lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2C[C@H](Nc3ncc4ccccc4n3)[C@@H](F)C2)cc1
InChIKey: GQFCNTKPAFRBKK-HKUYNNGSSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51946
Assay: Protein Kinase Assay Condition A (Thiol Containing Conditions): A radiometric protein kinase assay (33PanQinase® Activity Assay) was used for measuring the kinase activity of the three protein kinases. All kinase assays were performed in 96-well FlashPlates™ from PerkinElmer (Boston, Mass., USA) in a 50 μl reaction volume. The reaction cocktail was pipetted in four steps in the following order:20 μl of assay buffer (standard buffer)5 μl of ATP solution (in H2O)5 μl of test compound (in 10% DMSO)20 μl enzyme/substrate mixThe assay for all protein kinases contained 70 mM HEPES-NaOH pH 7.5, 3 mM MgCl2, 3 mM MnCl2, 3 μM Na-orthovanadate, 1.2 mM DTT, 50 μg/ml PEG20000, ATP (variable concentrations, corresponding to the apparent ATP-Km of the respective kinase), [γ-33P]-ATP (approx. 9×1005 cpm per well), protein kinase (variable amounts), and substrate (variable amounts).
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 405.43, ALogP 3.03, HBA 5, HBD 2, PSA 87.22, QED 0.64
Compound (SMILES): CC(C)(C)OC(=O)N1CC[C@](CO)(Nc2cc(-c3cnc(N)nc3)nc(N3CCOCC3)n2)C1
InChIKey: AYKSFHQCPBPUPW-QFIPXVFZSA-N
Target: PI3K p110 beta/p85 alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P42338
Assay: Inhibition of recombinant human PI3K p110beta/p85alpha using phosphatidylinositol 4,5-bisphosphate as substrate preincubated for 15 mins followed by addition of ATP and measured after 30 mins by fluorescence polarisation assay
Measurement: Ki = 54 nM (pChEMBL 7.269999980926514)
Descriptors: MW 472.55, ALogP 1.14, HBA 11, HBD 3, PSA 151.85, QED 0.57
Compound (SMILES): CCC1(Nc2ncc(Cl)c(-c3c[nH]c4ccccc34)n2)CCCNC1
InChIKey: ICAYWDBIWWQYCA-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: Inhibition of CDK9/Cyclin T1 (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 15 mins
Measurement: IC50 >= 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 355.87, ALogP 4.22, HBA 4, HBD 3, PSA 65.63, QED 0.66
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccncc4n3)C2)cc1
InChIKey: JVPPVCXAHQZJPI-QGZVFWFLSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51946
Assay: Inhibition of CDK7/cyclin H/MAT1 (unknown origin) assessed as incoporation of [33]Pi using RBER-IRStide as substrate and in presence of [gamma-33P]-ATP measured after 60 mins by microplate scintillation counter
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 388.43, ALogP 2.48, HBA 6, HBD 2, PSA 100.11, QED 0.65
Compound (SMILES): CC(=O)c1cnc(N[C@H]2CCCNC2)nc1-c1c[nH]c2ccccc12
InChIKey: VBXUAFKZCVKOQN-ZDUSSCGKSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: Inhibition of CDK9/Cyclin T1 (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 15 mins
Measurement: IC50 >= 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 335.41, ALogP 2.99, HBA 5, HBD 3, PSA 82.7, QED 0.64
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4cc(F)ccc4n3)C2)cc1C
InChIKey: KXKAWIWAQIOGGO-GOSISDBHSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51946
Assay: Protein Kinase Assay Condition A (Thiol Containing Conditions): A radiometric protein kinase assay (33PanQinase® Activity Assay) was used for measuring the kinase activity of the three protein kinases. All kinase assays were performed in 96-well FlashPlates™ from PerkinElmer (Boston, Mass., USA) in a 50 μl reaction volume. The reaction cocktail was pipetted in four steps in the following order:20 μl of assay buffer (standard buffer)5 μl of ATP solution (in H2O)5 μl of test compound (in 10% DMSO)20 μl enzyme/substrate mixThe assay for all protein kinases contained 70 mM HEPES-NaOH pH 7.5, 3 mM MgCl2, 3 mM MnCl2, 3 μM Na-orthovanadate, 1.2 mM DTT, 50 μg/ml PEG20000, ATP (variable concentrations, corresponding to the apparent ATP-Km of the respective kinase), [γ-33P]-ATP (approx. 9×1005 cpm per well), protein kinase (variable amounts), and substrate (variable amounts).
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 419.46, ALogP 3.53, HBA 5, HBD 2, PSA 87.22, QED 0.62
Compound (SMILES): Fc1cccc2c(-c3nc(N[C@H]4CCCNC4)ncc3Cl)c[nH]c12
InChIKey: IVVMEAPLRJRWHE-JTQLQIEISA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: Inhibition of CDK9/Cyclin T1 (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 15 mins
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 345.81, ALogP 3.58, HBA 4, HBD 3, PSA 65.63, QED 0.68
Compound (SMILES): CC(=O)c1cccc2c(-c3nc(N[C@H]4CCCNC4)ncc3Cl)c[nH]c12
InChIKey: RPWBQONKJLUMGK-LBPRGKRZSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: Inhibition of CDK9/Cyclin T1 (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 15 mins
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 369.86, ALogP 3.64, HBA 5, HBD 3, PSA 82.7, QED 0.61
Compound (SMILES): CCc1cnc(N[C@@H]2CCCNC2)nc1-c1n[nH]c2ncccc12
InChIKey: RMQZFHNZKHTFFQ-GFCCVEGCSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: Inhibition of CDK9/Cyclin T1 (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 15 mins
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 323.4, ALogP 2.14, HBA 6, HBD 3, PSA 91.41, QED 0.68
Compound (SMILES): COc1cc(OC)c2c(N3CCN(C)CC3)nc(-c3cc(C)c(OCCCCCC(=O)NO)c(C)c3)nc2c1
InChIKey: NTUCJWZWDDQYER-UHFFFAOYSA-N
Target: Histone deacetylase 3/NCoR1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O15379
Assay: Inhibition of recombinant human GST-fused HDAC3/NCOR1 (397 to 503 residues) expressed in baculovirus infected insect cells using Ac-Leu-Gly-Lys(Ac)-AMC as substrate measured after 30 mins by fluorescence assay
Measurement: IC50 = 79.17 nM (pChEMBL 7.099999904632568)
Descriptors: MW 537.66, ALogP 4.13, HBA 9, HBD 2, PSA 109.28, QED 0.21
Compound (SMILES): Ic1cnc(N[C@H]2CCCNC2)nc1-c1c[nH]c2ccccc12
InChIKey: BRLYHLKTEZGXJD-NSHDSACASA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: Inhibition of CDK9/Cyclin T1 (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 15 mins
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 419.27, ALogP 3.39, HBA 4, HBD 3, PSA 65.63, QED 0.57
Compound (SMILES): Fc1cccc2c(-c3nc(N[C@H]4CCCNC4)ncc3Cl)n[nH]c12
InChIKey: LOVXTLJVBKIDNT-VIFPVBQESA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: Inhibition of CDK9/Cyclin T1 (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 15 mins
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 346.8, ALogP 2.98, HBA 5, HBD 3, PSA 78.52, QED 0.68
Compound (SMILES): COCCN1CCC[C@H](Nc2ncc(Cl)c(-c3c[nH]c4ccccc34)n2)C1
InChIKey: WNTWPMDPWXFJJJ-AWEZNQCLSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: Inhibition of CDK9/Cyclin T1 (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 15 mins
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 385.9, ALogP 3.8, HBA 5, HBD 2, PSA 66.07, QED 0.68
Compound (SMILES): FC(F)(F)c1cnc(NC2C3CCC2NC3)nc1-c1c[nH]c2ccccc12
InChIKey: TXZFORDUGWJTSQ-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: Inhibition of CDK9/Cyclin T1 (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 15 mins
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 373.38, ALogP 3.81, HBA 4, HBD 3, PSA 65.63, QED 0.65
Compound (SMILES): C[C@]1(O)CCN(C(=O)c2ccc3c(-c4nc(N[C@H]5CCCNC5)ncc4C(F)(F)F)c[nH]c3c2)C1
InChIKey: OJCCNWLOIVOTIV-WNSKOXEYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: Inhibition of CDK9/Cyclin T1 (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 15 mins
Measurement: IC50 >= 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 488.51, ALogP 3.4, HBA 6, HBD 4, PSA 106.17, QED 0.45
Compound (SMILES): FC(F)(F)c1cnc(N[C@H]2CNC[C@@H](c3nnc4ccccn34)C2)nc1-c1c[nH]c2ccccc12
InChIKey: IJQBKJGUIDXXLI-LSDHHAIUSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: Inhibition of CDK9/Cyclin T1 (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 15 mins
Measurement: IC50 >= 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 478.48, ALogP 4.24, HBA 7, HBD 3, PSA 95.82, QED 0.36
Compound (SMILES): CS(=O)(=O)c1ccc2c(-c3nc(N[C@H]4CCCNC4)ncc3C(F)(F)F)c[nH]c2c1
InChIKey: XNWQJSPBCYZFAU-NSHDSACASA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24941
Assay: Inhibition of CDK2/cyclin E1 (unknown origin) using 5-FAM-labeled peptide as substrate in presence of ATP by mobility shift assay
Measurement: IC50 = 299 nM (pChEMBL 6.519999980926514)
Descriptors: MW 439.46, ALogP 3.21, HBA 6, HBD 3, PSA 99.77, QED 0.58
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4cc(F)ccc4n3)C2)cc1
InChIKey: QVWJCPCDKVFGTB-GOSISDBHSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51946
Assay: Inhibition of CDK7/cyclin H/MAT1 (unknown origin) assessed as incoporation of [33]Pi using RBER-IRStide as substrate and in presence of [gamma-33P]-ATP measured after 60 mins by microplate scintillation counter
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 405.43, ALogP 3.22, HBA 5, HBD 2, PSA 87.22, QED 0.64
Compound (SMILES): CC(C)(C)OC(=O)N1CC[C@](CO)(Nc2cc(-c3cnc(N)nc3)nc(N3CCOCC3)n2)C1
InChIKey: AYKSFHQCPBPUPW-QFIPXVFZSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of recombinant human PI3K p110delta/p85alpha using phosphatidylinositol 4,5-bisphosphate as substrate preincubated for 15 mins followed by addition of ATP and measured after 30 mins by fluorescence polarisation assay
Measurement: Ki = 2.1 nM (pChEMBL 8.680000305175781)
Descriptors: MW 472.55, ALogP 1.14, HBA 11, HBD 3, PSA 151.85, QED 0.57
Compound (SMILES): Nc1nn2c(-c3ccc(Br)cc3)ccnc2c1/N=N/c1ccc(S(N)(=O)=O)cc1
InChIKey: VPJWECUQRFSGFO-WCWDXBQESA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24941
Assay: Inhibition of CDK2/cyclin E (unknown origin) expressed in baculovirus infected Sf21 insect cells using histone H1 as substrate in presence of [gamma33P]ATP
Measurement: IC50 = 8000 nM (pChEMBL 5.099999904632568)
Descriptors: MW 472.33, ALogP 3.8, HBA 8, HBD 2, PSA 141.09, QED 0.43
Compound (SMILES): CS(=O)(=O)c1ccc2c(-c3nc(N[C@H]4CCCNC4)ncc3C(F)(F)F)c[nH]c2c1
InChIKey: XNWQJSPBCYZFAU-NSHDSACASA-N
Target: Cyclin-dependent kinase 7/ cyclin H (PROTEIN COMPLEX), Homo sapiens
UniProt: P51946
Assay: Binding affinity to full length CDK7 (1 to 346 residues) /N-terminal TEV cleavable 6His tagged full length cyclinH (1 to 323 residues) (unknown origin) expressed in baculovirus infected Sf9 cells by Surface plasmon resonance assay
Measurement: Kd = 0.1 nM (pChEMBL 10)
Descriptors: MW 439.46, ALogP 3.21, HBA 6, HBD 3, PSA 99.77, QED 0.58
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4cc(F)ccc4n3)C2)cc1
InChIKey: QVWJCPCDKVFGTB-GOSISDBHSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51946
Assay: Inhibition of CDK7/cyclin H/MAT1 (unknown origin) assessed as incoporation of [33]Pi using RBER-IRStide as substrate and in presence of [gamma-33P]-ATP measured after 60 mins under thiol free condition by microplate scintillation counter
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 405.43, ALogP 3.22, HBA 5, HBD 2, PSA 87.22, QED 0.64
Compound (SMILES): Nc1nn2c(-c3ccc(Br)cc3)ccnc2c1/N=N/c1ccc(S(N)(=O)=O)cc1
InChIKey: VPJWECUQRFSGFO-WCWDXBQESA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: Inhibition of human full-length N-terminal GST/His6-tagged CDK9 (1 to 372 residues)/His6-tagged Cyclin-T1 (1 to 726 residues) expressed in sf9 cells using (YSPTSPS)2KK peptide as substrate in presence of [gamma33P]ATP
Measurement: IC50 > 12500 nM (pChEMBL 4.9029998779296875)
Descriptors: MW 472.33, ALogP 3.8, HBA 8, HBD 2, PSA 141.09, QED 0.43
Compound (SMILES): CS(=O)(=O)c1ccc2c(-c3nc(N[C@H]4CCCNC4)ncc3C(F)(F)F)c[nH]c2c1
InChIKey: XNWQJSPBCYZFAU-NSHDSACASA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: Inhibition of CDK9/cyclin T1 (unknown origin) using 5-FAM-labeled peptide as substrate in presence of ATP by mobility shift assay
Measurement: IC50 = 133 nM (pChEMBL 6.880000114440918)
Descriptors: MW 439.46, ALogP 3.21, HBA 6, HBD 3, PSA 99.77, QED 0.58
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4cc(F)ccc4n3)C2)cc1
InChIKey: QVWJCPCDKVFGTB-GOSISDBHSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51946
Assay: Protein Kinase Assay Condition A (Thiol Containing Conditions): A radiometric protein kinase assay (33PanQinase® Activity Assay) was used for measuring the kinase activity of the three protein kinases. All kinase assays were performed in 96-well FlashPlates™ from PerkinElmer (Boston, Mass., USA) in a 50 μl reaction volume. The reaction cocktail was pipetted in four steps in the following order:20 μl of assay buffer (standard buffer)5 μl of ATP solution (in H2O)5 μl of test compound (in 10% DMSO)20 μl enzyme/substrate mixThe assay for all protein kinases contained 70 mM HEPES-NaOH pH 7.5, 3 mM MgCl2, 3 mM MnCl2, 3 μM Na-orthovanadate, 1.2 mM DTT, 50 μg/ml PEG20000, ATP (variable concentrations, corresponding to the apparent ATP-Km of the respective kinase), [γ-33P]-ATP (approx. 9×1005 cpm per well), protein kinase (variable amounts), and substrate (variable amounts).
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 405.43, ALogP 3.22, HBA 5, HBD 2, PSA 87.22, QED 0.64
Compound (SMILES): CS(=O)(=O)c1ccc2c(-c3nc(N[C@H]4CCCNC4)ncc3C(F)(F)F)c[nH]c2c1
InChIKey: XNWQJSPBCYZFAU-NSHDSACASA-N
Target: CDK12/Cyclin K (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NYV4
Assay: Inhibition of CDK12/cyclin K (unknown origin) using 5-FAM-labeled peptide as substrate in presence of ATP by mobility shift assay
Measurement: IC50 = 69 nM (pChEMBL 7.159999847412109)
Descriptors: MW 439.46, ALogP 3.21, HBA 6, HBD 3, PSA 99.77, QED 0.58
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4cc(F)ccc4n3)C2)cc1
InChIKey: QVWJCPCDKVFGTB-GOSISDBHSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51946
Assay: Protein Kinase Assay Condition B (Thiol-Free Conditions): A radiometric protein kinase assay (33PanQinase® Activity Assay) was used for measuring the kinase activity of the protein kinase. All kinase assays were performed in 96-well FlashPlates from PerkinElmer (Boston, Mass., USA) in a 50 microliter reaction volume. The reaction cocktail was pipetted in four steps in the following order: 20 microliter of assay buffer (standard buffer)5 microliter of ATP solution (in H2O)5 microliter of test compound (in 10% DMSO)20 microliter enzyme/substrate mix. Each assay for the protein kinase contained 70 mM HEPES-NaOH pH 7.5, 3 mM MgCl2, 3 mM MnCl2, 3 microM Na-orthovanadate, 1 mM TCEP, 50 μg/ml PEG20000, ATP (corresponding to the apparent ATP-Km of the kinase, see Table A), [gamma-33P]-ATP (approx. 6×10×E5 cpm per well), with the protein kinase and relevant substrate being used in pre-determined amounts, depending on the kinase in question. For all experiments labeled as Thiol-free, all glutathione was exchanged from protein preparations so as to be removed from the assay and final buffer conditions contained no thiol-containing reagents. In addition, the DTT in the thiol-containing assays is replaced by TCEP in the thiol-free assays and all enzymes and substrates are produced under thiol-free conditions for the thiol-free assays.
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 405.43, ALogP 3.22, HBA 5, HBD 2, PSA 87.22, QED 0.64
Compound (SMILES): Cn1c(=O)n(CC(=O)N2CCC2)c2cc(-c3ccc(C(F)(F)F)s3)cnc21
InChIKey: VBYDZMQKWHOANY-UHFFFAOYSA-N
Target: Glutamate NMDA receptor; GRIN1/GRIN2B (PROTEIN COMPLEX), Homo sapiens
UniProt: Q13224
Assay: Biological Assay (standard): NMDA receptors are ion channels that are highly permeable to Ca2+ ions, rendering it possible to monitor NMDA receptor function using cell-based calcium flux assay. In this assay, co-agonists glutamate and glycine are added to cells heterologously expressing human GluN1/GluN2B NMDA receptors to initiate cellular Ca2+ influx. The time course of the changes in intracellular calcium is measured using a fluorescent dye and a FLIPR (Fluorometric Imaging Plate Reader) device.Twenty four hours before measurements, the expression of the NMDA receptors in the stable cell line is induced with Tet-On inducible system in the presence of a non-selective NMDA receptor blocker. On the day of the experiment, cell culture media is carefully washed and the cells are loaded with Calcium 5 Dye Kit (Molecular Devices) in dye loading buffer containing 137 mM NaCl, 4 mM KCl, 2 mM CaCl2), 0.5 mM MgCl2, 10 mM HEPES and 5 mM D-glucose; pH 7.4. After 1 h incubation at the room temperature, the dye is washed away with the assay buffer (137 mM NaCl, 4 mM KCl, 2 mM CaCl2), 0.01 mM EDTA, 10 mM HEPES and 5 mM D-glucose; pH 7.4) In the FLIPR TETRA reader, various concentrations of the test compounds are added to the cells for 5 min while fluorescence is monitored to detect potential agonist activity. Next, co-agonists, glutamate and glycine are added for another 5 minutes. The concentration of glutamate corresponding to ~EC40 used to maximize the assay's signal window and ability to detect NMDA receptor antagonists and negative allosteric modulators. A saturating concentration (10 μM) of glycine is also present in the assay. A non-selective NMDA receptor antagonist, (+)MK-801 is used as a positive control for antagonist activity. The fluorescent signal in the presence of test compounds is quantified and normalized to the signal defined by the appropriate control wells.
Measurement: IC50 = 31 nM (pChEMBL 7.510000228881836)
Descriptors: MW 396.39, ALogP 2.71, HBA 6, HBD 0, PSA 60.13, QED 0.68
Compound (SMILES): Cn1c(=O)n(CC(=O)N2CCC2)c2cc(-c3ccc(C(F)(F)F)s3)cnc21
InChIKey: VBYDZMQKWHOANY-UHFFFAOYSA-N
Target: Glutamate NMDA receptor; GRIN1/GRIN2B (PROTEIN COMPLEX), Homo sapiens
UniProt: Q13224
Assay: Biological Assay (standard): NMDA receptors are ion channels that are highly permeable to Ca2+ ions, rendering it possible to monitor NMDA receptor function using cell-based calcium flux assay. In this assay, co-agonists glutamate and glycine are added to cells heterologously expressing human GluN1/GluN2B NMDA receptors to initiate cellular Ca2+ influx. The time course of the changes in intracellular calcium is measured using a fluorescent dye and a FLIPR (Fluorometric Imaging Plate Reader) device.Twenty four hours before measurements, the expression of the NMDA receptors in the stable cell line is induced with Tet-On inducible system in the presence of a non-selective NMDA receptor blocker. On the day of the experiment, cell culture media is carefully washed and the cells are loaded with Calcium 5 Dye Kit (Molecular Devices) in dye loading buffer containing 137 mM NaCl, 4 mM KCl, 2 mM CaCl2), 0.5 mM MgCl2, 10 mM HEPES and 5 mM D-glucose; pH 7.4. After 1 h incubation at the room temperature, the dye is washed away with the assay buffer (137 mM NaCl, 4 mM KCl, 2 mM CaCl2), 0.01 mM EDTA, 10 mM HEPES and 5 mM D-glucose; pH 7.4) In the FLIPR TETRA reader, various concentrations of the test compounds are added to the cells for 5 min while fluorescence is monitored to detect potential agonist activity. Next, co-agonists, glutamate and glycine are added for another 5 minutes. The concentration of glutamate corresponding to ~EC40 used to maximize the assay's signal window and ability to detect NMDA receptor antagonists and negative allosteric modulators. A saturating concentration (10 μM) of glycine is also present in the assay. A non-selective NMDA receptor antagonist, (+)MK-801 is used as a positive control for antagonist activity. The fluorescent signal in the presence of test compounds is quantified and normalized to the signal defined by the appropriate control wells.
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 396.39, ALogP 2.71, HBA 6, HBD 0, PSA 60.13, QED 0.68
Compound (SMILES): O=c1[nH]cc(-c2ccc3c(-c4nc(N[C@H]5CCCNC5)ncc4C(F)(F)F)c[nH]c3c2)c(=O)[nH]1
InChIKey: MTLJCKRPLWHNCD-LBPRGKRZSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7/Cyclin H/MAT1 (unknown origin) using 5-FAM-CDK7tide peptide substrate incubated for 35 mins
Measurement: IC50 < 20 nM (pChEMBL 7.698999881744385)
Descriptors: MW 471.44, ALogP 2.85, HBA 6, HBD 5, PSA 131.35, QED 0.31
Compound (SMILES): CS(=O)(=O)c1ccc2c(-c3nc(N[C@H]4CCCNC4)ncc3C(F)(F)F)c[nH]c2c1
InChIKey: XNWQJSPBCYZFAU-NSHDSACASA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7/Cyclin H/MAT1 (unknown origin) using 5-FAM-CDK7tide peptide substrate incubated for 35 mins
Measurement: IC50 < 20 nM (pChEMBL 7.698999881744385)
Descriptors: MW 439.46, ALogP 3.21, HBA 6, HBD 3, PSA 99.77, QED 0.58
Compound (SMILES): CC1(C)CNC[C@@H](Nc2ncc(C(F)(F)F)c(-c3c[nH]c4cc(S(C)(=O)=O)ccc34)n2)C1
InChIKey: MJLQPTUXPJMBNG-LBPRGKRZSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7/Cyclin H/MAT1 (unknown origin) using 5-FAM-CDK7tide peptide substrate incubated for 35 mins
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 467.52, ALogP 3.85, HBA 6, HBD 3, PSA 99.77, QED 0.54
Compound (SMILES): COCCn1cc(-c2nc(N[C@H]3CCCNC3)ncc2C(F)(F)F)c2ccccc21
InChIKey: QMZHENYYIFYXKE-AWEZNQCLSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7/Cyclin H/MAT1 (unknown origin) using 5-FAM-CDK7tide peptide substrate incubated for 35 mins
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 419.45, ALogP 3.93, HBA 6, HBD 2, PSA 64, QED 0.63
Compound (SMILES): CN1CCC[C@H](Nc2ncc(C(F)(F)F)c(-c3c[nH]c4cc(S(C)(=O)=O)ccc34)n2)C1
InChIKey: IVBPBUTZXUYNRK-LBPRGKRZSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7/Cyclin H/MAT1 (unknown origin) using 5-FAM-CDK7tide peptide substrate incubated for 35 mins
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 453.49, ALogP 3.55, HBA 6, HBD 2, PSA 90.98, QED 0.63
Compound (SMILES): CNC(=O)c1ccc2c(-c3nc(N[C@H]4CCCNC4)ncc3C(F)(F)F)c[nH]c2n1
InChIKey: KNKBXFUDTNASDX-JTQLQIEISA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7/Cyclin H/MAT1 (unknown origin) using 5-FAM-CDK7tide peptide substrate incubated for 35 mins
Measurement: IC50 < 20 nM (pChEMBL 7.698999881744385)
Descriptors: MW 419.41, ALogP 2.56, HBA 6, HBD 4, PSA 107.62, QED 0.52
Compound (SMILES): FC(F)(F)c1cnc(N[C@H]2CCC3(CCCCC3)NC2)nc1-c1c[nH]c2ccccc12
InChIKey: CYFIMAMUCGZHIA-HNNXBMFYSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7/Cyclin H/MAT1 (unknown origin) using 5-FAM-CDK7tide peptide substrate incubated for 35 mins
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 429.49, ALogP 5.51, HBA 4, HBD 3, PSA 65.63, QED 0.51
Compound (SMILES): O=C(O)c1ccc2c(-c3nc(N[C@H]4CCCNC4)ncc3C(F)(F)F)c[nH]c2c1
InChIKey: BIJOFIPILXKNKU-NSHDSACASA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7/Cyclin H/MAT1 (unknown origin) using 5-FAM-CDK7tide peptide substrate incubated for 35 mins
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 405.38, ALogP 3.51, HBA 5, HBD 4, PSA 102.93, QED 0.53
Compound (SMILES): CNc1nc(Nc2ccc(-n3cnc(C)n3)c(OC)c2)nc2c1C(C)(O)CC2c1ccc(F)cc1
InChIKey: VZFDGCDPRGKJRJ-UHFFFAOYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q92542
Assay: Modulation of gamma secretase (unknown origin) assessed as inhibition of amyloid beta (1 to 42 residues) production
Measurement: IC50 = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 475.53, ALogP 4.04, HBA 9, HBD 3, PSA 110.01, QED 0.38
Compound (SMILES): N#Cc1cn(-c2ccc3c(-c4nc(N[C@H]5CCCNC5)ncc4C(F)(F)F)c[nH]c3c2)cn1
InChIKey: BSOWCBLZANLKRO-ZDUSSCGKSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7/Cyclin H/MAT1 (unknown origin) using 5-FAM-CDK7tide peptide substrate incubated for 35 mins
Measurement: IC50 < 20 nM (pChEMBL 7.698999881744385)
Descriptors: MW 452.44, ALogP 3.86, HBA 7, HBD 3, PSA 107.24, QED 0.43
Compound (SMILES): Fc1cncc(-c2ccc3c(-c4nc(N[C@H]5CCCNC5)ncc4C(F)(F)F)c[nH]c3c2)c1
InChIKey: PDCIXCSHUGGJPD-INIZCTEOSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7/Cyclin H/MAT1 (unknown origin) using 5-FAM-CDK7tide peptide substrate incubated for 35 mins
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 456.45, ALogP 5.01, HBA 5, HBD 3, PSA 78.52, QED 0.38
Compound (SMILES): CCc1cnc(N[C@H]2CCCNC2)nc1-c1n[nH]c2nc(C#N)ccc12
InChIKey: RNEYCMVMZFAUCY-ZDUSSCGKSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7/Cyclin H/MAT1 (unknown origin) using 5-FAM-CDK7tide peptide substrate incubated for 35 mins
Measurement: IC50 < 20 nM (pChEMBL 7.698999881744385)
Descriptors: MW 348.41, ALogP 2.01, HBA 7, HBD 3, PSA 115.2, QED 0.66
Compound (SMILES): Cc1nnc(C23CC(Nc4nc(Oc5cccc(Cl)c5)n(C(C)C)n4)(C2)C3)o1
InChIKey: MXHDDQMKDNLNRY-UHFFFAOYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q92542
Assay: Modulatory activity of gamma secretase in human H4 cells overexpressing human APP695 K595N/M596L mutant assessed as decrease in amyloidbeta42 levels at 24 hrs by Alphalisa method
Measurement: IC50 = 214 nM (pChEMBL 6.670000076293945)
Descriptors: MW 400.87, ALogP 4.28, HBA 8, HBD 1, PSA 90.89, QED 0.66
Compound (SMILES): Cc1n[nH]cc1-c1ccc2[nH]cc(-c3nc(N[C@H]4CCCNC4)ncc3C(F)(F)F)c2c1
InChIKey: BPYMZTBMBKFQPY-AWEZNQCLSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7/Cyclin H/MAT1 (unknown origin) using 5-FAM-CDK7tide peptide substrate incubated for 35 mins
Measurement: IC50 < 20 nM (pChEMBL 7.698999881744385)
Descriptors: MW 441.46, ALogP 4.51, HBA 5, HBD 4, PSA 94.31, QED 0.37
Compound (SMILES): O=S(=O)(c1ccc2c(-c3nc(N[C@H]4CCCNC4)ncc3C(F)(F)F)c[nH]c2c1)C(F)F
InChIKey: JMDJVTKHPSFJBK-JTQLQIEISA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7/Cyclin H/MAT1 (unknown origin) using 5-FAM-CDK7tide peptide substrate incubated for 35 mins
Measurement: IC50 < 20 nM (pChEMBL 7.698999881744385)
Descriptors: MW 475.44, ALogP 3.8, HBA 6, HBD 3, PSA 99.77, QED 0.49
Compound (SMILES): NS(=O)(=O)c1ccc(-c2ccc3c(-c4nc(N[C@H]5CCCNC5)ncc4C(F)(F)F)c[nH]c3c2)cc1
InChIKey: WOSCFDBVQAKFEG-INIZCTEOSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7/Cyclin H/MAT1 (unknown origin) using 5-FAM-CDK7tide peptide substrate incubated for 35 mins
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 516.55, ALogP 4.12, HBA 6, HBD 4, PSA 125.79, QED 0.32
Compound (SMILES): CCC(=O)N[C@H]1CNC[C@@H](Nc2ncc(C(F)(F)F)c(-c3c[nH]c4c(S(C)(=O)=O)cccc34)n2)C1
InChIKey: OFVNWSJOGCICRX-OLZOCXBDSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7/Cyclin H/MAT1 (unknown origin) using 5-FAM-CDK7tide peptide substrate incubated for 35 mins
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 510.54, ALogP 2.72, HBA 7, HBD 4, PSA 128.87, QED 0.4
Compound (SMILES): CCC1(Nc2ncc(Cl)c(-c3c[nH]c4ccccc34)n2)CCCNC1
InChIKey: ICAYWDBIWWQYCA-UHFFFAOYSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7/Cyclin H/MAT1 (unknown origin) using 5-FAM-CDK7tide peptide substrate incubated for 35 mins
Measurement: IC50 >= 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 355.87, ALogP 4.22, HBA 4, HBD 3, PSA 65.63, QED 0.66
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccncc4n3)C2)cc1
InChIKey: JVPPVCXAHQZJPI-QGZVFWFLSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Protein Kinase Assay Condition A (Thiol Containing Conditions): A radiometric protein kinase assay (33PanQinase® Activity Assay) was used for measuring the kinase activity of the three protein kinases. All kinase assays were performed in 96-well FlashPlates™ from PerkinElmer (Boston, Mass., USA) in a 50 μl reaction volume. The reaction cocktail was pipetted in four steps in the following order:20 μl of assay buffer (standard buffer)5 μl of ATP solution (in H2O)5 μl of test compound (in 10% DMSO)20 μl enzyme/substrate mixThe assay for all protein kinases contained 70 mM HEPES-NaOH pH 7.5, 3 mM MgCl2, 3 mM MnCl2, 3 μM Na-orthovanadate, 1.2 mM DTT, 50 μg/ml PEG20000, ATP (variable concentrations, corresponding to the apparent ATP-Km of the respective kinase), [γ-33P]-ATP (approx. 9×1005 cpm per well), protein kinase (variable amounts), and substrate (variable amounts).
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 388.43, ALogP 2.48, HBA 6, HBD 2, PSA 100.11, QED 0.65
Compound (SMILES): CC(=O)c1cnc(N[C@H]2CCCNC2)nc1-c1c[nH]c2ccccc12
InChIKey: VBXUAFKZCVKOQN-ZDUSSCGKSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7/Cyclin H/MAT1 (unknown origin) using 5-FAM-CDK7tide peptide substrate incubated for 35 mins
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 335.41, ALogP 2.99, HBA 5, HBD 3, PSA 82.7, QED 0.64
Compound (SMILES): COc1nc(-c2csc(Nc3c4c(nn3C3CCCCC3)CCCC4)n2)ccc1-n1cnc(C)c1
InChIKey: UIDMHMNKHAKPDY-UHFFFAOYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q92542
Assay: Modulation of gamma secretase in human SH-SY5Y cells overexpressing wild type APP751 assessed as inhibition of amyloid beta (35 to 42 residues) formation incubated for overnight by ELISA
Measurement: IC50 = 63 nM (pChEMBL 7.199999809265137)
Descriptors: MW 489.65, ALogP 6.03, HBA 9, HBD 1, PSA 82.68, QED 0.36
Compound (SMILES): Fc1cccc2c(-c3nc(N[C@H]4CCCNC4)ncc3Cl)c[nH]c12
InChIKey: IVVMEAPLRJRWHE-JTQLQIEISA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7/Cyclin H/MAT1 (unknown origin) using 5-FAM-CDK7tide peptide substrate incubated for 35 mins
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 345.81, ALogP 3.58, HBA 4, HBD 3, PSA 65.63, QED 0.68
Compound (SMILES): CC(=O)c1cccc2c(-c3nc(N[C@H]4CCCNC4)ncc3Cl)c[nH]c12
InChIKey: RPWBQONKJLUMGK-LBPRGKRZSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7/Cyclin H/MAT1 (unknown origin) using 5-FAM-CDK7tide peptide substrate incubated for 35 mins
Measurement: IC50 < 20 nM (pChEMBL 7.698999881744385)
Descriptors: MW 369.86, ALogP 3.64, HBA 5, HBD 3, PSA 82.7, QED 0.61
Compound (SMILES): COc1nc(-c2csc(Nc3c4c(nn3C3CCOC3)CCCC4)n2)ccc1-n1cnc(C)c1
InChIKey: BEQGSOVGFACSGG-UHFFFAOYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q92542
Assay: Modulation of gamma secretase in human SH-SY5Y cells overexpressing wild type APP751 assessed as inhibition of amyloid beta (35 to 42 residues) formation incubated for overnight by ELISA
Measurement: IC50 = 102 nM (pChEMBL 6.989999771118164)
Descriptors: MW 477.59, ALogP 4.49, HBA 10, HBD 1, PSA 91.91, QED 0.44
Compound (SMILES): CCc1cnc(N[C@@H]2CCCNC2)nc1-c1n[nH]c2ncccc12
InChIKey: RMQZFHNZKHTFFQ-GFCCVEGCSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7/Cyclin H/MAT1 (unknown origin) using 5-FAM-CDK7tide peptide substrate incubated for 35 mins
Measurement: IC50 < 20 nM (pChEMBL 7.698999881744385)
Descriptors: MW 323.4, ALogP 2.14, HBA 6, HBD 3, PSA 91.41, QED 0.68
Compound (SMILES): Ic1cnc(N[C@H]2CCCNC2)nc1-c1c[nH]c2ccccc12
InChIKey: BRLYHLKTEZGXJD-NSHDSACASA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7/Cyclin H/MAT1 (unknown origin) using 5-FAM-CDK7tide peptide substrate incubated for 35 mins
Measurement: IC50 < 20 nM (pChEMBL 7.698999881744385)
Descriptors: MW 419.27, ALogP 3.39, HBA 4, HBD 3, PSA 65.63, QED 0.57
Compound (SMILES): Fc1cccc2c(-c3nc(N[C@H]4CCCNC4)ncc3Cl)n[nH]c12
InChIKey: LOVXTLJVBKIDNT-VIFPVBQESA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7/Cyclin H/MAT1 (unknown origin) using 5-FAM-CDK7tide peptide substrate incubated for 35 mins
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 346.8, ALogP 2.98, HBA 5, HBD 3, PSA 78.52, QED 0.68
Compound (SMILES): COCCN1CCC[C@H](Nc2ncc(Cl)c(-c3c[nH]c4ccccc34)n2)C1
InChIKey: WNTWPMDPWXFJJJ-AWEZNQCLSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7/Cyclin H/MAT1 (unknown origin) using 5-FAM-CDK7tide peptide substrate incubated for 35 mins
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 385.9, ALogP 3.8, HBA 5, HBD 2, PSA 66.07, QED 0.68
Compound (SMILES): FC(F)(F)c1cnc(NC2C3CCC2NC3)nc1-c1c[nH]c2ccccc12
InChIKey: TXZFORDUGWJTSQ-UHFFFAOYSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7/Cyclin H/MAT1 (unknown origin) using 5-FAM-CDK7tide peptide substrate incubated for 35 mins
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 373.38, ALogP 3.81, HBA 4, HBD 3, PSA 65.63, QED 0.65
Compound (SMILES): C[C@]1(O)CCN(C(=O)c2ccc3c(-c4nc(N[C@H]5CCCNC5)ncc4C(F)(F)F)c[nH]c3c2)C1
InChIKey: OJCCNWLOIVOTIV-WNSKOXEYSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7/Cyclin H/MAT1 (unknown origin) using 5-FAM-CDK7tide peptide substrate incubated for 35 mins
Measurement: IC50 < 20 nM (pChEMBL 7.698999881744385)
Descriptors: MW 488.51, ALogP 3.4, HBA 6, HBD 4, PSA 106.17, QED 0.45
Compound (SMILES): FC(F)(F)c1cnc(N[C@H]2CNC[C@@H](c3nnc4ccccn34)C2)nc1-c1c[nH]c2ccccc12
InChIKey: IJQBKJGUIDXXLI-LSDHHAIUSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7/Cyclin H/MAT1 (unknown origin) using 5-FAM-CDK7tide peptide substrate incubated for 35 mins
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 478.48, ALogP 4.24, HBA 7, HBD 3, PSA 95.82, QED 0.36
Compound (SMILES): C=CC(=O)Nc1ccc(O[C@@H]2CCC[C@@H](Nc3ncc(Cl)c(-c4c[nH]c5ccccc45)n3)C2)cc1
InChIKey: TWMKLBGOEVXSBH-UYAOXDASSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7/cyclin H/MNAT1 (unknown origin)
Measurement: IC50 = 587 nM (pChEMBL 6.230000019073486)
Descriptors: MW 487.99, ALogP 6.2, HBA 5, HBD 3, PSA 91.93, QED 0.27
Compound (SMILES): CCC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4cc(Cl)ccc4n3)C2)cc1
InChIKey: ZHOYYYIBRLNRRU-GOSISDBHSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7/cyclin H/MAT1 (unknown origin) assessed as incoporation of [33]Pi using RBER-IRStide as substrate and in presence of [gamma-33P]-ATP measured after 60 mins by microplate scintillation counter
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 423.9, ALogP 3.96, HBA 5, HBD 2, PSA 87.22, QED 0.65
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CCC[C@@H](Nc3ncc4ccc(Cl)cc4n3)C2)cc1
InChIKey: YEUXYLMZOGKIDT-LJQANCHMSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7/cyclin H/MAT1 (unknown origin) assessed as incoporation of [33]Pi using RBER-IRStide as substrate and in presence of [gamma-33P]-ATP measured after 60 mins by microplate scintillation counter
Measurement: IC50 = 30000 nM (pChEMBL 4.519999980926514)
Descriptors: MW 435.92, ALogP 4.12, HBA 5, HBD 2, PSA 87.22, QED 0.59
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccc(Cl)cc4n3)C2)cc1
InChIKey: HWTFMLLJQLAKMY-GOSISDBHSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7/cyclin H/MAT1 (unknown origin) assessed as incoporation of [33]Pi using RBER-IRStide as substrate and in presence of [gamma-33P]-ATP measured after 60 mins by microplate scintillation counter
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 421.89, ALogP 3.73, HBA 5, HBD 2, PSA 87.22, QED 0.61
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2C[C@H](Nc3ncc4ccccc4n3)[C@@H](F)C2)cc1
InChIKey: GQFCNTKPAFRBKK-HKUYNNGSSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7/cyclin H/MAT1 (unknown origin) assessed as incoporation of [33]Pi using RBER-IRStide as substrate and in presence of [gamma-33P]-ATP measured after 60 mins by microplate scintillation counter
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 405.43, ALogP 3.03, HBA 5, HBD 2, PSA 87.22, QED 0.64
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4cc(F)ccc4n3)C2)cc1C
InChIKey: KXKAWIWAQIOGGO-GOSISDBHSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7/cyclin H/MAT1 (unknown origin) assessed as incoporation of [33]Pi using RBER-IRStide as substrate and in presence of [gamma-33P]-ATP measured after 60 mins by microplate scintillation counter
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 419.46, ALogP 3.53, HBA 5, HBD 2, PSA 87.22, QED 0.62
Compound (SMILES): CCC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4cc(Cl)ccc4n3)C2)cc1
InChIKey: ZHOYYYIBRLNRRU-GOSISDBHSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Protein Kinase Assay Condition A (Thiol Containing Conditions): A radiometric protein kinase assay (33PanQinase® Activity Assay) was used for measuring the kinase activity of the three protein kinases. All kinase assays were performed in 96-well FlashPlates™ from PerkinElmer (Boston, Mass., USA) in a 50 μl reaction volume. The reaction cocktail was pipetted in four steps in the following order:20 μl of assay buffer (standard buffer)5 μl of ATP solution (in H2O)5 μl of test compound (in 10% DMSO)20 μl enzyme/substrate mixThe assay for all protein kinases contained 70 mM HEPES-NaOH pH 7.5, 3 mM MgCl2, 3 mM MnCl2, 3 μM Na-orthovanadate, 1.2 mM DTT, 50 μg/ml PEG20000, ATP (variable concentrations, corresponding to the apparent ATP-Km of the respective kinase), [γ-33P]-ATP (approx. 9×1005 cpm per well), protein kinase (variable amounts), and substrate (variable amounts).
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 423.9, ALogP 3.96, HBA 5, HBD 2, PSA 87.22, QED 0.65
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CCC[C@@H](Nc3ncc4ccc(Cl)cc4n3)C2)cc1
InChIKey: YEUXYLMZOGKIDT-LJQANCHMSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Protein Kinase Assay Condition A (Thiol Containing Conditions): A radiometric protein kinase assay (33PanQinase® Activity Assay) was used for measuring the kinase activity of the three protein kinases. All kinase assays were performed in 96-well FlashPlates™ from PerkinElmer (Boston, Mass., USA) in a 50 μl reaction volume. The reaction cocktail was pipetted in four steps in the following order:20 μl of assay buffer (standard buffer)5 μl of ATP solution (in H2O)5 μl of test compound (in 10% DMSO)20 μl enzyme/substrate mixThe assay for all protein kinases contained 70 mM HEPES-NaOH pH 7.5, 3 mM MgCl2, 3 mM MnCl2, 3 μM Na-orthovanadate, 1.2 mM DTT, 50 μg/ml PEG20000, ATP (variable concentrations, corresponding to the apparent ATP-Km of the respective kinase), [γ-33P]-ATP (approx. 9×1005 cpm per well), protein kinase (variable amounts), and substrate (variable amounts).
Measurement: IC50 = 65000 nM (pChEMBL 4.190000057220459)
Descriptors: MW 435.92, ALogP 4.12, HBA 5, HBD 2, PSA 87.22, QED 0.59
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccc(Cl)cc4n3)C2)cc1
InChIKey: HWTFMLLJQLAKMY-GOSISDBHSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Protein Kinase Assay Condition A (Thiol Containing Conditions): A radiometric protein kinase assay (33PanQinase® Activity Assay) was used for measuring the kinase activity of the three protein kinases. All kinase assays were performed in 96-well FlashPlates™ from PerkinElmer (Boston, Mass., USA) in a 50 μl reaction volume. The reaction cocktail was pipetted in four steps in the following order:20 μl of assay buffer (standard buffer)5 μl of ATP solution (in H2O)5 μl of test compound (in 10% DMSO)20 μl enzyme/substrate mixThe assay for all protein kinases contained 70 mM HEPES-NaOH pH 7.5, 3 mM MgCl2, 3 mM MnCl2, 3 μM Na-orthovanadate, 1.2 mM DTT, 50 μg/ml PEG20000, ATP (variable concentrations, corresponding to the apparent ATP-Km of the respective kinase), [γ-33P]-ATP (approx. 9×1005 cpm per well), protein kinase (variable amounts), and substrate (variable amounts).
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 421.89, ALogP 3.73, HBA 5, HBD 2, PSA 87.22, QED 0.61
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2C[C@H](Nc3ncc4ccccc4n3)[C@@H](F)C2)cc1
InChIKey: GQFCNTKPAFRBKK-HKUYNNGSSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Protein Kinase Assay Condition A (Thiol Containing Conditions): A radiometric protein kinase assay (33PanQinase® Activity Assay) was used for measuring the kinase activity of the three protein kinases. All kinase assays were performed in 96-well FlashPlates™ from PerkinElmer (Boston, Mass., USA) in a 50 μl reaction volume. The reaction cocktail was pipetted in four steps in the following order:20 μl of assay buffer (standard buffer)5 μl of ATP solution (in H2O)5 μl of test compound (in 10% DMSO)20 μl enzyme/substrate mixThe assay for all protein kinases contained 70 mM HEPES-NaOH pH 7.5, 3 mM MgCl2, 3 mM MnCl2, 3 μM Na-orthovanadate, 1.2 mM DTT, 50 μg/ml PEG20000, ATP (variable concentrations, corresponding to the apparent ATP-Km of the respective kinase), [γ-33P]-ATP (approx. 9×1005 cpm per well), protein kinase (variable amounts), and substrate (variable amounts).
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 405.43, ALogP 3.03, HBA 5, HBD 2, PSA 87.22, QED 0.64
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccncc4n3)C2)cc1
InChIKey: JVPPVCXAHQZJPI-QGZVFWFLSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7/cyclin H/MAT1 (unknown origin) assessed as incoporation of [33]Pi using RBER-IRStide as substrate and in presence of [gamma-33P]-ATP measured after 60 mins by microplate scintillation counter
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 388.43, ALogP 2.48, HBA 6, HBD 2, PSA 100.11, QED 0.65
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4cc(F)ccc4n3)C2)cc1C
InChIKey: KXKAWIWAQIOGGO-GOSISDBHSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Protein Kinase Assay Condition A (Thiol Containing Conditions): A radiometric protein kinase assay (33PanQinase® Activity Assay) was used for measuring the kinase activity of the three protein kinases. All kinase assays were performed in 96-well FlashPlates™ from PerkinElmer (Boston, Mass., USA) in a 50 μl reaction volume. The reaction cocktail was pipetted in four steps in the following order:20 μl of assay buffer (standard buffer)5 μl of ATP solution (in H2O)5 μl of test compound (in 10% DMSO)20 μl enzyme/substrate mixThe assay for all protein kinases contained 70 mM HEPES-NaOH pH 7.5, 3 mM MgCl2, 3 mM MnCl2, 3 μM Na-orthovanadate, 1.2 mM DTT, 50 μg/ml PEG20000, ATP (variable concentrations, corresponding to the apparent ATP-Km of the respective kinase), [γ-33P]-ATP (approx. 9×1005 cpm per well), protein kinase (variable amounts), and substrate (variable amounts).
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 419.46, ALogP 3.53, HBA 5, HBD 2, PSA 87.22, QED 0.62
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4cc(F)ccc4n3)C2)cc1
InChIKey: QVWJCPCDKVFGTB-GOSISDBHSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7/cyclin H/MAT1 (unknown origin) assessed as incoporation of [33]Pi using RBER-IRStide as substrate and in presence of [gamma-33P]-ATP measured after 60 mins by microplate scintillation counter
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 405.43, ALogP 3.22, HBA 5, HBD 2, PSA 87.22, QED 0.64
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4cc(F)ccc4n3)C2)cc1
InChIKey: QVWJCPCDKVFGTB-GOSISDBHSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7/cyclin H/MAT1 (unknown origin) assessed as incoporation of [33]Pi using RBER-IRStide as substrate and in presence of [gamma-33P]-ATP measured after 60 mins under thiol free condition by microplate scintillation counter
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 405.43, ALogP 3.22, HBA 5, HBD 2, PSA 87.22, QED 0.64
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4cc(F)ccc4n3)C2)cc1
InChIKey: QVWJCPCDKVFGTB-GOSISDBHSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Protein Kinase Assay Condition A (Thiol Containing Conditions): A radiometric protein kinase assay (33PanQinase® Activity Assay) was used for measuring the kinase activity of the three protein kinases. All kinase assays were performed in 96-well FlashPlates™ from PerkinElmer (Boston, Mass., USA) in a 50 μl reaction volume. The reaction cocktail was pipetted in four steps in the following order:20 μl of assay buffer (standard buffer)5 μl of ATP solution (in H2O)5 μl of test compound (in 10% DMSO)20 μl enzyme/substrate mixThe assay for all protein kinases contained 70 mM HEPES-NaOH pH 7.5, 3 mM MgCl2, 3 mM MnCl2, 3 μM Na-orthovanadate, 1.2 mM DTT, 50 μg/ml PEG20000, ATP (variable concentrations, corresponding to the apparent ATP-Km of the respective kinase), [γ-33P]-ATP (approx. 9×1005 cpm per well), protein kinase (variable amounts), and substrate (variable amounts).
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 405.43, ALogP 3.22, HBA 5, HBD 2, PSA 87.22, QED 0.64
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4cc(F)ccc4n3)C2)cc1
InChIKey: QVWJCPCDKVFGTB-GOSISDBHSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Protein Kinase Assay Condition B (Thiol-Free Conditions): A radiometric protein kinase assay (33PanQinase® Activity Assay) was used for measuring the kinase activity of the protein kinase. All kinase assays were performed in 96-well FlashPlates from PerkinElmer (Boston, Mass., USA) in a 50 microliter reaction volume. The reaction cocktail was pipetted in four steps in the following order: 20 microliter of assay buffer (standard buffer)5 microliter of ATP solution (in H2O)5 microliter of test compound (in 10% DMSO)20 microliter enzyme/substrate mix. Each assay for the protein kinase contained 70 mM HEPES-NaOH pH 7.5, 3 mM MgCl2, 3 mM MnCl2, 3 microM Na-orthovanadate, 1 mM TCEP, 50 μg/ml PEG20000, ATP (corresponding to the apparent ATP-Km of the kinase, see Table A), [gamma-33P]-ATP (approx. 6×10×E5 cpm per well), with the protein kinase and relevant substrate being used in pre-determined amounts, depending on the kinase in question. For all experiments labeled as Thiol-free, all glutathione was exchanged from protein preparations so as to be removed from the assay and final buffer conditions contained no thiol-containing reagents. In addition, the DTT in the thiol-containing assays is replaced by TCEP in the thiol-free assays and all enzymes and substrates are produced under thiol-free conditions for the thiol-free assays.
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 405.43, ALogP 3.22, HBA 5, HBD 2, PSA 87.22, QED 0.64
Compound (SMILES): CNc1nc(Nc2ccc(-n3cnc(C)n3)c(OC)c2)nc2c1C(C)(O)CC2c1ccc(F)cc1
InChIKey: VZFDGCDPRGKJRJ-UHFFFAOYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96BI3
Assay: Modulation of gamma secretase (unknown origin) assessed as inhibition of amyloid beta (1 to 42 residues) production
Measurement: IC50 = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 475.53, ALogP 4.04, HBA 9, HBD 3, PSA 110.01, QED 0.38