lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Clc1cnc(NC2CNCCC2c2ccccc2)nc1-c1c[nH]c2ccccc12
InChIKey: NVZYIDRYPJCALC-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 403.92, ALogP 4.84, HBA 4, HBD 3, PSA 65.63, QED 0.46
Compound (SMILES): Cc1c(-c2ccc3c(-c4nc(N[C@H]5CCCNC5)ncc4C(F)(F)F)c[nH]c3c2)c[nH]c(=O)c1C#N
InChIKey: DBUJAJWRYRZVAL-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 7.698999881744385)
Descriptors: MW 493.49, ALogP 4.34, HBA 6, HBD 4, PSA 122.28, QED 0.34
Compound (SMILES): C[C@H]1CCNC[C@H]1Nc1ncc(C(F)(F)F)c(-c2c[nH]c3ccccc23)n1
InChIKey: YGVSSBPHNLLAHU-MEDUHNTESA-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 375.4, ALogP 4.05, HBA 4, HBD 3, PSA 65.63, QED 0.65
Compound (SMILES): Cc1cc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3n(n2)CCC[C@H]3Oc2ccc(Cl)cc2)ncn1
InChIKey: MJLRPASHEJEXBJ-IMLKGASGSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q92542
Assay: Inhibition of human gamma secretase assessed as reduction in Abeta42 production
Measurement: IC50 = 10.3 nM (pChEMBL 7.989999771118164)
Descriptors: MW 465.99, ALogP 4.27, HBA 8, HBD 1, PSA 80.99, QED 0.6
Compound (SMILES): Fc1cnc2[nH]cc(-c3nc(N[C@H]4CCCNC4)ncc3C(F)(F)F)c2c1
InChIKey: FFOLBBUXUFLVCD-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 380.35, ALogP 3.34, HBA 5, HBD 3, PSA 78.52, QED 0.61
Compound (SMILES): N#Cc1ccc2c(-c3nc(N[C@H]4CCCNC4)ncc3C(F)(F)F)c[nH]c2c1C#N
InChIKey: DUGSEWFNPLJUEV-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 411.39, ALogP 3.55, HBA 6, HBD 3, PSA 113.21, QED 0.61
Compound (SMILES): CCc1cnc(N[C@H]2CCCNC2)nc1-c1c[nH]c2nc(C#N)ccc12
InChIKey: IPIWQVGRFNIMQX-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 347.43, ALogP 2.62, HBA 6, HBD 3, PSA 102.31, QED 0.67
Compound (SMILES): Cc1ccc2[nH]cc(-c3nc(N[C@H]4CCCNC4)ncc3Cl)c2c1
InChIKey: XWOQCKJZIGPMAB-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 341.85, ALogP 3.75, HBA 4, HBD 3, PSA 65.63, QED 0.68
Compound (SMILES): Cc1noc([C@H]2CC[C@H](Nc3ncc(C(F)(F)F)c(-c4c[nH]c5cc(C#N)ccc45)n3)CN2)n1
InChIKey: BUUPGVFPOSYWOV-SUMWQHHRSA-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 468.44, ALogP 4.11, HBA 8, HBD 3, PSA 128.34, QED 0.41
Compound (SMILES): CNC(=O)[C@@H]1CNC[C@@H](Nc2ncc(C(F)(F)F)c(-c3c[nH]c4ccccc34)n2)C1
InChIKey: QWTLJZSIFBCFBX-RYUDHWBXSA-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 418.42, ALogP 2.78, HBA 5, HBD 4, PSA 94.73, QED 0.52
Compound (SMILES): Cn1ncc2ccc(-c3ccc4c(-c5nc(N[C@H]6CCCNC6)ncc5C(F)(F)F)c[nH]c4c3)cc21
InChIKey: JHMADRGGYHZRPX-SFHVURJKSA-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 491.52, ALogP 5.36, HBA 6, HBD 3, PSA 83.45, QED 0.32
Compound (SMILES): CC(C(=O)Nc1cc(C2CC2)[nH]n1)c1cccc(C2CCN(C(=O)/C=C/CN(C)C)CC2)c1
InChIKey: JDYQFGCWGWMKSX-VMPITWQZSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Biochemical Assay: The ability of compounds to inhibit CDK7 kinase activity was tested in a TR-FRET assay using 5 nM of CDK7/CycH/MNAT1 obtained from Invitrogen, USA. Test compounds were pre-incubated with the kinase at room temperature for 60 min. After the incubation, substrate mix [100 nM Ultra-light MBP (Perkin Elmer, USA) and 1 mM ATP (Sigma)] was added. The above reaction was stopped by the addition of 40 mM EDTA after 60 minutes of kinase reaction. 1 nM Eu-labelled antiphospho-MBP antibody [Perkin Elmer, USA] was added, mixed well and the fluorescence emission at 615 nm and 665 nm [excitation at 340 nm] was measured. The final DMSO concentration in the assay was 1%. For IC50 determination, appropriate concentrations were made by ⅓rd serial dilutions of 10 mM DMSO stock solution of test compound. All the fluorescence measurements were made in a Victor 3 Multilabel Counter [Perkin Elmer, USA]. The IC50 was determined by fitting the dose response data to sigmoidal curve fitting equation using GraphPad Prism software V5. To identify compounds that inhibit CDK7 irreversibly, time depended inhibition studies were carried by pre-incubating compound with the enzyme at three time points (20, 60 and 180 min) and carrying out assay as described above.
Measurement: IC50 > 100 nM (pChEMBL 7)
Descriptors: MW 449.6, ALogP 3.85, HBA 4, HBD 2, PSA 81.33, QED 0.6
Compound (SMILES): N#Cc1ccc2c(-c3nc(N[C@H]4CCCNC4)ncc3OC(F)F)c[nH]c2c1
InChIKey: FTHWYCLTONRIMR-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 384.39, ALogP 3.26, HBA 6, HBD 3, PSA 98.65, QED 0.62
Compound (SMILES): CC[C@H]1CC[C@H](Nc2ncc(C(F)(F)F)c(-c3c[nH]c4ccccc34)n2)CN1
InChIKey: SUQQDRCRQDKHCI-STQMWFEESA-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 389.43, ALogP 4.59, HBA 4, HBD 3, PSA 65.63, QED 0.61
Compound (SMILES): Cc1nnc(-c2ccc(Nc3nc4n(n3)CCCN4c3cccc(Cl)c3)cc2)o1
InChIKey: BFAHJNDZUPNGPN-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 = 95 nM (pChEMBL 7.019999980926514)
Descriptors: MW 407.87, ALogP 4.58, HBA 8, HBD 1, PSA 84.9, QED 0.53
Compound (SMILES): N[C@@H](c1ccccc1)[C@@H](O)CN(Cc1ccccc1)S(=O)(=O)c1ccc(Cl)c(Cl)c1
InChIKey: LGXZEBGEBDJZBV-VXKWHMMOSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q92542
Assay: Inhibition of gamma-secretase (unknown origin) expressed in HEK293 cells cotransfected with Notch1-VP16-GAL4 fusion and Gal4 luciferase reporter plasmid incubated for 24 hrs by luciferase reporter gene assay luminescence assay
Measurement: IC50 = 3400 nM (pChEMBL 5.46999979019165)
Descriptors: MW 465.4, ALogP 4.25, HBA 4, HBD 2, PSA 83.63, QED 0.52
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4cc(OC)ccc4n3)C2)cc1
InChIKey: PWIPCKSOLCEBRW-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 = 30000 nM (pChEMBL 4.519999980926514)
Descriptors: MW 417.47, ALogP 3.09, HBA 6, HBD 2, PSA 96.45, QED 0.6
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccc(=O)[nH]c4n3)C2)cc1
InChIKey: QOHQFRKLSIBCRS-MRXNPFEDSA-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 404.43, ALogP 1.77, HBA 6, HBD 3, PSA 120.08, QED 0.56
Compound (SMILES): C=C(CC)C(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccccc4n3)C2)cc1
InChIKey: JKHQLEAMZNVIPI-HXUWFJFHSA-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 415.5, ALogP 3.86, HBA 5, HBD 2, PSA 87.22, QED 0.6
Compound (SMILES): C=CS(=O)(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccccc4n3)C2)cc1
InChIKey: QSERWBXLEKAYCJ-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 423.5, ALogP 2.84, HBA 6, HBD 2, PSA 104.29, QED 0.63
Compound (SMILES): CN(C)C/C=C/C(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccccc4n3)C2)cc1
InChIKey: SXMMHTKZUYOEJX-WKOQKXSESA-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 444.54, ALogP 3.01, HBA 6, HBD 2, PSA 90.46, QED 0.54
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccc(F)cc4n3)C2)cc1
InChIKey: AJSYOLPHCHQLPB-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 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](Nc3ncc4ccccc4n3)C2)cc1
InChIKey: PWEDJMTYYMURIC-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 385.43, ALogP 2.53, HBA 5, HBD 2, PSA 87.22, QED 0.67
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccc(C)cc4n3)C2)cc1
InChIKey: YRQZGISKFWGSDA-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 = 1000 nM (pChEMBL 6)
Descriptors: MW 401.47, ALogP 3.39, HBA 5, HBD 2, PSA 87.22, QED 0.64
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4cc(OC)ccc4n3)C2)cc1
InChIKey: PWIPCKSOLCEBRW-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 = 65000 nM (pChEMBL 4.190000057220459)
Descriptors: MW 417.47, ALogP 3.09, HBA 6, HBD 2, PSA 96.45, QED 0.6
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccc(=O)[nH]c4n3)C2)cc1
InChIKey: QOHQFRKLSIBCRS-MRXNPFEDSA-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 404.43, ALogP 1.77, HBA 6, HBD 3, PSA 120.08, QED 0.56
Compound (SMILES): C=C(CC)C(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccccc4n3)C2)cc1
InChIKey: JKHQLEAMZNVIPI-HXUWFJFHSA-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 415.5, ALogP 3.86, HBA 5, HBD 2, PSA 87.22, QED 0.6
Compound (SMILES): C=CS(=O)(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccccc4n3)C2)cc1
InChIKey: QSERWBXLEKAYCJ-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 423.5, ALogP 2.84, HBA 6, HBD 2, PSA 104.29, QED 0.63
Compound (SMILES): CN(C)C/C=C/C(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccccc4n3)C2)cc1
InChIKey: SXMMHTKZUYOEJX-WKOQKXSESA-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 444.54, ALogP 3.01, HBA 6, HBD 2, PSA 90.46, QED 0.54
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccc(F)cc4n3)C2)cc1
InChIKey: AJSYOLPHCHQLPB-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 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](Nc3ncc4ccccc4n3)C2)cc1
InChIKey: PWEDJMTYYMURIC-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 < 100 nM (pChEMBL 7)
Descriptors: MW 385.43, ALogP 2.53, HBA 5, HBD 2, PSA 87.22, QED 0.67
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccc(C)cc4n3)C2)cc1
InChIKey: YRQZGISKFWGSDA-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 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 401.47, ALogP 3.39, HBA 5, HBD 2, PSA 87.22, QED 0.64
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccccc4n3)C2)cc1C
InChIKey: IYJULXBZNSIWSN-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 401.47, ALogP 3.39, HBA 5, HBD 2, PSA 87.22, QED 0.64
Compound (SMILES): CCC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccccc4n3)C2)cc1
InChIKey: CYWJCWFAPFOQOP-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 389.46, ALogP 3.3, HBA 5, HBD 2, PSA 87.22, QED 0.7
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccccc4n3)C2)cn1
InChIKey: LRKRQTMUHJKJQW-MRXNPFEDSA-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 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](Nc3ncc4ccccc4n3)C2)cc1C
InChIKey: IYJULXBZNSIWSN-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 401.47, ALogP 3.39, HBA 5, HBD 2, PSA 87.22, QED 0.64
Compound (SMILES): CCC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccccc4n3)C2)cc1
InChIKey: CYWJCWFAPFOQOP-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 389.46, ALogP 3.3, HBA 5, HBD 2, PSA 87.22, QED 0.7
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccccc4n3)C2)cn1
InChIKey: LRKRQTMUHJKJQW-MRXNPFEDSA-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 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](Nc3ncc4ccccc4n3)C2)cc1C
InChIKey: IYJULXBZNSIWSN-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 401.47, ALogP 3.39, HBA 5, HBD 2, PSA 87.22, QED 0.64
Compound (SMILES): CCC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccccc4n3)C2)cc1
InChIKey: CYWJCWFAPFOQOP-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 389.46, ALogP 3.3, HBA 5, HBD 2, PSA 87.22, QED 0.7
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccccc4n3)C2)cn1
InChIKey: LRKRQTMUHJKJQW-MRXNPFEDSA-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 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](Nc3ncc4ccccc4n3)C2)cc1C
InChIKey: IYJULXBZNSIWSN-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 401.47, ALogP 3.39, HBA 5, HBD 2, PSA 87.22, QED 0.64
Compound (SMILES): CCC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccccc4n3)C2)cc1
InChIKey: CYWJCWFAPFOQOP-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 389.46, ALogP 3.3, HBA 5, HBD 2, PSA 87.22, QED 0.7
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccccc4n3)C2)cn1
InChIKey: LRKRQTMUHJKJQW-MRXNPFEDSA-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 388.43, ALogP 2.48, HBA 6, HBD 2, PSA 100.11, QED 0.65
Compound (SMILES): CCn1nc(C(C)(C)C)cc1Nc1nc(-c2ccc(-n3cnc(C)c3)cc2)cs1
InChIKey: XPRAODNQZLOGJH-UHFFFAOYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96BI3
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 = 339 nM (pChEMBL 6.46999979019165)
Descriptors: MW 406.56, ALogP 5.56, HBA 7, HBD 1, PSA 60.56, QED 0.47
Compound (SMILES): C[C@@H]1NC(=O)[C@@H]2CSSC[C@@H]3NC(=O)[C@H](CSSC[C@H](NC(=O)[C@H](C)NC(=O)[C@@H]4CCCN4C(=O)[C@H](Cc4c[nH]cn4)NC3=O)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc3c[nH]cn3)C(=O)N[C@@H](Cc3ccccc3)C(=O)N[C@@H](CO)C(=O)N2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)CNC1=O
InChIKey: UREONIRHHJQFMZ-WQTQUTKDSA-N
Target: CHRNA1/CHRNB1/CHRNG/CHRND (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P25108
Assay: Inhibition of rat (alpha1)2betagammadelta expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced channel current response at -70 mV holding potential by two-electrode voltage-clamp assay
Measurement: IC50 = 7.54 nM (pChEMBL 8.119999885559082)
Descriptors: MW 1725.99
Compound (SMILES): Cc1cc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3n(n2)CCC[C@H]3Oc2ccc(Cl)cc2)ncn1
InChIKey: MJLRPASHEJEXBJ-IMLKGASGSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96BI3
Assay: Inhibition of human gamma secretase assessed as reduction in Abeta42 production
Measurement: IC50 = 10.3 nM (pChEMBL 7.989999771118164)
Descriptors: MW 465.99, ALogP 4.27, HBA 8, HBD 1, PSA 80.99, QED 0.6
Compound (SMILES): Cc1nnc(-c2ccc(Nc3nc4n(n3)CCCN4c3cccc(Cl)c3)cc2)o1
InChIKey: BFAHJNDZUPNGPN-UHFFFAOYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96BI3
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 = 95 nM (pChEMBL 7.019999980926514)
Descriptors: MW 407.87, ALogP 4.58, HBA 8, HBD 1, PSA 84.9, QED 0.53
Compound (SMILES): N[C@@H](c1ccccc1)[C@@H](O)CN(Cc1ccccc1)S(=O)(=O)c1ccc(Cl)c(Cl)c1
InChIKey: LGXZEBGEBDJZBV-VXKWHMMOSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96BI3
Assay: Inhibition of gamma-secretase (unknown origin) expressed in HEK293 cells cotransfected with Notch1-VP16-GAL4 fusion and Gal4 luciferase reporter plasmid incubated for 24 hrs by luciferase reporter gene assay luminescence assay
Measurement: IC50 = 3400 nM (pChEMBL 5.46999979019165)
Descriptors: MW 465.4, ALogP 4.25, HBA 4, HBD 2, PSA 83.63, QED 0.52
Compound (SMILES): CCn1nc(C(C)(C)C)cc1Nc1nc(-c2ccc(-n3cnc(C)c3)cc2)cs1
InChIKey: XPRAODNQZLOGJH-UHFFFAOYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: P49768
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 = 339 nM (pChEMBL 6.46999979019165)
Descriptors: MW 406.56, ALogP 5.56, HBA 7, HBD 1, PSA 60.56, QED 0.47
Compound (SMILES): Cc1cc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3n(n2)CCC[C@H]3Oc2ccc(Cl)cc2)ncn1
InChIKey: MJLRPASHEJEXBJ-IMLKGASGSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: P49768
Assay: Inhibition of human gamma secretase assessed as reduction in Abeta42 production
Measurement: IC50 = 10.3 nM (pChEMBL 7.989999771118164)
Descriptors: MW 465.99, ALogP 4.27, HBA 8, HBD 1, PSA 80.99, QED 0.6
Compound (SMILES): Cc1nnc(-c2ccc(Nc3nc4n(n3)CCCN4c3cccc(Cl)c3)cc2)o1
InChIKey: BFAHJNDZUPNGPN-UHFFFAOYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: P49768
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 = 95 nM (pChEMBL 7.019999980926514)
Descriptors: MW 407.87, ALogP 4.58, HBA 8, HBD 1, PSA 84.9, QED 0.53
Compound (SMILES): N[C@@H](c1ccccc1)[C@@H](O)CN(Cc1ccccc1)S(=O)(=O)c1ccc(Cl)c(Cl)c1
InChIKey: LGXZEBGEBDJZBV-VXKWHMMOSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: P49768
Assay: Inhibition of gamma-secretase (unknown origin) expressed in HEK293 cells cotransfected with Notch1-VP16-GAL4 fusion and Gal4 luciferase reporter plasmid incubated for 24 hrs by luciferase reporter gene assay luminescence assay
Measurement: IC50 = 3400 nM (pChEMBL 5.46999979019165)
Descriptors: MW 465.4, ALogP 4.25, HBA 4, HBD 2, PSA 83.63, QED 0.52
Compound (SMILES): CCn1nc(C(C)(C)C)cc1Nc1nc(-c2ccc(-n3cnc(C)c3)cc2)cs1
InChIKey: XPRAODNQZLOGJH-UHFFFAOYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8WW43
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 = 339 nM (pChEMBL 6.46999979019165)
Descriptors: MW 406.56, ALogP 5.56, HBA 7, HBD 1, PSA 60.56, QED 0.47
Compound (SMILES): Cc1cc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3n(n2)CCC[C@H]3Oc2ccc(Cl)cc2)ncn1
InChIKey: MJLRPASHEJEXBJ-IMLKGASGSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8WW43
Assay: Inhibition of human gamma secretase assessed as reduction in Abeta42 production
Measurement: IC50 = 10.3 nM (pChEMBL 7.989999771118164)
Descriptors: MW 465.99, ALogP 4.27, HBA 8, HBD 1, PSA 80.99, QED 0.6
Compound (SMILES): Cc1nnc(-c2ccc(Nc3nc4n(n3)CCCN4c3cccc(Cl)c3)cc2)o1
InChIKey: BFAHJNDZUPNGPN-UHFFFAOYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8WW43
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 = 95 nM (pChEMBL 7.019999980926514)
Descriptors: MW 407.87, ALogP 4.58, HBA 8, HBD 1, PSA 84.9, QED 0.53
Compound (SMILES): N[C@@H](c1ccccc1)[C@@H](O)CN(Cc1ccccc1)S(=O)(=O)c1ccc(Cl)c(Cl)c1
InChIKey: LGXZEBGEBDJZBV-VXKWHMMOSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8WW43
Assay: Inhibition of gamma-secretase (unknown origin) expressed in HEK293 cells cotransfected with Notch1-VP16-GAL4 fusion and Gal4 luciferase reporter plasmid incubated for 24 hrs by luciferase reporter gene assay luminescence assay
Measurement: IC50 = 3400 nM (pChEMBL 5.46999979019165)
Descriptors: MW 465.4, ALogP 4.25, HBA 4, HBD 2, PSA 83.63, QED 0.52
Compound (SMILES): CC(=O)N(C)c1cccc(Nc2nc(C)c(-c3cc4c(c(S(C)(=O)=O)c3)C(=O)N([C@@H](C)C3CC3)C4)s2)n1
InChIKey: KWHLMLQDUKNHBO-HNNXBMFYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Enzymatic Activity Assay : The activity of recombinant human PI3Kγ ((aa144-1102)-6His) and PI3Kα, β, δ (6-His(p110-p85α)) was determined by measuring the ADP level after phosphorylation of DiC8-PIP2 using a commercially available ADP-Glo kit from Promega. The assay was carried out in white low volume 384 well plates in a final volume of 14 μl at R.T. The assay conditions contained the following: 50 mM Tris buffer pH 7.4, 2.1 mM DTT, 3 mM MgCl2, 0.05% CHAPS, 20 μM ATP, 80 μM DiC8-PIP2 and 1.2 nM PI3Kα, β, γ or 0.6 nM PI3Kδ. Potential inhibitors were made up in DMSO and then diluted in the assay to give a final concentration of not exceeding 1% (v/v) DMSO. A 10-point half-log dilution series of the inhibitors (highest concentration typically 0.1 μM for δ or γ and 33 μM for a or 1) was tested and the pIC50 determined using a 4-parameter logistic equation in a non-linear curve fitting routine. Routinely, inhibitors were pre-incubated with 3 μl of enzyme for 15 min prior to the addition of 2 μl substrate mixture for a further 60 min enzyme reaction. The phosphorylation was stopped with the addition of 3 μl ADP-Glo reagent (stop solution) followed by a 40 min incubation. Prior to detection 6 μl of ADP-Glo Kinase Detection Reagent was added and the plates were read in a micro plate reader using a Luminescence filter. All additions were followed by a short centrifugation step.
Measurement: IC50 = 127 nM (pChEMBL 6.900000095367432)
Descriptors: MW 539.68, ALogP 4.4, HBA 8, HBD 1, PSA 112.57, QED 0.47
Compound (SMILES): CCc1cccc(N2CCN(CC(O)CCNCCC(C(=O)N(C)C)(c3ccccc3)c3ccccc3)CC2)c1Cl
InChIKey: ZXLUAMSMIJONAJ-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]-N-methylspiperone from human dopamine D4 receptor expressed in HEK293 cell membranes incubated for 60 mins by microbeta scintillation counting analysis
Measurement: Ki = 1260 nM (pChEMBL 5.900000095367432)
Descriptors: MW 577.21, ALogP 4.83, HBA 5, HBD 2, PSA 59.05, QED 0.29
Compound (SMILES): COc1cc(OC)c(NC(=O)Cc2cn(C)c3ccccc23)cc1Cl
InChIKey: MLQWIWGLWAXAFA-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O95136
Assay: Antagonist activity at human S1P2 receptor expressed in CHO cells assessed as inhibition of [35S]GTPgammaS binding
Measurement: IC50 = 19240 nM (pChEMBL 4.71999979019165)
Descriptors: MW 358.83, ALogP 4.03, HBA 4, HBD 1, PSA 52.49, QED 0.75
Compound (SMILES): CC[C@@H]1CN2CC[C@@]3(O)C(=Nc4cccc(-c5ccoc5)c43)[C@@H]2C[C@@H]1/C(=C\OC)C(=O)OC
InChIKey: XLDZPTJGCMJSBF-BHKYNAABSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity at human MOR receptor expressed in HTLA cells co-expressing TEV-fused-beta-arrestin2 assessed as induction of beta-arrestin2 recruitment by Tango assay
Measurement: EC50 = 10964.78 nM (pChEMBL 4.960000038146973)
Descriptors: MW 450.54, ALogP 4.04, HBA 7, HBD 1, PSA 84.5, QED 0.42
Compound (SMILES): O=C(c1ccc(Oc2ccccc2)cc1Cl)c1c[nH]c2ncnc(N[C@H]3CC[C@H](CO)OC3)c12
InChIKey: JSFCZQSJQXFJDS-MAUKXSAKSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Radiometric Assay: Enzyme assay using full length recombinant active form of wild-type BTK and BTK-C481S was measured as described previously (Anastassiadis T, et al., Nat. Biotechnol. 29(11):1039-45 (2011)). Compounds were tested in 10-point dose IC50 mode with 3-fold serial dilution starting at 1 or 10 μM concentration. BTK kinase activity was assayed in a buffer solution containing 20 mM Hepes (pH 7.5), 10 mM MgCl2, 1 mM EGTA, 0.02% Brij35, 0.02 mg/ml BSA, 0.1 mM Na3VO4, 2 mM DTT, 1% DMSO. Compounds in 100% DMSO were mixed with kinase (8 nM wild-type BTK or 5 nM BTK-C481S mutant) with substrate into the kinase reaction mixture by Acoustic technology (Echo550; nanoliter range) and incubated for 20 min at room temp. The reaction was initiated by adding 10 μM ATP containing 33P-ATP into the mixture and incubated for 2 hours at room temperature. Kinase activity was detected by P81 filter-binding 33P radioisotope based radiometric method. All compounds were tested in duplicate. The raw data was fit to a 4-parameter logistic model to derive the IC50 value for kinase activity inhibition.
Measurement: IC50 = 9.7 nM (pChEMBL 8.010000228881836)
Descriptors: MW 478.94, ALogP 4.59, HBA 7, HBD 3, PSA 109.36, QED 0.33
Compound (SMILES): CNS(=O)(=O)c1cc(-c2sc(Nc3cccc(N4CCOCC4=O)n3)nc2C)cc2c1C(=O)N([C@@H](C)C1CC1)C2
InChIKey: FZLQVDKBOUEZHS-INIZCTEOSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of recombinant human PI3Kalpha assessed as reduction in ADP production using Dic8-PIP2 as substrate pre-treated for 15 mins followed by substrate addition measured after 60 mins by ADP-glo assay
Measurement: IC50 = 39.81 nM (pChEMBL 7.400000095367432)
Descriptors: MW 582.71, ALogP 3.28, HBA 9, HBD 2, PSA 133.83, QED 0.41
Compound (SMILES): CC1(C)Oc2cc(C3(CCCCCCC#N)CCCC3)cc(O)c2[C@@H]2C[C@H](CO)CC[C@H]21
InChIKey: CUUVQTMUEVFQHL-YMPZKCBVSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Agonist activity at 3xHA tagged human CB1 receptor expressed in CHO-K1 cells assessed as reduction in forskolin-stimulated cAMP accumulation incubated for 30 mins by cAMP assay
Measurement: EC50 = 0.31 nM (pChEMBL 9.510000228881836)
Descriptors: MW 439.64, ALogP 6.73, HBA 4, HBD 2, PSA 73.48, QED 0.44
Compound (SMILES): Cc1nc2ccc(-c3cc(N)nc(N)c3)nc2n1C[C@H](C)Oc1ccccc1
InChIKey: PUGXENIKUPHCAF-ZDUSSCGKSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of wild type full length DYRK1A (unknown origin) in human U2OS cells assessed as reduction in pSER520 autophosphorylation incubated for 5 hrs by western blot analysis
Measurement: IC50 = 73 nM (pChEMBL 7.139999866485596)
Descriptors: MW 374.45, ALogP 3.43, HBA 7, HBD 2, PSA 104.87, QED 0.55
Compound (SMILES): CCOC(=O)/C=C\Sc1ncc(C(=O)O)c(=O)[nH]1
InChIKey: CYVGZIFZCGRMHT-ARJAWSKDSA-N
Target: Lysine-specific demethylase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: O75164
Assay: Inhibition of human N-terminal His6-tagged KDM4A (M1 to L359 residues) expressed in Escherichia coli using H3K9(Me3) as substrate preincubated for 15 mins followed by substrate addition and measured after 20 mins by Alphascreen assay
Measurement: IC50 = 11200 nM (pChEMBL 4.949999809265137)
Descriptors: MW 270.27, ALogP 0.64, HBA 6, HBD 2, PSA 109.35, QED 0.35
Compound (SMILES): Cc1ccc2c(c1)Oc1cc(C)ccc1C2NC(=O)c1ccc(C(F)(F)F)[nH]c1=O
InChIKey: GNZIEIKTMKBQKP-UHFFFAOYSA-N
Target: 3-hydroxyacyl-CoA dehydrogenase type-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99714
Assay: Inhibition of HSD17B10 (unknown origin) using estradiol as substrate incubated for 3 hrs and measured after 1 hr by NADH Glo luminescence assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 414.38, ALogP 4.64, HBA 3, HBD 2, PSA 71.19, QED 0.64
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@@H]2CSSC[C@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@@H]3CCCN3C(=O)[C@H](CCCNC(=N)N)NC1=O)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)NCC(=O)NCC(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N2
InChIKey: WEJHFJXWIBZZTQ-AHUOXLFJSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Mus musculus
UniProt: P32300
Assay: Displacement of [3H]-diprenorphine from mouse DOR expressed in HEK293 cell membranes by radioligand binding assay relative to control
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 1790.25
Compound (SMILES): C=CC(=O)N1CCN(CCCCCn2nc(-c3ccc(OC)cc3)c3c(N)ncnc32)CC1
InChIKey: HDQPOEXAULBBSR-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 (445 to 753 residues) expressed in Escherichia coli BL21 (DE3) by HTRF assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 449.56, ALogP 2.58, HBA 8, HBD 1, PSA 102.4, QED 0.4