lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=C1CN=C(n2cnc(C3CC3)c2)C=C2c3cccc(-c4ccc(F)nc4F)c3CCN12
InChIKey: NKPUWTADMNLUBA-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P41594
Assay: Induced Intracellular Calcium Assay: Activity of compounds of the present invention with respect to mGluR1 antagonism was examined by an assay based on measurements of L-glutamate induced intracellular calcium increases using a 96 well plate-based Fluorometric Imaging Plate Reader (FLIPR), and CHO cells stably expressing human mGluR1. L-glutamate induced robust calcium responses via human mGluR1 in a concentration-dependent manner and in the low micromolar range.
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 431.45, ALogP 3.79, HBA 5, HBD 0, PSA 63.38, QED 0.58
Compound (SMILES): Cn1c(=O)c(Sc2ccc(F)cc2)cc2cnc(Nc3ccc4[nH]ccc4c3)nc21
InChIKey: FJECSOOLAWUZAB-UHFFFAOYSA-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 > 10000 nM (pChEMBL 5)
Descriptors: MW 417.47, ALogP 4.84, HBA 6, HBD 2, PSA 75.6, QED 0.44
Compound (SMILES): N#C[C@H]1C[C@H](O)CC[C@@H]1n1cc(C(N)=O)c(Nc2ccc(C(F)(F)F)cc2)n1
InChIKey: LHCPZEOULPJAHA-YVLXSGLVSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Biochemical Activity Assay: The assays were performed in 384-well, low volume microtiter assay plates in a final reaction volume of 9 ul. Dose-response curves were generated by incubating 3 nM of each kinase together with 2 uM of a fluorescently labeled substrate peptide specific for each enzyme (Jak1 and Jak3 substrate FITC-Ahx-KKSRGDYMTMQIG-NH2, Jak2 and Tyk2 substrate 5(6)-Carboxyfluorescein-Ahx-GGEEEEYFELVKKKK) in 50 mM Hepes pH 7.5, 0.02% Tween 20, 0.02% BSA, 1 mM DTT, 10 uM Na3VO4, 10 mM ß-Glycerolphosphate, specific concentrations of MgCl2 (Jak1 12 mM, Jak2 and Tyk2 9 mM, Jak3 1.5 mM) and 45 uM ATP for 60 min at 30° C. in the presence or absence of compound diluted in DMSO. Kinase reaction were terminated by adding 15 ul STOP buffer (100 mM HEPES pH 7.5, 5% DMSO, 0.1% Caliper coating reagent, 10 mM EDTA, and 0.015% Brij35.
Measurement: IC50 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 393.37, ALogP 2.97, HBA 6, HBD 3, PSA 116.96, QED 0.74
Compound (SMILES): CN(C)[C@H]1CC[C@H](n2cc(C(N)=O)c(Nc3ccc(Cl)cc3)n2)[C@@H](C#N)C1
InChIKey: YTWLQRKOBJUYNS-PVUWLOKVSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in HEK293 cells by patch clamp method
Measurement: IC50 = 3000 nM (pChEMBL 5.519999980926514)
Descriptors: MW 386.89, ALogP 3.17, HBA 6, HBD 2, PSA 99.97, QED 0.82
Compound (SMILES): CC1(C)Oc2ccc(-c3cncnc3)cc2C2(COC(N)=N2)C12COC2
InChIKey: WRPYZOUQPVZQFZ-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Cellular Assay of Aβ Production: Test Example 3: The potency of compounds against BACE1 activity was determined in a cellular assay of Aβ production. Human SK-N-BE(2) neuroblastoma cells (ATCC No. CRL-2271) were plated at 96,000 cells/well/100 uL in 96-well plates in RPMI1640 medium/10% fetal bovine serum (FBS)/penicillin-streptomycin and cultured for 24 hours at 37° C., 5% CO2. Test compounds were dissolved in dimethyl sulfoxide and diluted with dimethyl sulfoxide and put into RPMI1640/5% FBS/penicillin-streptomycin media (final dimethyl sulfoxide concentration is 0.5%). The culture media in 96-well plates were replaced by 125 uL/well of the media containing test compounds. After incubation for 6 hours at 37° C., 5% CO2, 30 uL of the media were transferred into a fresh 96-well plate and used for Aβ40 assay by an enzyme-linked immunosorbent assay (ELISA) kit (#27718, Immuno-Biological Laboratories, Japan) according to the manufacturer's protocol. Cell viability was measured by CellTiter-Glo Luminescent Cell Viability Assay (#7571, Promega) after removal of 30 uL of the media for the Aβ assay.
Measurement: IC50 = 72 nM (pChEMBL 7.139999866485596)
Descriptors: MW 352.39, ALogP 1.87, HBA 7, HBD 1, PSA 91.85, QED 0.84
Compound (SMILES): CC#Cc1cncc(-c2ccc3c(c2)C2(COC(N)=N2)C2(COC2)CO3)c1
InChIKey: KPXCLUUQECRYFF-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Cellular Assay of Aβ Production: Test Example 3: The potency of compounds against BACE1 activity was determined in a cellular assay of Aβ production. Human SK-N-BE(2) neuroblastoma cells (ATCC No. CRL-2271) were plated at 96,000 cells/well/100 uL in 96-well plates in RPMI1640 medium/10% fetal bovine serum (FBS)/penicillin-streptomycin and cultured for 24 hours at 37° C., 5% CO2. Test compounds were dissolved in dimethyl sulfoxide and diluted with dimethyl sulfoxide and put into RPMI1640/5% FBS/penicillin-streptomycin media (final dimethyl sulfoxide concentration is 0.5%). The culture media in 96-well plates were replaced by 125 uL/well of the media containing test compounds. After incubation for 6 hours at 37° C., 5% CO2, 30 uL of the media were transferred into a fresh 96-well plate and used for Aβ40 assay by an enzyme-linked immunosorbent assay (ELISA) kit (#27718, Immuno-Biological Laboratories, Japan) according to the manufacturer's protocol. Cell viability was measured by CellTiter-Glo Luminescent Cell Viability Assay (#7571, Promega) after removal of 30 uL of the media for the Aβ assay.
Measurement: IC50 = 99 nM (pChEMBL 7)
Descriptors: MW 361.4, ALogP 2.07, HBA 6, HBD 1, PSA 78.96, QED 0.79
Compound (SMILES): Cc1cnc(-c2cccc3c2CCN2C(=O)CN=C(n4cnc(C5CC5)c4)C=C32)o1
InChIKey: RCNPMPFRYJOVFT-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13255
Assay: Induced Intracellular Calcium Assay: Activity of compounds of the present invention was examined by determination to what extent the glutamate-induced elevation of the intracellular calcium concentration in L(tk−) cells expressing human mGluR5a receptors (see L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886, 1995) is inhibited by utilizing methods as described e.g. by L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886 (1995) and P. J. Flor et al., J. Neurochem. Vol. 67, pages 58-63 (1996).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 399.45, ALogP 3.41, HBA 6, HBD 0, PSA 76.52, QED 0.66
Compound (SMILES): O=C1CN=C(n2cnc(C3CC3)c2)C=C2c3cccc(-c4ccc(F)nc4F)c3CCN12
InChIKey: NKPUWTADMNLUBA-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13255
Assay: Induced Intracellular Calcium Assay: Activity of compounds of the present invention was examined by determination to what extent the glutamate-induced elevation of the intracellular calcium concentration in L(tk−) cells expressing human mGluR5a receptors (see L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886, 1995) is inhibited by utilizing methods as described e.g. by L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886 (1995) and P. J. Flor et al., J. Neurochem. Vol. 67, pages 58-63 (1996).
Measurement: IC50 = 3206 nM (pChEMBL 5.489999771118164)
Descriptors: MW 431.45, ALogP 3.79, HBA 5, HBD 0, PSA 63.38, QED 0.58
Compound (SMILES): Cn1c(=O)c(Sc2ccc(F)cc2)cc2cnc(Nc3ccc4[nH]ccc4c3)nc21
InChIKey: FJECSOOLAWUZAB-UHFFFAOYSA-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 > 10000 nM (pChEMBL 5)
Descriptors: MW 417.47, ALogP 4.84, HBA 6, HBD 2, PSA 75.6, QED 0.44
Compound (SMILES): CN(C)[C@H]1CC[C@H](n2cc(C(N)=O)c(Nc3ccc(Cl)cc3)n2)[C@@H](C#N)C1
InChIKey: YTWLQRKOBJUYNS-PVUWLOKVSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: HTRF Assay: The ability of compounds to inhibit the activity of JAK1, JAK2, JAK3, and Tyk2 was measured using a recombinant purified GST-tagged catalytic domain for each enzyme (Invitrogen JAK1 #M4290, JAK2 #M4290, JAK3 #M4290, Tyk2 #M4290) in an HTRF format biochemical assay. The reactions employed a common peptide substrate, LCB-EQEDEPEGDYFEWLW-NH2 (in-house). The basic assay protocol is as follows: First, 250 mL of diluted compounds in DMSO were dispensed into the wells of a dry 384-well Black plate (Greiner #781076) using a Labcyte Echo 555 acoustic dispenser. Subsequent reagent additions employed an Agilent Bravo. Next, 18 uL of 1.11x enzyme and 1.11x substrate in 1x assay buffer (Invitrogen kinase buffer #PV3189, 2 mM DTT, 0.05% BSA) were added to the wells and shaken and then preincubated for 30 minutes at ambient temperature to allow compound binding to equilibrate. After equilibration, 2 uL of 10xATP in 1x assay buffer was added to initiate the kinase reaction.
Measurement: IC50 = 0.55 nM (pChEMBL 9.260000228881836)
Descriptors: MW 386.89, ALogP 3.17, HBA 6, HBD 2, PSA 99.97, QED 0.82
Compound (SMILES): CC1(C)Oc2ccc(-c3cncnc3)cc2C2(COC(N)=N2)C12COC2
InChIKey: WRPYZOUQPVZQFZ-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Cellular Assay of Aβ Production: Test Example 3: The potency of compounds against BACE1 activity was determined in a cellular assay of Aβ production. Human SK-N-BE(2) neuroblastoma cells (ATCC No. CRL-2271) were plated at 96,000 cells/well/100 uL in 96-well plates in RPMI1640 medium/10% fetal bovine serum (FBS)/penicillin-streptomycin and cultured for 24 hours at 37° C., 5% CO2. Test compounds were dissolved in dimethyl sulfoxide and diluted with dimethyl sulfoxide and put into RPMI1640/5% FBS/penicillin-streptomycin media (final dimethyl sulfoxide concentration is 0.5%). The culture media in 96-well plates were replaced by 125 uL/well of the media containing test compounds. After incubation for 6 hours at 37° C., 5% CO2, 30 uL of the media were transferred into a fresh 96-well plate and used for Aβ40 assay by an enzyme-linked immunosorbent assay (ELISA) kit (#27718, Immuno-Biological Laboratories, Japan) according to the manufacturer's protocol. Cell viability was measured by CellTiter-Glo Luminescent Cell Viability Assay (#7571, Promega) after removal of 30 uL of the media for the Aβ assay.
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 352.39, ALogP 1.87, HBA 7, HBD 1, PSA 91.85, QED 0.84
Compound (SMILES): CC#Cc1cncc(-c2ccc3c(c2)C2(COC(N)=N2)C2(COC2)CO3)c1
InChIKey: KPXCLUUQECRYFF-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Cellular Assay of Aβ Production: Test Example 3: The potency of compounds against BACE1 activity was determined in a cellular assay of Aβ production. Human SK-N-BE(2) neuroblastoma cells (ATCC No. CRL-2271) were plated at 96,000 cells/well/100 uL in 96-well plates in RPMI1640 medium/10% fetal bovine serum (FBS)/penicillin-streptomycin and cultured for 24 hours at 37° C., 5% CO2. Test compounds were dissolved in dimethyl sulfoxide and diluted with dimethyl sulfoxide and put into RPMI1640/5% FBS/penicillin-streptomycin media (final dimethyl sulfoxide concentration is 0.5%). The culture media in 96-well plates were replaced by 125 uL/well of the media containing test compounds. After incubation for 6 hours at 37° C., 5% CO2, 30 uL of the media were transferred into a fresh 96-well plate and used for Aβ40 assay by an enzyme-linked immunosorbent assay (ELISA) kit (#27718, Immuno-Biological Laboratories, Japan) according to the manufacturer's protocol. Cell viability was measured by CellTiter-Glo Luminescent Cell Viability Assay (#7571, Promega) after removal of 30 uL of the media for the Aβ assay.
Measurement: IC50 = 96 nM (pChEMBL 7.019999980926514)
Descriptors: MW 361.4, ALogP 2.07, HBA 6, HBD 1, PSA 78.96, QED 0.79
Compound (SMILES): Cc1cnc(-c2cccc3c2CCN2C(=O)CN=C(n4cnc(C5CC5)c4)C=C32)o1
InChIKey: RCNPMPFRYJOVFT-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P41594
Assay: Induced Intracellular Calcium Assay: Activity of compounds of the present invention with respect to mGluR1 antagonism was examined by an assay based on measurements of L-glutamate induced intracellular calcium increases using a 96 well plate-based Fluorometric Imaging Plate Reader (FLIPR), and CHO cells stably expressing human mGluR1. L-glutamate induced robust calcium responses via human mGluR1 in a concentration-dependent manner and in the low micromolar range.
Measurement: IC50 = 56 nM (pChEMBL 7.25)
Descriptors: MW 399.45, ALogP 3.41, HBA 6, HBD 0, PSA 76.52, QED 0.66
Compound (SMILES): O=C1CN=C(n2cnc(C3CC3)c2)C=C2c3cccc(-c4ccc(F)nc4F)c3CCN12
InChIKey: NKPUWTADMNLUBA-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P41594
Assay: Induced Intracellular Calcium Assay: Activity of compounds of the present invention with respect to mGluR1 antagonism was examined by an assay based on measurements of L-glutamate induced intracellular calcium increases using a 96 well plate-based Fluorometric Imaging Plate Reader (FLIPR), and CHO cells stably expressing human mGluR1. L-glutamate induced robust calcium responses via human mGluR1 in a concentration-dependent manner and in the low micromolar range.
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 431.45, ALogP 3.79, HBA 5, HBD 0, PSA 63.38, QED 0.58
Compound (SMILES): Cn1c(=O)c(Sc2ccc(F)cc2)cc2cnc(Nc3ccc4[nH]ccc4c3)nc21
InChIKey: FJECSOOLAWUZAB-UHFFFAOYSA-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 > 10000 nM (pChEMBL 5)
Descriptors: MW 417.47, ALogP 4.84, HBA 6, HBD 2, PSA 75.6, QED 0.44
Compound (SMILES): CN(C)[C@H]1CC[C@H](n2cc(C(N)=O)c(Nc3ccc(Cl)cc3)n2)[C@@H](C#N)C1
InChIKey: YTWLQRKOBJUYNS-PVUWLOKVSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: HTRF Assay: The ability of compounds to inhibit the activity of JAK1, JAK2, JAK3, and Tyk2 was measured using a recombinant purified GST-tagged catalytic domain for each enzyme (Invitrogen JAK1 #M4290, JAK2 #M4290, JAK3 #M4290, Tyk2 #M4290) in an HTRF format biochemical assay. The reactions employed a common peptide substrate, LCB-EQEDEPEGDYFEWLW-NH2 (in-house). The basic assay protocol is as follows: First, 250 mL of diluted compounds in DMSO were dispensed into the wells of a dry 384-well Black plate (Greiner #781076) using a Labcyte Echo 555 acoustic dispenser. Subsequent reagent additions employed an Agilent Bravo. Next, 18 uL of 1.11x enzyme and 1.11x substrate in 1x assay buffer (Invitrogen kinase buffer #PV3189, 2 mM DTT, 0.05% BSA) were added to the wells and shaken and then preincubated for 30 minutes at ambient temperature to allow compound binding to equilibrate. After equilibration, 2 uL of 10xATP in 1x assay buffer was added to initiate the kinase reaction.
Measurement: IC50 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 386.89, ALogP 3.17, HBA 6, HBD 2, PSA 99.97, QED 0.82
Compound (SMILES): Cc1cnc(-c2cccc3c2CCN2C(=O)CN=C(n4cnc(C5CC5)c4)C=C32)o1
InChIKey: RCNPMPFRYJOVFT-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13255
Assay: Induced Intracellular Calcium Assay: Activity of compounds of the present invention was examined by determination to what extent the glutamate-induced elevation of the intracellular calcium concentration in L(tk−) cells expressing human mGluR5a receptors (see L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886, 1995) is inhibited by utilizing methods as described e.g. by L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886 (1995) and P. J. Flor et al., J. Neurochem. Vol. 67, pages 58-63 (1996).
Measurement: IC50 = 1857 nM (pChEMBL 5.730000019073486)
Descriptors: MW 399.45, ALogP 3.41, HBA 6, HBD 0, PSA 76.52, QED 0.66
Compound (SMILES): O=C1CN=C(n2cnc(C3CC3)c2)C=C2c3cccc(-c4ccc(F)nc4F)c3CCN12
InChIKey: NKPUWTADMNLUBA-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13255
Assay: Induced Intracellular Calcium Assay: Activity of compounds of the present invention was examined by determination to what extent the glutamate-induced elevation of the intracellular calcium concentration in L(tk−) cells expressing human mGluR5a receptors (see L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886, 1995) is inhibited by utilizing methods as described e.g. by L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886 (1995) and P. J. Flor et al., J. Neurochem. Vol. 67, pages 58-63 (1996).
Measurement: IC50 = 561 nM (pChEMBL 6.25)
Descriptors: MW 431.45, ALogP 3.79, HBA 5, HBD 0, PSA 63.38, QED 0.58
Compound (SMILES): Cc1cnc(-c2cccc3c2CCN2C(=O)CN=C(n4cnc(C5CC5)c4)C=C32)o1
InChIKey: RCNPMPFRYJOVFT-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P41594
Assay: Induced Intracellular Calcium Assay: Activity of compounds of the present invention with respect to mGluR1 antagonism was examined by an assay based on measurements of L-glutamate induced intracellular calcium increases using a 96 well plate-based Fluorometric Imaging Plate Reader (FLIPR), and CHO cells stably expressing human mGluR1. L-glutamate induced robust calcium responses via human mGluR1 in a concentration-dependent manner and in the low micromolar range.
Measurement: IC50 = 69 nM (pChEMBL 7.159999847412109)
Descriptors: MW 399.45, ALogP 3.41, HBA 6, HBD 0, PSA 76.52, QED 0.66
Compound (SMILES): O=C1CN=C(n2cnc(C3CC3)c2)C=C2c3cccc(-c4ccc(F)nc4F)c3CCN12
InChIKey: NKPUWTADMNLUBA-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P41594
Assay: Induced Intracellular Calcium Assay: Activity of compounds of the present invention with respect to mGluR1 antagonism was examined by an assay based on measurements of L-glutamate induced intracellular calcium increases using a 96 well plate-based Fluorometric Imaging Plate Reader (FLIPR), and CHO cells stably expressing human mGluR1. L-glutamate induced robust calcium responses via human mGluR1 in a concentration-dependent manner and in the low micromolar range.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 431.45, ALogP 3.79, HBA 5, HBD 0, PSA 63.38, QED 0.58
Compound (SMILES): Cc1cnc(-c2cccc3c2CCN2C(=O)CN=C(n4cnc(C5CC5)c4)C=C32)o1
InChIKey: RCNPMPFRYJOVFT-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13255
Assay: Induced Intracellular Calcium Assay: Activity of compounds of the present invention was examined by determination to what extent the glutamate-induced elevation of the intracellular calcium concentration in L(tk−) cells expressing human mGluR5a receptors (see L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886, 1995) is inhibited by utilizing methods as described e.g. by L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886 (1995) and P. J. Flor et al., J. Neurochem. Vol. 67, pages 58-63 (1996).
Measurement: IC50 = 5860 nM (pChEMBL 5.230000019073486)
Descriptors: MW 399.45, ALogP 3.41, HBA 6, HBD 0, PSA 76.52, QED 0.66
Compound (SMILES): O=C1CN=C(n2cnc(C3CC3)c2)C=C2c3cccc(-c4ccc(F)nc4F)c3CCN12
InChIKey: NKPUWTADMNLUBA-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13255
Assay: Induced Intracellular Calcium Assay: Activity of compounds of the present invention was examined by determination to what extent the glutamate-induced elevation of the intracellular calcium concentration in L(tk−) cells expressing human mGluR5a receptors (see L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886, 1995) is inhibited by utilizing methods as described e.g. by L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886 (1995) and P. J. Flor et al., J. Neurochem. Vol. 67, pages 58-63 (1996).
Measurement: IC50 = 702 nM (pChEMBL 6.150000095367432)
Descriptors: MW 431.45, ALogP 3.79, HBA 5, HBD 0, PSA 63.38, QED 0.58
Compound (SMILES): Cn1c(=O)c(Sc2ccc(F)cc2)cc2cnc(Nc3ccc4[nH]ccc4c3)nc21
InChIKey: FJECSOOLAWUZAB-UHFFFAOYSA-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 > 10000 nM (pChEMBL 5)
Descriptors: MW 417.47, ALogP 4.84, HBA 6, HBD 2, PSA 75.6, QED 0.44
Compound (SMILES): Cn1c(=O)c(Sc2ccc(F)cc2)cc2cnc(Nc3ccc4[nH]ccc4c3)nc21
InChIKey: FJECSOOLAWUZAB-UHFFFAOYSA-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 = 8847 nM (pChEMBL 5.050000190734863)
Descriptors: MW 417.47, ALogP 4.84, HBA 6, HBD 2, PSA 75.6, QED 0.44
Compound (SMILES): O=C1CN=C(n2cnc(C3CC3)c2)C=C2c3cccc(-c4ccc(F)nc4F)c3CCN12
InChIKey: NKPUWTADMNLUBA-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13255
Assay: Induced Intracellular Calcium Assay: Activity of compounds of the present invention was examined by determination to what extent the glutamate-induced elevation of the intracellular calcium concentration in L(tk−) cells expressing human mGluR5a receptors (see L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886, 1995) is inhibited by utilizing methods as described e.g. by L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886 (1995) and P. J. Flor et al., J. Neurochem. Vol. 67, pages 58-63 (1996).
Measurement: IC50 = 672 nM (pChEMBL 6.170000076293945)
Descriptors: MW 431.45, ALogP 3.79, HBA 5, HBD 0, PSA 63.38, QED 0.58
Compound (SMILES): Cn1c(=O)c(Sc2ccc(F)cc2)cc2cnc(Nc3ccc4[nH]ccc4c3)nc21
InChIKey: FJECSOOLAWUZAB-UHFFFAOYSA-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 > 10000 nM (pChEMBL 5)
Descriptors: MW 417.47, ALogP 4.84, HBA 6, HBD 2, PSA 75.6, QED 0.44
Compound (SMILES): O=C1CN=C(n2cnc(C3CC3)c2)C=C2c3cccc(-c4ccc(F)nc4F)c3CCN12
InChIKey: NKPUWTADMNLUBA-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P41594
Assay: Induced Intracellular Calcium Assay: Activity of compounds of the present invention with respect to mGluR1 antagonism was examined by an assay based on measurements of L-glutamate induced intracellular calcium increases using a 96 well plate-based Fluorometric Imaging Plate Reader (FLIPR), and CHO cells stably expressing human mGluR1. L-glutamate induced robust calcium responses via human mGluR1 in a concentration-dependent manner and in the low micromolar range.
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 431.45, ALogP 3.79, HBA 5, HBD 0, PSA 63.38, QED 0.58
Compound (SMILES): O=C1CN=C(n2cnc(C3CC3)c2)C=C2c3cccc(-c4ccc(F)nc4F)c3CCN12
InChIKey: NKPUWTADMNLUBA-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13255
Assay: Induced Intracellular Calcium Assay: Activity of compounds of the present invention was examined by determination to what extent the glutamate-induced elevation of the intracellular calcium concentration in L(tk−) cells expressing human mGluR5a receptors (see L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886, 1995) is inhibited by utilizing methods as described e.g. by L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886 (1995) and P. J. Flor et al., J. Neurochem. Vol. 67, pages 58-63 (1996).
Measurement: IC50 = 2079 nM (pChEMBL 5.679999828338623)
Descriptors: MW 431.45, ALogP 3.79, HBA 5, HBD 0, PSA 63.38, QED 0.58
Compound (SMILES): Cn1c(=O)c(Sc2ccc(F)cc2)cc2cnc(Nc3ccc4[nH]ccc4c3)nc21
InChIKey: FJECSOOLAWUZAB-UHFFFAOYSA-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 > 10000 nM (pChEMBL 5)
Descriptors: MW 417.47, ALogP 4.84, HBA 6, HBD 2, PSA 75.6, QED 0.44
Compound (SMILES): O=C1CN=C(n2cnc(C3CC3)c2)C=C2c3cccc(-c4ccc(F)nc4F)c3CCN12
InChIKey: NKPUWTADMNLUBA-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P41594
Assay: Induced Intracellular Calcium Assay: Activity of compounds of the present invention with respect to mGluR1 antagonism was examined by an assay based on measurements of L-glutamate induced intracellular calcium increases using a 96 well plate-based Fluorometric Imaging Plate Reader (FLIPR), and CHO cells stably expressing human mGluR1. L-glutamate induced robust calcium responses via human mGluR1 in a concentration-dependent manner and in the low micromolar range.
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 431.45, ALogP 3.79, HBA 5, HBD 0, PSA 63.38, QED 0.58
Compound (SMILES): Cn1c(=O)c(Sc2ccc(F)cc2)cc2cnc(Nc3ccc4[nH]ccc4c3)nc21
InChIKey: FJECSOOLAWUZAB-UHFFFAOYSA-N
Target: Ribosomal protein S6 kinase alpha-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15418
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 = 4253 nM (pChEMBL 5.369999885559082)
Descriptors: MW 417.47, ALogP 4.84, HBA 6, HBD 2, PSA 75.6, QED 0.44
Compound (SMILES): O=C1CN=C(n2cnc(C3CC3)c2)C=C2c3cccc(-c4ccc(F)nc4F)c3CCN12
InChIKey: NKPUWTADMNLUBA-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13255
Assay: Induced Intracellular Calcium Assay: Activity of compounds of the present invention was examined by determination to what extent the glutamate-induced elevation of the intracellular calcium concentration in L(tk−) cells expressing human mGluR5a receptors (see L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886, 1995) is inhibited by utilizing methods as described e.g. by L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886 (1995) and P. J. Flor et al., J. Neurochem. Vol. 67, pages 58-63 (1996).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 431.45, ALogP 3.79, HBA 5, HBD 0, PSA 63.38, QED 0.58
Compound (SMILES): Cn1c(=O)c(Sc2ccc(F)cc2)cc2cnc(Nc3ccc4[nH]ccc4c3)nc21
InChIKey: FJECSOOLAWUZAB-UHFFFAOYSA-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 = 7818 nM (pChEMBL 5.110000133514404)
Descriptors: MW 417.47, ALogP 4.84, HBA 6, HBD 2, PSA 75.6, QED 0.44
Compound (SMILES): O=C1CN=C(n2cnc(C3CC3)c2)C=C2c3cccc(-c4ccc(F)nc4F)c3CCN12
InChIKey: NKPUWTADMNLUBA-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13255
Assay: Induced Intracellular Calcium Assay: Activity of compounds of the present invention was examined by determination to what extent the glutamate-induced elevation of the intracellular calcium concentration in L(tk−) cells expressing human mGluR5a receptors (see L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886, 1995) is inhibited by utilizing methods as described e.g. by L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886 (1995) and P. J. Flor et al., J. Neurochem. Vol. 67, pages 58-63 (1996).
Measurement: IC50 = 814 nM (pChEMBL 6.090000152587891)
Descriptors: MW 431.45, ALogP 3.79, HBA 5, HBD 0, PSA 63.38, QED 0.58
Compound (SMILES): Cn1c(=O)c(Sc2ccc(F)cc2)cc2cnc(Nc3ccc4[nH]ccc4c3)nc21
InChIKey: FJECSOOLAWUZAB-UHFFFAOYSA-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 = 6148 nM (pChEMBL 5.210000038146973)
Descriptors: MW 417.47, ALogP 4.84, HBA 6, HBD 2, PSA 75.6, QED 0.44
Compound (SMILES): O=C1CN=C(n2cnc(C3CC3)c2)C=C2c3cccc(-c4ccc(F)nc4F)c3CCN12
InChIKey: NKPUWTADMNLUBA-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P41594
Assay: Induced Intracellular Calcium Assay: Activity of compounds of the present invention with respect to mGluR1 antagonism was examined by an assay based on measurements of L-glutamate induced intracellular calcium increases using a 96 well plate-based Fluorometric Imaging Plate Reader (FLIPR), and CHO cells stably expressing human mGluR1. L-glutamate induced robust calcium responses via human mGluR1 in a concentration-dependent manner and in the low micromolar range.
Measurement: IC50 = 88 nM (pChEMBL 7.059999942779541)
Descriptors: MW 431.45, ALogP 3.79, HBA 5, HBD 0, PSA 63.38, QED 0.58
Compound (SMILES): Cn1c(=O)c(Sc2ccc(F)cc2)cc2cnc(Nc3ccc4[nH]ccc4c3)nc21
InChIKey: FJECSOOLAWUZAB-UHFFFAOYSA-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 = 2785 nM (pChEMBL 5.550000190734863)
Descriptors: MW 417.47, ALogP 4.84, HBA 6, HBD 2, PSA 75.6, QED 0.44
Compound (SMILES): O=C1CN=C(n2cnc(C3CC3)c2)C=C2c3cccc(-c4ccc(F)nc4F)c3CCN12
InChIKey: NKPUWTADMNLUBA-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13255
Assay: Induced Intracellular Calcium Assay: Activity of compounds of the present invention was examined by determination to what extent the glutamate-induced elevation of the intracellular calcium concentration in L(tk−) cells expressing human mGluR5a receptors (see L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886, 1995) is inhibited by utilizing methods as described e.g. by L. P. Daggett et al., Neuropharm. Vol. 34, pages 871-886 (1995) and P. J. Flor et al., J. Neurochem. Vol. 67, pages 58-63 (1996).
Measurement: IC50 > 6000 nM (pChEMBL 5.2220001220703125)
Descriptors: MW 431.45, ALogP 3.79, HBA 5, HBD 0, PSA 63.38, QED 0.58
Compound (SMILES): Cn1c(=O)c(Sc2ccc(F)cc2)cc2cnc(Nc3ccc4[nH]ccc4c3)nc21
InChIKey: FJECSOOLAWUZAB-UHFFFAOYSA-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 > 10000 nM (pChEMBL 5)
Descriptors: MW 417.47, ALogP 4.84, HBA 6, HBD 2, PSA 75.6, QED 0.44
Compound (SMILES): O=C1CN=C(n2cnc(C3CC3)c2)C=C2c3cccc(-c4ccc(F)nc4F)c3CCN12
InChIKey: NKPUWTADMNLUBA-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P41594
Assay: Induced Intracellular Calcium Assay: Activity of compounds of the present invention with respect to mGluR1 antagonism was examined by an assay based on measurements of L-glutamate induced intracellular calcium increases using a 96 well plate-based Fluorometric Imaging Plate Reader (FLIPR), and CHO cells stably expressing human mGluR1. L-glutamate induced robust calcium responses via human mGluR1 in a concentration-dependent manner and in the low micromolar range.
Measurement: IC50 = 136 nM (pChEMBL 6.869999885559082)
Descriptors: MW 431.45, ALogP 3.79, HBA 5, HBD 0, PSA 63.38, QED 0.58
Compound (SMILES): O=C1CN=C(n2cnc(C3CC3)c2)C=C2c3cccc(-c4ccc(F)nc4F)c3CCN12
InChIKey: NKPUWTADMNLUBA-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P41594
Assay: Induced Intracellular Calcium Assay: Activity of compounds of the present invention with respect to mGluR1 antagonism was examined by an assay based on measurements of L-glutamate induced intracellular calcium increases using a 96 well plate-based Fluorometric Imaging Plate Reader (FLIPR), and CHO cells stably expressing human mGluR1. L-glutamate induced robust calcium responses via human mGluR1 in a concentration-dependent manner and in the low micromolar range.
Measurement: IC50 = 153 nM (pChEMBL 6.820000171661377)
Descriptors: MW 431.45, ALogP 3.79, HBA 5, HBD 0, PSA 63.38, QED 0.58
Compound (SMILES): Cn1c(=O)c(Sc2ccc(F)cc2)cc2cnc(Nc3ccc4[nH]ccc4c3)nc21
InChIKey: FJECSOOLAWUZAB-UHFFFAOYSA-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 > 10000 nM (pChEMBL 5)
Descriptors: MW 417.47, ALogP 4.84, HBA 6, HBD 2, PSA 75.6, QED 0.44
Compound (SMILES): Cn1c(=O)c(Sc2ccc(F)cc2)cc2cnc(Nc3ccc4[nH]ccc4c3)nc21
InChIKey: FJECSOOLAWUZAB-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase PLK2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYY3
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 = 201 nM (pChEMBL 6.699999809265137)
Descriptors: MW 417.47, ALogP 4.84, HBA 6, HBD 2, PSA 75.6, QED 0.44
Compound (SMILES): Cn1c(=O)c(Sc2ccc(F)cc2)cc2cnc(Nc3ccc4[nH]ccc4c3)nc21
InChIKey: FJECSOOLAWUZAB-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
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 > 10000 nM (pChEMBL 5)
Descriptors: MW 417.47, ALogP 4.84, HBA 6, HBD 2, PSA 75.6, QED 0.44
Compound (SMILES): Cn1c(=O)c(Sc2ccc(F)cc2)cc2cnc(Nc3ccc4[nH]ccc4c3)nc21
InChIKey: FJECSOOLAWUZAB-UHFFFAOYSA-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 = 8062 nM (pChEMBL 5.090000152587891)
Descriptors: MW 417.47, ALogP 4.84, HBA 6, HBD 2, PSA 75.6, QED 0.44
Compound (SMILES): Cn1c(=O)c(Sc2ccc(F)cc2)cc2cnc(Nc3ccc4[nH]ccc4c3)nc21
InChIKey: FJECSOOLAWUZAB-UHFFFAOYSA-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 = 8998 nM (pChEMBL 5.050000190734863)
Descriptors: MW 417.47, ALogP 4.84, HBA 6, HBD 2, PSA 75.6, QED 0.44
Compound (SMILES): Cn1c(=O)c(Sc2ccc(F)cc2)cc2cnc(Nc3ccc4[nH]ccc4c3)nc21
InChIKey: FJECSOOLAWUZAB-UHFFFAOYSA-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 = 9900 nM (pChEMBL 5)
Descriptors: MW 417.47, ALogP 4.84, HBA 6, HBD 2, PSA 75.6, QED 0.44
Compound (SMILES): Cn1c(=O)c(Sc2ccc(F)cc2)cc2cnc(Nc3ccc4[nH]ccc4c3)nc21
InChIKey: FJECSOOLAWUZAB-UHFFFAOYSA-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 > 10000 nM (pChEMBL 5)
Descriptors: MW 417.47, ALogP 4.84, HBA 6, HBD 2, PSA 75.6, QED 0.44
Compound (SMILES): COC[C@@H](NC(=O)c1cc(F)c(N(C)[C@@H]2CCN(c3ncnc4[nH]ccc34)C2)c(F)c1)c1ccccc1
InChIKey: QXVLADQSKJNARQ-AUSIDOKSSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Enzymatic Assay: JAK1/2/3 kinase assay are performed in vitro using Kit-Tyr 6 Peptide (Invitrogen, Cat. No. PV4122). TYK2 kinase assay are performed in vitro using Z'-LYTE™ Kinase Assay Kit-Tyr 3 Peptide (Invitrogen, Cat. No. PV3192). Recombinant human JAK1/2/3 or TYK2 catalytic domains are from Invitrogen (Cat No. PV4774/PV4210/PV3855/PV4790); All reactions (20 μL) are started by adding 2.5 μL of the testing compound in 4% DMSO solution, 5 μL of Kinase/Peptide substrate Mixture (3.2, 0.04, 0.2 or 8 μg/mL for Recombinant human JAK1/2/3 catalytic domains, 4 μM for Z-LYTE™ Tyr 6 peptide or Z-LYTE™ Tyr 3 peptide) or Phospho-Peptide solution (Invitrogen, Cat. No. PV3192, diluted with 1.33× Kinase Buffer), 2.5 μL ATP Solution (300/100/40/100M, JAK1/JAK2/JAK3/TYK2) or 1.33× Kinase Buffer (Invitrogen, Cat. No. PV3189, 5× diluted with distilled water). The 384-well assay plate (Corning, Cat. No. 3575) is mixed and incubated at room temperature for 1 hour. 5 μL of the Development Solution (Dilute Development Reagent A (Cat. No. PV3297) is diluted to 1/64 with Development Buffer (Cat. No. PV3127) for JAK1, JAK2 and JAK3 assay; Development Reagent A (Cat. No. PV3297) is diluted to 1/2048 with Development Buffer (Cat. No. PV3127) for TYK2 assay. The diluted Development Solution is then added to each well, mixed and incubated at room temperature for another 1 hour. The kinase reaction is then stopped by adding 5 μL of the Stop Reagent (Invitrogen, Cat. No. PV3094), and the plate is read with Wallac 1420 VICTOR3 Multilabel Counter (PerkinElmer™) at 445 nm and 520 nm fluorescence. All compounds are initially tested at 8 different concentrations (1 μM down to 0.0003 μM) using a 1:3 serial dilution scheme.
Measurement: IC50 = 0.055 nM (pChEMBL 10.260000228881836)
Descriptors: MW 506.56, ALogP 4.07, HBA 6, HBD 2, PSA 86.38, QED 0.37
Compound (SMILES): Cc1c(-c2ccc(F)cc2)nnc(N2CCN(c3cnc(C(C)(C)O)cn3)[C@H](C)C2)c1C
InChIKey: LOCCROWNKPBTNX-OAHLLOKOSA-N
Target: Protein smoothened (SINGLE PROTEIN), Mus musculus
UniProt: P56726
Assay: Inhibition of mouse recombinant Shh protein in mouse TMHh12 cells assessed as inhibition of 25 nM Smo agonist-induced hedgehog signalling response by Gli-luciferase reporter gene assay
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 436.54, ALogP 3.63, HBA 7, HBD 1, PSA 78.27, QED 0.67