lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1ccc(-n2nc(C(C)(C)C)cc2NC(=O)Nc2ccc(OCc3ccnc4[nH]c(=O)cnc34)c3ccccc23)cc1
InChIKey: AUCMAJMDOAHHEL-UHFFFAOYSA-N
Target: Tyrosine-protein kinase HCK (SINGLE PROTEIN), Homo sapiens
UniProt: P08631
Assay: Fluorescence Resonance Energy Transfer (FRET) Assay: The enzyme inhibitory activity of test compounds was determined by fluorescence resonance energy transfer (FRET) using synthetic peptides labelled with both donor and acceptor fluorophores (Z-LYTE, Invitrogen). Recombinant, phosphorylated p38 MAPK (MAPK12:Millipore) was diluted in HEPES buffer, mixed with compound at the desired final concentrations and incubated for 2 hr at RT. The FRET peptide (2 uM) and ATP (100 uM) were next added to the enzyme/compound mixture and incubated for 1 hr. Development reagent (protease) was added for 1 hr prior to detection in a fluorescence microplate reader. The site-specific protease only cleaves non-phosphorylated peptide and eliminates the FRET signal. Phosphorylation levels of each reaction were calculated using the ratio of coumarin emission (donor) over fluorescein emission (acceptor) with high ratios indicating high phosphorylation levels and low ratios indicating low phosphorylation levels.
Measurement: IC50 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 589.66, ALogP 6.19, HBA 8, HBD 3, PSA 136.05, QED 0.2
Compound (SMILES): COc1ccc(-n2nc(C(C)(C)C)cc2NC(=O)Nc2ccc(Oc3ncnc4[nH]c(=O)cnc34)c3ccccc23)cc1
InChIKey: NADBSABGTQOEQF-UHFFFAOYSA-N
Target: Tyrosine-protein kinase HCK (SINGLE PROTEIN), Homo sapiens
UniProt: P08631
Assay: Fluorescence Resonance Energy Transfer (FRET) Assay: The enzyme inhibitory activity of test compounds was determined by fluorescence resonance energy transfer (FRET) using synthetic peptides labelled with both donor and acceptor fluorophores (Z-LYTE, Invitrogen). Recombinant, phosphorylated p38 MAPK (MAPK12:Millipore) was diluted in HEPES buffer, mixed with compound at the desired final concentrations and incubated for 2 hr at RT. The FRET peptide (2 uM) and ATP (100 uM) were next added to the enzyme/compound mixture and incubated for 1 hr. Development reagent (protease) was added for 1 hr prior to detection in a fluorescence microplate reader. The site-specific protease only cleaves non-phosphorylated peptide and eliminates the FRET signal. Phosphorylation levels of each reaction were calculated using the ratio of coumarin emission (donor) over fluorescein emission (acceptor) with high ratios indicating high phosphorylation levels and low ratios indicating low phosphorylation levels.
Measurement: IC50 = 458 nM (pChEMBL 6.340000152587891)
Descriptors: MW 576.62, ALogP 5.79, HBA 9, HBD 3, PSA 148.94, QED 0.23
Compound (SMILES): C[C@]12CCC(=O)C=C1C1CC1[C@@H]1C2CC[C@@]2(C)C1C1CC1[C@@]21CCC(=O)C1
InChIKey: ZOQCHOPYQLCJAE-ZORRQXKKSA-N
Target: Progesterone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06401
Assay: Binding Assay: Using cytosol from progesterone receptor-expressing insect cells (Hi5), competitive binding to the progesterone receptor was determined from the ability to displace 3H-progesterone as reference substance from the receptor. If a compound has an affinity corresponding to progesterone, this corresponds to a competition factor (CF) of 1. CF values greater than 1 are characterized by a lower affinity for the progesterone receptor, and CF values of less than 1 are characterized by higher affinity.
Measurement: IC50 = 43.3 nM (pChEMBL 7.360000133514404)
Descriptors: MW 364.53, ALogP 4.97, HBA 2, HBD 0, PSA 34.14, QED 0.61
Compound (SMILES): C[C@]12CC[C@H]3[C@@H](C=CC4=CC(=O)CC[C@@H]43)[C@@H]1CC[C@@]21C=CC(=O)O1
InChIKey: JYYDMSJVMDLMPR-XUJOMZSTSA-N
Target: Progesterone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06401
Assay: Binding Assay: Using cytosol from progesterone receptor-expressing insect cells (Hi5), competitive binding to the progesterone receptor was determined from the ability to displace 3H-progesterone as reference substance from the receptor. If a compound has an affinity corresponding to progesterone, this corresponds to a competition factor (CF) of 1. CF values greater than 1 are characterized by a lower affinity for the progesterone receptor, and CF values of less than 1 are characterized by higher affinity.
Measurement: IC50 = 230 nM (pChEMBL 6.639999866485596)
Descriptors: MW 324.42, ALogP 3.76, HBA 3, HBD 0, PSA 43.37, QED 0.64
Compound (SMILES): C[C@@H]1CC2=CC(=O)CC[C@@H]2[C@H]2CC[C@@]3(C)[C@@H](CC[C@@]34C=CC(=O)O4)[C@@H]21
InChIKey: OWJRNHUDJKJKDG-BRPNSIIGSA-N
Target: Progesterone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06401
Assay: Binding Assay: Using cytosol from progesterone receptor-expressing insect cells (Hi5), competitive binding to the progesterone receptor was determined from the ability to displace 3H-progesterone as reference substance from the receptor. If a compound has an affinity corresponding to progesterone, this corresponds to a competition factor (CF) of 1. CF values greater than 1 are characterized by a lower affinity for the progesterone receptor, and CF values of less than 1 are characterized by higher affinity.
Measurement: IC50 = 310 nM (pChEMBL 6.510000228881836)
Descriptors: MW 340.46, ALogP 4.23, HBA 3, HBD 0, PSA 43.37, QED 0.62
Compound (SMILES): CC[C@@H]1CC2=CC(=O)CC[C@@H]2[C@H]2CC[C@@]3(C)[C@@H](CC[C@@]34C=CC(=O)O4)[C@H]12
InChIKey: KAUYWBKESXHYHY-BUDYZGGTSA-N
Target: Progesterone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06401
Assay: Binding Assay: Using cytosol from progesterone receptor-expressing insect cells (Hi5), competitive binding to the progesterone receptor was determined from the ability to displace 3H-progesterone as reference substance from the receptor. If a compound has an affinity corresponding to progesterone, this corresponds to a competition factor (CF) of 1. CF values greater than 1 are characterized by a lower affinity for the progesterone receptor, and CF values of less than 1 are characterized by higher affinity.
Measurement: IC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 354.49, ALogP 4.62, HBA 3, HBD 0, PSA 43.37, QED 0.65
Compound (SMILES): C=C[C@@H]1CC2=CC(=O)CC[C@@H]2[C@H]2CC[C@@]3(C)[C@@H](CC[C@@]34C=CC(=O)O4)[C@@H]21
InChIKey: NPQJUXZKYVHMNY-BUDYZGGTSA-N
Target: Progesterone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06401
Assay: Binding Assay: Using cytosol from progesterone receptor-expressing insect cells (Hi5), competitive binding to the progesterone receptor was determined from the ability to displace 3H-progesterone as reference substance from the receptor. If a compound has an affinity corresponding to progesterone, this corresponds to a competition factor (CF) of 1. CF values greater than 1 are characterized by a lower affinity for the progesterone receptor, and CF values of less than 1 are characterized by higher affinity.
Measurement: IC50 = 760 nM (pChEMBL 6.119999885559082)
Descriptors: MW 352.47, ALogP 4.39, HBA 3, HBD 0, PSA 43.37, QED 0.52
Compound (SMILES): C[C@]12CC[C@H]3[C@@H](CCC4=CC(=O)CC[C@@H]43)[C@@H]1CC1(CC1)[C@@]21C=CC(=O)O1
InChIKey: YOVQILQTFYDVHU-UFMMEHHESA-N
Target: Progesterone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06401
Assay: Binding Assay: Using cytosol from progesterone receptor-expressing insect cells (Hi5), competitive binding to the progesterone receptor was determined from the ability to displace 3H-progesterone as reference substance from the receptor. If a compound has an affinity corresponding to progesterone, this corresponds to a competition factor (CF) of 1. CF values greater than 1 are characterized by a lower affinity for the progesterone receptor, and CF values of less than 1 are characterized by higher affinity.
Measurement: IC50 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 352.47, ALogP 4.37, HBA 3, HBD 0, PSA 43.37, QED 0.61
Compound (SMILES): CC[C@]12CC[C@H]3[C@@H](CCC4=CC(=O)CC[C@@H]43)[C@@H]1CC[C@@]21C=CC(=O)O1
InChIKey: INHWHLPFIVXVHK-TVASPAASSA-N
Target: Progesterone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06401
Assay: Binding Assay: Using cytosol from progesterone receptor-expressing insect cells (Hi5), competitive binding to the progesterone receptor was determined from the ability to displace 3H-progesterone as reference substance from the receptor. If a compound has an affinity corresponding to progesterone, this corresponds to a competition factor (CF) of 1. CF values greater than 1 are characterized by a lower affinity for the progesterone receptor, and CF values of less than 1 are characterized by higher affinity.
Measurement: IC50 = 45 nM (pChEMBL 7.349999904632568)
Descriptors: MW 340.46, ALogP 4.37, HBA 3, HBD 0, PSA 43.37, QED 0.67
Compound (SMILES): CC[C@]12CC[C@H]3[C@@H](C=CC4=CC(=O)CC[C@@H]43)[C@@H]1CC[C@@]21C=CC(=O)O1
InChIKey: IECGUXKNALUNRX-TVASPAASSA-N
Target: Progesterone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06401
Assay: Binding Assay: Using cytosol from progesterone receptor-expressing insect cells (Hi5), competitive binding to the progesterone receptor was determined from the ability to displace 3H-progesterone as reference substance from the receptor. If a compound has an affinity corresponding to progesterone, this corresponds to a competition factor (CF) of 1. CF values greater than 1 are characterized by a lower affinity for the progesterone receptor, and CF values of less than 1 are characterized by higher affinity.
Measurement: IC50 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 338.45, ALogP 4.15, HBA 3, HBD 0, PSA 43.37, QED 0.67
Compound (SMILES): CC[C@]12CC[C@H]3[C@@H]([C@H](C)CC4=CC(=O)CC[C@@H]43)[C@@H]1CC[C@@]21C=CC(=O)O1
InChIKey: UWRFZHBVLLTGSN-BUDYZGGTSA-N
Target: Progesterone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06401
Assay: Binding Assay: Using cytosol from progesterone receptor-expressing insect cells (Hi5), competitive binding to the progesterone receptor was determined from the ability to displace 3H-progesterone as reference substance from the receptor. If a compound has an affinity corresponding to progesterone, this corresponds to a competition factor (CF) of 1. CF values greater than 1 are characterized by a lower affinity for the progesterone receptor, and CF values of less than 1 are characterized by higher affinity.
Measurement: IC50 = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 354.49, ALogP 4.62, HBA 3, HBD 0, PSA 43.37, QED 0.65
Compound (SMILES): CC[C@@H]1CC2=CC(=O)CC[C@@H]2[C@H]2CC[C@@]3(CC)[C@@H](CC[C@@]34C=CC(=O)O4)[C@H]12
InChIKey: QOKBDMCTJPOERX-VDXMOKCDSA-N
Target: Progesterone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06401
Assay: Binding Assay: Using cytosol from progesterone receptor-expressing insect cells (Hi5), competitive binding to the progesterone receptor was determined from the ability to displace 3H-progesterone as reference substance from the receptor. If a compound has an affinity corresponding to progesterone, this corresponds to a competition factor (CF) of 1. CF values greater than 1 are characterized by a lower affinity for the progesterone receptor, and CF values of less than 1 are characterized by higher affinity.
Measurement: IC50 = 670 nM (pChEMBL 6.170000076293945)
Descriptors: MW 368.52, ALogP 5.01, HBA 3, HBD 0, PSA 43.37, QED 0.64
Compound (SMILES): C=C[C@@H]1CC2=CC(=O)CC[C@@H]2[C@H]2CC[C@@]3(CC)[C@@H](CC[C@@]34C=CC(=O)O4)[C@@H]21
InChIKey: OTRYZVITNGFGQP-VDXMOKCDSA-N
Target: Progesterone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06401
Assay: Binding Assay: Using cytosol from progesterone receptor-expressing insect cells (Hi5), competitive binding to the progesterone receptor was determined from the ability to displace 3H-progesterone as reference substance from the receptor. If a compound has an affinity corresponding to progesterone, this corresponds to a competition factor (CF) of 1. CF values greater than 1 are characterized by a lower affinity for the progesterone receptor, and CF values of less than 1 are characterized by higher affinity.
Measurement: IC50 = 450 nM (pChEMBL 6.349999904632568)
Descriptors: MW 366.5, ALogP 4.78, HBA 3, HBD 0, PSA 43.37, QED 0.52
Compound (SMILES): CC[C@]12CC[C@H]3[C@@H]([C@H](C4CC4)CC4=CC(=O)CC[C@@H]43)[C@@H]1CC[C@@]21C=CC(=O)O1
InChIKey: VVMUECDKKOQFSV-LDQMMROCSA-N
Target: Progesterone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06401
Assay: Binding Assay: Using cytosol from progesterone receptor-expressing insect cells (Hi5), competitive binding to the progesterone receptor was determined from the ability to displace 3H-progesterone as reference substance from the receptor. If a compound has an affinity corresponding to progesterone, this corresponds to a competition factor (CF) of 1. CF values greater than 1 are characterized by a lower affinity for the progesterone receptor, and CF values of less than 1 are characterized by higher affinity.
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 380.53, ALogP 5.01, HBA 3, HBD 0, PSA 43.37, QED 0.63
Compound (SMILES): C[C@]12CC[C@H]3[C@@H]([C@H](C4CC4)CC4=CC(=O)CC[C@@H]43)[C@@H]1CC[C@@]21C=CC(=O)O1
InChIKey: CIILJZJOLQZJTP-FSSNKTKLSA-N
Target: Progesterone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06401
Assay: Binding Assay: Using cytosol from progesterone receptor-expressing insect cells (Hi5), competitive binding to the progesterone receptor was determined from the ability to displace 3H-progesterone as reference substance from the receptor. If a compound has an affinity corresponding to progesterone, this corresponds to a competition factor (CF) of 1. CF values greater than 1 are characterized by a lower affinity for the progesterone receptor, and CF values of less than 1 are characterized by higher affinity.
Measurement: IC50 = 2600 nM (pChEMBL 5.579999923706055)
Descriptors: MW 366.5, ALogP 4.62, HBA 3, HBD 0, PSA 43.37, QED 0.64
Compound (SMILES): CC[C@]12CC[C@H]3[C@@H](CCC4=C(Cl)C(=O)CC[C@@H]43)[C@@H]1CC[C@@]21C=CC(=O)O1
InChIKey: MLKWIDHTFVOTCU-JNHIHOPKSA-N
Target: Progesterone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06401
Assay: Binding Assay: Using cytosol from progesterone receptor-expressing insect cells (Hi5), competitive binding to the progesterone receptor was determined from the ability to displace 3H-progesterone as reference substance from the receptor. If a compound has an affinity corresponding to progesterone, this corresponds to a competition factor (CF) of 1. CF values greater than 1 are characterized by a lower affinity for the progesterone receptor, and CF values of less than 1 are characterized by higher affinity.
Measurement: IC50 = 750 nM (pChEMBL 6.119999885559082)
Descriptors: MW 374.91, ALogP 4.94, HBA 3, HBD 0, PSA 43.37, QED 0.61
Compound (SMILES): C[C@]12CC[C@H]3[C@@H](CCC4=C(Cl)C(=O)CC[C@@H]43)[C@@H]1CC[C@@]21C=CC(=O)O1
InChIKey: ONJDMPZEYBMANI-ZBKBXQEDSA-N
Target: Progesterone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06401
Assay: Binding Assay: Using cytosol from progesterone receptor-expressing insect cells (Hi5), competitive binding to the progesterone receptor was determined from the ability to displace 3H-progesterone as reference substance from the receptor. If a compound has an affinity corresponding to progesterone, this corresponds to a competition factor (CF) of 1. CF values greater than 1 are characterized by a lower affinity for the progesterone receptor, and CF values of less than 1 are characterized by higher affinity.
Measurement: IC50 = 1200 nM (pChEMBL 5.920000076293945)
Descriptors: MW 360.88, ALogP 4.55, HBA 3, HBD 0, PSA 43.37, QED 0.6
Compound (SMILES): CC[C@]12CC[C@H]3[C@@H](C[C@@H](CO)C4=CC(=O)CC[C@@H]43)[C@@H]1CC[C@@]21C=CC(=O)O1
InChIKey: XMUYZDADNDVJIS-DVCXALKBSA-N
Target: Progesterone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06401
Assay: Binding Assay: Using cytosol from progesterone receptor-expressing insect cells (Hi5), competitive binding to the progesterone receptor was determined from the ability to displace 3H-progesterone as reference substance from the receptor. If a compound has an affinity corresponding to progesterone, this corresponds to a competition factor (CF) of 1. CF values greater than 1 are characterized by a lower affinity for the progesterone receptor, and CF values of less than 1 are characterized by higher affinity.
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 370.49, ALogP 3.59, HBA 4, HBD 1, PSA 63.6, QED 0.75
Compound (SMILES): CC[C@]12CC[C@H]3[C@@H](CC4(CC4)C4=CC(=O)CC[C@@H]43)[C@@H]1CC[C@@]21C=CC(=O)O1
InChIKey: WLZJZUASQWXOGD-KAFBVOGGSA-N
Target: Progesterone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06401
Assay: Binding Assay: Using cytosol from progesterone receptor-expressing insect cells (Hi5), competitive binding to the progesterone receptor was determined from the ability to displace 3H-progesterone as reference substance from the receptor. If a compound has an affinity corresponding to progesterone, this corresponds to a competition factor (CF) of 1. CF values greater than 1 are characterized by a lower affinity for the progesterone receptor, and CF values of less than 1 are characterized by higher affinity.
Measurement: IC50 = 49 nM (pChEMBL 7.309999942779541)
Descriptors: MW 366.5, ALogP 4.76, HBA 3, HBD 0, PSA 43.37, QED 0.63
Compound (SMILES): C[C@]12CC[C@H]3[C@@H](C[C@@H](CO)C4=CC(=O)CC[C@@H]43)[C@@H]1CC[C@@]21C=CC(=O)O1
InChIKey: IZIRUZCMNOMEER-NIRRKYISSA-N
Target: Progesterone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06401
Assay: Binding Assay: Using cytosol from progesterone receptor-expressing insect cells (Hi5), competitive binding to the progesterone receptor was determined from the ability to displace 3H-progesterone as reference substance from the receptor. If a compound has an affinity corresponding to progesterone, this corresponds to a competition factor (CF) of 1. CF values greater than 1 are characterized by a lower affinity for the progesterone receptor, and CF values of less than 1 are characterized by higher affinity.
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 356.46, ALogP 3.2, HBA 4, HBD 1, PSA 63.6, QED 0.73
Compound (SMILES): C[C@]12CC[C@H]3[C@@H](CC4(CC4)C4=CC(=O)CC[C@@H]43)[C@@H]1CC[C@@]21C=CC(=O)O1
InChIKey: RZLNRXBPGQEHEO-RFYWBZLDSA-N
Target: Progesterone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06401
Assay: Binding Assay: Using cytosol from progesterone receptor-expressing insect cells (Hi5), competitive binding to the progesterone receptor was determined from the ability to displace 3H-progesterone as reference substance from the receptor. If a compound has an affinity corresponding to progesterone, this corresponds to a competition factor (CF) of 1. CF values greater than 1 are characterized by a lower affinity for the progesterone receptor, and CF values of less than 1 are characterized by higher affinity.
Measurement: IC50 = 44 nM (pChEMBL 7.360000133514404)
Descriptors: MW 352.47, ALogP 4.37, HBA 3, HBD 0, PSA 43.37, QED 0.61
Compound (SMILES): C=CCNC(=O)Nc1ccc2ncc(-c3ccc(O)cc3)nc2n1
InChIKey: YJKXDIOKQBBMGE-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 = 76 nM (pChEMBL 7.119999885559082)
Descriptors: MW 321.34, ALogP 2.7, HBA 5, HBD 3, PSA 100.03, QED 0.64
Compound (SMILES): C=CCNC(=S)Nc1ccc2ncc(-c3ccc(O)cc3)nc2n1
InChIKey: YKMUCILEPVJXKD-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 = 392 nM (pChEMBL 6.409999847412109)
Descriptors: MW 337.41, ALogP 2.87, HBA 5, HBD 3, PSA 82.96, QED 0.5
Compound (SMILES): CCNC(=O)Nc1ccc2ncc(-c3ccc(O)cc3)nc2n1
InChIKey: PNCIDFREJJEVBL-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 309.33, ALogP 2.54, HBA 5, HBD 3, PSA 100.03, QED 0.69
Compound (SMILES): CNC(=S)Nc1ccc2ncc(-c3ccc(N)cc3)nc2n1
InChIKey: USGVEHCAIMTSAY-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 = 2500 nM (pChEMBL 5.599999904632568)
Descriptors: MW 310.39, ALogP 2.19, HBA 5, HBD 3, PSA 88.75, QED 0.49
Compound (SMILES): CCN(C(C)=O)C(=O)Nc1ccc2ncc(-c3ccccc3)nc2n1
InChIKey: MRGFJFFONCTHQQ-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 = 9500 nM (pChEMBL 5.019999980926514)
Descriptors: MW 335.37, ALogP 3.09, HBA 5, HBD 1, PSA 88.08, QED 0.79
Compound (SMILES): CCNC(=O)Nc1ccc2ncc(-c3ccc(N)cc3)nc2n1
InChIKey: DMXCVLZRMWJPCA-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 = 944 nM (pChEMBL 6.03000020980835)
Descriptors: MW 308.35, ALogP 2.42, HBA 5, HBD 3, PSA 105.82, QED 0.64
Compound (SMILES): O=C(NCCCCO)Nc1ccc2ncc(-c3ccccc3)nc2n1
InChIKey: KSANTJWSQWXRNO-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 = 155 nM (pChEMBL 6.809999942779541)
Descriptors: MW 337.38, ALogP 2.59, HBA 5, HBD 3, PSA 100.03, QED 0.6
Compound (SMILES): O=C(NCCCO)Nc1ccc2ncc(-c3ccccc3)nc2n1
InChIKey: KDBTVTHVLHESLV-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 = 711 nM (pChEMBL 6.150000095367432)
Descriptors: MW 323.36, ALogP 2.2, HBA 5, HBD 3, PSA 100.03, QED 0.63
Compound (SMILES): CCNC(=O)Nc1ccc2ncc(-c3ccc(OCCCN4CCOCC4)cc3)nc2n1
InChIKey: RSIBWWOEXPPUAQ-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 = 1800 nM (pChEMBL 5.75)
Descriptors: MW 436.52, ALogP 2.93, HBA 7, HBD 2, PSA 101.5, QED 0.52
Compound (SMILES): CCNC(=S)Nc1ccc2ncc(-c3ccc(O)cc3)nc2n1
InChIKey: SNKCWSSPDZFKAC-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 = 954 nM (pChEMBL 6.019999980926514)
Descriptors: MW 325.4, ALogP 2.7, HBA 5, HBD 3, PSA 82.96, QED 0.64
Compound (SMILES): CCNC(=O)Nc1ccc2ncc(-c3cccc(C(=O)O)c3)nc2n1
InChIKey: QNIVPEHJNNEEOH-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 = 1900 nM (pChEMBL 5.71999979019165)
Descriptors: MW 337.34, ALogP 2.53, HBA 5, HBD 3, PSA 117.1, QED 0.67
Compound (SMILES): CCNC(=O)Nc1ccc2ncc(-c3ccc(OC)c(OC)c3)nc2n1
InChIKey: LBYOKLSZLMKBIX-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 = 939 nM (pChEMBL 6.03000020980835)
Descriptors: MW 353.38, ALogP 2.85, HBA 6, HBD 2, PSA 98.26, QED 0.73
Compound (SMILES): CCNC(=O)Nc1ccc2ncc(-c3ccc(N)c(OC)c3)nc2n1
InChIKey: OSIQMNBZAZZAPD-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 = 592 nM (pChEMBL 6.230000019073486)
Descriptors: MW 338.37, ALogP 2.42, HBA 6, HBD 3, PSA 115.05, QED 0.63
Compound (SMILES): CCNC(=O)Nc1ccc2ncc(-c3cccc(C(N)=O)c3)nc2n1
InChIKey: TYSNQGSJHRKLOK-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 336.36, ALogP 1.93, HBA 5, HBD 3, PSA 122.89, QED 0.67
Compound (SMILES): CCNC(=O)Nc1ccc2ncc(Nc3ccc(OC)cc3)nc2n1
InChIKey: JPLMDPDGRQRZLI-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 338.37, ALogP 2.92, HBA 6, HBD 3, PSA 101.06, QED 0.66
Compound (SMILES): CCNC(=O)Nc1ccc2ncc(Nc3ccc(Cl)cc3)nc2n1
InChIKey: AMEPZSMWNFKIQF-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 342.79, ALogP 3.56, HBA 5, HBD 3, PSA 91.83, QED 0.67
Compound (SMILES): CCNC(=O)Nc1ccc2ncc(Nc3cccnc3)nc2n1
InChIKey: OYSDFAWPEZXUOW-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 309.33, ALogP 2.3, HBA 6, HBD 3, PSA 104.72, QED 0.68
Compound (SMILES): CCNC(=O)Nc1ccc2ncc(Nc3ccc(CC)cc3)nc2n1
InChIKey: LAPGAXMRDYDFSJ-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 336.4, ALogP 3.47, HBA 5, HBD 3, PSA 91.83, QED 0.66
Compound (SMILES): CCNC(=O)Nc1ccc2ncc(Nc3ccc(C)c(OC)c3)nc2n1
InChIKey: YBERBXAVYCSDAR-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 = 26900 nM (pChEMBL 4.570000171661377)
Descriptors: MW 352.4, ALogP 3.23, HBA 6, HBD 3, PSA 101.06, QED 0.65
Compound (SMILES): CCNC(=O)Nc1ccc2ncc(Nc3ccc(O)cc3)nc2n1
InChIKey: IUDFOZAYTBFWBG-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 = 19600 nM (pChEMBL 4.710000038146973)
Descriptors: MW 324.34, ALogP 2.62, HBA 6, HBD 4, PSA 112.06, QED 0.55
Compound (SMILES): CCNC(=O)Nc1ccc2ncc(Nc3ccc(C)cn3)nc2n1
InChIKey: NMPMPTIKEGQVIS-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 = 19400 nM (pChEMBL 4.710000038146973)
Descriptors: MW 323.36, ALogP 2.61, HBA 6, HBD 3, PSA 104.72, QED 0.68
Compound (SMILES): CCNC(=O)Nc1ccc2ncc(Nc3ccn(C)n3)nc2n1
InChIKey: LNUNIEGZMOEYOV-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 = 13700 nM (pChEMBL 4.860000133514404)
Descriptors: MW 312.34, ALogP 1.64, HBA 7, HBD 3, PSA 109.65, QED 0.68
Compound (SMILES): CCNC(=O)Nc1ccc2ncc(Nc3ccc(F)cc3)nc2n1
InChIKey: FIHFDFLGUOPQCN-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 326.34, ALogP 3.05, HBA 5, HBD 3, PSA 91.83, QED 0.69
Compound (SMILES): COc1cc(-c2cnc3ccc(NC(=O)NCCCCO)nc3n2)ccc1O
InChIKey: DCTSFNQDKNOVNW-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 383.41, ALogP 2.3, HBA 7, HBD 4, PSA 129.49, QED 0.46
Compound (SMILES): CCNC(=O)Nc1ccc2ncc(-c3ccc(O)cc3Cl)nc2n1
InChIKey: MWVGADULZNNNBD-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28482
Assay: Cell-Free Kinase Assay: The inhibitory effect of the compounds according to the invention was tested on various serine/threonine, tyrosine and lipid kinases in enzymatic assays. Recombinant human kinases such as, for example, Erk2, PI3Kalpha, -beta, -gamma, -delta, p38alpha, p38gamma, Jnk1, Jnk2 and others were used in this case, partly as full-length kinases, partly as shortened fragments, but at least consisting of the functional kinase domains. The commercial kinase proteins (Proqinase, Upstate) were used as recombinant fusion proteins with GST (glutathion-S-transferase) or His-Tag. Depending on the type of substrate, the various kinase reactions were quantified by means of suitable ALPHA beads (Perkin-Elmer). The substance testing is described in detail hereinafter for the Erk assay. Selected test results of the Erk2, PD3Kalpha, p38alpha and Jnk2 assays are given below.
Measurement: IC50 = 103 nM (pChEMBL 6.989999771118164)
Descriptors: MW 343.77, ALogP 3.19, HBA 5, HBD 3, PSA 100.03, QED 0.68