lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1cnc(-c2cc(N3CCC(NC(=O)CN(C)C)CC3)ncc2Cl)c(C)c1
InChIKey: URKKDINNSQCVMY-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 = 19.2 nM (pChEMBL 7.71999979019165)
Descriptors: MW 401.94, ALogP 3.06, HBA 5, HBD 1, PSA 61.36, QED 0.83
Compound (SMILES): Cc1ccc(-c2cccc(N3CCC(NS(C)(=O)=O)CC3)n2)nc1
InChIKey: CUVTYUMVTZJELY-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 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 346.46, ALogP 1.97, HBA 5, HBD 1, PSA 75.19, QED 0.92
Compound (SMILES): Cc1ccc(-c2nc(N3CCC(NS(C)(=O)=O)CC3)ccc2Cl)nc1
InChIKey: NWYXETFNIUDPRH-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 nM (pChEMBL 7.769999980926514)
Descriptors: MW 380.9, ALogP 2.62, HBA 5, HBD 1, PSA 75.19, QED 0.88
Compound (SMILES): Cc1cnc(-c2cc(N3CCC(CS(N)(=O)=O)CC3)ncc2Cl)c(C)c1
InChIKey: BOXLEZKOEYHBKG-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 = 11.1 nM (pChEMBL 7.960000038146973)
Descriptors: MW 394.93, ALogP 2.92, HBA 5, HBD 1, PSA 89.18, QED 0.86
Compound (SMILES): Cc1ccc(-c2nc(N3CCC(NS(C)(=O)=O)CC3)ncc2Cl)nc1
InChIKey: BDNGRZRQJSFVDU-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 = 58.9 nM (pChEMBL 7.230000019073486)
Descriptors: MW 381.89, ALogP 2.02, HBA 6, HBD 1, PSA 88.08, QED 0.87
Compound (SMILES): Cc1ccc(-c2nc(N3CCC(NS(C)(=O)=O)CC3)ccc2Br)nc1
InChIKey: NAOPBCISQQKFDC-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 nM (pChEMBL 7.400000095367432)
Descriptors: MW 425.35, ALogP 2.73, HBA 5, HBD 1, PSA 75.19, QED 0.82
Compound (SMILES): CCS(=O)(=O)NC1CCN(c2cc(-c3ncc(C)cc3C)c(Cl)cn2)CC1
InChIKey: ZYCKBJNDZSHUAA-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 = 11.6 nM (pChEMBL 7.940000057220459)
Descriptors: MW 408.96, ALogP 3.32, HBA 5, HBD 1, PSA 75.19, QED 0.82
Compound (SMILES): Cc1cnc(-c2cc(N3CCC(NC(=O)CCS(C)(=O)=O)CC3)ncc2Cl)c(C)c1
InChIKey: RAHBTVQAKXOZGK-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 = 14.7 nM (pChEMBL 7.829999923706055)
Descriptors: MW 450.99, ALogP 2.93, HBA 6, HBD 1, PSA 92.26, QED 0.73
Compound (SMILES): COCCS(=O)(=O)NC1CCN(c2ccc(Cl)c(-c3ccccn3)n2)CC1
InChIKey: XITJZIHYTZJZMU-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 = 26.7 nM (pChEMBL 7.570000171661377)
Descriptors: MW 410.93, ALogP 2.33, HBA 6, HBD 1, PSA 84.42, QED 0.75
Compound (SMILES): Cc1cccnc1-c1cc(N2[C@@H]3CC[C@H]2[C@@H](NS(C)(=O)=O)C3)ncc1Cl
InChIKey: PZZQRDUOMXENJO-KCXAZCMYSA-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 = 100 nM (pChEMBL 7)
Descriptors: MW 392.91, ALogP 2.76, HBA 5, HBD 1, PSA 75.19, QED 0.87
Compound (SMILES): Cc1cc(C#N)cnc1-c1cc(N2CCC(NS(C)(=O)=O)CC2)ncc1Cl
InChIKey: CAEFZYVUNVRPNJ-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 = 95.6 nM (pChEMBL 7.019999980926514)
Descriptors: MW 405.91, ALogP 2.5, HBA 6, HBD 1, PSA 98.98, QED 0.84
Compound (SMILES): O=S(=O)(CCO)NC1CCN(c2ccc(Cl)c(-c3ccccn3)n2)CC1
InChIKey: QHUHZMQXBVZZCQ-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 = 15.2 nM (pChEMBL 7.820000171661377)
Descriptors: MW 396.9, ALogP 1.68, HBA 6, HBD 2, PSA 95.42, QED 0.77
Compound (SMILES): Cc1cnc(-c2cc(N3CCC(NS(=O)(=O)C4CC4)CC3)ncc2Cl)c(C)c1
InChIKey: ZHDUKDXAHHRNJY-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 = 11.5 nM (pChEMBL 7.940000057220459)
Descriptors: MW 420.97, ALogP 3.46, HBA 5, HBD 1, PSA 75.19, QED 0.8
Compound (SMILES): CS(=O)(=O)CCC(=O)NC1CCN(c2ccc(Cl)c(-c3ccccn3)n2)CC1
InChIKey: MVBSQTFOFONMAN-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 = 31.3 nM (pChEMBL 7.5)
Descriptors: MW 422.94, ALogP 2.32, HBA 6, HBD 1, PSA 92.26, QED 0.77
Compound (SMILES): CN(C)CC(=O)NC1CCN(c2ccc(Cl)c(-c3ccccn3)n2)CC1
InChIKey: ZXAJIVIHZVIUIP-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 373.89, ALogP 2.44, HBA 5, HBD 1, PSA 61.36, QED 0.87
Compound (SMILES): O=C(CCO)NC1CCN(c2ccc(Cl)c(-c3ccccn3)n2)CC1
InChIKey: GQYUXKDHSSZFBX-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 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 360.85, ALogP 2.26, HBA 5, HBD 2, PSA 78.35, QED 0.85
Compound (SMILES): CC(C)(O)CC(=O)NC1CCN(c2ccc(Cl)c(-c3ccccn3)n2)CC1
InChIKey: BDNRABUDGIZFHB-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 = 30.5 nM (pChEMBL 7.519999980926514)
Descriptors: MW 388.9, ALogP 3.04, HBA 5, HBD 2, PSA 78.35, QED 0.82
Compound (SMILES): CCS(=O)(=O)NC1CCN(c2ccc(Cl)c(-c3ccccn3)n2)CC1
InChIKey: PDNIQUYVEYMKHW-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 380.9, ALogP 2.71, HBA 5, HBD 1, PSA 75.19, QED 0.86
Compound (SMILES): O=S(=O)(NC1CCN(c2ccc(Cl)c(-c3ccccn3)n2)CC1)C1CC1
InChIKey: UAQRYKDFSUJIDJ-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 = 16.5 nM (pChEMBL 7.78000020980835)
Descriptors: MW 392.91, ALogP 2.85, HBA 5, HBD 1, PSA 75.19, QED 0.85
Compound (SMILES): Cc1cnc(-c2cc(N3CCC(S(C)(=O)=O)CC3)ncc2Cl)c(C)c1
InChIKey: OKTAWFFPKYHBIB-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 = 114 nM (pChEMBL 6.940000057220459)
Descriptors: MW 379.91, ALogP 3.43, HBA 5, HBD 0, PSA 63.16, QED 0.82
Compound (SMILES): COCC(=O)NC1CCN(c2cc(-c3ncc(C)cc3C)c(Cl)cn2)CC1
InChIKey: DMVPZMMEBRRFJX-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 nM (pChEMBL 7.400000095367432)
Descriptors: MW 388.9, ALogP 3.15, HBA 5, HBD 1, PSA 67.35, QED 0.85
Compound (SMILES): COCCS(=O)(=O)N1CCN(c2ccc(Cl)c(-c3ccccn3)n2)CC1
InChIKey: ADILYQIMCWQSFQ-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 = 328 nM (pChEMBL 6.480000019073486)
Descriptors: MW 396.9, ALogP 1.9, HBA 6, HBD 0, PSA 75.63, QED 0.74
Compound (SMILES): CS(=O)(=O)NC1CCN(c2ncc(Cl)c(-c3ccccn3)c2F)CC1
InChIKey: LPSYJKZXUUPNFZ-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 = 84.6 nM (pChEMBL 7.070000171661377)
Descriptors: MW 384.86, ALogP 2.45, HBA 5, HBD 1, PSA 75.19, QED 0.88
Compound (SMILES): Cc1cnc(-c2c(Cl)cnc(N3CCC(NC(=O)CCS(C)(=O)=O)CC3)c2F)c(C)c1
InChIKey: NKJKYAXHDKBHME-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 = 17.8 nM (pChEMBL 7.75)
Descriptors: MW 468.98, ALogP 3.07, HBA 6, HBD 1, PSA 92.26, QED 0.7
Compound (SMILES): Cc1cnc(-c2nc(N3CCC(NC(=O)CO)CC3)ccc2Cl)c(C)c1
InChIKey: OXUFJDJVMRECDW-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 = 47.7 nM (pChEMBL 7.320000171661377)
Descriptors: MW 374.87, ALogP 2.49, HBA 5, HBD 2, PSA 78.35, QED 0.86
Compound (SMILES): Cc1cnc(-c2ccnc(N3CCN(C(=O)CCS(C)(=O)=O)CC3)c2)c(C)c1
InChIKey: RZOKTVMRGRINNO-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 = 11.6 nM (pChEMBL 7.940000057220459)
Descriptors: MW 402.52, ALogP 1.84, HBA 6, HBD 0, PSA 83.47, QED 0.76
Compound (SMILES): Cc1cnc(-c2cc(N3CCN(C(=O)CCS(C)(=O)=O)CC3)ncc2F)c(C)c1
InChIKey: TWUKUPMOZOFTDI-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 = 20.4 nM (pChEMBL 7.690000057220459)
Descriptors: MW 420.51, ALogP 1.98, HBA 6, HBD 0, PSA 83.47, QED 0.74
Compound (SMILES): Cc1cnc(-c2ccnc(N3CCC(NS(C)(=O)=O)CC3)c2)c(C)c1
InChIKey: BZHBKLCVXLRTGJ-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 = 12.2 nM (pChEMBL 7.909999847412109)
Descriptors: MW 360.48, ALogP 2.28, HBA 5, HBD 1, PSA 75.19, QED 0.91
Compound (SMILES): Cc1cc(F)cnc1-c1cc(N2CCC(NC(=O)CCS(C)(=O)=O)CC2)ncc1Cl
InChIKey: ZVBZRDUDKIIWNT-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 = 29.8 nM (pChEMBL 7.53000020980835)
Descriptors: MW 454.96, ALogP 2.76, HBA 6, HBD 1, PSA 92.26, QED 0.72
Compound (SMILES): Cc1cc(F)cnc1-c1cc(N2CCC(NC(=O)CN(C)C)CC2)ncc1Cl
InChIKey: SAHLPSOSRRQTMX-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 = 66.2 nM (pChEMBL 7.179999828338623)
Descriptors: MW 405.9, ALogP 2.89, HBA 5, HBD 1, PSA 61.36, QED 0.83
Compound (SMILES): Cc1cc(F)cnc1-c1cc(N2CCC(NC(=O)CC(C)(C)O)CC2)ncc1Cl
InChIKey: TXSPKHYNWJVLFY-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 = 52.2 nM (pChEMBL 7.28000020980835)
Descriptors: MW 420.92, ALogP 3.49, HBA 5, HBD 2, PSA 78.35, QED 0.77
Compound (SMILES): Cc1ccc(-c2nc(N3CCN(C(=O)CCS(C)(=O)=O)CC3)ccc2Cl)nc1
InChIKey: AJKBDTUEJZYFPG-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 = 22.5 nM (pChEMBL 7.650000095367432)
Descriptors: MW 422.94, ALogP 2.19, HBA 6, HBD 0, PSA 83.47, QED 0.73
Compound (SMILES): Cc1cc(F)cnc1-c1cc(N2CCN(C(=O)CC(C)(C)O)CC2)ncc1Cl
InChIKey: JUMKVJURQNKOMY-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 = 33.4 nM (pChEMBL 7.480000019073486)
Descriptors: MW 406.89, ALogP 3.05, HBA 5, HBD 1, PSA 69.56, QED 0.84
Compound (SMILES): Cc1cc(F)cnc1-c1cc(N2CCC(NS(=O)(=O)CCO)CC2)ncc1Cl
InChIKey: JKCRRWRQNIBLLH-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 = 20.7 nM (pChEMBL 7.679999828338623)
Descriptors: MW 428.92, ALogP 2.13, HBA 6, HBD 2, PSA 95.42, QED 0.73
Compound (SMILES): Cc1cc(F)cnc1-c1cc(N2CCN(S(=O)(=O)CCO)CC2)ncc1Cl
InChIKey: XVZAWPKDDXDFFY-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 = 80.9 nM (pChEMBL 7.090000152587891)
Descriptors: MW 414.89, ALogP 1.69, HBA 6, HBD 1, PSA 86.63, QED 0.8
Compound (SMILES): Cc1cc(F)cnc1-c1cc(N2CCN(C(=O)CCS(C)(=O)=O)CC2)ncc1Cl
InChIKey: GIXOJLMTQABZDC-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 = 7.11 nM (pChEMBL 8.149999618530273)
Descriptors: MW 440.93, ALogP 2.33, HBA 6, HBD 0, PSA 83.47, QED 0.71
Compound (SMILES): Cc1cc(F)cnc1-c1cc(N2CCN(S(=O)(=O)CC(C)(C)O)CC2)ncc1Cl
InChIKey: PFKYBJVKVXVCBR-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 = 11.4 nM (pChEMBL 7.940000057220459)
Descriptors: MW 442.94, ALogP 2.47, HBA 6, HBD 1, PSA 86.63, QED 0.77
Compound (SMILES): Cc1cc(F)cnc1-c1cc(N2CCC(NS(=O)(=O)CC(C)(C)O)CC2)ncc1Cl
InChIKey: AWJHRWCVUAAGRU-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 = 10.6 nM (pChEMBL 7.96999979019165)
Descriptors: MW 456.97, ALogP 2.9, HBA 6, HBD 2, PSA 95.42, QED 0.69