lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O[C@@H]1[C@@H]([C@H](O)c2ccccc2)CNC[C@H]1O
InChIKey: AQILKYRWFPWHAA-DDHJBXDOSA-N
Target: Lysosomal acid glucosylceramidase (SINGLE PROTEIN), Homo sapiens
UniProt: P04062
Assay: Enzyme Inhibition Assay: The enzyme inhibition assays used monitored the ability of a test compound to bind and prevent the hydrolysis of a fluorogenic substrate in a concentration-dependent mariner. Specifically, the enzyme activity of recombinant human GCase (rhGCase; Cerezyme, Genzyme Corp.) was measured using the 4-methylumbelliferyl-β-D-glucopyranoside (4-MU-β-D-Glc) fluorogenic substrate in the absence or in the presence of varying amounts of each test compound.
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 223.27, ALogP -0.34, HBA 4, HBD 4, PSA 72.72, QED 0.55
Compound (SMILES): CC(C)(O)[C@H]1CNC[C@@H](O)[C@@H]1O
InChIKey: PVGDVTWSNAIFDH-RRKCRQDMSA-N
Target: Lysosomal acid glucosylceramidase (SINGLE PROTEIN), Homo sapiens
UniProt: P04062
Assay: Enzyme Inhibition Assay: The enzyme inhibition assays used monitored the ability of a test compound to bind and prevent the hydrolysis of a fluorogenic substrate in a concentration-dependent mariner. Specifically, the enzyme activity of recombinant human GCase (rhGCase; Cerezyme, Genzyme Corp.) was measured using the 4-methylumbelliferyl-β-D-glucopyranoside (4-MU-β-D-Glc) fluorogenic substrate in the absence or in the presence of varying amounts of each test compound.
Measurement: IC50 = 29 nM (pChEMBL 7.539999961853027)
Descriptors: MW 175.23, ALogP -1.3, HBA 4, HBD 4, PSA 72.72, QED 0.4
Compound (SMILES): CC[C@@H](F)C1CNC[C@@H](O)[C@@H]1O
InChIKey: JJOAXUOFRVBCHL-UIYHXYAWSA-N
Target: Lysosomal acid glucosylceramidase (SINGLE PROTEIN), Homo sapiens
UniProt: P04062
Assay: Enzyme Inhibition Assay: The enzyme inhibition assays used monitored the ability of a test compound to bind and prevent the hydrolysis of a fluorogenic substrate in a concentration-dependent mariner. Specifically, the enzyme activity of recombinant human GCase (rhGCase; Cerezyme, Genzyme Corp.) was measured using the 4-methylumbelliferyl-β-D-glucopyranoside (4-MU-β-D-Glc) fluorogenic substrate in the absence or in the presence of varying amounts of each test compound.
Measurement: IC50 = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 177.22, ALogP -0.32, HBA 3, HBD 3, PSA 52.49, QED 0.54
Compound (SMILES): Cc1ccc(F)cc1-c1ccc2cc(NC(=O)C3C[C@@H]3C)ncc2c1
InChIKey: BKDVILNWHYFSDN-YTJLLHSVSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 0.8 nM (pChEMBL 9.100000381469727)
Descriptors: MW 334.39, ALogP 4.94, HBA 2, HBD 1, PSA 41.99, QED 0.74
Compound (SMILES): Cc1ccc(F)cc1-c1ccc2cc(NC(=O)C3C[C@H]3C)ncc2c1
InChIKey: BKDVILNWHYFSDN-BSOCMFCZSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Enzyme Assay: Using the following procedure, varying concentration of compounds of the invention were assessed for their ability to inhibit c-Abl enzyme's phosphorylation of 5-FAM-EAIYAHPFAKKK-CONH2 (Caliper LifeSciences, cat #760346) peptide substrate in the presence of ATP at Km app. The phosphorylated product is detected using the Caliper mobility shift detection method where product and substrate are electrophoretically separated.
Measurement: Ki = 0.5 nM (pChEMBL 9.300000190734863)
Descriptors: MW 334.39, ALogP 4.94, HBA 2, HBD 1, PSA 41.99, QED 0.74
Compound (SMILES): CN[C@@H]1CC2OC([C@@H]1OC)n1c3ccccc3c3c4c(c5c6ccccc6n2c5c31)C(=O)NC4
InChIKey: YISMQBFJYDFMAL-AESIHLKFSA-N
Target: Mast/stem cell growth factor receptor Kit (SINGLE PROTEIN), Homo sapiens
UniProt: P10721
Assay: Kinase Inhibition Assay: The compound of Example 39, 2-(1H-indol-5-ylamino)-6-(2,4-difluorophenylsulfonyl)-8-methylpyrido[2,3-d]pyrimidin-7(8H)-one, was subjected to a kinase inhibition assay for the kinases. Compounds were tested in 5 dose IC50 mode with 10-fold serial dilution starting at 10 μM. Staurosporine, a known protein kinase inhibitor, was tested in 5-dose IC50 mode with 3-fold serial dilution starting at 20 μM. Reactions were carried out in 10 μM ATP. The results are shown in Table 5. The results show that the compound of Example 39 is a kinase inhibitor highly selective for the kinase Plk2.
Measurement: IC50 = 0.18 nM (pChEMBL 9.739999771118164)
Descriptors: MW 452.51, ALogP 4.18, HBA 6, HBD 2, PSA 69.45, QED 0.42
Compound (SMILES): N#Cc1ccc(Oc2ccc(S(=O)(=O)Nc3ccc(F)cn3)cc2C#N)cc1Cl
InChIKey: ABKCBHGHCYFDNT-UHFFFAOYSA-N
Target: Organic anion transporter 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TCC7
Assay: Inhibition of OAT3 (unknown origin)
Measurement: IC50 = 720 nM (pChEMBL 6.139999866485596)
Descriptors: MW 428.83, ALogP 4.21, HBA 6, HBD 1, PSA 115.87, QED 0.65
Compound (SMILES): NC(=O)c1nn(CC(=O)N2[C@@H]3C[C@@H]3C[C@H]2C(=O)Nc2cccc(Br)n2)c2ccccc12
InChIKey: CWZUTHDJLNZLCM-DFBGVHRSSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 483.33, ALogP 1.92, HBA 6, HBD 2, PSA 123.21, QED 0.54
Compound (SMILES): CC[C@@H](C[C@H]1COC(N)=N1)c1ccccc1
InChIKey: IXDKFUBXESWHSL-JQWIXIFHSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 218.3, ALogP 2.28, HBA 3, HBD 1, PSA 47.61, QED 0.84
Compound (SMILES): CC(F)[C@H]1CNC[C@@H](O)[C@@H]1O
InChIKey: ADGVYUWMIQUOME-UVSCYPECSA-N
Target: Lysosomal acid glucosylceramidase (SINGLE PROTEIN), Homo sapiens
UniProt: P04062
Assay: Enzyme Inhibition Assay: The enzyme inhibition assays used monitored the ability of a test compound to bind and prevent the hydrolysis of a fluorogenic substrate in a concentration-dependent mariner. Specifically, the enzyme activity of recombinant human GCase (rhGCase; Cerezyme, Genzyme Corp.) was measured using the 4-methylumbelliferyl-β-D-glucopyranoside (4-MU-β-D-Glc) fluorogenic substrate in the absence or in the presence of varying amounts of each test compound.
Measurement: Ki = 0.9 nM (pChEMBL 9.050000190734863)
Descriptors: MW 163.19, ALogP -0.71, HBA 3, HBD 3, PSA 52.49, QED 0.48
Compound (SMILES): CC(O)[C@H]1CNC[C@@H](O)[C@@H]1O
InChIKey: YEZMDJVWNQIFDP-UVSCYPECSA-N
Target: Lysosomal acid glucosylceramidase (SINGLE PROTEIN), Homo sapiens
UniProt: P04062
Assay: Enzyme Inhibition Assay: The enzyme inhibition assays used monitored the ability of a test compound to bind and prevent the hydrolysis of a fluorogenic substrate in a concentration-dependent mariner. Specifically, the enzyme activity of recombinant human GCase (rhGCase; Cerezyme, Genzyme Corp.) was measured using the 4-methylumbelliferyl-β-D-glucopyranoside (4-MU-β-D-Glc) fluorogenic substrate in the absence or in the presence of varying amounts of each test compound.
Measurement: Ki = 10 nM (pChEMBL 8)
Descriptors: MW 161.2, ALogP -1.69, HBA 4, HBD 4, PSA 72.72, QED 0.37
Compound (SMILES): CN[C@@H]1CC2OC([C@@H]1OC)n1c3ccccc3c3c4c(c5c6ccccc6n2c5c31)C(=O)NC4
InChIKey: YISMQBFJYDFMAL-AESIHLKFSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Kinase Inhibition Assay: The compound of Example 39, 2-(1H-indol-5-ylamino)-6-(2,4-difluorophenylsulfonyl)-8-methylpyrido[2,3-d]pyrimidin-7(8H)-one, was subjected to a kinase inhibition assay for the kinases. Compounds were tested in 5 dose IC50 mode with 10-fold serial dilution starting at 10 μM. Staurosporine, a known protein kinase inhibitor, was tested in 5-dose IC50 mode with 3-fold serial dilution starting at 20 μM. Reactions were carried out in 10 μM ATP. The results are shown in Table 5. The results show that the compound of Example 39 is a kinase inhibitor highly selective for the kinase Plk2.
Measurement: IC50 = 438.1 nM (pChEMBL 6.360000133514404)
Descriptors: MW 452.51, ALogP 4.18, HBA 6, HBD 2, PSA 69.45, QED 0.42
Compound (SMILES): N#Cc1ccc(Oc2ccc(S(=O)(=O)Nc3ccc(F)cn3)cc2C#N)cc1Cl
InChIKey: ABKCBHGHCYFDNT-UHFFFAOYSA-N
Target: Solute carrier family 22 member 6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q4U2R8
Assay: Inhibition of OAT1 (unknown origin)
Measurement: IC50 = 14000 nM (pChEMBL 4.849999904632568)
Descriptors: MW 428.83, ALogP 4.21, HBA 6, HBD 1, PSA 115.87, QED 0.65
Compound (SMILES): NC(=O)c1nn(CC(=O)N2[C@@H]3C[C@@H]3C[C@H]2C(=O)Nc2cccc(Br)n2)c2ccccc12
InChIKey: CWZUTHDJLNZLCM-DFBGVHRSSA-N
Target: Complement factor D (SINGLE PROTEIN), Homo sapiens
UniProt: P00746
Assay: Inhibition of complement factor D in human whole blood assessed as decrease in zymosan-induced AP activation mediated soluble MAC complex formation preincubated for 15 mins followed by zymosan addition measured after 40 mins by ELISA
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 483.33, ALogP 1.92, HBA 6, HBD 2, PSA 123.21, QED 0.54
Compound (SMILES): CC(F)[C@H]1CNC[C@@H](O)[C@@H]1O
InChIKey: ADGVYUWMIQUOME-UVSCYPECSA-N
Target: Lysosomal acid glucosylceramidase (SINGLE PROTEIN), Homo sapiens
UniProt: P04062
Assay: Enzyme Inhibition Assay: The enzyme inhibition assays used monitored the ability of a test compound to bind and prevent the hydrolysis of a fluorogenic substrate in a concentration-dependent mariner. Specifically, the enzyme activity of recombinant human GCase (rhGCase; Cerezyme, Genzyme Corp.) was measured using the 4-methylumbelliferyl-β-D-glucopyranoside (4-MU-β-D-Glc) fluorogenic substrate in the absence or in the presence of varying amounts of each test compound.
Measurement: IC50 = 17.1 nM (pChEMBL 7.769999980926514)
Descriptors: MW 163.19, ALogP -0.71, HBA 3, HBD 3, PSA 52.49, QED 0.48
Compound (SMILES): CC(O)[C@H]1CNC[C@@H](O)[C@@H]1O
InChIKey: YEZMDJVWNQIFDP-UVSCYPECSA-N
Target: Lysosomal acid glucosylceramidase (SINGLE PROTEIN), Homo sapiens
UniProt: P04062
Assay: Enzyme Inhibition Assay: The enzyme inhibition assays used monitored the ability of a test compound to bind and prevent the hydrolysis of a fluorogenic substrate in a concentration-dependent mariner. Specifically, the enzyme activity of recombinant human GCase (rhGCase; Cerezyme, Genzyme Corp.) was measured using the 4-methylumbelliferyl-β-D-glucopyranoside (4-MU-β-D-Glc) fluorogenic substrate in the absence or in the presence of varying amounts of each test compound.
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 161.2, ALogP -1.69, HBA 4, HBD 4, PSA 72.72, QED 0.37
Compound (SMILES): CN[C@@H]1CC2OC([C@@H]1OC)n1c3ccccc3c3c4c(c5c6ccccc6n2c5c31)C(=O)NC4
InChIKey: YISMQBFJYDFMAL-AESIHLKFSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Kinase Inhibition Assay: The compound of Example 39, 2-(1H-indol-5-ylamino)-6-(2,4-difluorophenylsulfonyl)-8-methylpyrido[2,3-d]pyrimidin-7(8H)-one, was subjected to a kinase inhibition assay for the kinases. Compounds were tested in 5 dose IC50 mode with 10-fold serial dilution starting at 10 μM. Staurosporine, a known protein kinase inhibitor, was tested in 5-dose IC50 mode with 3-fold serial dilution starting at 20 μM. Reactions were carried out in 10 μM ATP. The results are shown in Table 5. The results show that the compound of Example 39 is a kinase inhibitor highly selective for the kinase Plk2.
Measurement: IC50 = 37.32 nM (pChEMBL 7.429999828338623)
Descriptors: MW 452.51, ALogP 4.18, HBA 6, HBD 2, PSA 69.45, QED 0.42
Compound (SMILES): N#Cc1ccc(Oc2ccc(S(=O)(=O)Nc3ccc(F)cn3)cc2C#N)cc1Cl
InChIKey: ABKCBHGHCYFDNT-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 = 17500 nM (pChEMBL 4.760000228881836)
Descriptors: MW 428.83, ALogP 4.21, HBA 6, HBD 1, PSA 115.87, QED 0.65
Compound (SMILES): NC(=O)c1nn(CC(=O)N2[C@@H]3C[C@@H]3C[C@H]2C(=O)Nc2cccc(Br)n2)c2ccccc12
InChIKey: CWZUTHDJLNZLCM-DFBGVHRSSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin) using diclofenac as substrate
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 483.33, ALogP 1.92, HBA 6, HBD 2, PSA 123.21, QED 0.54
Compound (SMILES): CC(F)[C@H]1CNC[C@@H](O)[C@@H]1O
InChIKey: ADGVYUWMIQUOME-UVSCYPECSA-N
Target: Lysosomal acid glucosylceramidase (SINGLE PROTEIN), Homo sapiens
UniProt: P04062
Assay: Enzyme Inhibition Assay: The enzyme inhibition assays used monitored the ability of a test compound to bind and prevent the hydrolysis of a fluorogenic substrate in a concentration-dependent mariner. Specifically, the enzyme activity of recombinant human GCase (rhGCase; Cerezyme, Genzyme Corp.) was measured using the 4-methylumbelliferyl-β-D-glucopyranoside (4-MU-β-D-Glc) fluorogenic substrate in the absence or in the presence of varying amounts of each test compound.
Measurement: Ki = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 163.19, ALogP -0.71, HBA 3, HBD 3, PSA 52.49, QED 0.48
Compound (SMILES): CC(O)[C@H]1CNC[C@@H](O)[C@@H]1O
InChIKey: YEZMDJVWNQIFDP-UVSCYPECSA-N
Target: Lysosomal acid glucosylceramidase (SINGLE PROTEIN), Homo sapiens
UniProt: P04062
Assay: Enzyme Inhibition Assay: The enzyme inhibition assays used monitored the ability of a test compound to bind and prevent the hydrolysis of a fluorogenic substrate in a concentration-dependent mariner. Specifically, the enzyme activity of recombinant human GCase (rhGCase; Cerezyme, Genzyme Corp.) was measured using the 4-methylumbelliferyl-β-D-glucopyranoside (4-MU-β-D-Glc) fluorogenic substrate in the absence or in the presence of varying amounts of each test compound.
Measurement: Ki = 35 nM (pChEMBL 7.460000038146973)
Descriptors: MW 161.2, ALogP -1.69, HBA 4, HBD 4, PSA 72.72, QED 0.37
Compound (SMILES): CN[C@@H]1CC2OC([C@@H]1OC)n1c3ccccc3c3c4c(c5c6ccccc6n2c5c31)C(=O)NC4
InChIKey: YISMQBFJYDFMAL-AESIHLKFSA-N
Target: Serine/threonine-protein kinase Nek1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96PY6
Assay: Kinase Inhibition Assay: The compound of Example 39, 2-(1H-indol-5-ylamino)-6-(2,4-difluorophenylsulfonyl)-8-methylpyrido[2,3-d]pyrimidin-7(8H)-one, was subjected to a kinase inhibition assay for the kinases. Compounds were tested in 5 dose IC50 mode with 10-fold serial dilution starting at 10 μM. Staurosporine, a known protein kinase inhibitor, was tested in 5-dose IC50 mode with 3-fold serial dilution starting at 20 μM. Reactions were carried out in 10 μM ATP. The results are shown in Table 5. The results show that the compound of Example 39 is a kinase inhibitor highly selective for the kinase Plk2.
Measurement: IC50 = 432.6 nM (pChEMBL 6.360000133514404)
Descriptors: MW 452.51, ALogP 4.18, HBA 6, HBD 2, PSA 69.45, QED 0.42
Compound (SMILES): N#Cc1ccc(Oc2ccc(S(=O)(=O)Nc3ccc(F)cn3)cc2C#N)cc1Cl
InChIKey: ABKCBHGHCYFDNT-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 428.83, ALogP 4.21, HBA 6, HBD 1, PSA 115.87, QED 0.65
Compound (SMILES): NC(=O)c1nn(CC(=O)N2[C@@H]3C[C@@H]3C[C@H]2C(=O)Nc2cccc(Br)n2)c2ccccc12
InChIKey: CWZUTHDJLNZLCM-DFBGVHRSSA-N
Target: Complement factor D (SINGLE PROTEIN), Homo sapiens
UniProt: P00746
Assay: Inhibition of human complement factor D using Z-L-Lys-SBzl hydrochloride as substrate preincubated for 15 mins followed by substrate addition and measured by colorimetric method based esterolytic assay
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 483.33, ALogP 1.92, HBA 6, HBD 2, PSA 123.21, QED 0.54
Compound (SMILES): CC(F)[C@H]1CNC[C@@H](O)[C@@H]1O
InChIKey: ADGVYUWMIQUOME-UVSCYPECSA-N
Target: Lysosomal acid glucosylceramidase (SINGLE PROTEIN), Homo sapiens
UniProt: P04062
Assay: Enzyme Inhibition Assay: The enzyme inhibition assays used monitored the ability of a test compound to bind and prevent the hydrolysis of a fluorogenic substrate in a concentration-dependent mariner. Specifically, the enzyme activity of recombinant human GCase (rhGCase; Cerezyme, Genzyme Corp.) was measured using the 4-methylumbelliferyl-β-D-glucopyranoside (4-MU-β-D-Glc) fluorogenic substrate in the absence or in the presence of varying amounts of each test compound.
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 163.19, ALogP -0.71, HBA 3, HBD 3, PSA 52.49, QED 0.48
Compound (SMILES): CC(O)[C@H]1CNC[C@@H](O)[C@@H]1O
InChIKey: YEZMDJVWNQIFDP-UVSCYPECSA-N
Target: Lysosomal acid glucosylceramidase (SINGLE PROTEIN), Homo sapiens
UniProt: P04062
Assay: Enzyme Inhibition Assay: The enzyme inhibition assays used monitored the ability of a test compound to bind and prevent the hydrolysis of a fluorogenic substrate in a concentration-dependent mariner. Specifically, the enzyme activity of recombinant human GCase (rhGCase; Cerezyme, Genzyme Corp.) was measured using the 4-methylumbelliferyl-β-D-glucopyranoside (4-MU-β-D-Glc) fluorogenic substrate in the absence or in the presence of varying amounts of each test compound.
Measurement: IC50 = 66 nM (pChEMBL 7.179999828338623)
Descriptors: MW 161.2, ALogP -1.69, HBA 4, HBD 4, PSA 72.72, QED 0.37
Compound (SMILES): CN[C@@H]1CC2OC([C@@H]1OC)n1c3ccccc3c3c4c(c5c6ccccc6n2c5c31)C(=O)NC4
InChIKey: YISMQBFJYDFMAL-AESIHLKFSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Kinase Inhibition Assay: The compound of Example 39, 2-(1H-indol-5-ylamino)-6-(2,4-difluorophenylsulfonyl)-8-methylpyrido[2,3-d]pyrimidin-7(8H)-one, was subjected to a kinase inhibition assay for the kinases. Compounds were tested in 5 dose IC50 mode with 10-fold serial dilution starting at 10 μM. Staurosporine, a known protein kinase inhibitor, was tested in 5-dose IC50 mode with 3-fold serial dilution starting at 20 μM. Reactions were carried out in 10 μM ATP. The results are shown in Table 5. The results show that the compound of Example 39 is a kinase inhibitor highly selective for the kinase Plk2.
Measurement: IC50 = 0.55 nM (pChEMBL 9.260000228881836)
Descriptors: MW 452.51, ALogP 4.18, HBA 6, HBD 2, PSA 69.45, QED 0.42
Compound (SMILES): N#Cc1ccc(Oc2ccc(S(=O)(=O)Nc3ccc(F)cn3)cc2C#N)cc1Cl
InChIKey: ABKCBHGHCYFDNT-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin)
Measurement: IC50 = 17200 nM (pChEMBL 4.760000228881836)
Descriptors: MW 428.83, ALogP 4.21, HBA 6, HBD 1, PSA 115.87, QED 0.65
Compound (SMILES): CN[C@@H]1CC2OC([C@@H]1OC)n1c3ccccc3c3c4c(c5c6ccccc6n2c5c31)C(=O)NC4
InChIKey: YISMQBFJYDFMAL-AESIHLKFSA-N
Target: Tyrosine-protein kinase ZAP-70 (SINGLE PROTEIN), Homo sapiens
UniProt: P43403
Assay: Kinase Inhibition Assay: The compound of Example 39, 2-(1H-indol-5-ylamino)-6-(2,4-difluorophenylsulfonyl)-8-methylpyrido[2,3-d]pyrimidin-7(8H)-one, was subjected to a kinase inhibition assay for the kinases. Compounds were tested in 5 dose IC50 mode with 10-fold serial dilution starting at 10 μM. Staurosporine, a known protein kinase inhibitor, was tested in 5-dose IC50 mode with 3-fold serial dilution starting at 20 μM. Reactions were carried out in 10 μM ATP. The results are shown in Table 5. The results show that the compound of Example 39 is a kinase inhibitor highly selective for the kinase Plk2.
Measurement: IC50 = 87.49 nM (pChEMBL 7.059999942779541)
Descriptors: MW 452.51, ALogP 4.18, HBA 6, HBD 2, PSA 69.45, QED 0.42
Compound (SMILES): N#Cc1ccc(Oc2ccc(S(=O)(=O)Nc3ccc(F)cn3)cc2C#N)cc1Cl
InChIKey: ABKCBHGHCYFDNT-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 = 4200 nM (pChEMBL 5.380000114440918)
Descriptors: MW 428.83, ALogP 4.21, HBA 6, HBD 1, PSA 115.87, QED 0.65
Compound (SMILES): CN[C@@H]1CC2OC([C@@H]1OC)n1c3ccccc3c3c4c(c5c6ccccc6n2c5c31)C(=O)NC4
InChIKey: YISMQBFJYDFMAL-AESIHLKFSA-N
Target: Protein kinase C zeta type (SINGLE PROTEIN), Homo sapiens
UniProt: Q05513
Assay: Kinase Inhibition Assay: The compound of Example 39, 2-(1H-indol-5-ylamino)-6-(2,4-difluorophenylsulfonyl)-8-methylpyrido[2,3-d]pyrimidin-7(8H)-one, was subjected to a kinase inhibition assay for the kinases. Compounds were tested in 5 dose IC50 mode with 10-fold serial dilution starting at 10 μM. Staurosporine, a known protein kinase inhibitor, was tested in 5-dose IC50 mode with 3-fold serial dilution starting at 20 μM. Reactions were carried out in 10 μM ATP. The results are shown in Table 5. The results show that the compound of Example 39 is a kinase inhibitor highly selective for the kinase Plk2.
Measurement: IC50 = 204.2 nM (pChEMBL 6.690000057220459)
Descriptors: MW 452.51, ALogP 4.18, HBA 6, HBD 2, PSA 69.45, QED 0.42
Compound (SMILES): N#Cc1ccc(Oc2ccc(S(=O)(=O)Nc3ccc(F)cn3)cc2C#N)cc1Cl
InChIKey: ABKCBHGHCYFDNT-UHFFFAOYSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of CYP2C8 (unknown origin)
Measurement: IC50 = 11900 nM (pChEMBL 4.920000076293945)
Descriptors: MW 428.83, ALogP 4.21, HBA 6, HBD 1, PSA 115.87, QED 0.65
Compound (SMILES): CN[C@@H]1CC2OC([C@@H]1OC)n1c3ccccc3c3c4c(c5c6ccccc6n2c5c31)C(=O)NC4
InChIKey: YISMQBFJYDFMAL-AESIHLKFSA-N
Target: Tyrosine-protein kinase Blk (SINGLE PROTEIN), Homo sapiens
UniProt: P51451
Assay: Kinase Inhibition Assay: The compound of Example 39, 2-(1H-indol-5-ylamino)-6-(2,4-difluorophenylsulfonyl)-8-methylpyrido[2,3-d]pyrimidin-7(8H)-one, was subjected to a kinase inhibition assay for the kinases. Compounds were tested in 5 dose IC50 mode with 10-fold serial dilution starting at 10 μM. Staurosporine, a known protein kinase inhibitor, was tested in 5-dose IC50 mode with 3-fold serial dilution starting at 20 μM. Reactions were carried out in 10 μM ATP. The results are shown in Table 5. The results show that the compound of Example 39 is a kinase inhibitor highly selective for the kinase Plk2.
Measurement: IC50 = 7.4 nM (pChEMBL 8.130000114440918)
Descriptors: MW 452.51, ALogP 4.18, HBA 6, HBD 2, PSA 69.45, QED 0.42
Compound (SMILES): N#Cc1ccc(Oc2ccc(S(=O)(=O)Nc3ccc(F)cn3)cc2C#N)cc1Cl
InChIKey: ABKCBHGHCYFDNT-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 (unknown origin)
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 428.83, ALogP 4.21, HBA 6, HBD 1, PSA 115.87, QED 0.65
Compound (SMILES): CN[C@@H]1CC2OC([C@@H]1OC)n1c3ccccc3c3c4c(c5c6ccccc6n2c5c31)C(=O)NC4
InChIKey: YISMQBFJYDFMAL-AESIHLKFSA-N
Target: Macrophage-stimulating protein receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q04912
Assay: Kinase Inhibition Assay: The compound of Example 39, 2-(1H-indol-5-ylamino)-6-(2,4-difluorophenylsulfonyl)-8-methylpyrido[2,3-d]pyrimidin-7(8H)-one, was subjected to a kinase inhibition assay for the kinases. Compounds were tested in 5 dose IC50 mode with 10-fold serial dilution starting at 10 μM. Staurosporine, a known protein kinase inhibitor, was tested in 5-dose IC50 mode with 3-fold serial dilution starting at 20 μM. Reactions were carried out in 10 μM ATP. The results are shown in Table 5. The results show that the compound of Example 39 is a kinase inhibitor highly selective for the kinase Plk2.
Measurement: IC50 = 1791 nM (pChEMBL 5.75)
Descriptors: MW 452.51, ALogP 4.18, HBA 6, HBD 2, PSA 69.45, QED 0.42
Compound (SMILES): N#Cc1ccc(Oc2ccc(S(=O)(=O)Nc3ccc(F)cn3)cc2C#N)cc1Cl
InChIKey: ABKCBHGHCYFDNT-UHFFFAOYSA-N
Target: Solute carrier family 22 member 12 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96S37
Assay: Inhibition of human C-terminal eGFP-tagged URAT1 long isoform expressed in CHO cells assessed as decrease in [14C]-uric acid uptake preincubated for 15 mins followed by [14C]-uric acid addition and incubated in dark for 3 hrs by scintillation counting method
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 428.83, ALogP 4.21, HBA 6, HBD 1, PSA 115.87, QED 0.65
Compound (SMILES): CN[C@@H]1CC2OC([C@@H]1OC)n1c3ccccc3c3c4c(c5c6ccccc6n2c5c31)C(=O)NC4
InChIKey: YISMQBFJYDFMAL-AESIHLKFSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Kinase Inhibition Assay: The compound of Example 39, 2-(1H-indol-5-ylamino)-6-(2,4-difluorophenylsulfonyl)-8-methylpyrido[2,3-d]pyrimidin-7(8H)-one, was subjected to a kinase inhibition assay for the kinases. Compounds were tested in 5 dose IC50 mode with 10-fold serial dilution starting at 10 μM. Staurosporine, a known protein kinase inhibitor, was tested in 5-dose IC50 mode with 3-fold serial dilution starting at 20 μM. Reactions were carried out in 10 μM ATP. The results are shown in Table 5. The results show that the compound of Example 39 is a kinase inhibitor highly selective for the kinase Plk2.
Measurement: IC50 = 15.59 nM (pChEMBL 7.809999942779541)
Descriptors: MW 452.51, ALogP 4.18, HBA 6, HBD 2, PSA 69.45, QED 0.42
Compound (SMILES): N#Cc1ccc(Oc2ccc(S(=O)(=O)Nc3ccc(F)cn3)cc2C#N)cc1Cl
InChIKey: ABKCBHGHCYFDNT-UHFFFAOYSA-N
Target: Solute carrier family 22 member 12 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96S37
Assay: Inhibition Assay: Assay compound plates were prepared by diluting the compounds of formula (I) with chloride-free buffer (125 mM Na-gluconate, 4.8 mM K-gluconate, 1.3 mM Ca-gluconate, 1.2 mM KH2PO4, 1.2 mM MgSO4, 5.6 mM D-glucose, 25 mM HEPES, pH 7.4 with NaOH) in 100% DMSO to a final concentration of 1% DMSO. [14C]-Uric Uric acid working stock was made by addition of radiolabeled compound to a final concentration of 120 nM in chloride-free buffer. In all wells, the final assay concentration of solvent (DMSO) was 0.25%; the final assay concentration of [14C]-uric acid was 30 nM in chloride-free buffer and the final compound of formula (I) concentrations ranged from 0 to 10 uM. The vehicle comparator was DMSO (i.e. no inhibition of uric acid transport) and the pharmacological blockade (i.e. 100% inhibition of uric acid transport) was defined by benzbromarone at 10 uM final assay concentration.After pre-incubation, cells were washed with 50 uL of chloride-free buffer.
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 428.83, ALogP 4.21, HBA 6, HBD 1, PSA 115.87, QED 0.65
Compound (SMILES): CN[C@@H]1CC2OC([C@@H]1OC)n1c3ccccc3c3c4c(c5c6ccccc6n2c5c31)C(=O)NC4
InChIKey: YISMQBFJYDFMAL-AESIHLKFSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Kinase Inhibition Assay: The compound of Example 39, 2-(1H-indol-5-ylamino)-6-(2,4-difluorophenylsulfonyl)-8-methylpyrido[2,3-d]pyrimidin-7(8H)-one, was subjected to a kinase inhibition assay for the kinases. Compounds were tested in 5 dose IC50 mode with 10-fold serial dilution starting at 10 μM. Staurosporine, a known protein kinase inhibitor, was tested in 5-dose IC50 mode with 3-fold serial dilution starting at 20 μM. Reactions were carried out in 10 μM ATP. The results are shown in Table 5. The results show that the compound of Example 39 is a kinase inhibitor highly selective for the kinase Plk2.
Measurement: IC50 = 4.66 nM (pChEMBL 8.329999923706055)
Descriptors: MW 452.51, ALogP 4.18, HBA 6, HBD 2, PSA 69.45, QED 0.42
Compound (SMILES): CN[C@@H]1CC2OC([C@@H]1OC)n1c3ccccc3c3c4c(c5c6ccccc6n2c5c31)C(=O)NC4
InChIKey: YISMQBFJYDFMAL-AESIHLKFSA-N
Target: Angiopoietin-1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q02763
Assay: Kinase Inhibition Assay: The compound of Example 39, 2-(1H-indol-5-ylamino)-6-(2,4-difluorophenylsulfonyl)-8-methylpyrido[2,3-d]pyrimidin-7(8H)-one, was subjected to a kinase inhibition assay for the kinases. Compounds were tested in 5 dose IC50 mode with 10-fold serial dilution starting at 10 μM. Staurosporine, a known protein kinase inhibitor, was tested in 5-dose IC50 mode with 3-fold serial dilution starting at 20 μM. Reactions were carried out in 10 μM ATP. The results are shown in Table 5. The results show that the compound of Example 39 is a kinase inhibitor highly selective for the kinase Plk2.
Measurement: IC50 = 719.8 nM (pChEMBL 6.139999866485596)
Descriptors: MW 452.51, ALogP 4.18, HBA 6, HBD 2, PSA 69.45, QED 0.42
Compound (SMILES): CN[C@@H]1CC2OC([C@@H]1OC)n1c3ccccc3c3c4c(c5c6ccccc6n2c5c31)C(=O)NC4
InChIKey: YISMQBFJYDFMAL-AESIHLKFSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Kinase Inhibition Assay: The compound of Example 39, 2-(1H-indol-5-ylamino)-6-(2,4-difluorophenylsulfonyl)-8-methylpyrido[2,3-d]pyrimidin-7(8H)-one, was subjected to a kinase inhibition assay for the kinases. Compounds were tested in 5 dose IC50 mode with 10-fold serial dilution starting at 10 μM. Staurosporine, a known protein kinase inhibitor, was tested in 5-dose IC50 mode with 3-fold serial dilution starting at 20 μM. Reactions were carried out in 10 μM ATP. The results are shown in Table 5. The results show that the compound of Example 39 is a kinase inhibitor highly selective for the kinase Plk2.
Measurement: IC50 = 0.32 nM (pChEMBL 9.489999771118164)
Descriptors: MW 452.51, ALogP 4.18, HBA 6, HBD 2, PSA 69.45, QED 0.42
Compound (SMILES): CN[C@@H]1CC2OC([C@@H]1OC)n1c3ccccc3c3c4c(c5c6ccccc6n2c5c31)C(=O)NC4
InChIKey: YISMQBFJYDFMAL-AESIHLKFSA-N
Target: Calcium/calmodulin-dependent protein kinase type II subunit gamma (SINGLE PROTEIN), Homo sapiens
UniProt: Q13555
Assay: Kinase Inhibition Assay: The compound of Example 39, 2-(1H-indol-5-ylamino)-6-(2,4-difluorophenylsulfonyl)-8-methylpyrido[2,3-d]pyrimidin-7(8H)-one, was subjected to a kinase inhibition assay for the kinases. Compounds were tested in 5 dose IC50 mode with 10-fold serial dilution starting at 10 μM. Staurosporine, a known protein kinase inhibitor, was tested in 5-dose IC50 mode with 3-fold serial dilution starting at 20 μM. Reactions were carried out in 10 μM ATP. The results are shown in Table 5. The results show that the compound of Example 39 is a kinase inhibitor highly selective for the kinase Plk2.
Measurement: IC50 = 0.7 nM (pChEMBL 9.149999618530273)
Descriptors: MW 452.51, ALogP 4.18, HBA 6, HBD 2, PSA 69.45, QED 0.42
Compound (SMILES): CN[C@@H]1CC2OC([C@@H]1OC)n1c3ccccc3c3c4c(c5c6ccccc6n2c5c31)C(=O)NC4
InChIKey: YISMQBFJYDFMAL-AESIHLKFSA-N
Target: Serine/threonine-protein kinase Nek1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96PY6
Assay: Kinase Inhibition Assay: The compound of Example 39, 2-(1H-indol-5-ylamino)-6-(2,4-difluorophenylsulfonyl)-8-methylpyrido[2,3-d]pyrimidin-7(8H)-one, was subjected to a kinase inhibition assay for the kinases. Compounds were tested in 5 dose IC50 mode with 10-fold serial dilution starting at 10 μM. Staurosporine, a known protein kinase inhibitor, was tested in 5-dose IC50 mode with 3-fold serial dilution starting at 20 μM. Reactions were carried out in 10 μM ATP. The results are shown in Table 5. The results show that the compound of Example 39 is a kinase inhibitor highly selective for the kinase Plk2.
Measurement: IC50 = 150.4 nM (pChEMBL 6.820000171661377)
Descriptors: MW 452.51, ALogP 4.18, HBA 6, HBD 2, PSA 69.45, QED 0.42
Compound (SMILES): CN[C@@H]1CC2OC([C@@H]1OC)n1c3ccccc3c3c4c(c5c6ccccc6n2c5c31)C(=O)NC4
InChIKey: YISMQBFJYDFMAL-AESIHLKFSA-N
Target: Serine/threonine-protein kinase WNK2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y3S1
Assay: Kinase Inhibition Assay: The compound of Example 39, 2-(1H-indol-5-ylamino)-6-(2,4-difluorophenylsulfonyl)-8-methylpyrido[2,3-d]pyrimidin-7(8H)-one, was subjected to a kinase inhibition assay for the kinases. Compounds were tested in 5 dose IC50 mode with 10-fold serial dilution starting at 10 μM. Staurosporine, a known protein kinase inhibitor, was tested in 5-dose IC50 mode with 3-fold serial dilution starting at 20 μM. Reactions were carried out in 10 μM ATP. The results are shown in Table 5. The results show that the compound of Example 39 is a kinase inhibitor highly selective for the kinase Plk2.
Measurement: IC50 = 8086 nM (pChEMBL 5.090000152587891)
Descriptors: MW 452.51, ALogP 4.18, HBA 6, HBD 2, PSA 69.45, QED 0.42
Compound (SMILES): CN[C@@H]1CC2OC([C@@H]1OC)n1c3ccccc3c3c4c(c5c6ccccc6n2c5c31)C(=O)NC4
InChIKey: YISMQBFJYDFMAL-AESIHLKFSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Kinase Inhibition Assay: The compound of Example 39, 2-(1H-indol-5-ylamino)-6-(2,4-difluorophenylsulfonyl)-8-methylpyrido[2,3-d]pyrimidin-7(8H)-one, was subjected to a kinase inhibition assay for the kinases. Compounds were tested in 5 dose IC50 mode with 10-fold serial dilution starting at 10 μM. Staurosporine, a known protein kinase inhibitor, was tested in 5-dose IC50 mode with 3-fold serial dilution starting at 20 μM. Reactions were carried out in 10 μM ATP. The results are shown in Table 5. The results show that the compound of Example 39 is a kinase inhibitor highly selective for the kinase Plk2.
Measurement: IC50 = 384.5 nM (pChEMBL 6.420000076293945)
Descriptors: MW 452.51, ALogP 4.18, HBA 6, HBD 2, PSA 69.45, QED 0.42
Compound (SMILES): CN[C@@H]1CC2OC([C@@H]1OC)n1c3ccccc3c3c4c(c5c6ccccc6n2c5c31)C(=O)NC4
InChIKey: YISMQBFJYDFMAL-AESIHLKFSA-N
Target: Mitogen-activated protein kinase kinase kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99683
Assay: Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Assay: The assay measures the phosphorylation level of a biotinylated peptide substrate by the ASK1 kinase using HTRF detection (6.1). This is a competitive, time-resolved fluorescence resonance energy transfer (TR-FRET) immunoassay, based on HTRF KinEASE-STK manual from Cisbio (6.1). Test compound, 1 uM STK3 peptide substrate, 4 nM of ASK1 kinase are incubated with 10 mM MOP buffer, pH. 7.0 containing 10 mM Mg-acetate, 0.025% NP-40, 1 mM DTT, 0.05% BSA and 1.5% glycerol for 30 minutes then 100 uM ATP is added to start the kinase reaction and incubated for 3 hr. Peptide antibody labeled with 1x Eu3+ Cryptate buffer containing 10 mM EDTA and 125 nM Streptavidin XL665 are added to stop the reaction and phosphorylated peptide substrate is detected using Envision 2103 Multilabeled reader from PerkinElmer. The fluorescence is measured at 615 nm (Cryptate) and 665 nm (XL665) and a ratio of 665 nm/615 nm is calculated for each well.
Measurement: IC50 = 6.3 nM (pChEMBL 8.199999809265137)
Descriptors: MW 452.51, ALogP 4.18, HBA 6, HBD 2, PSA 69.45, QED 0.42
Compound (SMILES): CN[C@@H]1CC2OC([C@@H]1OC)n1c3ccccc3c3c4c(c5c6ccccc6n2c5c31)C(=O)NC4
InChIKey: YISMQBFJYDFMAL-AESIHLKFSA-N
Target: Proto-oncogene tyrosine-protein kinase Src (SINGLE PROTEIN), Homo sapiens
UniProt: P12931
Assay: Kinase Inhibition Assay: The compound of Example 39, 2-(1H-indol-5-ylamino)-6-(2,4-difluorophenylsulfonyl)-8-methylpyrido[2,3-d]pyrimidin-7(8H)-one, was subjected to a kinase inhibition assay for the kinases. Compounds were tested in 5 dose IC50 mode with 10-fold serial dilution starting at 10 μM. Staurosporine, a known protein kinase inhibitor, was tested in 5-dose IC50 mode with 3-fold serial dilution starting at 20 μM. Reactions were carried out in 10 μM ATP. The results are shown in Table 5. The results show that the compound of Example 39 is a kinase inhibitor highly selective for the kinase Plk2.
Measurement: IC50 = 4.01 nM (pChEMBL 8.399999618530273)
Descriptors: MW 452.51, ALogP 4.18, HBA 6, HBD 2, PSA 69.45, QED 0.42
Compound (SMILES): CN[C@@H]1CC2OC([C@@H]1OC)n1c3ccccc3c3c4c(c5c6ccccc6n2c5c31)C(=O)NC4
InChIKey: YISMQBFJYDFMAL-AESIHLKFSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Kinase Inhibition Assay: The compound of Example 39, 2-(1H-indol-5-ylamino)-6-(2,4-difluorophenylsulfonyl)-8-methylpyrido[2,3-d]pyrimidin-7(8H)-one, was subjected to a kinase inhibition assay for the kinases. Compounds were tested in 5 dose IC50 mode with 10-fold serial dilution starting at 10 μM. Staurosporine, a known protein kinase inhibitor, was tested in 5-dose IC50 mode with 3-fold serial dilution starting at 20 μM. Reactions were carried out in 10 μM ATP. The results are shown in Table 5. The results show that the compound of Example 39 is a kinase inhibitor highly selective for the kinase Plk2.
Measurement: IC50 = 183.5 nM (pChEMBL 6.739999771118164)
Descriptors: MW 452.51, ALogP 4.18, HBA 6, HBD 2, PSA 69.45, QED 0.42
Compound (SMILES): CN[C@@H]1CC2OC([C@@H]1OC)n1c3ccccc3c3c4c(c5c6ccccc6n2c5c31)C(=O)NC4
InChIKey: YISMQBFJYDFMAL-AESIHLKFSA-N
Target: Tyrosine-protein kinase Lyn (SINGLE PROTEIN), Homo sapiens
UniProt: P07948
Assay: Kinase Inhibition Assay: The compound of Example 39, 2-(1H-indol-5-ylamino)-6-(2,4-difluorophenylsulfonyl)-8-methylpyrido[2,3-d]pyrimidin-7(8H)-one, was subjected to a kinase inhibition assay for the kinases. Compounds were tested in 5 dose IC50 mode with 10-fold serial dilution starting at 10 μM. Staurosporine, a known protein kinase inhibitor, was tested in 5-dose IC50 mode with 3-fold serial dilution starting at 20 μM. Reactions were carried out in 10 μM ATP. The results are shown in Table 5. The results show that the compound of Example 39 is a kinase inhibitor highly selective for the kinase Plk2.
Measurement: IC50 = 24.32 nM (pChEMBL 7.610000133514404)
Descriptors: MW 452.51, ALogP 4.18, HBA 6, HBD 2, PSA 69.45, QED 0.42
Compound (SMILES): CN[C@@H]1CC2OC([C@@H]1OC)n1c3ccccc3c3c4c(c5c6ccccc6n2c5c31)C(=O)NC4
InChIKey: YISMQBFJYDFMAL-AESIHLKFSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Kinase Inhibition Assay: The compound of Example 39, 2-(1H-indol-5-ylamino)-6-(2,4-difluorophenylsulfonyl)-8-methylpyrido[2,3-d]pyrimidin-7(8H)-one, was subjected to a kinase inhibition assay for the kinases. Compounds were tested in 5 dose IC50 mode with 10-fold serial dilution starting at 10 μM. Staurosporine, a known protein kinase inhibitor, was tested in 5-dose IC50 mode with 3-fold serial dilution starting at 20 μM. Reactions were carried out in 10 μM ATP. The results are shown in Table 5. The results show that the compound of Example 39 is a kinase inhibitor highly selective for the kinase Plk2.
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 452.51, ALogP 4.18, HBA 6, HBD 2, PSA 69.45, QED 0.42
Compound (SMILES): CN[C@@H]1CC2OC([C@@H]1OC)n1c3ccccc3c3c4c(c5c6ccccc6n2c5c31)C(=O)NC4
InChIKey: YISMQBFJYDFMAL-AESIHLKFSA-N
Target: Serine/threonine-protein kinase pim-3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86V86
Assay: Kinase Inhibition Assay: The compound of Example 39, 2-(1H-indol-5-ylamino)-6-(2,4-difluorophenylsulfonyl)-8-methylpyrido[2,3-d]pyrimidin-7(8H)-one, was subjected to a kinase inhibition assay for the kinases. Compounds were tested in 5 dose IC50 mode with 10-fold serial dilution starting at 10 μM. Staurosporine, a known protein kinase inhibitor, was tested in 5-dose IC50 mode with 3-fold serial dilution starting at 20 μM. Reactions were carried out in 10 μM ATP. The results are shown in Table 5. The results show that the compound of Example 39 is a kinase inhibitor highly selective for the kinase Plk2.
Measurement: IC50 = 0.57 nM (pChEMBL 9.239999771118164)
Descriptors: MW 452.51, ALogP 4.18, HBA 6, HBD 2, PSA 69.45, QED 0.42
Compound (SMILES): CN[C@@H]1CC2OC([C@@H]1OC)n1c3ccccc3c3c4c(c5c6ccccc6n2c5c31)C(=O)NC4
InChIKey: YISMQBFJYDFMAL-AESIHLKFSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Kinase Inhibition Assay: The compound of Example 39, 2-(1H-indol-5-ylamino)-6-(2,4-difluorophenylsulfonyl)-8-methylpyrido[2,3-d]pyrimidin-7(8H)-one, was subjected to a kinase inhibition assay for the kinases. Compounds were tested in 5 dose IC50 mode with 10-fold serial dilution starting at 10 μM. Staurosporine, a known protein kinase inhibitor, was tested in 5-dose IC50 mode with 3-fold serial dilution starting at 20 μM. Reactions were carried out in 10 μM ATP. The results are shown in Table 5. The results show that the compound of Example 39 is a kinase inhibitor highly selective for the kinase Plk2.
Measurement: IC50 = 62.16 nM (pChEMBL 7.210000038146973)
Descriptors: MW 452.51, ALogP 4.18, HBA 6, HBD 2, PSA 69.45, QED 0.42
Compound (SMILES): CN[C@@H]1CC2OC([C@@H]1OC)n1c3ccccc3c3c4c(c5c6ccccc6n2c5c31)C(=O)NC4
InChIKey: YISMQBFJYDFMAL-AESIHLKFSA-N
Target: Serine/threonine-protein kinase PLK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53350
Assay: Kinase Inhibition Assay: The compound of Example 39, 2-(1H-indol-5-ylamino)-6-(2,4-difluorophenylsulfonyl)-8-methylpyrido[2,3-d]pyrimidin-7(8H)-one, was subjected to a kinase inhibition assay for the kinases. Compounds were tested in 5 dose IC50 mode with 10-fold serial dilution starting at 10 μM. Staurosporine, a known protein kinase inhibitor, was tested in 5-dose IC50 mode with 3-fold serial dilution starting at 20 μM. Reactions were carried out in 10 μM ATP. The results are shown in Table 5. The results show that the compound of Example 39 is a kinase inhibitor highly selective for the kinase Plk2.
Measurement: IC50 = 3673 nM (pChEMBL 5.429999828338623)
Descriptors: MW 452.51, ALogP 4.18, HBA 6, HBD 2, PSA 69.45, QED 0.42
Compound (SMILES): CN[C@@H]1CC2OC([C@@H]1OC)n1c3ccccc3c3c4c(c5c6ccccc6n2c5c31)C(=O)NC4
InChIKey: YISMQBFJYDFMAL-AESIHLKFSA-N
Target: Tyrosine-protein kinase Lck (SINGLE PROTEIN), Homo sapiens
UniProt: P06239
Assay: Kinase Inhibition Assay: The compound of Example 39, 2-(1H-indol-5-ylamino)-6-(2,4-difluorophenylsulfonyl)-8-methylpyrido[2,3-d]pyrimidin-7(8H)-one, was subjected to a kinase inhibition assay for the kinases. Compounds were tested in 5 dose IC50 mode with 10-fold serial dilution starting at 10 μM. Staurosporine, a known protein kinase inhibitor, was tested in 5-dose IC50 mode with 3-fold serial dilution starting at 20 μM. Reactions were carried out in 10 μM ATP. The results are shown in Table 5. The results show that the compound of Example 39 is a kinase inhibitor highly selective for the kinase Plk2.
Measurement: IC50 = 2.21 nM (pChEMBL 8.65999984741211)
Descriptors: MW 452.51, ALogP 4.18, HBA 6, HBD 2, PSA 69.45, QED 0.42
Compound (SMILES): CN[C@@H]1CC2OC([C@@H]1OC)n1c3ccccc3c3c4c(c5c6ccccc6n2c5c31)C(=O)NC4
InChIKey: YISMQBFJYDFMAL-AESIHLKFSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Kinase Inhibition Assay: The compound of Example 39, 2-(1H-indol-5-ylamino)-6-(2,4-difluorophenylsulfonyl)-8-methylpyrido[2,3-d]pyrimidin-7(8H)-one, was subjected to a kinase inhibition assay for the kinases. Compounds were tested in 5 dose IC50 mode with 10-fold serial dilution starting at 10 μM. Staurosporine, a known protein kinase inhibitor, was tested in 5-dose IC50 mode with 3-fold serial dilution starting at 20 μM. Reactions were carried out in 10 μM ATP. The results are shown in Table 5. The results show that the compound of Example 39 is a kinase inhibitor highly selective for the kinase Plk2.
Measurement: IC50 = 142.5 nM (pChEMBL 6.849999904632568)
Descriptors: MW 452.51, ALogP 4.18, HBA 6, HBD 2, PSA 69.45, QED 0.42
Compound (SMILES): CN[C@@H]1CC2OC([C@@H]1OC)n1c3ccccc3c3c4c(c5c6ccccc6n2c5c31)C(=O)NC4
InChIKey: YISMQBFJYDFMAL-AESIHLKFSA-N
Target: Cyclin-dependent kinase 6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00534
Assay: Kinase Inhibition Assay: The compound of Example 39, 2-(1H-indol-5-ylamino)-6-(2,4-difluorophenylsulfonyl)-8-methylpyrido[2,3-d]pyrimidin-7(8H)-one, was subjected to a kinase inhibition assay for the kinases. Compounds were tested in 5 dose IC50 mode with 10-fold serial dilution starting at 10 μM. Staurosporine, a known protein kinase inhibitor, was tested in 5-dose IC50 mode with 3-fold serial dilution starting at 20 μM. Reactions were carried out in 10 μM ATP. The results are shown in Table 5. The results show that the compound of Example 39 is a kinase inhibitor highly selective for the kinase Plk2.
Measurement: IC50 = 242.6 nM (pChEMBL 6.619999885559082)
Descriptors: MW 452.51, ALogP 4.18, HBA 6, HBD 2, PSA 69.45, QED 0.42
Compound (SMILES): CN[C@@H]1CC2OC([C@@H]1OC)n1c3ccccc3c3c4c(c5c6ccccc6n2c5c31)C(=O)NC4
InChIKey: YISMQBFJYDFMAL-AESIHLKFSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Kinase Inhibition Assay: The compound of Example 39, 2-(1H-indol-5-ylamino)-6-(2,4-difluorophenylsulfonyl)-8-methylpyrido[2,3-d]pyrimidin-7(8H)-one, was subjected to a kinase inhibition assay for the kinases. Compounds were tested in 5 dose IC50 mode with 10-fold serial dilution starting at 10 μM. Staurosporine, a known protein kinase inhibitor, was tested in 5-dose IC50 mode with 3-fold serial dilution starting at 20 μM. Reactions were carried out in 10 μM ATP. The results are shown in Table 5. The results show that the compound of Example 39 is a kinase inhibitor highly selective for the kinase Plk2.
Measurement: IC50 = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 452.51, ALogP 4.18, HBA 6, HBD 2, PSA 69.45, QED 0.42
Compound (SMILES): CN[C@@H]1CC2OC([C@@H]1OC)n1c3ccccc3c3c4c(c5c6ccccc6n2c5c31)C(=O)NC4
InChIKey: YISMQBFJYDFMAL-AESIHLKFSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Enzymatic Assay: Briefly, specific kinase/substrate pairs along with required cofactors were prepared in reaction buffer. Compounds were delivered into the reaction, followed 15-20 minutes later by addition of a mixture of ATP (Sigma, St. Louis Mo.) and 33P ATP (Perkin Elmer, Waltham Mass.) to a final concentration of 10 μM. Reactions were carried out at room temperature for 120 min, followed by spotting of the reaction mixtures onto P81 ion exchange filter paper (Whatman Inc., Piscataway, N.J.). Unbound phosphate was removed by extensive washing of filters in 0.75% phosphoric acid. After subtraction of background derived from control reactions containing inactive enzyme, kinase activity data was expressed as the percent of remaining kinase activity in test samples compared to vehicle (dimethyl sulfoxide) reactions. IC50 values and curve fits were obtained using Prism (GraphPad Software). Reaction Conditions: Buffer Conditions: 20 mM Hepes (pH 7.5), 10 mM MgCl2, 1 mM EGTA, 0.02% Brij35, 0.02 mg/mL BSA, 0.1 mM Na3VO4, 2 mM DTT, and 1% DMSO. ATP concentration: 10 μM. Reaction Time: 2 hours. Compound 3 was tested at 10 concentrations as follows with a comparison to the common kinase inhibitor reference compound staurosporine. Compounds were tested in a 10-point IC50 mode with 3-fold serial dilution starting at 10 uM. Control Compound was tested in a 10-point IC50 with 3-fold serial dilution starting at 20 uM. All kinase reactions were performed at 10 uM ATP. Test concentrations are provided below in molar units (M).
Measurement: IC50 = 4.97 nM (pChEMBL 8.300000190734863)
Descriptors: MW 452.51, ALogP 4.18, HBA 6, HBD 2, PSA 69.45, QED 0.42
Compound (SMILES): CN[C@@H]1CC2OC([C@@H]1OC)n1c3ccccc3c3c4c(c5c6ccccc6n2c5c31)C(=O)NC4
InChIKey: YISMQBFJYDFMAL-AESIHLKFSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Enzymatic Assay: Briefly, specific kinase/substrate pairs along with required cofactors were prepared in reaction buffer. Compounds were delivered into the reaction, followed 15-20 minutes later by addition of a mixture of ATP (Sigma, St. Louis Mo.) and 33P ATP (Perkin Elmer, Waltham Mass.) to a final concentration of 10 μM. Reactions were carried out at room temperature for 120 min, followed by spotting of the reaction mixtures onto P81 ion exchange filter paper (Whatman Inc., Piscataway, N.J.). Unbound phosphate was removed by extensive washing of filters in 0.75% phosphoric acid. After subtraction of background derived from control reactions containing inactive enzyme, kinase activity data was expressed as the percent of remaining kinase activity in test samples compared to vehicle (dimethyl sulfoxide) reactions. IC50 values and curve fits were obtained using Prism (GraphPad Software). Reaction Conditions: Buffer Conditions: 20 mM Hepes (pH 7.5), 10 mM MgCl2, 1 mM EGTA, 0.02% Brij35, 0.02 mg/mL BSA, 0.1 mM Na3VO4, 2 mM DTT, and 1% DMSO. ATP concentration: 10 μM. Reaction Time: 2 hours. Compound 3 was tested at 10 concentrations as follows with a comparison to the common kinase inhibitor reference compound staurosporine. Compounds were tested in a 10-point IC50 mode with 3-fold serial dilution starting at 10 uM. Control Compound was tested in a 10-point IC50 with 3-fold serial dilution starting at 20 uM. All kinase reactions were performed at 10 uM ATP. Test concentrations are provided below in molar units (M).
Measurement: IC50 = 0.0192 nM (pChEMBL 10.720000267028809)
Descriptors: MW 452.51, ALogP 4.18, HBA 6, HBD 2, PSA 69.45, QED 0.42