluted test agent, 20 μL of a tritiated Smo antagonist (15 nM stock solution), and 50 μL of membrane preparation (40 μg total protein per well). The plates are sealed and mixed at room temperature for 5 min, incubated at room temperature for 2 hours, then washed 5 times with 100 μL/each of wash buffer and vacuum dried for 8 seconds at 8 inches Hg. The plate is then dried for one hour in a 60° C. oven prior to the addition of 45 μL of Microscint 20 (Packard, #6013621) to each well and incubation at RT for 30 minutes to 1 hour. The plate is counted in a TopCount scintillation counter (Perkin Elmer).
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 464.98, ALogP 1.6, HBA 7, HBD 2, PSA 112.49, QED 0.71
Compound (SMILES): Cc1cccnc1-c1cc(N2CC(C(=O)N(C)[C@@H]3CS(=O)(=O)C[C@H]3O)C2)ncc1Cl
InChIKey: BDIUPYVIEMNOIL-IAGOWNOFSA-N
Target: Protein smoothened (SINGLE PROTEIN), Homo sapiens
UniProt: Q99835
Assay: Radioligand Competition Binding Assay: For the binding competition assay, 100 μL of Assay Buffer was added to all the wells of a 96 well GF/B filter plate (Millipore MultiScreen-HTS-FB cat# MSFBN6B50) for 10 minutes to pre-wet the filter prior to evacuation of the buffer (8 inches Hg for 8 seconds). To the pre-wet wells is added: 20 μL of Assay Buffer, 10 μL diluted test agent, 20 μL of a tritiated Smo antagonist (15 nM stock solution), and 50 μL of membrane preparation (40 μg total protein per well). The plates are sealed and mixed at room temperature for 5 min, incubated at room temperature for 2 hours, then washed 5 times with 100 μL/each of wash buffer and vacuum dried for 8 seconds at 8 inches Hg. The plate is then dried for one hour in a 60° C. oven prior to the addition of 45 μL of Microscint 20 (Packard, #6013621) to each well and incubation at RT for 30 minutes to 1 hour. The plate is counted in a TopCount scintillation counter (Perkin Elmer).
Measurement: IC50 = 189 nM (pChEMBL 6.71999979019165)
Descriptors: MW 450.95, ALogP 1.16, HBA 7, HBD 1, PSA 103.7, QED 0.74
Compound (SMILES): Cc1cccnc1-c1cc(N2CCC(C(=O)N(C)[C@@H]3CS(=O)(=O)C[C@H]3O)CC2)ncc1Cl
InChIKey: RIKZWYQHWWQAGA-RTBURBONSA-N
Target: Protein smoothened (SINGLE PROTEIN), Homo sapiens
UniProt: Q99835
Assay: Radioligand Competition Binding Assay: For the binding competition assay, 100 μL of Assay Buffer was added to all the wells of a 96 well GF/B filter plate (Millipore MultiScreen-HTS-FB cat# MSFBN6B50) for 10 minutes to pre-wet the filter prior to evacuation of the buffer (8 inches Hg for 8 seconds). To the pre-wet wells is added: 20 μL of Assay Buffer, 10 μL diluted test agent, 20 μL of a tritiated Smo antagonist (15 nM stock solution), and 50 μL of membrane preparation (40 μg total protein per well). The plates are sealed and mixed at room temperature for 5 min, incubated at room temperature for 2 hours, then washed 5 times with 100 μL/each of wash buffer and vacuum dried for 8 seconds at 8 inches Hg. The plate is then dried for one hour in a 60° C. oven prior to the addition of 45 μL of Microscint 20 (Packard, #6013621) to each well and incubation at RT for 30 minutes to 1 hour. The plate is counted in a TopCount scintillation counter (Perkin Elmer).
Measurement: IC50 = 42.4 nM (pChEMBL 7.369999885559082)
Descriptors: MW 479, ALogP 1.94, HBA 7, HBD 1, PSA 103.7, QED 0.72
Compound (SMILES): Cc1cccnc1-c1cc(N2CCC(C(=O)N[C@H]3CC[C@@H](O)CC3)CC2)ncc1Cl
InChIKey: ISYJQZYGORBUCM-HDICACEKSA-N
Target: Protein smoothened (SINGLE PROTEIN), Homo sapiens
UniProt: Q99835
Assay: Radioligand Competition Binding Assay: For the binding competition assay, 100 μL of Assay Buffer was added to all the wells of a 96 well GF/B filter plate (Millipore MultiScreen-HTS-FB cat# MSFBN6B50) for 10 minutes to pre-wet the filter prior to evacuation of the buffer (8 inches Hg for 8 seconds). To the pre-wet wells is added: 20 μL of Assay Buffer, 10 μL diluted test agent, 20 μL of a tritiated Smo antagonist (15 nM stock solution), and 50 μL of membrane preparation (40 μg total protein per well). The plates are sealed and mixed at room temperature for 5 min, incubated at room temperature for 2 hours, then washed 5 times with 100 μL/each of wash buffer and vacuum dried for 8 seconds at 8 inches Hg. The plate is then dried for one hour in a 60° C. oven prior to the addition of 45 μL of Microscint 20 (Packard, #6013621) to each well and incubation at RT for 30 minutes to 1 hour. The plate is counted in a TopCount scintillation counter (Perkin Elmer).
Measurement: IC50 = 72.9 nM (pChEMBL 7.139999866485596)
Descriptors: MW 428.96, ALogP 3.74, HBA 5, HBD 2, PSA 78.35, QED 0.78
Compound (SMILES): Cc1cccnc1-c1cc(N2CCC(C(=O)NC3CCCCC3O)CC2)ncc1Cl
InChIKey: NTTNRQXSHZICRR-UHFFFAOYSA-N
Target: Protein smoothened (SINGLE PROTEIN), Homo sapiens
UniProt: Q99835
Assay: Radioligand Competition Binding Assay: For the binding competition assay, 100 μL of Assay Buffer was added to all the wells of a 96 well GF/B filter plate (Millipore MultiScreen-HTS-FB cat# MSFBN6B50) for 10 minutes to pre-wet the filter prior to evacuation of the buffer (8 inches Hg for 8 seconds). To the pre-wet wells is added: 20 μL of Assay Buffer, 10 μL diluted test agent, 20 μL of a tritiated Smo antagonist (15 nM stock solution), and 50 μL of membrane preparation (40 μg total protein per well). The plates are sealed and mixed at room temperature for 5 min, incubated at room temperature for 2 hours, then washed 5 times with 100 μL/each of wash buffer and vacuum dried for 8 seconds at 8 inches Hg. The plate is then dried for one hour in a 60° C. oven prior to the addition of 45 μL of Microscint 20 (Packard, #6013621) to each well and incubation at RT for 30 minutes to 1 hour. The plate is counted in a TopCount scintillation counter (Perkin Elmer).
Measurement: IC50 = 28.3 nM (pChEMBL 7.550000190734863)
Descriptors: MW 428.96, ALogP 3.74, HBA 5, HBD 2, PSA 78.35, QED 0.78
Compound (SMILES): Cc1cccnc1-c1cc(N2CCC(C(=O)NCCc3nc4cccnc4n3C)CC2)ncc1Cl
InChIKey: UNDKTNMPMFCHOS-UHFFFAOYSA-N
Target: Protein smoothened (SINGLE PROTEIN), Homo sapiens
UniProt: Q99835
Assay: Radioligand Competition Binding Assay: For the binding competition assay, 100 μL of Assay Buffer was added to all the wells of a 96 well GF/B filter plate (Millipore MultiScreen-HTS-FB cat# MSFBN6B50) for 10 minutes to pre-wet the filter prior to evacuation of the buffer (8 inches Hg for 8 seconds). To the pre-wet wells is added: 20 μL of Assay Buffer, 10 μL diluted test agent, 20 μL of a tritiated Smo antagonist (15 nM stock solution), and 50 μL of membrane preparation (40 μg total protein per well). The plates are sealed and mixed at room temperature for 5 min, incubated at room temperature for 2 hours, then washed 5 times with 100 μL/each of wash buffer and vacuum dried for 8 seconds at 8 inches Hg. The plate is then dried for one hour in a 60° C. oven prior to the addition of 45 μL of Microscint 20 (Packard, #6013621) to each well and incubation at RT for 30 minutes to 1 hour. The plate is counted in a TopCount scintillation counter (Perkin Elmer).
Measurement: IC50 = 154 nM (pChEMBL 6.809999942779541)
Descriptors: MW 490.01, ALogP 3.96, HBA 7, HBD 1, PSA 88.83, QED 0.44
Compound (SMILES): Cc1cccnc1-c1cc(N2CCC(C(=O)NCC3CN(CC4CC4)C(=O)CO3)CC2)ncc1Cl
InChIKey: LGMVLETUCZMVHX-UHFFFAOYSA-N
Target: Protein smoothened (SINGLE PROTEIN), Homo sapiens
UniProt: Q99835
Assay: Radioligand Competition Binding Assay: For the binding competition assay, 100 μL of Assay Buffer was added to all the wells of a 96 well GF/B filter plate (Millipore MultiScreen-HTS-FB cat# MSFBN6B50) for 10 minutes to pre-wet the filter prior to evacuation of the buffer (8 inches Hg for 8 seconds). To the pre-wet wells is added: 20 μL of Assay Buffer, 10 μL diluted test agent, 20 μL of a tritiated Smo antagonist (15 nM stock solution), and 50 μL of membrane preparation (40 μg total protein per well). The plates are sealed and mixed at room temperature for 5 min, incubated at room temperature for 2 hours, then washed 5 times with 100 μL/each of wash buffer and vacuum dried for 8 seconds at 8 inches Hg. The plate is then dried for one hour in a 60° C. oven prior to the addition of 45 μL of Microscint 20 (Packard, #6013621) to each well and incubation at RT for 30 minutes to 1 hour. The plate is counted in a TopCount scintillation counter (Perkin Elmer).
Measurement: IC50 = 25.5 nM (pChEMBL 7.590000152587891)
Descriptors: MW 498.03, ALogP 3.08, HBA 6, HBD 1, PSA 87.66, QED 0.63
Compound (SMILES): Cc1cccnc1-c1cc(N2CCC(C(=O)Nc3cccc(CO)n3)CC2)ncc1Cl
InChIKey: JJVGDTHJKOIFNP-UHFFFAOYSA-N
Target: Protein smoothened (SINGLE PROTEIN), Homo sapiens
UniProt: Q99835
Assay: Radioligand Competition Binding Assay: For the binding competition assay, 100 μL of Assay Buffer was added to all the wells of a 96 well GF/B filter plate (Millipore MultiScreen-HTS-FB cat# MSFBN6B50) for 10 minutes to pre-wet the filter prior to evacuation of the buffer (8 inches Hg for 8 seconds). To the pre-wet wells is added: 20 μL of Assay Buffer, 10 μL diluted test agent, 20 μL of a tritiated Smo antagonist (15 nM stock solution), and 50 μL of membrane preparation (40 μg total protein per well). The plates are sealed and mixed at room temperature for 5 min, incubated at room temperature for 2 hours, then washed 5 times with 100 μL/each of wash buffer and vacuum dried for 8 seconds at 8 inches Hg. The plate is then dried for one hour in a 60° C. oven prior to the addition of 45 μL of Microscint 20 (Packard, #6013621) to each well and incubation at RT for 30 minutes to 1 hour. The plate is counted in a TopCount scintillation counter (Perkin Elmer).
Measurement: IC50 = 93.3 nM (pChEMBL 7.03000020980835)
Descriptors: MW 437.93, ALogP 3.85, HBA 6, HBD 2, PSA 91.24, QED 0.63
Compound (SMILES): Cc1cccnc1-c1cc(N2CCC(C(=O)NC3(CO)CCCC3)CC2)ncc1Cl
InChIKey: MWWLSQSQXQTMIH-UHFFFAOYSA-N
Target: Protein smoothened (SINGLE PROTEIN), Homo sapiens
UniProt: Q99835
Assay: Radioligand Competition Binding Assay: For the binding competition assay, 100 μL of Assay Buffer was added to all the wells of a 96 well GF/B filter plate (Millipore MultiScreen-HTS-FB cat# MSFBN6B50) for 10 minutes to pre-wet the filter prior to evacuation of the buffer (8 inches Hg for 8 seconds). To the pre-wet wells is added: 20 μL of Assay Buffer, 10 μL diluted test agent, 20 μL of a tritiated Smo antagonist (15 nM stock solution), and 50 μL of membrane preparation (40 μg total protein per well). The plates are sealed and mixed at room temperature for 5 min, incubated at room temperature for 2 hours, then washed 5 times with 100 μL/each of wash buffer and vacuum dried for 8 seconds at 8 inches Hg. The plate is then dried for one hour in a 60° C. oven prior to the addition of 45 μL of Microscint 20 (Packard, #6013621) to each well and incubation at RT for 30 minutes to 1 hour. The plate is counted in a TopCount scintillation counter (Perkin Elmer).
Measurement: IC50 = 25.8 nM (pChEMBL 7.590000152587891)
Descriptors: MW 428.96, ALogP 3.74, HBA 5, HBD 2, PSA 78.35, QED 0.76
Compound (SMILES): Cc1cccnc1-c1cc(N2CCC(C(=O)NC3CCOCC3)CC2)ncc1Cl
InChIKey: WIAGYIIRVTVVAJ-UHFFFAOYSA-N
Target: Protein smoothened (SINGLE PROTEIN), Homo sapiens
UniProt: Q99835
Assay: Radioligand Competition Binding Assay: For the binding competition assay, 100 μL of Assay Buffer was added to all the wells of a 96 well GF/B filter plate (Millipore MultiScreen-HTS-FB cat# MSFBN6B50) for 10 minutes to pre-wet the filter prior to evacuation of the buffer (8 inches Hg for 8 seconds). To the pre-wet wells is added: 20 μL of Assay Buffer, 10 μL diluted test agent, 20 μL of a tritiated Smo antagonist (15 nM stock solution), and 50 μL of membrane preparation (40 μg total protein per well). The plates are sealed and mixed at room temperature for 5 min, incubated at room temperature for 2 hours, then washed 5 times with 100 μL/each of wash buffer and vacuum dried for 8 seconds at 8 inches Hg. The plate is then dried for one hour in a 60° C. oven prior to the addition of 45 μL of Microscint 20 (Packard, #6013621) to each well and incubation at RT for 30 minutes to 1 hour. The plate is counted in a TopCount scintillation counter (Perkin Elmer).
Measurement: IC50 = 52.5 nM (pChEMBL 7.28000020980835)
Descriptors: MW 414.94, ALogP 3.62, HBA 5, HBD 1, PSA 67.35, QED 0.83
Compound (SMILES): CC(=O)c1cnc2ccc(-c3ccncc3)nc2c1N[C@H]1CC[C@H](CN(C)C)CC1
InChIKey: NKCHIXRHDOVERC-UAPYVXQJSA-N
Target: Maternal embryonic leucine zipper kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q14680
Assay: Kinase Assay: MELK activity was determined in the presence or absence of compounds using fluorescein isothiocyanate-labeled (FITC-labeled) histone H3 peptide as a substrate. The extent of FITC-labeled histone H3 peptide phosphorylation was measured by immobilized metal ion affinity-based fluorescence polarization (IMAP) technology (Sportsman J R, et al., Assay Drug Dev. Technol. 2: 205-14, 2004) using IMAP FP Progressive Binding System (Molecular Devices Corporation). Test compounds were dissolved in DMSO at 12.5 mM and then serially diluted as the DMSO concentration in the assays to be 1%. The serially diluted compounds, 0.8 ng/micro-L PBK (Carna Biosciences) and 100 nM FITC-labeled histone H3 peptide were reacted in a reaction buffer (20 mM HEPES, 0.01% Tween-20, 0.3 mM MgCl2, 2 mM dithiothreitol, 50 micro-M ATP, pH 7.4) at room temperature for 1 hour. The reaction was stopped by the addition of three fold assay volume of progressive binding solution. Following 0.5 hour incubation at room temperature.
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 403.53, ALogP 4.43, HBA 6, HBD 1, PSA 71.01, QED 0.61
Compound (SMILES): CC(=O)c1cnc2ccc(-c3cnc(C#N)nc3)nc2c1N[C@H]1CC[C@H](CN(C)C)CC1
InChIKey: PTIKWHGFZNDTPO-SAABIXHNSA-N
Target: Maternal embryonic leucine zipper kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q14680
Assay: Kinase Assay: MELK activity was determined in the presence or absence of compounds using fluorescein isothiocyanate-labeled (FITC-labeled) histone H3 peptide as a substrate. The extent of FITC-labeled histone H3 peptide phosphorylation was measured by immobilized metal ion affinity-based fluorescence polarization (IMAP) technology (Sportsman J R, et al., Assay Drug Dev. Technol. 2: 205-14, 2004) using IMAP FP Progressive Binding System (Molecular Devices Corporation). Test compounds were dissolved in DMSO at 12.5 mM and then serially diluted as the DMSO concentration in the assays to be 1%. The serially diluted compounds, 0.8 ng/micro-L PBK (Carna Biosciences) and 100 nM FITC-labeled histone H3 peptide were reacted in a reaction buffer (20 mM HEPES, 0.01% Tween-20, 0.3 mM MgCl2, 2 mM dithiothreitol, 50 micro-M ATP, pH 7.4) at room temperature for 1 hour. The reaction was stopped by the addition of three fold assay volume of progressive binding solution. Following 0.5 hour incubation at room temperature.
Measurement: IC50 = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 429.53, ALogP 3.69, HBA 8, HBD 1, PSA 107.69, QED 0.59
Compound (SMILES): CC(=O)c1cnc2ccc(-c3c(C)n[nH]c3C)nc2c1N[C@H]1CC[C@H](CN(C)C)CC1
InChIKey: MAIRXTLEGWHTAJ-IYARVYRRSA-N
Target: Maternal embryonic leucine zipper kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q14680
Assay: Kinase Assay: MELK activity was determined in the presence or absence of compounds using fluorescein isothiocyanate-labeled (FITC-labeled) histone H3 peptide as a substrate. The extent of FITC-labeled histone H3 peptide phosphorylation was measured by immobilized metal ion affinity-based fluorescence polarization (IMAP) technology (Sportsman J R, et al., Assay Drug Dev. Technol. 2: 205-14, 2004) using IMAP FP Progressive Binding System (Molecular Devices Corporation). Test compounds were dissolved in DMSO at 12.5 mM and then serially diluted as the DMSO concentration in the assays to be 1%. The serially diluted compounds, 0.8 ng/micro-L PBK (Carna Biosciences) and 100 nM FITC-labeled histone H3 peptide were reacted in a reaction buffer (20 mM HEPES, 0.01% Tween-20, 0.3 mM MgCl2, 2 mM dithiothreitol, 50 micro-M ATP, pH 7.4) at room temperature for 1 hour. The reaction was stopped by the addition of three fold assay volume of progressive binding solution. Following 0.5 hour incubation at room temperature.
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 420.56, ALogP 4.37, HBA 6, HBD 2, PSA 86.8, QED 0.58
Compound (SMILES): CC(=O)c1cnc2ccc(-c3cc(C)c(O)c(C)c3)nc2c1N[C@H]1CC[C@H](CN(C)C)CC1
InChIKey: XJHYWAHLWAFFNT-XUTJKUGGSA-N
Target: Maternal embryonic leucine zipper kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q14680
Assay: Kinase Assay: MELK activity was determined in the presence or absence of compounds using fluorescein isothiocyanate-labeled (FITC-labeled) histone H3 peptide as a substrate. The extent of FITC-labeled histone H3 peptide phosphorylation was measured by immobilized metal ion affinity-based fluorescence polarization (IMAP) technology (Sportsman J R, et al., Assay Drug Dev. Technol. 2: 205-14, 2004) using IMAP FP Progressive Binding System (Molecular Devices Corporation). Test compounds were dissolved in DMSO at 12.5 mM and then serially diluted as the DMSO concentration in the assays to be 1%. The serially diluted compounds, 0.8 ng/micro-L PBK (Carna Biosciences) and 100 nM FITC-labeled histone H3 peptide were reacted in a reaction buffer (20 mM HEPES, 0.01% Tween-20, 0.3 mM MgCl2, 2 mM dithiothreitol, 50 micro-M ATP, pH 7.4) at room temperature for 1 hour. The reaction was stopped by the addition of three fold assay volume of progressive binding solution. Following 0.5 hour incubation at room temperature.
Measurement: IC50 = 4.7 nM (pChEMBL 8.329999923706055)
Descriptors: MW 446.6, ALogP 5.35, HBA 6, HBD 2, PSA 78.35, QED 0.5
Compound (SMILES): CC(=O)c1cnc2ccc(-c3cc(Cl)c(O)c(Cl)c3)nc2c1Nc1ccc(CN2CCCC2)cc1
InChIKey: XPMNOLGQYXKBRX-UHFFFAOYSA-N
Target: Maternal embryonic leucine zipper kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q14680
Assay: Kinase Assay: MELK activity was determined in the presence or absence of compounds using fluorescein isothiocyanate-labeled (FITC-labeled) histone H3 peptide as a substrate. The extent of FITC-labeled histone H3 peptide phosphorylation was measured by immobilized metal ion affinity-based fluorescence polarization (IMAP) technology (Sportsman J R, et al., Assay Drug Dev. Technol. 2: 205-14, 2004) using IMAP FP Progressive Binding System (Molecular Devices Corporation). Test compounds were dissolved in DMSO at 12.5 mM and then serially diluted as the DMSO concentration in the assays to be 1%. The serially diluted compounds, 0.8 ng/micro-L PBK (Carna Biosciences) and 100 nM FITC-labeled histone H3 peptide were reacted in a reaction buffer (20 mM HEPES, 0.01% Tween-20, 0.3 mM MgCl2, 2 mM dithiothreitol, 50 micro-M ATP, pH 7.4) at room temperature for 1 hour. The reaction was stopped by the addition of three fold assay volume of progressive binding solution. Following 0.5 hour incubation at room temperature.
Measurement: IC50 = 4.3 nM (pChEMBL 8.369999885559082)
Descriptors: MW 507.42, ALogP 6.85, HBA 6, HBD 2, PSA 78.35, QED 0.28