lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1nc2ccccc2nc1-c1cc2nc(N3CC[C@@H](F)C3)cc(NC3CCOCC3)n2n1
InChIKey: WJHNQPZRFNFKBI-MRXNPFEDSA-N
Target: Phosphodiesterase (SINGLE PROTEIN), Bos taurus
UniProt: F1MPW5
Assay: Inhibition Assay: The PDE assay was performed according to a modified method referred to a report of Kotera et al. (Kotera et al., Biochem. Pharmacol., vol. 60, pp. 1333-1341, 2000), by the radiolabeled nucleotide method.Specifically, the measurements of the inhibitory activities were carried out in the following method.(Method) The test compounds were dissolved in dimethyl sulfoxide (DMSO). 2 uL of the compound solution was added to 96 well plate, and the reaction mixture (20 uL of PDE enzyme solution in 50 mM Tris-HCl, pH 8.0, 40 uL of the assay buffer (50 mM Tris-HCl, pH 8.0, 2 mM MgCl2, 0.07% 2-mercaptoethanol, and 0.825 mg/mL bovine serum albumin), and 20 uL of 1 mg/mL snake venom in 50 mM Tris-HCl, pH8.0) was added to the 96 well plate. The enzyme reaction was started by adding and mixing with substrate solution of 20 L containing approximate 35 nM 3H-cAMP in 50 mM Tris-HCl, pH 8.0. The final concentration of cAMP in the reaction mixtures was 7 nM.
Measurement: IC50 = 0.83 nM (pChEMBL 9.079999923706055)
Descriptors: MW 447.52, ALogP 3.79, HBA 8, HBD 1, PSA 80.47, QED 0.51
Compound (SMILES): Cc1nc2ccc(F)cc2nc1-c1cc2nc(N3CC[C@@H](F)C3)cc(NCC(C)(C)O)n2n1
InChIKey: PUJFXPWIBOJQHB-OAHLLOKOSA-N
Target: Phosphodiesterase (SINGLE PROTEIN), Bos taurus
UniProt: F1MPW5
Assay: Inhibition Assay: The PDE assay was performed according to a modified method referred to a report of Kotera et al. (Kotera et al., Biochem. Pharmacol., vol. 60, pp. 1333-1341, 2000), by the radiolabeled nucleotide method.Specifically, the measurements of the inhibitory activities were carried out in the following method.(Method) The test compounds were dissolved in dimethyl sulfoxide (DMSO). 2 uL of the compound solution was added to 96 well plate, and the reaction mixture (20 uL of PDE enzyme solution in 50 mM Tris-HCl, pH 8.0, 40 uL of the assay buffer (50 mM Tris-HCl, pH 8.0, 2 mM MgCl2, 0.07% 2-mercaptoethanol, and 0.825 mg/mL bovine serum albumin), and 20 uL of 1 mg/mL snake venom in 50 mM Tris-HCl, pH8.0) was added to the 96 well plate. The enzyme reaction was started by adding and mixing with substrate solution of 20 L containing approximate 35 nM 3H-cAMP in 50 mM Tris-HCl, pH 8.0. The final concentration of cAMP in the reaction mixtures was 7 nM.
Measurement: IC50 = 0.09 nM (pChEMBL 10.050000190734863)
Descriptors: MW 453.5, ALogP 3.52, HBA 8, HBD 2, PSA 91.47, QED 0.48
Compound (SMILES): Cc1nc2ccccc2nc1-c1cc2nc(N3CC=CC3)cc(NC3CCOCC3)n2n1
InChIKey: NXSZPBOXTRGSSN-UHFFFAOYSA-N
Target: Phosphodiesterase (SINGLE PROTEIN), Bos taurus
UniProt: F1MPW5
Assay: Inhibition Assay: The PDE assay was performed according to a modified method referred to a report of Kotera et al. (Kotera et al., Biochem. Pharmacol., vol. 60, pp. 1333-1341, 2000), by the radiolabeled nucleotide method.Specifically, the measurements of the inhibitory activities were carried out in the following method.(Method) The test compounds were dissolved in dimethyl sulfoxide (DMSO). 2 uL of the compound solution was added to 96 well plate, and the reaction mixture (20 uL of PDE enzyme solution in 50 mM Tris-HCl, pH 8.0, 40 uL of the assay buffer (50 mM Tris-HCl, pH 8.0, 2 mM MgCl2, 0.07% 2-mercaptoethanol, and 0.825 mg/mL bovine serum albumin), and 20 uL of 1 mg/mL snake venom in 50 mM Tris-HCl, pH8.0) was added to the 96 well plate. The enzyme reaction was started by adding and mixing with substrate solution of 20 L containing approximate 35 nM 3H-cAMP in 50 mM Tris-HCl, pH 8.0. The final concentration of cAMP in the reaction mixtures was 7 nM.
Measurement: IC50 = 0.2 nM (pChEMBL 9.699999809265137)
Descriptors: MW 427.51, ALogP 3.62, HBA 8, HBD 1, PSA 80.47, QED 0.5
Compound (SMILES): Cc1nc2ccccc2nc1-c1cc2nc(N3CCCC3)cc(OC3CCOCC3)n2n1
InChIKey: PTBPZEFWJQZLHT-UHFFFAOYSA-N
Target: Phosphodiesterase (SINGLE PROTEIN), Bos taurus
UniProt: F1MPW5
Assay: Inhibition Assay: The PDE assay was performed according to a modified method referred to a report of Kotera et al. (Kotera et al., Biochem. Pharmacol., vol. 60, pp. 1333-1341, 2000), by the radiolabeled nucleotide method.Specifically, the measurements of the inhibitory activities were carried out in the following method.(Method) The test compounds were dissolved in dimethyl sulfoxide (DMSO). 2 uL of the compound solution was added to 96 well plate, and the reaction mixture (20 uL of PDE enzyme solution in 50 mM Tris-HCl, pH 8.0, 40 uL of the assay buffer (50 mM Tris-HCl, pH 8.0, 2 mM MgCl2, 0.07% 2-mercaptoethanol, and 0.825 mg/mL bovine serum albumin), and 20 uL of 1 mg/mL snake venom in 50 mM Tris-HCl, pH8.0) was added to the 96 well plate. The enzyme reaction was started by adding and mixing with substrate solution of 20 L containing approximate 35 nM 3H-cAMP in 50 mM Tris-HCl, pH 8.0. The final concentration of cAMP in the reaction mixtures was 7 nM.
Measurement: IC50 = 0.38 nM (pChEMBL 9.420000076293945)
Descriptors: MW 430.51, ALogP 3.81, HBA 8, HBD 0, PSA 77.67, QED 0.49
Compound (SMILES): Cc1nc2ccccc2nc1-c1cc2nc(C3=CCCC3)cc(NC3CCOCC3)n2n1
InChIKey: SXZGYWIXXAXAPI-UHFFFAOYSA-N
Target: Phosphodiesterase (SINGLE PROTEIN), Bos taurus
UniProt: F1MPW5
Assay: Inhibition Assay: The PDE assay was performed according to a modified method referred to a report of Kotera et al. (Kotera et al., Biochem. Pharmacol., vol. 60, pp. 1333-1341, 2000), by the radiolabeled nucleotide method.Specifically, the measurements of the inhibitory activities were carried out in the following method.(Method) The test compounds were dissolved in dimethyl sulfoxide (DMSO). 2 uL of the compound solution was added to 96 well plate, and the reaction mixture (20 uL of PDE enzyme solution in 50 mM Tris-HCl, pH 8.0, 40 uL of the assay buffer (50 mM Tris-HCl, pH 8.0, 2 mM MgCl2, 0.07% 2-mercaptoethanol, and 0.825 mg/mL bovine serum albumin), and 20 uL of 1 mg/mL snake venom in 50 mM Tris-HCl, pH8.0) was added to the 96 well plate. The enzyme reaction was started by adding and mixing with substrate solution of 20 L containing approximate 35 nM 3H-cAMP in 50 mM Tris-HCl, pH 8.0. The final concentration of cAMP in the reaction mixtures was 7 nM.
Measurement: IC50 = 0.22 nM (pChEMBL 9.65999984741211)
Descriptors: MW 426.52, ALogP 4.81, HBA 7, HBD 1, PSA 77.23, QED 0.5
Compound (SMILES): Cc1nc2ccc(F)cc2nc1-c1cc2nc(N3CC[C@@H](F)C3)cc(N[C@H]3CC[C@](C)(O)CC3)n2n1
InChIKey: FOHXAFIDDJBWDT-UYPAYLBCSA-N
Target: Phosphodiesterase (SINGLE PROTEIN), Bos taurus
UniProt: F1MPW5
Assay: Inhibition Assay: The PDE assay was performed according to a modified method referred to a report of Kotera et al. (Kotera et al., Biochem. Pharmacol., vol. 60, pp. 1333-1341, 2000), by the radiolabeled nucleotide method.Specifically, the measurements of the inhibitory activities were carried out in the following method.(Method) The test compounds were dissolved in dimethyl sulfoxide (DMSO). 2 uL of the compound solution was added to 96 well plate, and the reaction mixture (20 uL of PDE enzyme solution in 50 mM Tris-HCl, pH 8.0, 40 uL of the assay buffer (50 mM Tris-HCl, pH 8.0, 2 mM MgCl2, 0.07% 2-mercaptoethanol, and 0.825 mg/mL bovine serum albumin), and 20 uL of 1 mg/mL snake venom in 50 mM Tris-HCl, pH8.0) was added to the 96 well plate. The enzyme reaction was started by adding and mixing with substrate solution of 20 L containing approximate 35 nM 3H-cAMP in 50 mM Tris-HCl, pH 8.0. The final concentration of cAMP in the reaction mixtures was 7 nM.
Measurement: IC50 = 0.09 nM (pChEMBL 10.050000190734863)
Descriptors: MW 493.56, ALogP 4.44, HBA 8, HBD 2, PSA 91.47, QED 0.43
Compound (SMILES): Cc1nc2ccccc2nc1-c1cc2nc(N3CCCC3)cc(N3CCCC3)n2n1
InChIKey: HYNGQPREEKTTSZ-UHFFFAOYSA-N
Target: Phosphodiesterase (SINGLE PROTEIN), Bos taurus
UniProt: F1MPW5
Assay: Inhibition Assay: The PDE assay was performed according to a modified method referred to a report of Kotera et al. (Kotera et al., Biochem. Pharmacol., vol. 60, pp. 1333-1341, 2000), by the radiolabeled nucleotide method.Specifically, the measurements of the inhibitory activities were carried out in the following method.(Method) The test compounds were dissolved in dimethyl sulfoxide (DMSO). 2 uL of the compound solution was added to 96 well plate, and the reaction mixture (20 uL of PDE enzyme solution in 50 mM Tris-HCl, pH 8.0, 40 uL of the assay buffer (50 mM Tris-HCl, pH 8.0, 2 mM MgCl2, 0.07% 2-mercaptoethanol, and 0.825 mg/mL bovine serum albumin), and 20 uL of 1 mg/mL snake venom in 50 mM Tris-HCl, pH8.0) was added to the 96 well plate. The enzyme reaction was started by adding and mixing with substrate solution of 20 L containing approximate 35 nM 3H-cAMP in 50 mM Tris-HCl, pH 8.0. The final concentration of cAMP in the reaction mixtures was 7 nM.
Measurement: IC50 = 0.57 nM (pChEMBL 9.239999771118164)
Descriptors: MW 399.5, ALogP 3.85, HBA 7, HBD 0, PSA 62.45, QED 0.52
Compound (SMILES): Cc1nc2ccccc2nc1-c1cc2nc(N3CCCC3)cc(NC[C@H](O)C(F)(F)F)n2n1
InChIKey: GSTVEULKMNBCLW-KRWDZBQOSA-N
Target: Phosphodiesterase (SINGLE PROTEIN), Bos taurus
UniProt: F1MPW5
Assay: Inhibition Assay: The PDE assay was performed according to a modified method referred to a report of Kotera et al. (Kotera et al., Biochem. Pharmacol., vol. 60, pp. 1333-1341, 2000), by the radiolabeled nucleotide method.Specifically, the measurements of the inhibitory activities were carried out in the following method.(Method) The test compounds were dissolved in dimethyl sulfoxide (DMSO). 2 uL of the compound solution was added to 96 well plate, and the reaction mixture (20 uL of PDE enzyme solution in 50 mM Tris-HCl, pH 8.0, 40 uL of the assay buffer (50 mM Tris-HCl, pH 8.0, 2 mM MgCl2, 0.07% 2-mercaptoethanol, and 0.825 mg/mL bovine serum albumin), and 20 uL of 1 mg/mL snake venom in 50 mM Tris-HCl, pH8.0) was added to the 96 well plate. The enzyme reaction was started by adding and mixing with substrate solution of 20 L containing approximate 35 nM 3H-cAMP in 50 mM Tris-HCl, pH 8.0. The final concentration of cAMP in the reaction mixtures was 7 nM.
Measurement: IC50 = 0.13 nM (pChEMBL 9.890000343322754)
Descriptors: MW 457.46, ALogP 3.58, HBA 8, HBD 2, PSA 91.47, QED 0.47
Compound (SMILES): Cc1nc2ccccc2nc1-c1cc2nc(N3CCCC3)cc(NCCC#N)n2n1
InChIKey: NDJDREBPYNBNPG-UHFFFAOYSA-N
Target: Phosphodiesterase (SINGLE PROTEIN), Bos taurus
UniProt: F1MPW5
Assay: Inhibition Assay: The PDE assay was performed according to a modified method referred to a report of Kotera et al. (Kotera et al., Biochem. Pharmacol., vol. 60, pp. 1333-1341, 2000), by the radiolabeled nucleotide method.Specifically, the measurements of the inhibitory activities were carried out in the following method.(Method) The test compounds were dissolved in dimethyl sulfoxide (DMSO). 2 uL of the compound solution was added to 96 well plate, and the reaction mixture (20 uL of PDE enzyme solution in 50 mM Tris-HCl, pH 8.0, 40 uL of the assay buffer (50 mM Tris-HCl, pH 8.0, 2 mM MgCl2, 0.07% 2-mercaptoethanol, and 0.825 mg/mL bovine serum albumin), and 20 uL of 1 mg/mL snake venom in 50 mM Tris-HCl, pH8.0) was added to the 96 well plate. The enzyme reaction was started by adding and mixing with substrate solution of 20 L containing approximate 35 nM 3H-cAMP in 50 mM Tris-HCl, pH 8.0. The final concentration of cAMP in the reaction mixtures was 7 nM.
Measurement: IC50 = 0.052 nM (pChEMBL 10.279999732971191)
Descriptors: MW 398.47, ALogP 3.57, HBA 8, HBD 1, PSA 95.03, QED 0.51
Compound (SMILES): CO[C@H]1CC[C@H](Nc2cc(N3CCCC3)nc3cc(-c4nc5cc(C(F)(F)F)ccc5nc4C)nn23)CC1
InChIKey: AEKWGTXTPJUUPF-WGSAOQKQSA-N
Target: Phosphodiesterase (SINGLE PROTEIN), Bos taurus
UniProt: F1MPW5
Assay: Inhibition Assay: The PDE assay was performed according to a modified method referred to a report of Kotera et al. (Kotera et al., Biochem. Pharmacol., vol. 60, pp. 1333-1341, 2000), by the radiolabeled nucleotide method.Specifically, the measurements of the inhibitory activities were carried out in the following method.(Method) The test compounds were dissolved in dimethyl sulfoxide (DMSO). 2 uL of the compound solution was added to 96 well plate, and the reaction mixture (20 uL of PDE enzyme solution in 50 mM Tris-HCl, pH 8.0, 40 uL of the assay buffer (50 mM Tris-HCl, pH 8.0, 2 mM MgCl2, 0.07% 2-mercaptoethanol, and 0.825 mg/mL bovine serum albumin), and 20 uL of 1 mg/mL snake venom in 50 mM Tris-HCl, pH8.0) was added to the 96 well plate. The enzyme reaction was started by adding and mixing with substrate solution of 20 L containing approximate 35 nM 3H-cAMP in 50 mM Tris-HCl, pH 8.0. The final concentration of cAMP in the reaction mixtures was 7 nM.
Measurement: IC50 = 0.045 nM (pChEMBL 10.350000381469727)
Descriptors: MW 525.58, ALogP 5.64, HBA 8, HBD 1, PSA 80.47, QED 0.36
Compound (SMILES): COCCN(CCCO)c1cc(N2CCCC2)nc2cc(-c3nc4cc(C)ccc4nc3C)nn12
InChIKey: LBZFKRHQZFCWNK-UHFFFAOYSA-N
Target: Phosphodiesterase (SINGLE PROTEIN), Bos taurus
UniProt: F1MPW5
Assay: Inhibition Assay: The PDE assay was performed according to a modified method referred to a report of Kotera et al. (Kotera et al., Biochem. Pharmacol., vol. 60, pp. 1333-1341, 2000), by the radiolabeled nucleotide method.Specifically, the measurements of the inhibitory activities were carried out in the following method.(Method) The test compounds were dissolved in dimethyl sulfoxide (DMSO). 2 uL of the compound solution was added to 96 well plate, and the reaction mixture (20 uL of PDE enzyme solution in 50 mM Tris-HCl, pH 8.0, 40 uL of the assay buffer (50 mM Tris-HCl, pH 8.0, 2 mM MgCl2, 0.07% 2-mercaptoethanol, and 0.825 mg/mL bovine serum albumin), and 20 uL of 1 mg/mL snake venom in 50 mM Tris-HCl, pH8.0) was added to the 96 well plate. The enzyme reaction was started by adding and mixing with substrate solution of 20 L containing approximate 35 nM 3H-cAMP in 50 mM Tris-HCl, pH 8.0. The final concentration of cAMP in the reaction mixtures was 7 nM.
Measurement: IC50 = 0.019 nM (pChEMBL 10.720000267028809)
Descriptors: MW 475.6, ALogP 3.39, HBA 9, HBD 1, PSA 91.91, QED 0.39
Compound (SMILES): Cc1nc2ccccc2nc1-c1cc2nc(N3CC[C@@H](F)C3)cc(NC3COC3)n2n1
InChIKey: AIAQWURPUZZGAZ-CQSZACIVSA-N
Target: Phosphodiesterase (SINGLE PROTEIN), Bos taurus
UniProt: F1MPW5
Assay: Inhibition Assay: The PDE assay was performed according to a modified method referred to a report of Kotera et al. (Kotera et al., Biochem. Pharmacol., vol. 60, pp. 1333-1341, 2000), by the radiolabeled nucleotide method.Specifically, the measurements of the inhibitory activities were carried out in the following method.(Method) The test compounds were dissolved in dimethyl sulfoxide (DMSO). 2 uL of the compound solution was added to 96 well plate, and the reaction mixture (20 uL of PDE enzyme solution in 50 mM Tris-HCl, pH 8.0, 40 uL of the assay buffer (50 mM Tris-HCl, pH 8.0, 2 mM MgCl2, 0.07% 2-mercaptoethanol, and 0.825 mg/mL bovine serum albumin), and 20 uL of 1 mg/mL snake venom in 50 mM Tris-HCl, pH8.0) was added to the 96 well plate. The enzyme reaction was started by adding and mixing with substrate solution of 20 L containing approximate 35 nM 3H-cAMP in 50 mM Tris-HCl, pH 8.0. The final concentration of cAMP in the reaction mixtures was 7 nM.
Measurement: IC50 = 0.65 nM (pChEMBL 9.1899995803833)
Descriptors: MW 419.46, ALogP 3.01, HBA 8, HBD 1, PSA 80.47, QED 0.54
Compound (SMILES): Cc1nc2ccccc2nc1-c1cc2nc(N3CC[C@@H](F)C3)cc(NCC(C)(C)O)n2n1
InChIKey: JHCPAZKUUMSOAO-OAHLLOKOSA-N
Target: Phosphodiesterase (SINGLE PROTEIN), Bos taurus
UniProt: F1MPW5
Assay: Inhibition Assay: The PDE assay was performed according to a modified method referred to a report of Kotera et al. (Kotera et al., Biochem. Pharmacol., vol. 60, pp. 1333-1341, 2000), by the radiolabeled nucleotide method.Specifically, the measurements of the inhibitory activities were carried out in the following method.(Method) The test compounds were dissolved in dimethyl sulfoxide (DMSO). 2 uL of the compound solution was added to 96 well plate, and the reaction mixture (20 uL of PDE enzyme solution in 50 mM Tris-HCl, pH 8.0, 40 uL of the assay buffer (50 mM Tris-HCl, pH 8.0, 2 mM MgCl2, 0.07% 2-mercaptoethanol, and 0.825 mg/mL bovine serum albumin), and 20 uL of 1 mg/mL snake venom in 50 mM Tris-HCl, pH8.0) was added to the 96 well plate. The enzyme reaction was started by adding and mixing with substrate solution of 20 L containing approximate 35 nM 3H-cAMP in 50 mM Tris-HCl, pH 8.0. The final concentration of cAMP in the reaction mixtures was 7 nM.
Measurement: IC50 = 0.32 nM (pChEMBL 9.489999771118164)
Descriptors: MW 435.51, ALogP 3.38, HBA 8, HBD 2, PSA 91.47, QED 0.5
Compound (SMILES): Cc1nc2ccccc2nc1-c1cc2nc(N3CC[C@@H](F)C3)cc(NC3CC3)n2n1
InChIKey: YQNAXQZQBACMPY-CQSZACIVSA-N
Target: Phosphodiesterase (SINGLE PROTEIN), Bos taurus
UniProt: F1MPW5
Assay: Inhibition Assay: The PDE assay was performed according to a modified method referred to a report of Kotera et al. (Kotera et al., Biochem. Pharmacol., vol. 60, pp. 1333-1341, 2000), by the radiolabeled nucleotide method.Specifically, the measurements of the inhibitory activities were carried out in the following method.(Method) The test compounds were dissolved in dimethyl sulfoxide (DMSO). 2 uL of the compound solution was added to 96 well plate, and the reaction mixture (20 uL of PDE enzyme solution in 50 mM Tris-HCl, pH 8.0, 40 uL of the assay buffer (50 mM Tris-HCl, pH 8.0, 2 mM MgCl2, 0.07% 2-mercaptoethanol, and 0.825 mg/mL bovine serum albumin), and 20 uL of 1 mg/mL snake venom in 50 mM Tris-HCl, pH8.0) was added to the 96 well plate. The enzyme reaction was started by adding and mixing with substrate solution of 20 L containing approximate 35 nM 3H-cAMP in 50 mM Tris-HCl, pH 8.0. The final concentration of cAMP in the reaction mixtures was 7 nM.
Measurement: IC50 = 0.87 nM (pChEMBL 9.0600004196167)
Descriptors: MW 403.47, ALogP 3.77, HBA 7, HBD 1, PSA 71.24, QED 0.56
Compound (SMILES): CCc1nc2ccccc2nc1-c1cc2nc(N3CC[C@@H](F)C3)cc(N[C@H]3CC[C@H](OC)CC3)n2n1
InChIKey: KAORWWPQUXWOPH-GUDVDZBRSA-N
Target: Phosphodiesterase (SINGLE PROTEIN), Bos taurus
UniProt: F1MPW5
Assay: Inhibition Assay: The PDE assay was performed according to a modified method referred to a report of Kotera et al. (Kotera et al., Biochem. Pharmacol., vol. 60, pp. 1333-1341, 2000), by the radiolabeled nucleotide method.Specifically, the measurements of the inhibitory activities were carried out in the following method.(Method) The test compounds were dissolved in dimethyl sulfoxide (DMSO). 2 uL of the compound solution was added to 96 well plate, and the reaction mixture (20 uL of PDE enzyme solution in 50 mM Tris-HCl, pH 8.0, 40 uL of the assay buffer (50 mM Tris-HCl, pH 8.0, 2 mM MgCl2, 0.07% 2-mercaptoethanol, and 0.825 mg/mL bovine serum albumin), and 20 uL of 1 mg/mL snake venom in 50 mM Tris-HCl, pH8.0) was added to the 96 well plate. The enzyme reaction was started by adding and mixing with substrate solution of 20 L containing approximate 35 nM 3H-cAMP in 50 mM Tris-HCl, pH 8.0. The final concentration of cAMP in the reaction mixtures was 7 nM.
Measurement: IC50 = 0.39 nM (pChEMBL 9.40999984741211)
Descriptors: MW 489.6, ALogP 4.82, HBA 8, HBD 1, PSA 80.47, QED 0.42
Compound (SMILES): C[C@]1(O)CC[C@H](Nc2cc(N3CC[C@@H](F)C3)nc3cc(-c4nc5ccccc5nc4C(F)(F)F)nn23)CC1
InChIKey: ZIOYUZLEJLAEIS-WHEFHEQHSA-N
Target: Phosphodiesterase (SINGLE PROTEIN), Bos taurus
UniProt: F1MPW5
Assay: Inhibition Assay: The PDE assay was performed according to a modified method referred to a report of Kotera et al. (Kotera et al., Biochem. Pharmacol., vol. 60, pp. 1333-1341, 2000), by the radiolabeled nucleotide method.Specifically, the measurements of the inhibitory activities were carried out in the following method.(Method) The test compounds were dissolved in dimethyl sulfoxide (DMSO). 2 uL of the compound solution was added to 96 well plate, and the reaction mixture (20 uL of PDE enzyme solution in 50 mM Tris-HCl, pH 8.0, 40 uL of the assay buffer (50 mM Tris-HCl, pH 8.0, 2 mM MgCl2, 0.07% 2-mercaptoethanol, and 0.825 mg/mL bovine serum albumin), and 20 uL of 1 mg/mL snake venom in 50 mM Tris-HCl, pH8.0) was added to the 96 well plate. The enzyme reaction was started by adding and mixing with substrate solution of 20 L containing approximate 35 nM 3H-cAMP in 50 mM Tris-HCl, pH 8.0. The final concentration of cAMP in the reaction mixtures was 7 nM.
Measurement: IC50 = 0.18 nM (pChEMBL 9.739999771118164)
Descriptors: MW 529.54, ALogP 5.01, HBA 8, HBD 2, PSA 91.47, QED 0.36
Compound (SMILES): Cc1nc2ccc(F)cc2nc1-c1cc2nc(N3CCCC3)cc(N[C@H]3CCCC[C@@H]3O)n2n1
InChIKey: MDZHSRLIIINMDG-RXVVDRJESA-N
Target: Phosphodiesterase (SINGLE PROTEIN), Bos taurus
UniProt: F1MPW5
Assay: Inhibition Assay: The PDE assay was performed according to a modified method referred to a report of Kotera et al. (Kotera et al., Biochem. Pharmacol., vol. 60, pp. 1333-1341, 2000), by the radiolabeled nucleotide method.Specifically, the measurements of the inhibitory activities were carried out in the following method.(Method) The test compounds were dissolved in dimethyl sulfoxide (DMSO). 2 uL of the compound solution was added to 96 well plate, and the reaction mixture (20 uL of PDE enzyme solution in 50 mM Tris-HCl, pH 8.0, 40 uL of the assay buffer (50 mM Tris-HCl, pH 8.0, 2 mM MgCl2, 0.07% 2-mercaptoethanol, and 0.825 mg/mL bovine serum albumin), and 20 uL of 1 mg/mL snake venom in 50 mM Tris-HCl, pH8.0) was added to the 96 well plate. The enzyme reaction was started by adding and mixing with substrate solution of 20 L containing approximate 35 nM 3H-cAMP in 50 mM Tris-HCl, pH 8.0. The final concentration of cAMP in the reaction mixtures was 7 nM.
Measurement: IC50 = 0.035 nM (pChEMBL 10.460000038146973)
Descriptors: MW 461.55, ALogP 4.1, HBA 8, HBD 2, PSA 91.47, QED 0.47
Compound (SMILES): Cc1nc2c(C)cccc2nc1-c1cc2nc(N3CCCC3)cc(NC3CCOCC3)n2n1
InChIKey: IXJCGIUWGZEIRT-UHFFFAOYSA-N
Target: Phosphodiesterase (SINGLE PROTEIN), Bos taurus
UniProt: F1MPW5
Assay: Inhibition Assay: The PDE assay was performed according to a modified method referred to a report of Kotera et al. (Kotera et al., Biochem. Pharmacol., vol. 60, pp. 1333-1341, 2000), by the radiolabeled nucleotide method.Specifically, the measurements of the inhibitory activities were carried out in the following method.(Method) The test compounds were dissolved in dimethyl sulfoxide (DMSO). 2 uL of the compound solution was added to 96 well plate, and the reaction mixture (20 uL of PDE enzyme solution in 50 mM Tris-HCl, pH 8.0, 40 uL of the assay buffer (50 mM Tris-HCl, pH 8.0, 2 mM MgCl2, 0.07% 2-mercaptoethanol, and 0.825 mg/mL bovine serum albumin), and 20 uL of 1 mg/mL snake venom in 50 mM Tris-HCl, pH8.0) was added to the 96 well plate. The enzyme reaction was started by adding and mixing with substrate solution of 20 L containing approximate 35 nM 3H-cAMP in 50 mM Tris-HCl, pH 8.0. The final concentration of cAMP in the reaction mixtures was 7 nM.
Measurement: IC50 = 0.78 nM (pChEMBL 9.109999656677246)
Descriptors: MW 443.56, ALogP 4.15, HBA 8, HBD 1, PSA 80.47, QED 0.51
Compound (SMILES): Cc1ccc2nc(-c3cc4nc(N5CCCC5)cc(NC5CCOCC5)n4n3)c(C)nc2c1
InChIKey: HVLJDVRJYFMPMT-UHFFFAOYSA-N
Target: Phosphodiesterase (SINGLE PROTEIN), Bos taurus
UniProt: F1MPW5
Assay: Inhibition Assay: The PDE assay was performed according to a modified method referred to a report of Kotera et al. (Kotera et al., Biochem. Pharmacol., vol. 60, pp. 1333-1341, 2000), by the radiolabeled nucleotide method.Specifically, the measurements of the inhibitory activities were carried out in the following method.(Method) The test compounds were dissolved in dimethyl sulfoxide (DMSO). 2 uL of the compound solution was added to 96 well plate, and the reaction mixture (20 uL of PDE enzyme solution in 50 mM Tris-HCl, pH 8.0, 40 uL of the assay buffer (50 mM Tris-HCl, pH 8.0, 2 mM MgCl2, 0.07% 2-mercaptoethanol, and 0.825 mg/mL bovine serum albumin), and 20 uL of 1 mg/mL snake venom in 50 mM Tris-HCl, pH8.0) was added to the 96 well plate. The enzyme reaction was started by adding and mixing with substrate solution of 20 L containing approximate 35 nM 3H-cAMP in 50 mM Tris-HCl, pH 8.0. The final concentration of cAMP in the reaction mixtures was 7 nM.
Measurement: IC50 = 0.46 nM (pChEMBL 9.34000015258789)
Descriptors: MW 443.56, ALogP 4.15, HBA 8, HBD 1, PSA 80.47, QED 0.51
Compound (SMILES): CC(=O)N1CCC(Nc2cc(N3CCCC3)nc3cc(-c4nc5cc(C)ccc5nc4C)nn23)CC1
InChIKey: ZJCDWLAKTMKECY-UHFFFAOYSA-N
Target: Phosphodiesterase (SINGLE PROTEIN), Bos taurus
UniProt: F1MPW5
Assay: Inhibition Assay: The PDE assay was performed according to a modified method referred to a report of Kotera et al. (Kotera et al., Biochem. Pharmacol., vol. 60, pp. 1333-1341, 2000), by the radiolabeled nucleotide method.Specifically, the measurements of the inhibitory activities were carried out in the following method.(Method) The test compounds were dissolved in dimethyl sulfoxide (DMSO). 2 uL of the compound solution was added to 96 well plate, and the reaction mixture (20 uL of PDE enzyme solution in 50 mM Tris-HCl, pH 8.0, 40 uL of the assay buffer (50 mM Tris-HCl, pH 8.0, 2 mM MgCl2, 0.07% 2-mercaptoethanol, and 0.825 mg/mL bovine serum albumin), and 20 uL of 1 mg/mL snake venom in 50 mM Tris-HCl, pH8.0) was added to the 96 well plate. The enzyme reaction was started by adding and mixing with substrate solution of 20 L containing approximate 35 nM 3H-cAMP in 50 mM Tris-HCl, pH 8.0. The final concentration of cAMP in the reaction mixtures was 7 nM.
Measurement: IC50 = 0.044 nM (pChEMBL 10.359999656677246)
Descriptors: MW 484.61, ALogP 3.98, HBA 8, HBD 1, PSA 91.55, QED 0.47
Compound (SMILES): CCCN1CCC(Nc2cc(N3CCCC3)nc3cc(-c4nc5cc(C)ccc5nc4C)nn23)CC1
InChIKey: JAYHRUNQAZMYCV-UHFFFAOYSA-N
Target: Phosphodiesterase (SINGLE PROTEIN), Bos taurus
UniProt: F1MPW5
Assay: Inhibition Assay: The PDE assay was performed according to a modified method referred to a report of Kotera et al. (Kotera et al., Biochem. Pharmacol., vol. 60, pp. 1333-1341, 2000), by the radiolabeled nucleotide method.Specifically, the measurements of the inhibitory activities were carried out in the following method.(Method) The test compounds were dissolved in dimethyl sulfoxide (DMSO). 2 uL of the compound solution was added to 96 well plate, and the reaction mixture (20 uL of PDE enzyme solution in 50 mM Tris-HCl, pH 8.0, 40 uL of the assay buffer (50 mM Tris-HCl, pH 8.0, 2 mM MgCl2, 0.07% 2-mercaptoethanol, and 0.825 mg/mL bovine serum albumin), and 20 uL of 1 mg/mL snake venom in 50 mM Tris-HCl, pH8.0) was added to the 96 well plate. The enzyme reaction was started by adding and mixing with substrate solution of 20 L containing approximate 35 nM 3H-cAMP in 50 mM Tris-HCl, pH 8.0. The final concentration of cAMP in the reaction mixtures was 7 nM.
Measurement: IC50 = 0.15 nM (pChEMBL 9.819999694824219)
Descriptors: MW 484.65, ALogP 4.84, HBA 8, HBD 1, PSA 74.48, QED 0.42
Compound (SMILES): C[C@H]1C[C@@H](c2ccncc2NC(=O)c2ccc(F)c(-c3c(F)cc(C4(F)CCOCC4)cc3F)n2)C[C@@H](N)[C@H]1OCCS(C)(=O)=O
InChIKey: UNUIYTCZSVJTMB-MKHVAHMFSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: AlphaScreen Assay: Pim 1, Pim 2 & Pim 3 AlphaScreen assays using high ATP (11-125.times. ATP Km) were used to determine the biochemical activity of the inhibitors. The activity of Pim 1, Pim 2, & Pim 3 is measured using a homogeneous bead based system quantifying the amount of phosphorylated peptide substrate resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed to a white 384-well plate at 0.25 .mu.l per well. To start the reaction, 5 .mu.l of 100 nM Bad peptide (Biotin-AGAGRSRHSSYPAGT-OH (SEQ ID NO:1)) and ATP (concentrations described below) in assay buffer (50 mM Hepes, pH=7.5, 5 mM MgCl.sub.2, 0.05% BSA, 0.01% Tween-20, 1 mM DTT) is added to each well. This is followed by the addition of 5 .mu.l/well of Pim 1, Pim 2 or Pim 3 kinase in assay buffer (concentrations described below). Final assay concentrations (described below) are in 2.5% DMSO. The reactions are performed for .about.2 hours.
Measurement: IC50 = 0.05 nM (pChEMBL 10.300000190734863)
Descriptors: MW 664.72, ALogP 5.06, HBA 8, HBD 2, PSA 133.5, QED 0.3
Compound (SMILES): COCCOc1cc(F)c(-c2nc(C(=O)Nc3cnccc3[C@H]3C[C@@H](N)[C@@H](OCCS(C)(=O)=O)[C@@H](C)C3)ccc2F)c(F)c1
InChIKey: MXLKCGYBUFWTAU-GBHNBHKPSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: AlphaScreen Assay: Pim 1, Pim 2 & Pim 3 AlphaScreen assays using high ATP (11-125.times. ATP Km) were used to determine the biochemical activity of the inhibitors. The activity of Pim 1, Pim 2, & Pim 3 is measured using a homogeneous bead based system quantifying the amount of phosphorylated peptide substrate resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed to a white 384-well plate at 0.25 .mu.l per well. To start the reaction, 5 .mu.l of 100 nM Bad peptide (Biotin-AGAGRSRHSSYPAGT-OH (SEQ ID NO:1)) and ATP (concentrations described below) in assay buffer (50 mM Hepes, pH=7.5, 5 mM MgCl.sub.2, 0.05% BSA, 0.01% Tween-20, 1 mM DTT) is added to each well. This is followed by the addition of 5 .mu.l/well of Pim 1, Pim 2 or Pim 3 kinase in assay buffer (concentrations described below). Final assay concentrations (described below) are in 2.5% DMSO. The reactions are performed for .about.2 hours.
Measurement: IC50 = 2.54 nM (pChEMBL 8.600000381469727)
Descriptors: MW 636.69, ALogP 4.11, HBA 9, HBD 2, PSA 142.73, QED 0.28
Compound (SMILES): C[C@H]1CN(c2ccncc2NC(=O)c2csc(-c3c(F)cccc3F)n2)C[C@@H](N)[C@H]1n1ccnn1
InChIKey: DXLJDEPUAKIDEU-QSZISKGPSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: AlphaScreen Assay: Pim 1, Pim 2 & Pim 3 AlphaScreen assays using high ATP (11-125.times. ATP Km) were used to determine the biochemical activity of the inhibitors. The activity of Pim 1, Pim 2, & Pim 3 is measured using a homogeneous bead based system quantifying the amount of phosphorylated peptide substrate resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed to a white 384-well plate at 0.25 .mu.l per well. To start the reaction, 5 .mu.l of 100 nM Bad peptide (Biotin-AGAGRSRHSSYPAGT-OH (SEQ ID NO:1)) and ATP (concentrations described below) in assay buffer (50 mM Hepes, pH=7.5, 5 mM MgCl.sub.2, 0.05% BSA, 0.01% Tween-20, 1 mM DTT) is added to each well. This is followed by the addition of 5 .mu.l/well of Pim 1, Pim 2 or Pim 3 kinase in assay buffer (concentrations described below). Final assay concentrations (described below) are in 2.5% DMSO. The reactions are performed for .about.2 hours.
Measurement: IC50 = 2.55 nM (pChEMBL 8.59000015258789)
Descriptors: MW 496.55, ALogP 3.35, HBA 9, HBD 2, PSA 114.85, QED 0.44
Compound (SMILES): COCCOc1cc(F)c(-c2nc(C(=O)Nc3cnccc3C3C[C@@H](N)[C@@H](n4ccnn4)[C@@H](C)C3)ccc2F)c(F)c1
InChIKey: WYFWPBSKKJQUBK-WBKNDOLQSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: AlphaScreen Assay: Pim 1, Pim 2 & Pim 3 AlphaScreen assays using high ATP (11-125.times. ATP Km) were used to determine the biochemical activity of the inhibitors. The activity of Pim 1, Pim 2, & Pim 3 is measured using a homogeneous bead based system quantifying the amount of phosphorylated peptide substrate resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed to a white 384-well plate at 0.25 .mu.l per well. To start the reaction, 5 .mu.l of 100 nM Bad peptide (Biotin-AGAGRSRHSSYPAGT-OH (SEQ ID NO:1)) and ATP (concentrations described below) in assay buffer (50 mM Hepes, pH=7.5, 5 mM MgCl.sub.2, 0.05% BSA, 0.01% Tween-20, 1 mM DTT) is added to each well. This is followed by the addition of 5 .mu.l/well of Pim 1, Pim 2 or Pim 3 kinase in assay buffer (concentrations described below). Final assay concentrations (described below) are in 2.5% DMSO. The reactions are performed for .about.2 hours.
Measurement: IC50 = 0.04 nM (pChEMBL 10.399999618530273)
Descriptors: MW 581.6, ALogP 4.51, HBA 9, HBD 2, PSA 130.07, QED 0.28
Compound (SMILES): C[C@H]1C[C@@H](c2ccncc2NC(=O)c2csc(-c3c(F)cccc3F)n2)C[C@@H](N)[C@H]1OCCS(C)(=O)=O
InChIKey: KDBWXGCLBVMYIK-JTFHBLMLSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: AlphaScreen Assay: Pim 1, Pim 2 & Pim 3 AlphaScreen assays using high ATP (11-125.times. ATP Km) were used to determine the biochemical activity of the inhibitors. The activity of Pim 1, Pim 2, & Pim 3 is measured using a homogeneous bead based system quantifying the amount of phosphorylated peptide substrate resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed to a white 384-well plate at 0.25 .mu.l per well. To start the reaction, 5 .mu.l of 100 nM Bad peptide (Biotin-AGAGRSRHSSYPAGT-OH (SEQ ID NO:1)) and ATP (concentrations described below) in assay buffer (50 mM Hepes, pH=7.5, 5 mM MgCl.sub.2, 0.05% BSA, 0.01% Tween-20, 1 mM DTT) is added to each well. This is followed by the addition of 5 .mu.l/well of Pim 1, Pim 2 or Pim 3 kinase in assay buffer (concentrations described below). Final assay concentrations (described below) are in 2.5% DMSO. The reactions are performed for .about.2 hours.
Measurement: IC50 = 0.57 nM (pChEMBL 9.239999771118164)
Descriptors: MW 550.65, ALogP 4.01, HBA 8, HBD 2, PSA 124.27, QED 0.43
Compound (SMILES): CO[C@H]1[C@H](N)C[C@H](c2ccncc2NC(=O)c2csc(-c3c(F)cccc3F)n2)C[C@@H]1C
InChIKey: XERUWQHYFFRDQN-VAAYTHEESA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: AlphaScreen Assay: Pim 1, Pim 2 & Pim 3 AlphaScreen assays using high ATP (11-125.times. ATP Km) were used to determine the biochemical activity of the inhibitors. The activity of Pim 1, Pim 2, & Pim 3 is measured using a homogeneous bead based system quantifying the amount of phosphorylated peptide substrate resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed to a white 384-well plate at 0.25 .mu.l per well. To start the reaction, 5 .mu.l of 100 nM Bad peptide (Biotin-AGAGRSRHSSYPAGT-OH (SEQ ID NO:1)) and ATP (concentrations described below) in assay buffer (50 mM Hepes, pH=7.5, 5 mM MgCl.sub.2, 0.05% BSA, 0.01% Tween-20, 1 mM DTT) is added to each well. This is followed by the addition of 5 .mu.l/well of Pim 1, Pim 2 or Pim 3 kinase in assay buffer (concentrations described below). Final assay concentrations (described below) are in 2.5% DMSO. The reactions are performed for .about.2 hours.
Measurement: IC50 = 22.07 nM (pChEMBL 7.659999847412109)
Descriptors: MW 458.53, ALogP 4.59, HBA 6, HBD 2, PSA 90.13, QED 0.58
Compound (SMILES): C[C@H]1C[C@@H](c2ccncc2NC(=O)c2nc(-c3c(F)cccc3F)sc2N)C[C@@H](N)[C@H]1OCCS(C)(=O)=O
InChIKey: USIJRQBCKOPRCW-TXXIPVIYSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: AlphaScreen Assay: Pim 1, Pim 2 & Pim 3 AlphaScreen assays using high ATP (11-125.times. ATP Km) were used to determine the biochemical activity of the inhibitors. The activity of Pim 1, Pim 2, & Pim 3 is measured using a homogeneous bead based system quantifying the amount of phosphorylated peptide substrate resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed to a white 384-well plate at 0.25 .mu.l per well. To start the reaction, 5 .mu.l of 100 nM Bad peptide (Biotin-AGAGRSRHSSYPAGT-OH (SEQ ID NO:1)) and ATP (concentrations described below) in assay buffer (50 mM Hepes, pH=7.5, 5 mM MgCl.sub.2, 0.05% BSA, 0.01% Tween-20, 1 mM DTT) is added to each well. This is followed by the addition of 5 .mu.l/well of Pim 1, Pim 2 or Pim 3 kinase in assay buffer (concentrations described below). Final assay concentrations (described below) are in 2.5% DMSO. The reactions are performed for .about.2 hours.
Measurement: IC50 = 0.78 nM (pChEMBL 9.109999656677246)
Descriptors: MW 565.67, ALogP 3.59, HBA 9, HBD 3, PSA 150.29, QED 0.38
Compound (SMILES): CCOCc1cc(F)c(-c2nc(C(=O)Nc3cnccc3[C@H]3C[C@@H](N)[C@H](OC)[C@@H](C)C3)ccc2F)c(F)c1
InChIKey: MMOSRHUYBPJLSR-DMRIYVASSA-N
Target: Serine/threonine-protein kinase pim-3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86V86
Assay: AlphaScreen Assay: Pim 1, Pim 2 & Pim 3 AlphaScreen assays using high ATP (11-125.times. ATP Km) were used to determine the biochemical activity of the inhibitors. The activity of Pim 1, Pim 2, & Pim 3 is measured using a homogeneous bead based system quantifying the amount of phosphorylated peptide substrate resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed to a white 384-well plate at 0.25 .mu.l per well. To start the reaction, 5 .mu.l of 100 nM Bad peptide (Biotin-AGAGRSRHSSYPAGT-OH (SEQ ID NO:1)) and ATP (concentrations described below) in assay buffer (50 mM Hepes, pH=7.5, 5 mM MgCl.sub.2, 0.05% BSA, 0.01% Tween-20, 1 mM DTT) is added to each well. This is followed by the addition of 5 .mu.l/well of Pim 1, Pim 2 or Pim 3 kinase in assay buffer (concentrations described below). Final assay concentrations (described below) are in 2.5% DMSO. The reactions are performed for .about.2 hours.
Measurement: IC50 = 2.49 nM (pChEMBL 8.600000381469727)
Descriptors: MW 528.58, ALogP 5.21, HBA 6, HBD 2, PSA 99.36, QED 0.42
Compound (SMILES): CO[C@H]1[C@H](N)C[C@H](c2ccncc2NC(=O)c2ccc(F)c(-c3c(F)cc(OC4CCOCC4)cc3F)n2)C[C@@H]1C
InChIKey: ITPBXRZSRGMCKW-PECJVUEUSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: AlphaScreen Assay: Pim 1, Pim 2 & Pim 3 AlphaScreen assays using high ATP (11-125.times. ATP Km) were used to determine the biochemical activity of the inhibitors. The activity of Pim 1, Pim 2, & Pim 3 is measured using a homogeneous bead based system quantifying the amount of phosphorylated peptide substrate resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed to a white 384-well plate at 0.25 .mu.l per well. To start the reaction, 5 .mu.l of 100 nM Bad peptide (Biotin-AGAGRSRHSSYPAGT-OH (SEQ ID NO:1)) and ATP (concentrations described below) in assay buffer (50 mM Hepes, pH=7.5, 5 mM MgCl.sub.2, 0.05% BSA, 0.01% Tween-20, 1 mM DTT) is added to each well. This is followed by the addition of 5 .mu.l/well of Pim 1, Pim 2 or Pim 3 kinase in assay buffer (concentrations described below). Final assay concentrations (described below) are in 2.5% DMSO. The reactions are performed for .about.2 hours.
Measurement: IC50 = 1.03 nM (pChEMBL 8.989999771118164)
Descriptors: MW 570.61, ALogP 5.23, HBA 7, HBD 2, PSA 108.59, QED 0.4
Compound (SMILES): CO[C@H]1[C@H](N)C[C@H](c2ccncc2NC(=O)c2ccc(F)c(-c3c(F)cc(C4(O)CCC4)cc3F)n2)C[C@@H]1C
InChIKey: NWDVLGCDUFSSHA-GZDINDOJSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: AlphaScreen Assay: Pim 1, Pim 2 & Pim 3 AlphaScreen assays using high ATP (11-125.times. ATP Km) were used to determine the biochemical activity of the inhibitors. The activity of Pim 1, Pim 2, & Pim 3 is measured using a homogeneous bead based system quantifying the amount of phosphorylated peptide substrate resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed to a white 384-well plate at 0.25 .mu.l per well. To start the reaction, 5 .mu.l of 100 nM Bad peptide (Biotin-AGAGRSRHSSYPAGT-OH (SEQ ID NO:1)) and ATP (concentrations described below) in assay buffer (50 mM Hepes, pH=7.5, 5 mM MgCl.sub.2, 0.05% BSA, 0.01% Tween-20, 1 mM DTT) is added to each well. This is followed by the addition of 5 .mu.l/well of Pim 1, Pim 2 or Pim 3 kinase in assay buffer (concentrations described below). Final assay concentrations (described below) are in 2.5% DMSO. The reactions are performed for .about.2 hours.
Measurement: IC50 = 0.03 nM (pChEMBL 10.520000457763672)
Descriptors: MW 540.59, ALogP 5.04, HBA 6, HBD 3, PSA 110.36, QED 0.4
Compound (SMILES): C[C@H]1C[C@@H](c2ccncc2NC(=O)c2ccc(F)c(-c3c(F)cc(C4(O)CCC4)cc3F)n2)C[C@@H](N)[C@@H]1OCCS(C)(=O)=O
InChIKey: MMQGQQIWWVVFQW-DFPRQKAASA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: AlphaScreen Assay: Pim 1, Pim 2 & Pim 3 AlphaScreen assays using high ATP (11-125.times. ATP Km) were used to determine the biochemical activity of the inhibitors. The activity of Pim 1, Pim 2, & Pim 3 is measured using a homogeneous bead based system quantifying the amount of phosphorylated peptide substrate resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed to a white 384-well plate at 0.25 .mu.l per well. To start the reaction, 5 .mu.l of 100 nM Bad peptide (Biotin-AGAGRSRHSSYPAGT-OH (SEQ ID NO:1)) and ATP (concentrations described below) in assay buffer (50 mM Hepes, pH=7.5, 5 mM MgCl.sub.2, 0.05% BSA, 0.01% Tween-20, 1 mM DTT) is added to each well. This is followed by the addition of 5 .mu.l/well of Pim 1, Pim 2 or Pim 3 kinase in assay buffer (concentrations described below). Final assay concentrations (described below) are in 2.5% DMSO. The reactions are performed for .about.2 hours.
Measurement: IC50 = 1.24 nM (pChEMBL 8.90999984741211)
Descriptors: MW 632.71, ALogP 4.46, HBA 8, HBD 3, PSA 144.5, QED 0.31
Compound (SMILES): C[C@H]1C[C@@H](c2ccncc2NC(=O)c2ccc(F)c(-c3c(F)cc(OC4CCOCC4)cc3F)n2)C[C@@H](N)[C@@H]1OCCS(C)(=O)=O
InChIKey: LKVRXZVHFRHSKB-FWVFMIEISA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: AlphaScreen Assay: Pim 1, Pim 2 & Pim 3 AlphaScreen assays using high ATP (11-125.times. ATP Km) were used to determine the biochemical activity of the inhibitors. The activity of Pim 1, Pim 2, & Pim 3 is measured using a homogeneous bead based system quantifying the amount of phosphorylated peptide substrate resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed to a white 384-well plate at 0.25 .mu.l per well. To start the reaction, 5 .mu.l of 100 nM Bad peptide (Biotin-AGAGRSRHSSYPAGT-OH (SEQ ID NO:1)) and ATP (concentrations described below) in assay buffer (50 mM Hepes, pH=7.5, 5 mM MgCl.sub.2, 0.05% BSA, 0.01% Tween-20, 1 mM DTT) is added to each well. This is followed by the addition of 5 .mu.l/well of Pim 1, Pim 2 or Pim 3 kinase in assay buffer (concentrations described below). Final assay concentrations (described below) are in 2.5% DMSO. The reactions are performed for .about.2 hours.
Measurement: IC50 = 2.69 nM (pChEMBL 8.569999694824219)
Descriptors: MW 662.73, ALogP 4.64, HBA 9, HBD 2, PSA 142.73, QED 0.32
Compound (SMILES): CC(C)Oc1cc(F)c(-c2nc(C(=O)Nc3cnccc3[C@H]3C[C@@H](N)[C@@H](OCCS(C)(=O)=O)[C@@H](C)C3)ccc2F)c(F)c1
InChIKey: YIECCVSVKBACNI-GBHNBHKPSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: AlphaScreen Assay: Pim 1, Pim 2 & Pim 3 AlphaScreen assays using high ATP (11-125.times. ATP Km) were used to determine the biochemical activity of the inhibitors. The activity of Pim 1, Pim 2, & Pim 3 is measured using a homogeneous bead based system quantifying the amount of phosphorylated peptide substrate resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed to a white 384-well plate at 0.25 .mu.l per well. To start the reaction, 5 .mu.l of 100 nM Bad peptide (Biotin-AGAGRSRHSSYPAGT-OH (SEQ ID NO:1)) and ATP (concentrations described below) in assay buffer (50 mM Hepes, pH=7.5, 5 mM MgCl.sub.2, 0.05% BSA, 0.01% Tween-20, 1 mM DTT) is added to each well. This is followed by the addition of 5 .mu.l/well of Pim 1, Pim 2 or Pim 3 kinase in assay buffer (concentrations described below). Final assay concentrations (described below) are in 2.5% DMSO. The reactions are performed for .about.2 hours.
Measurement: IC50 = 1.17 nM (pChEMBL 8.930000305175781)
Descriptors: MW 620.69, ALogP 4.87, HBA 8, HBD 2, PSA 133.5, QED 0.33
Compound (SMILES): CO[C@H]1[C@H](N)C[C@H](c2ccncc2NC(=O)c2ccc(F)c(-c3c(F)cc(OC(C)C)cc3F)n2)C[C@@H]1C
InChIKey: FKRJLOFLENGVAA-GZDINDOJSA-N
Target: Serine/threonine-protein kinase pim-3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86V86
Assay: AlphaScreen Assay: Pim 1, Pim 2 & Pim 3 AlphaScreen assays using high ATP (11-125.times. ATP Km) were used to determine the biochemical activity of the inhibitors. The activity of Pim 1, Pim 2, & Pim 3 is measured using a homogeneous bead based system quantifying the amount of phosphorylated peptide substrate resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed to a white 384-well plate at 0.25 .mu.l per well. To start the reaction, 5 .mu.l of 100 nM Bad peptide (Biotin-AGAGRSRHSSYPAGT-OH (SEQ ID NO:1)) and ATP (concentrations described below) in assay buffer (50 mM Hepes, pH=7.5, 5 mM MgCl.sub.2, 0.05% BSA, 0.01% Tween-20, 1 mM DTT) is added to each well. This is followed by the addition of 5 .mu.l/well of Pim 1, Pim 2 or Pim 3 kinase in assay buffer (concentrations described below). Final assay concentrations (described below) are in 2.5% DMSO. The reactions are performed for .about.2 hours.
Measurement: IC50 = 0.87 nM (pChEMBL 9.0600004196167)
Descriptors: MW 528.58, ALogP 5.46, HBA 6, HBD 2, PSA 99.36, QED 0.42
Compound (SMILES): COc1cc(F)c(-c2nc(C(=O)Nc3cnccc3[C@H]3C[C@@H](N)[C@H](OC)[C@@H](C)C3)ccc2F)c(F)c1
InChIKey: UEPBAYVBVVMZEN-VEYLPCSISA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: AlphaScreen Assay: Pim 1, Pim 2 & Pim 3 AlphaScreen assays using high ATP (11-125.times. ATP Km) were used to determine the biochemical activity of the inhibitors. The activity of Pim 1, Pim 2, & Pim 3 is measured using a homogeneous bead based system quantifying the amount of phosphorylated peptide substrate resulting from kinase-catalyzed phosphoryl transfer to a peptide substrate. Compounds to be tested are dissolved in 100% DMSO and directly distributed to a white 384-well plate at 0.25 .mu.l per well. To start the reaction, 5 .mu.l of 100 nM Bad peptide (Biotin-AGAGRSRHSSYPAGT-OH (SEQ ID NO:1)) and ATP (concentrations described below) in assay buffer (50 mM Hepes, pH=7.5, 5 mM MgCl.sub.2, 0.05% BSA, 0.01% Tween-20, 1 mM DTT) is added to each well. This is followed by the addition of 5 .mu.l/well of Pim 1, Pim 2 or Pim 3 kinase in assay buffer (concentrations described below). Final assay concentrations (described below) are in 2.5% DMSO. The reactions are performed for .about.2 hours.
Measurement: IC50 = 0.05 nM (pChEMBL 10.300000190734863)
Descriptors: MW 500.52, ALogP 4.68, HBA 6, HBD 2, PSA 99.36, QED 0.51