lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): C#Cc1cnc(N[C@H]2CCCNC2)nc1-c1cn(C)c2ccccc12
InChIKey: NCOIDVUPFYMHRJ-HNNXBMFYSA-N
Target: CDK12/Cyclin K (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NYV4
Assay: Inhibition of CDK12 (686 to 1082 residues) /Cyclin K (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 3 hrs
Measurement: IC50 >= 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 331.42, ALogP 2.78, HBA 5, HBD 2, PSA 54.77, QED 0.72
Compound (SMILES): N#Cc1ccc2c(-c3nc(N[C@H]4CCCNC4)ncc3C(F)(F)F)c[nH]c2n1
InChIKey: LBVWNRFNOZHXGU-NSHDSACASA-N
Target: CDK12/Cyclin K (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NYV4
Assay: Inhibition of CDK12 (686 to 1082 residues) /Cyclin K (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 3 hrs
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 387.37, ALogP 3.07, HBA 6, HBD 3, PSA 102.31, QED 0.64
Compound (SMILES): CC(=O)Nc1ccc2c(c1)O[C@H]([C@@H]1CCCN1C)CO2
InChIKey: UBNQTGCQLMZTOD-WFASDCNBSA-N
Target: Neuronal acetylcholine receptor; alpha4/beta2 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P12390
Assay: Displacement of [3H]-Epibatidine from alpha4beta2 nAChR in rat cerebral cortex membrane preincubated for 5 mins followed by [3H]-Epibatidine addition and measured after overnight incubation by liquid scintillation beta counter analysis
Measurement: Ki = 6500 nM (pChEMBL 5.190000057220459)
Descriptors: MW 276.34, ALogP 1.88, HBA 4, HBD 1, PSA 50.8, QED 0.9
Compound (SMILES): Cc1cccc2c(-c3nc(N[C@H]4CCCNC4)ncc3C(F)(F)F)c[nH]c12
InChIKey: QPXJKYBERAQULM-LBPRGKRZSA-N
Target: CDK12/Cyclin K (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NYV4
Assay: Inhibition of CDK12 (686 to 1082 residues) /Cyclin K (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 3 hrs
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 375.4, ALogP 4.12, HBA 4, HBD 3, PSA 65.63, QED 0.64
Compound (SMILES): CC#CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccccc4n3)C2)cc1
InChIKey: OGMQDTCYGLFVAY-LJQANCHMSA-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 399.45, ALogP 2.92, HBA 5, HBD 2, PSA 87.22, QED 0.66
Compound (SMILES): C[C@@H](O)c1cnc(N[C@H]2CCCNC2)nc1-c1c[nH]c2ccccc12
InChIKey: BDAPTFBNJVNHOV-OLZOCXBDSA-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 337.43, ALogP 2.84, HBA 5, HBD 4, PSA 85.86, QED 0.59
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CCC[C@@H](Nc3ncc4cc(OC)ccc4n3)C2)cc1
InChIKey: YUBUDGLTAQSHRH-LJQANCHMSA-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 = 65000 nM (pChEMBL 4.190000057220459)
Descriptors: MW 431.5, ALogP 3.48, HBA 6, HBD 2, PSA 96.45, QED 0.58
Compound (SMILES): C[C@]1(O)CC[C@H](c2cccc3c(-c4nc(N[C@H]5CCCNC5)ncc4C(F)(F)F)c[nH]c32)CC1
InChIKey: UWGQTQNIPQDTSH-YWTKSJFSSA-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 473.54, ALogP 5.22, HBA 5, HBD 4, PSA 85.86, QED 0.42
Compound (SMILES): O=C(N/N=C/c1ccc([N+](=O)[O-])o1)c1ccc(Cl)s1
InChIKey: VTQVJOQTJIYQIX-LFYBBSHMSA-N
Target: GroEL/GroES (PROTEIN COMPLEX), Escherichia coli
UniProt: Q548M1
Assay: Inhibition of Escherichia coli GroEL/ES assessed as inhibition of native malate dehydrogenase treated after denatured malate dehydrogenase completely refold in presence of NfsB nitroreductase
Measurement: IC50 > 56000 nM (pChEMBL 4.251999855041504)
Descriptors: MW 299.69, ALogP 2.67, HBA 6, HBD 1, PSA 97.74, QED 0.53
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccccc4n3)C2)c(C)c1
InChIKey: SNEOQNDRTVGPGR-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 401.47, ALogP 3.39, HBA 5, HBD 2, PSA 87.22, QED 0.64
Compound (SMILES): FC(F)(F)c1cnc(N[C@H]2CCCNC2)nc1-c1c[nH]c2cc(-c3cnccn3)ccc12
InChIKey: SOEGPCFMFUKWHZ-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 439.45, ALogP 4.26, HBA 6, HBD 3, PSA 91.41, QED 0.44
Compound (SMILES): CC(O)c1cnc(N[C@H]2CCCNC2)nc1-c1c[nH]c2ccccc12
InChIKey: BDAPTFBNJVNHOV-ABLWVSNPSA-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 337.43, ALogP 2.84, HBA 5, HBD 4, PSA 85.86, QED 0.59
Compound (SMILES): N=C(N)Nc1cccc(C(=O)NCC(=O)NC[C@H](NC(=O)[C@@H]2CCCN2S(=O)(=O)c2ccccc2)C(=O)O)c1
InChIKey: BMHOPYDAWFKHEW-OALUTQOASA-N
Target: Integrin alpha-V/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P05556
Assay: Cell adhesion assay to SW480: The blockade of integrin alpha 5 beta 1 provides a novel target for the treatment of asthma. As shown in FIGS. 1A and 1B, delivery of ATN-161, a low affinity yet specific inhibitor of alpha5beta1, reduces the magnitude of airway narrowing in vivo in mice sensitized and challenged with ovalbumin, a widely used model of allergic asthma. In the same model, it was found that mice with a specific deletion of this integrin in smooth muscle also have reduced airway narrowing. The intracellular actin-myosin cross-bridging pathway serves as a useful target. Modulating the interactions of the cell and the extracellular matrix impairs the ability of the smooth muscle to transmit tension effectively. The blockade of integrin alpha 5 beta 1 was tested in vitro with human cell lines as well as in vivo with a mouse model of airway hyperresponsiveness. Novel compounds as described herein, and identified in Table 1, have been synthesized and tested in vitro for their ability to inhibit cell adhesion mediated by alpha5beta1 (adhesion of the colon carcinoma cell line SW480 to fibronectin, a response that is entirely dependent on binding of alpha5beta1 to fibronectin).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 559.61, ALogP -0.74, HBA 7, HBD 7, PSA 223.88, QED 0.14
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccccc4n3)C2)cc1Cl
InChIKey: ONRGJWZQIHEWQH-MRXNPFEDSA-N
Target: CDK2/Cyclin A2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24941
Assay: Inhibition of CDK2/cyclin A2 (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 421.89, ALogP 3.73, HBA 5, HBD 2, PSA 87.22, QED 0.61
Compound (SMILES): C=Cc1cnc(N[C@H]2CCCNC2)nc1-c1c[nH]c2ccccc12
InChIKey: APJGSHNZRJYNOB-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 319.41, ALogP 3.43, HBA 4, HBD 3, PSA 65.63, QED 0.69
Compound (SMILES): Fc1cccc(-c2ccc3c(-c4nc(N[C@H]5CCCNC5)ncc4C(F)(F)F)c[nH]c3c2)c1
InChIKey: HVHMUOGPMMMIMX-KRWDZBQOSA-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 455.46, ALogP 5.61, HBA 4, HBD 3, PSA 65.63, QED 0.35
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CCC[C@@H](Nc3ncc4ccc(OC)cc4n3)C2)cc1
InChIKey: UYMLPZXKVJTMDC-LJQANCHMSA-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 = 65000 nM (pChEMBL 4.190000057220459)
Descriptors: MW 431.5, ALogP 3.48, HBA 6, HBD 2, PSA 96.45, QED 0.58
Compound (SMILES): CCC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccc(=O)[nH]c4n3)C2)cc1
InChIKey: HXMQLODVRVHQFU-MRXNPFEDSA-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 406.45, ALogP 1.99, HBA 6, HBD 3, PSA 120.08, QED 0.6
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccccc4n3)C2)c(OC)c1
InChIKey: IXRHEVMMVUNFRH-QGZVFWFLSA-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 417.47, ALogP 3.09, HBA 6, HBD 2, PSA 96.45, QED 0.6
Compound (SMILES): CCc1cnc(N[C@H]2CCCNC2)nc1-c1c[nH]c2c(S(C)(=O)=O)c(C#N)ccc12
InChIKey: SLIFZZITPODXKX-HNNXBMFYSA-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 424.53, ALogP 2.63, HBA 7, HBD 3, PSA 123.56, QED 0.58
Compound (SMILES): Cn1cc(-c2nc(N[C@H]3CCCNC3)ncc2C(F)(F)F)c2ccc(C#N)nc21
InChIKey: UIKSGIZKQSSSKQ-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 >= 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 401.4, ALogP 3.08, HBA 7, HBD 2, PSA 91.45, QED 0.7
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccccc4n3)C2)cc1F
InChIKey: GYQGWMAYFQZINJ-MRXNPFEDSA-N
Target: CDK2/Cyclin A2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24941
Assay: Inhibition of CDK2/cyclin A2 (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): CCC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3cc4ccccc4cn3)C2)cc1
InChIKey: HUKPFWLRPMADDJ-HXUWFJFHSA-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 388.47, ALogP 3.91, HBA 4, HBD 2, PSA 74.33, QED 0.69
Compound (SMILES): CNS(=O)(=O)c1ccc2c(-c3nc(N[C@H]4CCCNC4)ncc3C(F)(F)F)c[nH]c2c1
InChIKey: YOKJZKNQSMSTEA-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 454.48, ALogP 2.72, HBA 6, HBD 4, PSA 111.8, QED 0.47
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CCC[C@@H](Nc3cc4ccccc4cn3)C2)cc1
InChIKey: BJQKZYVLMUWQLN-OAQYLSRUSA-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 = 65000 nM (pChEMBL 4.190000057220459)
Descriptors: MW 400.48, ALogP 4.08, HBA 4, HBD 2, PSA 74.33, QED 0.63
Compound (SMILES): CCCCCc1ccc2c(-c3nc(N[C@H]4CCCNC4)ncc3C(F)(F)F)c[nH]c2c1
InChIKey: VSVASKKCTHTYJG-INIZCTEOSA-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 431.51, ALogP 5.54, HBA 4, HBD 3, PSA 65.63, QED 0.43
Compound (SMILES): CCC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccc(C#N)cc4n3)C2)cc1
InChIKey: YECFQQVVMJBGDA-LJQANCHMSA-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 414.47, ALogP 3.18, HBA 6, HBD 2, PSA 111.01, QED 0.66
Compound (SMILES): O=C(O)C[C@H](C(=O)N1CC[C@@H](CCc2ccc3c(n2)NCCC3)C1)c1cccc(Cl)c1
InChIKey: ZMWIYVLLRRYJEL-IERDGZPVSA-N
Target: Integrin alpha-V/beta-5 (PROTEIN COMPLEX), Homo sapiens
UniProt: P06756
Assay: Inhibition of human alphavbeta5 integrin stably expressed in human K562 cells assessed as inhibition of cell adhesion to vitronectin incubated for 30 mins by BCECF-AM staining based fluorescence assay
Measurement: IC50 = 125.89 nM (pChEMBL 6.900000095367432)
Descriptors: MW 441.96, ALogP 4.13, HBA 4, HBD 2, PSA 82.53, QED 0.67
Compound (SMILES): CN1CCC[C@H](Nc2ncc(Cl)c(-c3c[nH]c4ccccc34)n2)C1
InChIKey: XMRPPWFWJKGYOU-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 341.85, ALogP 3.78, HBA 4, HBD 2, PSA 56.84, QED 0.76
Compound (SMILES): CCC(=O)Nc1ccc(C(=O)N2CCC[C@@H](Nc3ncc4ccccc4n3)C2)cc1
InChIKey: VMTBHEBGKDRQTD-LJQANCHMSA-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 = 65000 nM (pChEMBL 4.190000057220459)
Descriptors: MW 403.49, ALogP 3.7, HBA 5, HBD 2, PSA 87.22, QED 0.68
Compound (SMILES): FC(F)(F)c1cnc(N[C@@H]2CNC[C@H](c3nnc4ccccn34)C2)nc1-c1c[nH]c2ccccc12
InChIKey: IJQBKJGUIDXXLI-CABCVRRESA-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 478.48, ALogP 4.24, HBA 7, HBD 3, PSA 95.82, QED 0.36
Compound (SMILES): Brc1cnc(N[C@@H]2CCCNC2)nc1-c1c[nH]c2ccccc12
InChIKey: XUBDCIJPSUUTBA-LLVKDONJSA-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 372.27, ALogP 3.55, HBA 4, HBD 3, PSA 65.63, QED 0.66
Compound (SMILES): C#Cc1cnc(N[C@H]2CCCNC2)nc1-c1cn(C)c2ccccc12
InChIKey: NCOIDVUPFYMHRJ-HNNXBMFYSA-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 331.42, ALogP 2.78, HBA 5, HBD 2, PSA 54.77, QED 0.72
Compound (SMILES): N#Cc1ccc2c(-c3nc(N[C@H]4CCCNC4)ncc3C(F)(F)F)c[nH]c2n1
InChIKey: LBVWNRFNOZHXGU-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 387.37, ALogP 3.07, HBA 6, HBD 3, PSA 102.31, QED 0.64
Compound (SMILES): Cc1cccc2c(-c3nc(N[C@H]4CCCNC4)ncc3C(F)(F)F)c[nH]c12
InChIKey: QPXJKYBERAQULM-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 375.4, ALogP 4.12, HBA 4, HBD 3, PSA 65.63, QED 0.64
Compound (SMILES): N=C(N)Nc1cccc(C(=O)NCC(=O)NC[C@H](NC(=O)[C@@H]2CCCN2S(=O)(=O)c2ccccc2)C(=O)O)c1
InChIKey: BMHOPYDAWFKHEW-OALUTQOASA-N
Target: Integrin alpha-V/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P05556
Assay: Cell adhesion assay to Hamster Ovary: The blockade of integrin alpha 5 beta 1 provides a novel target for the treatment of asthma. As shown in FIGS. 1A and 1B, delivery of ATN-161, a low affinity yet specific inhibitor of alpha5beta1, reduces the magnitude of airway narrowing in vivo in mice sensitized and challenged with ovalbumin, a widely used model of allergic asthma. In the same model, it was found that mice with a specific deletion of this integrin in smooth muscle also have reduced airway narrowing. The intracellular actin-myosin cross-bridging pathway serves as a useful target. Modulating the interactions of the cell and the extracellular matrix impairs the ability of the smooth muscle to transmit tension effectively. The blockade of integrin alpha 5 beta 1 was tested in vitro with human cell lines as well as in vivo with a mouse model of airway hyperresponsiveness. Novel compounds as described herein, and identified in Table 1, have been synthesized and tested in vitro for their ability to inhibit cell adhesion mediated by alphavbeta1 (adhesion of Chinese Hamster Ovary cells transfected with human alphav to the latency associated peptide of transforming growth factor beta, a response that is entirely dependent on binding of alphavbeta1 to LAP).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 559.61, ALogP -0.74, HBA 7, HBD 7, PSA 223.88, QED 0.14
Compound (SMILES): Nc1nn2c(-c3ccc(Cl)cc3)ccnc2c1/N=N/c1ccc(S(N)(=O)=O)cc1
InChIKey: ANPPRZRKIIVFGL-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 = 6400 nM (pChEMBL 5.190000057220459)
Descriptors: MW 427.88, ALogP 3.69, HBA 8, HBD 2, PSA 141.09, QED 0.48
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccccc4n3)C2)cc1Cl
InChIKey: ONRGJWZQIHEWQH-MRXNPFEDSA-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 421.89, ALogP 3.73, HBA 5, HBD 2, PSA 87.22, QED 0.61
Compound (SMILES): N#Cc1c(N2CCOCC2)sc(-c2nc[nH]n2)c1-c1ccc(NC(=O)N/N=C/c2ccccn2)cc1
InChIKey: HTRWIOXPFBBBCH-CCVNUDIWSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of N-terminal His6-tagged human recombinant full length PI3Kdelta co-expressed with human recombinant full length P85alpha in baculovirus infected Sf21 cells using PIP2 peptide as substrate incubated for 2 hrs in presence ATP by ADP-Glo Kinase Assay
Measurement: IC50 = 49 nM (pChEMBL 7.309999942779541)
Descriptors: MW 499.56, ALogP 3.46, HBA 9, HBD 3, PSA 144.21, QED 0.27
Compound (SMILES): CCc1cnc(N[C@H]2CCCNC2)nc1-c1c[nH]c2c(S(C)(=O)=O)c(C#N)ccc12
InChIKey: SLIFZZITPODXKX-HNNXBMFYSA-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 = 1638 nM (pChEMBL 5.789999961853027)
Descriptors: MW 424.53, ALogP 2.63, HBA 7, HBD 3, PSA 123.56, QED 0.58
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccccc4n3)C2)cc1F
InChIKey: GYQGWMAYFQZINJ-MRXNPFEDSA-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): Nc1nn2c(-c3ccc(Cl)cc3)ccnc2c1/N=N/c1ccc(S(N)(=O)=O)cc1
InChIKey: ANPPRZRKIIVFGL-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 427.88, ALogP 3.69, HBA 8, HBD 2, PSA 141.09, QED 0.48
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccccc4n3)C2)cc1Cl
InChIKey: ONRGJWZQIHEWQH-MRXNPFEDSA-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 = 100 nM (pChEMBL 7)
Descriptors: MW 421.89, ALogP 3.73, HBA 5, HBD 2, PSA 87.22, QED 0.61
Compound (SMILES): CCc1cnc(N[C@H]2CCCNC2)nc1-c1c[nH]c2c(S(C)(=O)=O)c(C#N)ccc12
InChIKey: SLIFZZITPODXKX-HNNXBMFYSA-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 = 0.15 nM (pChEMBL 9.819999694824219)
Descriptors: MW 424.53, ALogP 2.63, HBA 7, HBD 3, PSA 123.56, QED 0.58
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccccc4n3)C2)cc1F
InChIKey: GYQGWMAYFQZINJ-MRXNPFEDSA-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 = 100 nM (pChEMBL 7)
Descriptors: MW 405.43, ALogP 3.22, HBA 5, HBD 2, PSA 87.22, QED 0.64
Compound (SMILES): C[C@H](CN1CCC[C@@H]1C)NC(=O)c1ccc(-c2noc(C(F)(F)F)n2)cc1
InChIKey: DBWSFWPXCPNWRZ-NEPJUHHUSA-N
Target: Histone deacetylase 3/Nuclear receptor corepressor 2 (HDAC3/NCoR2) (PROTEIN COMPLEX), Homo sapiens
UniProt: O15379
Assay: Inhibition of HDAC3/NCOR2 (unknown origin) using Boc-Lys(Ac) as substrate by fluorogenic assay
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 382.39, ALogP 3.36, HBA 5, HBD 1, PSA 71.26, QED 0.86
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccccc4n3)C2)cc1Cl
InChIKey: ONRGJWZQIHEWQH-MRXNPFEDSA-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 421.89, ALogP 3.73, HBA 5, HBD 2, PSA 87.22, QED 0.61
Compound (SMILES): CCc1cnc(N[C@H]2CCCNC2)nc1-c1c[nH]c2c(S(C)(=O)=O)c(C#N)ccc12
InChIKey: SLIFZZITPODXKX-HNNXBMFYSA-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 = 907 nM (pChEMBL 6.039999961853027)
Descriptors: MW 424.53, ALogP 2.63, HBA 7, HBD 3, PSA 123.56, QED 0.58
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccccc4n3)C2)cc1F
InChIKey: GYQGWMAYFQZINJ-MRXNPFEDSA-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): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccccc4n3)C2)cc1Cl
InChIKey: ONRGJWZQIHEWQH-MRXNPFEDSA-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 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 421.89, ALogP 3.73, HBA 5, HBD 2, PSA 87.22, QED 0.61
Compound (SMILES): CCc1cnc(N[C@H]2CCCNC2)nc1-c1c[nH]c2c(S(C)(=O)=O)c(C#N)ccc12
InChIKey: SLIFZZITPODXKX-HNNXBMFYSA-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 = 215 nM (pChEMBL 6.670000076293945)
Descriptors: MW 424.53, ALogP 2.63, HBA 7, HBD 3, PSA 123.56, QED 0.58
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccccc4n3)C2)cc1F
InChIKey: GYQGWMAYFQZINJ-MRXNPFEDSA-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 = 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[C@@H](O)c1cnc(N[C@H]2CCCNC2)nc1-c1c[nH]c2ccccc12
InChIKey: BDAPTFBNJVNHOV-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 337.43, ALogP 2.84, HBA 5, HBD 4, PSA 85.86, QED 0.59
Compound (SMILES): C[C@]1(O)CC[C@H](c2cccc3c(-c4nc(N[C@H]5CCCNC5)ncc4C(F)(F)F)c[nH]c32)CC1
InChIKey: UWGQTQNIPQDTSH-YWTKSJFSSA-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 473.54, ALogP 5.22, HBA 5, HBD 4, PSA 85.86, QED 0.42
Compound (SMILES): CCn1nc2c(c1Nc1nc(-c3ccc(-n4cnc(C)c4)c(OC)n3)cs1)C(C)CC2(C)C
InChIKey: NONHWESJQFIAJQ-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 = 72 nM (pChEMBL 7.139999866485596)
Descriptors: MW 463.61, ALogP 5.45, HBA 9, HBD 1, PSA 82.68, QED 0.41
Compound (SMILES): FC(F)(F)c1cnc(N[C@H]2CCCNC2)nc1-c1c[nH]c2cc(-c3cnccn3)ccc12
InChIKey: SOEGPCFMFUKWHZ-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 439.45, ALogP 4.26, HBA 6, HBD 3, PSA 91.41, QED 0.44
Compound (SMILES): CC(O)c1cnc(N[C@H]2CCCNC2)nc1-c1c[nH]c2ccccc12
InChIKey: BDAPTFBNJVNHOV-ABLWVSNPSA-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 337.43, ALogP 2.84, HBA 5, HBD 4, PSA 85.86, QED 0.59
Compound (SMILES): C=Cc1cnc(N[C@H]2CCCNC2)nc1-c1c[nH]c2ccccc12
InChIKey: APJGSHNZRJYNOB-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 319.41, ALogP 3.43, HBA 4, HBD 3, PSA 65.63, QED 0.69
Compound (SMILES): c1ccc(Nc2cc3c(cn2)ncn3CC2CC2)cc1
InChIKey: GYSKOUFUCVGMOT-UHFFFAOYSA-N
Target: GABA-A receptor; alpha-5/beta-3/gamma-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P31644
Assay: Displacement of [3H]-Ro15-1788 from human GABAA alpha5beta3gamma2 by scintillation proximity assay
Measurement: Ki = 972 nM (pChEMBL 6.010000228881836)
Descriptors: MW 264.33, ALogP 3.58, HBA 4, HBD 1, PSA 42.74, QED 0.78
Compound (SMILES): Fc1cccc(-c2ccc3c(-c4nc(N[C@H]5CCCNC5)ncc4C(F)(F)F)c[nH]c3c2)c1
InChIKey: HVHMUOGPMMMIMX-KRWDZBQOSA-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 455.46, ALogP 5.61, HBA 4, HBD 3, PSA 65.63, QED 0.35
Compound (SMILES): CCc1cnc(N[C@H]2CCCNC2)nc1-c1c[nH]c2c(S(C)(=O)=O)c(C#N)ccc12
InChIKey: SLIFZZITPODXKX-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 424.53, ALogP 2.63, HBA 7, HBD 3, PSA 123.56, QED 0.58
Compound (SMILES): Cn1cc(-c2nc(N[C@H]3CCCNC3)ncc2C(F)(F)F)c2ccc(C#N)nc21
InChIKey: UIKSGIZKQSSSKQ-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 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 401.4, ALogP 3.08, HBA 7, HBD 2, PSA 91.45, QED 0.7
Compound (SMILES): CNS(=O)(=O)c1ccc2c(-c3nc(N[C@H]4CCCNC4)ncc3C(F)(F)F)c[nH]c2c1
InChIKey: YOKJZKNQSMSTEA-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 454.48, ALogP 2.72, HBA 6, HBD 4, PSA 111.8, QED 0.47
Compound (SMILES): CCCCCc1ccc2c(-c3nc(N[C@H]4CCCNC4)ncc3C(F)(F)F)c[nH]c2c1
InChIKey: VSVASKKCTHTYJG-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 431.51, ALogP 5.54, HBA 4, HBD 3, PSA 65.63, QED 0.43
Compound (SMILES): Cc1nnc(N2CC3CCC(C2)C3Nc2nc(Oc3cccc(Cl)c3)n(C(C)C)n2)o1
InChIKey: ZGHBXBLICFTIQX-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 = 42 nM (pChEMBL 7.380000114440918)
Descriptors: MW 443.94, ALogP 4.32, HBA 9, HBD 1, PSA 94.13, QED 0.6
Compound (SMILES): CN1CCC[C@H](Nc2ncc(Cl)c(-c3c[nH]c4ccccc34)n2)C1
InChIKey: XMRPPWFWJKGYOU-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 341.85, ALogP 3.78, HBA 4, HBD 2, PSA 56.84, QED 0.76
Compound (SMILES): FC(F)(F)c1cnc(N[C@@H]2CNC[C@H](c3nnc4ccccn34)C2)nc1-c1c[nH]c2ccccc12
InChIKey: IJQBKJGUIDXXLI-CABCVRRESA-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 478.48, ALogP 4.24, HBA 7, HBD 3, PSA 95.82, QED 0.36
Compound (SMILES): Cc1cc(Nc2cnc3c(c2)OCC(=O)N3C)nc2c1ncn2CC1CC1
InChIKey: SLTJCGDOKDTBSL-UHFFFAOYSA-N
Target: GABA-A receptor; alpha-5/beta-3/gamma-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P31644
Assay: Displacement of [3H]-Ro15-1788 from human GABAA alpha5beta3gamma2 by scintillation proximity assay
Measurement: Ki = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 364.41, ALogP 2.64, HBA 7, HBD 1, PSA 85.17, QED 0.77
Compound (SMILES): Brc1cnc(N[C@@H]2CCCNC2)nc1-c1c[nH]c2ccccc12
InChIKey: XUBDCIJPSUUTBA-LLVKDONJSA-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 372.27, ALogP 3.55, HBA 4, HBD 3, PSA 65.63, QED 0.66
Compound (SMILES): C#Cc1cnc(N[C@H]2CCCNC2)nc1-c1cn(C)c2ccccc12
InChIKey: NCOIDVUPFYMHRJ-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 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 331.42, ALogP 2.78, HBA 5, HBD 2, PSA 54.77, QED 0.72
Compound (SMILES): N#Cc1ccc2c(-c3nc(N[C@H]4CCCNC4)ncc3C(F)(F)F)c[nH]c2n1
InChIKey: LBVWNRFNOZHXGU-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 387.37, ALogP 3.07, HBA 6, HBD 3, PSA 102.31, QED 0.64
Compound (SMILES): COc1nc(-c2csc(Nc3c4c(nn3C3CCC3)CCC4)n2)ccc1-n1cnc(C)c1
InChIKey: HIZHNHITDDKGGY-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 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 447.57, ALogP 4.86, HBA 9, HBD 1, PSA 82.68, QED 0.45
Compound (SMILES): Cc1cccc2c(-c3nc(N[C@H]4CCCNC4)ncc3C(F)(F)F)c[nH]c12
InChIKey: QPXJKYBERAQULM-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 375.4, ALogP 4.12, HBA 4, HBD 3, PSA 65.63, QED 0.64
Compound (SMILES): Cc1nnc(C23CC(Nc4nc(Cc5ccc(Cl)cc5)cc(C(C)(C)O)n4)(C2)C3)o1
InChIKey: GNMZARMQZJSJSS-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 = 520 nM (pChEMBL 6.28000020980835)
Descriptors: MW 425.92, ALogP 3.93, HBA 7, HBD 2, PSA 96.96, QED 0.62
Compound (SMILES): CC(C)(O)CN(C[C@H](O)[C@@H](N)c1ccccc1)S(=O)(=O)c1ccc(Cl)c(Cl)c1
InChIKey: PYQRNCANJYCFSS-ROUUACIJSA-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 > 10000 nM (pChEMBL 5)
Descriptors: MW 447.38, ALogP 2.82, HBA 5, HBD 3, PSA 103.86, QED 0.58
Compound (SMILES): CC#CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccccc4n3)C2)cc1
InChIKey: OGMQDTCYGLFVAY-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 = 100 nM (pChEMBL 7)
Descriptors: MW 399.45, ALogP 2.92, HBA 5, HBD 2, PSA 87.22, QED 0.66