lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC(C)(CNC(=O)c1cccc(-c2noc(C(F)(F)F)n2)c1)c1coc(-c2ccccc2)n1
InChIKey: QTCSXAUJBQZZSN-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of recombinant human HDAC3 using fluorogenic substrate by fluorescence microplate reader assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 456.42, ALogP 5.12, HBA 6, HBD 1, PSA 94.05, QED 0.43
Compound (SMILES): Cn1cc(-c2nc3c(-c4ccnc(OC5CC5)c4)cnn3cc2OCCC(C)(C)O)cn1
InChIKey: KPXQGLYUMYUHHN-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes
Measurement: IC50 = 7800 nM (pChEMBL 5.110000133514404)
Descriptors: MW 434.5, ALogP 3.27, HBA 9, HBD 1, PSA 99.59, QED 0.45
Compound (SMILES): Cc1cc(N[C@H]2CCc3ccc(Cl)cc3C2)n2nc(C(C)(F)F)nc2n1
InChIKey: MIVYUYYPBSQCPE-AWEZNQCLSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of CYP2C8 in human liver microsomes using isoform-specific probe substrates in presence of NADPH-generating system by LC-MS analysis
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 377.83, ALogP 4.17, HBA 5, HBD 1, PSA 55.11, QED 0.74
Compound (SMILES): Cc1c(-c2ccc(C(N)=O)c3[nH]c4cc(C(C)(C)O)ccc4c23)cccc1-n1c(=O)cc2c(Cl)cccn2c1=O
InChIKey: RXHAROKPHMWUME-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Jak2 Tyrosine Kinase Assay: Compounds with activity against Jak2 tyrosine kinase have been observed to cause thrombocytopenia, anemia and neutropenia in human patients in clinical trials (see for example, see Pardanani, A., Leukemia, 26:1449 (2012)). Jak2 signaling occurs thru EPO and TPO, which control erythrocyte and platelet proliferation, respectively. Thus, inhibition of Jak2 tyrosine kinase can potentially lead to side-effects in the clinic. Btk inhibitors with improved selectivity over Jak2 tyrosine kinase are desired in order to minimize off target side-effects related to the inhibition of Jak2 tyrosine kinase.The assays were performed in V-bottom 384-well plates. The final assay volume was 30 μl prepared from 15 μl additions of enzyme and substrates (fluoresceinated peptide and ATP) and test compounds in assay buffer (100 mM HEPES pH 7.4, 10 mM MgCl2, 25 mM beta-glycerolphosphate, 0.015% Brij 35 surfactant and 4 mM DTT). The reaction was initiated by the combination of Jak2 tyrosine kinase with substrates and test compounds. The reaction mixture was incubated at room temperature for 60 minutes and terminated by adding 45 μL of 35 mM EDTA to each sample. The reaction mixture was analyzed on the Caliper LABCHIP® 3000 by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison to no enzyme control reactions for 100% inhibition and vehicle-only reactions for 0% inhibition. The final concentration of reagents in the assays is ATP, 30 μM; Jak2 fluorescent peptide, 1.5 μM; Jak2, 1 nM; and DMSO, 1.6%. Dose response curves were generated to determine the concentration required inhibiting 50% of kinase activity (IC50). Compounds were dissolved at 10 mM in DMSO and evaluated at eleven concentrations, each in duplicate. IC50 values were derived by non-linear regression analysis.
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 553.02, ALogP 5.04, HBA 6, HBD 3, PSA 122.59, QED 0.28
Compound (SMILES): Cc1nc(N2CCC3(CC2)CO[C@@H](C)[C@H]3N)c(CO)nc1-c1cccc(Cl)c1Cl
InChIKey: IKUYEYLZXGGCRD-ORAYPTAESA-N
Target: Tyrosine-protein phosphatase non-receptor type 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P29350
Assay: Inhibition of His6-fused human full length SHP1 expressed in Escherichia coli cells using DiFMUP as substrate preincubated for 30 mins followed by substrate addition and by fluorescence method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 437.37, ALogP 3.58, HBA 6, HBD 2, PSA 84.5, QED 0.76
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]1CSSC[C@@H](NC(=O)[C@@H](N)Cc2ccc(O)cc2)C(=O)NCC(=O)N[C@@H](Cc2ccccc2)C(=O)N1)C(=O)N[C@@H](Cc1ccccc1)C(N)=O
InChIKey: LHQONNLUWUCJOW-NHMULKRUSA-N
Target: Neuropeptide FF receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X5
Assay: Agonist activity at NPFFR2 (unknown origin) expressed in HEK293-A cells assessed as inhibition of forskolin-stimulated cAMP accumulation incubated for 30 mins by competition PKA binding assay
Measurement: EC50 = 190.55 nM (pChEMBL 6.71999979019165)
Descriptors: MW 1117.33
Compound (SMILES): CCn1c(-c2cnc(C)nc2)nc2c(-c3cnc4c(c3)[C@](C)(NCC(C)(C)F)C(=O)N4)ncnc21
InChIKey: YYXYTTPRFNUTKT-DEOSSOPVSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 475.53, ALogP 3.18, HBA 9, HBD 2, PSA 123.4, QED 0.44
Compound (SMILES): COc1ccc(-n2cc(-c3ccc4ccc(=O)oc4c3)c3cc(-c4ccc(C(=O)O)cc4)cnc32)cc1
InChIKey: CQHDXEWKDCKMHF-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P35236
Assay: Inhibition of PTPN7 (unknown origin) pre-incubated for 20 mins followed by fluorescence substrate addition and measured after 120 mins by DiFMUP assay
Measurement: IC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 488.5, ALogP 6.17, HBA 6, HBD 1, PSA 94.56, QED 0.29
Compound (SMILES): COc1nc(-c2csc(Nc3c4c(nn3CCF)CCCC4)n2)ccc1-n1cnc(C)c1
InChIKey: JEIIPIFVEMKMLA-UHFFFAOYSA-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 assay
Measurement: IC50 = 11400 nM (pChEMBL 4.940000057220459)
Descriptors: MW 453.55, ALogP 4.5, HBA 9, HBD 1, PSA 82.68, QED 0.44
Compound (SMILES): Cl.N[C@]1(C(=O)O)[C@@H]2[C@@H](C(=O)O)[C@@H]2[C@H](O)[C@H]1CSc1ccc(F)c(F)c1
InChIKey: XETSGLSGWGGOTN-JPWNOPPSSA-N
Target: Metabotropic glutamate receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14833
Assay: Agonist activity at human recombinant mGlu4 stably expressed in golden hamster AV12 cell membrane co-expressing Galpha15 assessed as assessed as increase in calcium influx incubated for 90 to 120 min by Fluo-4-AM dye based FLIPR assay
Measurement: EC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 359.35, ALogP 0.78, HBA 5, HBD 4, PSA 120.85, QED 0.57
Compound (SMILES): NC(=O)c1ccc2nc(-c3ccc(C4(N)CCC4)cc3)c(-c3ccccc3)n2n1
InChIKey: JBGYKRAZYDNCNV-UHFFFAOYSA-N
Target: RAC-gamma serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y243
Assay: NanoBRET (AKT3)
Measurement: EC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 383.46, ALogP 3.5, HBA 5, HBD 2, PSA 99.3, QED 0.56
Compound (SMILES): CC(C)(CNC(=O)c1cccc(-c2noc(C(F)(F)F)n2)c1)c1coc(-c2ccccc2)n1
InChIKey: QTCSXAUJBQZZSN-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombinant human HDAC6 using fluorogenic substrate by fluorescence microplate reader assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 456.42, ALogP 5.12, HBA 6, HBD 1, PSA 94.05, QED 0.43
Compound (SMILES): Cc1cc(N[C@H]2CCc3ccc(Cl)cc3C2)n2nc(C(C)(F)F)nc2n1
InChIKey: MIVYUYYPBSQCPE-AWEZNQCLSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using isoform-specific probe substrates in presence of NADPH-generating system by LC-MS analysis
Measurement: IC50 = 2700 nM (pChEMBL 5.570000171661377)
Descriptors: MW 377.83, ALogP 4.17, HBA 5, HBD 1, PSA 55.11, QED 0.74
Compound (SMILES): Cc1c(-c2ccc(C(N)=O)c3[nH]c4cc(C(C)(C)O)ccc4c23)cccc1-n1c(=O)cc2c(Cl)cccn2c1=O
InChIKey: RXHAROKPHMWUME-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Human Recombinant Btk Enzyme Assay: To V-bottom 384-well plates were added test compounds, human recombinant Btk (1 nM, INVITROGEN Corporation), fluoresceinated peptide (1.5 μM), ATP (20 μM), and assay buffer (20 mM HEPES pH 7.4, 10 mM MgCl2, 0.015% Brij 35 surfactant and 4 mM DTT in 1.6% DMSO), with a final volume of 30 μL. After incubating at room temperature for 60 min, the reaction was terminated by adding 45 μL of 35 mM EDTA to each sample. The reaction mixture was analyzed on the Caliper LABCHIP® 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison to no enzyme control reactions for 100% inhibition and no inhibitor controls for 0% inhibition. Dose response curves were generated to determine the concentration required for inhibiting 50% of kinase activity (IC50). Compounds were dissolved at 10 mM in DMSO and evaluated at eleven concentrations.
Measurement: IC50 = 0.41 nM (pChEMBL 9.390000343322754)
Descriptors: MW 553.02, ALogP 5.04, HBA 6, HBD 3, PSA 122.59, QED 0.28
Compound (SMILES): Cc1nc(N2CCC3(CC2)CO[C@@H](C)[C@H]3N)c(CO)nc1-c1cccc(Cl)c1Cl
InChIKey: IKUYEYLZXGGCRD-ORAYPTAESA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: Allosteric inhibition of [H2N-LN(pY)AQLWHA(PEG8)LTI(pY)ATIRRF-amide]-activated N-terminal His6-fused human full length SHP2 (Met 1 to Arg 593 residues) expressed in Escherichia coli BL21 (DE3) cells using DiFMUP as substrate preincubated for 30 followed by substrate addition and by fluorescence method
Measurement: IC50 = 1.5 nM (pChEMBL 8.819999694824219)
Descriptors: MW 437.37, ALogP 3.58, HBA 6, HBD 2, PSA 84.5, QED 0.76
Compound (SMILES): COc1ccc(-n2cc(-c3ccc4ccc(=O)oc4c3)c3cc(-c4ccc(C(=O)O)cc4)cnc32)cc1
InChIKey: CQHDXEWKDCKMHF-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 12 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05209
Assay: Inhibition of PTPN12 (unknown origin) pre-incubated for 20 mins followed by fluorescence substrate addition and measured after 120 mins by DiFMUP assay
Measurement: IC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 488.5, ALogP 6.17, HBA 6, HBD 1, PSA 94.56, QED 0.29
Compound (SMILES): Cl.N[C@]1(C(=O)O)[C@@H]2[C@@H](C(=O)O)[C@@H]2[C@H](O)[C@H]1CSc1ccc(F)c(F)c1
InChIKey: XETSGLSGWGGOTN-JPWNOPPSSA-N
Target: Metabotropic glutamate receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14833
Assay: Antagonist activity human recombinant mGlu4 stably expressed in golden hamster AV12 cell membrane co-expressing Galpha15 assessed as reduction in glutamate-induced calcium influx incubated for 90 to 120 min by Fluo-4-AM dye based FLIPR assay
Measurement: IC50 > 12500 nM (pChEMBL 4.9029998779296875)
Descriptors: MW 359.35, ALogP 0.78, HBA 5, HBD 4, PSA 120.85, QED 0.57
Compound (SMILES): NC(=O)c1ccc2nc(-c3ccc(C4(N)CCC4)cc3)c(-c3ccccc3)n2n1
InChIKey: JBGYKRAZYDNCNV-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: GPCRScan assay: inhibition of M1
Measurement: Ki = 1454.31 nM (pChEMBL 5.840000152587891)
Descriptors: MW 383.46, ALogP 3.5, HBA 5, HBD 2, PSA 99.3, QED 0.56
Compound (SMILES): CC(C)(CNC(=O)c1cccc(-c2noc(C(F)(F)F)n2)c1)c1coc(-c2ccccc2)n1
InChIKey: QTCSXAUJBQZZSN-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant human HDAC8 using fluorogenic substrate by fluorescence microplate reader assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 456.42, ALogP 5.12, HBA 6, HBD 1, PSA 94.05, QED 0.43
Compound (SMILES): Cc1cc(N[C@H]2CCc3ccc(Cl)cc3C2)n2nc(C(C)(F)F)nc2n1
InChIKey: MIVYUYYPBSQCPE-AWEZNQCLSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using isoform-specific probe substrates in presence of NADPH-generating system by LC-MS analysis
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 377.83, ALogP 4.17, HBA 5, HBD 1, PSA 55.11, QED 0.74
Compound (SMILES): Cc1c(-c2ccc(C(N)=O)c3[nH]c4cc(C(C)(C)O)ccc4c23)cccc1-n1c(=O)cc2c(Cl)cccn2c1=O
InChIKey: RXHAROKPHMWUME-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Jak2 Tyrosine Kinase Assay: Compounds with activity against Jak2 tyrosine kinase have been observed to cause thrombocytopenia, anemia and neutropenia in human patients in clinical trials (see for example, see Pardanani, A., Leukemia, 26:1449 (2012)). Jak2 signaling occurs thru EPO and TPO, which control erythrocyte and platelet proliferation, respectively. Thus, inhibition of Jak2 tyrosine kinase can potentially lead to side-effects in the clinic. Btk inhibitors with improved selectivity over Jak2 tyrosine kinase are desired in order to minimize off target side-effects related to the inhibition of Jak2 tyrosine kinase.The assays were performed in V-bottom 384-well plates. The final assay volume was 30 μl prepared from 15 μl additions of enzyme and substrates (fluoresceinated peptide and ATP) and test compounds in assay buffer (100 mM HEPES pH 7.4, 10 mM MgCl2, 25 mM beta-glycerolphosphate, 0.015% Brij 35 surfactant and 4 mM DTT). The reaction was initiated by the combination of Jak2 tyrosine kinase with substrates and test compounds. The reaction mixture was incubated at room temperature for 60 minutes and terminated by adding 45 μL of 35 mM EDTA to each sample. The reaction mixture was analyzed on the Caliper LABCHIP® 3000 by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison to no enzyme control reactions for 100% inhibition and vehicle-only reactions for 0% inhibition. The final concentration of reagents in the assays is ATP, 30 μM; Jak2 fluorescent peptide, 1.5 μM; Jak2, 1 nM; and DMSO, 1.6%. Dose response curves were generated to determine the concentration required inhibiting 50% of kinase activity (IC50). Compounds were dissolved at 10 mM in DMSO and evaluated at eleven concentrations, each in duplicate. IC50 values were derived by non-linear regression analysis.
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 553.02, ALogP 5.04, HBA 6, HBD 3, PSA 122.59, QED 0.28
Compound (SMILES): Cc1nc(N2CCC3(CC2)CO[C@@H](C)[C@H]3N)c(CO)nc1-c1cccc(Cl)c1Cl
InChIKey: IKUYEYLZXGGCRD-ORAYPTAESA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: Inhibition of SHP2 (unknown origin)
Measurement: IC50 = 0.583 nM (pChEMBL 9.229999542236328)
Descriptors: MW 437.37, ALogP 3.58, HBA 6, HBD 2, PSA 84.5, QED 0.76
Compound (SMILES): COc1ccc(-n2cc(-c3ccc4ccc(=O)oc4c3)c3cc(-c4ccc(C(=O)O)cc4)cnc32)cc1
InChIKey: CQHDXEWKDCKMHF-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P18031
Assay: Inhibition of PTPN1 (unknown origin) pre-incubated for 20 mins followed by fluorescence substrate addition and measured after 120 mins by DiFMUP assay
Measurement: IC50 = 410 nM (pChEMBL 6.389999866485596)
Descriptors: MW 488.5, ALogP 6.17, HBA 6, HBD 1, PSA 94.56, QED 0.29
Compound (SMILES): Cl.N[C@]1(C(=O)O)[C@@H]2[C@@H](C(=O)O)[C@@H]2[C@H](O)[C@H]1CSc1ccc(F)c(F)c1
InChIKey: XETSGLSGWGGOTN-JPWNOPPSSA-N
Target: Metabotropic glutamate receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: O15303
Assay: Antagonist activity at human recombinant mGlu6 stably expressed in golden hamster AV12 cell membrane co-expressing Galpha15 assessed as reduction in glutamate-induced calcium influx incubated for 90 to 120 min by Fluo-4-AM dye based FLIPR assay
Measurement: IC50 = 4010 nM (pChEMBL 5.400000095367432)
Descriptors: MW 359.35, ALogP 0.78, HBA 5, HBD 4, PSA 120.85, QED 0.57
Compound (SMILES): NC(=O)c1ccc2nc(-c3ccc(C4(N)CCC4)cc3)c(-c3ccccc3)n2n1
InChIKey: JBGYKRAZYDNCNV-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: GPCRScan assay: inhibition of M1
Measurement: Ki = 1348.96 nM (pChEMBL 5.869999885559082)
Descriptors: MW 383.46, ALogP 3.5, HBA 5, HBD 2, PSA 99.3, QED 0.56
Compound (SMILES): CC(C)(CNC(=O)c1cccc(-c2noc(C(F)(F)F)n2)c1)c1coc(-c2ccccc2)n1
InChIKey: QTCSXAUJBQZZSN-UHFFFAOYSA-N
Target: Histone deacetylase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56524
Assay: Inhibition of recombinant human HDAC4 using Ac-LGK(TFA)-AMC as substrate pre-incubated for 15 mins followed by substrate addition and measured after 60 mins by fluorescence based assay
Measurement: IC50 = 354 nM (pChEMBL 6.449999809265137)
Descriptors: MW 456.42, ALogP 5.12, HBA 6, HBD 1, PSA 94.05, QED 0.43
Compound (SMILES): Cc1nc(N2CCC3(CC2)CO[C@@H](C)[C@H]3N)c(CO)nc1-c1cccc(Cl)c1Cl
InChIKey: IKUYEYLZXGGCRD-ORAYPTAESA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: Inhibition of wildtype SHP2 (unknown origin)
Measurement: IC50 = 0.0583 nM (pChEMBL 10.229999542236328)
Descriptors: MW 437.37, ALogP 3.58, HBA 6, HBD 2, PSA 84.5, QED 0.76
Compound (SMILES): Cl.N[C@]1(C(=O)O)[C@@H]2[C@@H](C(=O)O)[C@@H]2[C@H](O)[C@H]1CSc1ccc(F)c(F)c1
InChIKey: XETSGLSGWGGOTN-JPWNOPPSSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P41594
Assay: Agonist activity at human recombinant mGlu5 stably expressed in golden hamster AV12 cell membrane co-expressing Gq assessed as assessed as increase in calcium influx incubated for 90 to 120 min by Fluo-4-AM dye based FLIPR assay
Measurement: EC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 359.35, ALogP 0.78, HBA 5, HBD 4, PSA 120.85, QED 0.57
Compound (SMILES): NC(=O)c1ccc2nc(-c3ccc(C4(N)CCC4)cc3)c(-c3ccccc3)n2n1
InChIKey: JBGYKRAZYDNCNV-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: Affinity Phenotypic Cellular interaction (CellTiter-Glo® Luminescent Cell Viability Assay (Promega; cell viability in BT-474 cells)) EUB0000637a AKT1
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 383.46, ALogP 3.5, HBA 5, HBD 2, PSA 99.3, QED 0.56
Compound (SMILES): CC(C)(CNC(=O)c1cccc(-c2noc(C(F)(F)F)n2)c1)c1coc(-c2ccccc2)n1
InChIKey: QTCSXAUJBQZZSN-UHFFFAOYSA-N
Target: Histone deacetylase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8WUI4
Assay: Inhibition of recombinant human HDAC7 using Ac-LGK(TFA)-AMC as substrate pre-incubated for 15 mins followed by substrate addition and measured after 60 mins by fluorescence based assay
Measurement: IC50 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 456.42, ALogP 5.12, HBA 6, HBD 1, PSA 94.05, QED 0.43
Compound (SMILES): Cc1nc(N2CCC3(CC2)CO[C@@H](C)[C@H]3N)c(CO)nc1-c1cccc(Cl)c1Cl
InChIKey: IKUYEYLZXGGCRD-ORAYPTAESA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: In-Vitro Safety Profile-Testing the Selectivity Over hErg: Inhibition of the ion channel hErg (or Kv11.1) current causes QT interval prolongation resulting in potentially fatal ventricular tachyarrhythmia called Torsade de Pointes. This is one of the major causes of cardiotoxicity and hErg channel activity is usually evaluated early in the drug development process to mitigate cardiotoxicity risk.hERG ion channel activity was assessed using a patch clamp technique in stable Kv11.1 (hERG) transfected human embryonic kidney cell line (HEK293). Whole cell recordings were carried out with an automated patch clamp device Patchliner™ from Nanion Technologies, Munich following manufacturer recommendation. Different concentrations of the test compound or reference, quinidine, were applied to whole cells suspension and current was measured using a pulse pattern with fixed amplitudes. The effect on Kv11.1 (hERG) ion channel activity was judged from the tail current amplitude and Changes in Kv11.1 (hERG) ion channel activity between control value (defined as 100%) and test compound and reported as percent change of control value of COI.
Measurement: Ki = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 437.37, ALogP 3.58, HBA 6, HBD 2, PSA 84.5, QED 0.76
Compound (SMILES): Cl.N[C@]1(C(=O)O)[C@@H]2[C@@H](C(=O)O)[C@@H]2[C@H](O)[C@H]1CSc1ccc(F)c(F)c1
InChIKey: XETSGLSGWGGOTN-JPWNOPPSSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P41594
Assay: Antagonist activity at human recombinant mGlu5 stably expressed in golden hamster AV12 cell membrane co-expressing Gq assessed as reduction in glutamate-induced calcium influx incubated for 90 to 120 min by Fluo-4-AM dye based FLIPR assay
Measurement: IC50 > 12500 nM (pChEMBL 4.9029998779296875)
Descriptors: MW 359.35, ALogP 0.78, HBA 5, HBD 4, PSA 120.85, QED 0.57
Compound (SMILES): NC(=O)c1ccc2nc(-c3ccc(C4(N)CCC4)cc3)c(-c3ccccc3)n2n1
InChIKey: JBGYKRAZYDNCNV-UHFFFAOYSA-N
Target: RAC-beta serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31751
Assay: Affinity Phenotypic Cellular interaction (CellTiter-Glo® Luminescent Cell Viability Assay (Promega; cell viability in BT-474 cells)) EUB0000637a AKT2
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 383.46, ALogP 3.5, HBA 5, HBD 2, PSA 99.3, QED 0.56
Compound (SMILES): CC(C)(CNC(=O)c1cccc(-c2noc(C(F)(F)F)n2)c1)c1coc(-c2ccccc2)n1
InChIKey: QTCSXAUJBQZZSN-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of recombinant human HDAC1 using Ac-LGK(Ac)-AMC as substrate preincubated for 30 mins followed by substrate addition and measured after 90 mins by fluorescence based assay
Measurement: IC50 = 45000 nM (pChEMBL 4.349999904632568)
Descriptors: MW 456.42, ALogP 5.12, HBA 6, HBD 1, PSA 94.05, QED 0.43
Compound (SMILES): Cl.N[C@]1(C(=O)O)[C@@H]2[C@@H](C(=O)O)[C@@H]2[C@H](O)[C@H]1CSc1ccc(F)c(F)c1
InChIKey: XETSGLSGWGGOTN-JPWNOPPSSA-N
Target: Metabotropic glutamate receptor 8 (SINGLE PROTEIN), Homo sapiens
UniProt: O00222
Assay: Agonist activity at human recombinant mGlu8 stably expressed in golden hamster AV12 cell membrane co-expressing Galpha15 assessed as assessed as increase in calcium influx incubated for 90 to 120 min by Fluo-4-AM dye based FLIPR assay
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 359.35, ALogP 0.78, HBA 5, HBD 4, PSA 120.85, QED 0.57
Compound (SMILES): NC(=O)c1ccc2nc(-c3ccc(C4(N)CCC4)cc3)c(-c3ccccc3)n2n1
InChIKey: JBGYKRAZYDNCNV-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: Affinity On-target Cellular interaction (TR-FRET assay (inhibition of AKT1-T308 phosphorylation in KPL-4 cells)) EUB0000637a AKT1
Measurement: IC50 = 0.9 nM (pChEMBL 9.050000190734863)
Descriptors: MW 383.46, ALogP 3.5, HBA 5, HBD 2, PSA 99.3, QED 0.56
Compound (SMILES): CC(C)(CNC(=O)c1cccc(-c2noc(C(F)(F)F)n2)c1)c1coc(-c2ccccc2)n1
InChIKey: QTCSXAUJBQZZSN-UHFFFAOYSA-N
Target: Histone deacetylase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQL6
Assay: Inhibition of recombinant human HDAC5 using Ac-LGK(TFA)-AMC as substrate pre-incubated for 15 mins followed by substrate addition and measured after 60 mins by fluorescence based assay
Measurement: IC50 = 216 nM (pChEMBL 6.670000076293945)
Descriptors: MW 456.42, ALogP 5.12, HBA 6, HBD 1, PSA 94.05, QED 0.43
Compound (SMILES): Cl.N[C@]1(C(=O)O)[C@@H]2[C@@H](C(=O)O)[C@@H]2[C@H](O)[C@H]1CSc1ccc(F)c(F)c1
InChIKey: XETSGLSGWGGOTN-JPWNOPPSSA-N
Target: Metabotropic glutamate receptor 8 (SINGLE PROTEIN), Homo sapiens
UniProt: O00222
Assay: Antagonist activity at human recombinant mGlu8 stably expressed in golden hamster AV12 cell membrane co-expressing Galpha15 assessed as reduction in glutamate-induced calcium influx incubated for 90 to 120 min by Fluo-4-AM dye based FLIPR assay
Measurement: EC50 = 1770 nM (pChEMBL 5.75)
Descriptors: MW 359.35, ALogP 0.78, HBA 5, HBD 4, PSA 120.85, QED 0.57
Compound (SMILES): NC(=O)c1ccc2nc(-c3ccc(C4(N)CCC4)cc3)c(-c3ccccc3)n2n1
InChIKey: JBGYKRAZYDNCNV-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: Affinity Biochemical interaction (TR-FRET-based in vitro kinase assays (10 µM ATP)) EUB0000637a AKT1
Measurement: IC50 = 5.2 nM (pChEMBL 8.279999732971191)
Descriptors: MW 383.46, ALogP 3.5, HBA 5, HBD 2, PSA 99.3, QED 0.56
Compound (SMILES): CC(C)(CNC(=O)c1cccc(-c2noc(C(F)(F)F)n2)c1)c1coc(-c2ccccc2)n1
InChIKey: QTCSXAUJBQZZSN-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant human HDAC8 using Ac-LGK(TFA)-AMC as substrate preincubated for 30 mins followed by substrate addition and measured after 90 mins by fluorescence based assay
Measurement: IC50 = 2100 nM (pChEMBL 5.679999828338623)
Descriptors: MW 456.42, ALogP 5.12, HBA 6, HBD 1, PSA 94.05, QED 0.43
Compound (SMILES): NC(=O)c1ccc2nc(-c3ccc(C4(N)CCC4)cc3)c(-c3ccccc3)n2n1
InChIKey: JBGYKRAZYDNCNV-UHFFFAOYSA-N
Target: RAC-beta serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31751
Assay: Affinity Biochemical interaction (TR-FRET-based in vitro kinase assays (10 µM ATP)) EUB0000637a AKT2
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 383.46, ALogP 3.5, HBA 5, HBD 2, PSA 99.3, QED 0.56
Compound (SMILES): CC(C)(CNC(=O)c1cccc(-c2noc(C(F)(F)F)n2)c1)c1coc(-c2ccccc2)n1
InChIKey: QTCSXAUJBQZZSN-UHFFFAOYSA-N
Target: Histone deacetylase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKV0
Assay: Inhibition of recombinant human HDAC9 using Ac-LGK(TFA)-AMC as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by fluorescence based assay
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 456.42, ALogP 5.12, HBA 6, HBD 1, PSA 94.05, QED 0.43
Compound (SMILES): NC(=O)c1ccc2nc(-c3ccc(C4(N)CCC4)cc3)c(-c3ccccc3)n2n1
InChIKey: JBGYKRAZYDNCNV-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: Selectivity interaction (Enzymatic assay (at 2 mM ATP)) EUB0000637a AKT1
Measurement: IC50 = 44 nM (pChEMBL 7.360000133514404)
Descriptors: MW 383.46, ALogP 3.5, HBA 5, HBD 2, PSA 99.3, QED 0.56
Compound (SMILES): NC(=O)c1ccc2nc(-c3ccc(C4(N)CCC4)cc3)c(-c3ccccc3)n2n1
InChIKey: JBGYKRAZYDNCNV-UHFFFAOYSA-N
Target: RAC-beta serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31751
Assay: Selectivity interaction (Enzymatic assay (at 2 mM ATP)) EUB0000637a AKT2
Measurement: IC50 = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 383.46, ALogP 3.5, HBA 5, HBD 2, PSA 99.3, QED 0.56
Compound (SMILES): NC(=O)c1ccc2nc(-c3ccc(C4(N)CCC4)cc3)c(-c3ccccc3)n2n1
InChIKey: JBGYKRAZYDNCNV-UHFFFAOYSA-N
Target: RAC-gamma serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y243
Assay: Selectivity interaction (Enzymatic assay (at 10 µM ATP)) EUB0000637a AKT3
Measurement: IC50 = 427 nM (pChEMBL 6.369999885559082)
Descriptors: MW 383.46, ALogP 3.5, HBA 5, HBD 2, PSA 99.3, QED 0.56
Compound (SMILES): NC(=O)c1ccc2nc(-c3ccc(C4(N)CCC4)cc3)c(-c3ccccc3)n2n1
InChIKey: JBGYKRAZYDNCNV-UHFFFAOYSA-N
Target: RAC-gamma serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y243
Assay: Selectivity interaction (KinomeScan (DiscoverX, competition-binding assay)) EUB0000637a AKT3
Measurement: Kd = 427 nM (pChEMBL 6.369999885559082)
Descriptors: MW 383.46, ALogP 3.5, HBA 5, HBD 2, PSA 99.3, QED 0.56
Compound (SMILES): NC(=O)c1ccc2nc(-c3ccc(C4(N)CCC4)cc3)c(-c3ccccc3)n2n1
InChIKey: JBGYKRAZYDNCNV-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P49759
Assay: Selectivity interaction (KinomeScan (DiscoverX, competition-binding assay)) EUB0000637a CLK1
Measurement: Kd = 310 nM (pChEMBL 6.510000228881836)
Descriptors: MW 383.46, ALogP 3.5, HBA 5, HBD 2, PSA 99.3, QED 0.56
Compound (SMILES): NC(=O)c1ccc2nc(-c3ccc(C4(N)CCC4)cc3)c(-c3ccccc3)n2n1
InChIKey: JBGYKRAZYDNCNV-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P17948
Assay: Selectivity interaction (KinomeScan (DiscoverX, competition-binding assay)) EUB0000637a FLT1
Measurement: Kd = 210 nM (pChEMBL 6.679999828338623)
Descriptors: MW 383.46, ALogP 3.5, HBA 5, HBD 2, PSA 99.3, QED 0.56
Compound (SMILES): NC(=O)c1ccc2nc(-c3ccc(C4(N)CCC4)cc3)c(-c3ccccc3)n2n1
InChIKey: JBGYKRAZYDNCNV-UHFFFAOYSA-N
Target: MAP kinase-interacting serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HBH9
Assay: Selectivity interaction (KinomeScan (DiscoverX, competition-binding assay)) EUB0000637a MKNK2
Measurement: Kd = 330 nM (pChEMBL 6.480000019073486)
Descriptors: MW 383.46, ALogP 3.5, HBA 5, HBD 2, PSA 99.3, QED 0.56
Compound (SMILES): NC(=O)c1ccc2nc(-c3ccc(C4(N)CCC4)cc3)c(-c3ccccc3)n2n1
InChIKey: JBGYKRAZYDNCNV-UHFFFAOYSA-N
Target: RAC-gamma serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y243
Assay: Inhibition of human his-tagged AKT3 (residues 117 to end) expressed in baculovirus infected Sf21 insect cells
Measurement: IC50 = 530 nM (pChEMBL 6.28000020980835)
Descriptors: MW 383.46, ALogP 3.5, HBA 5, HBD 2, PSA 99.3, QED 0.56
Compound (SMILES): NC(=O)c1ccc2nc(-c3ccc(C4(N)CCC4)cc3)c(-c3ccccc3)n2n1
InChIKey: JBGYKRAZYDNCNV-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: Kinase Assay: For the assay 50 nl of a 100 fold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384 well microtiter plate (Greiner Bio-One, Frickenhausen, Germany), 2 μl of a solution of Akt1 in assay buffer [50 mM TRIS/HCl pH 7.5, 5 mM MgCl2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22° C. to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction. Then the kinase reaction was started by the addition of 3 μl of a solution of adenosine-tri-phosphate (ATP, 16.7 μM=>final conc. in the 5 μl assay volume is 10 μM) and substrate (1.67 μM=>final conc. in the 5 μl assay volume is 1 μM) in assay buffer and the resulting mixture was incubated for a reaction time of 60 min at 22° C. The concentration of Akt1 in the assay was adjusted depending of the activity of the enzyme lot and was chosen appropriate to have the assay in the linear range, typical enzyme concentrations were in the range of about 0.05 ng/μl (final conc. in the 5 μl assay volume). The reaction was stopped by the addition of 5 μl of a solution of HTRF detection reagents (200 nM streptavidine-XL665 [Cisbio] and 1.5 nM anti-phosho-Serine antibody [Millipore, cat. #35-001] and 0.75 nM LANCE Eu-W 1024 labeled anti-mouse IgG antibody [Perkin Elmer]) in an aqueous EDTA-solution (100 mM EDTA, 0.1% (w/v) bovine serum albumin in 50 mM HEPES/NaOH pH 7.5). The resulting mixture was incubated 1 h at 22° C. to allow the binding of the biotinylated phosphorylated peptide to the streptavidine-XL665 and the antibodies. Subsequently the amount of phosphorylated substrate was evaluated by measurement of the resonance energy transfer from the anti-mouse-IgG-Eu-Chelate to the streptavidine-XL665. Therefore, the fluorescence emissions at 620 nm and 665 nm after excitation at 350 nm was measured in a HTRF reader, e.g. a Rubystar (BMG Labtechnologies, Offenburg, Germany) or a Viewlux (Perkin-Elmer).
Measurement: IC50 = 5.2 nM (pChEMBL 8.279999732971191)
Descriptors: MW 383.46, ALogP 3.5, HBA 5, HBD 2, PSA 99.3, QED 0.56
Compound (SMILES): NC(=O)c1ccc2nc(-c3ccc(C4(N)CCC4)cc3)c(-c3ccccc3)n2n1
InChIKey: JBGYKRAZYDNCNV-UHFFFAOYSA-N
Target: RAC-beta serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31751
Assay: Kinase Assay: His-tagged human recombinant kinase full-length Akt2 expressed in insect cells and activated by PDK1 was purchased form Invitrogen (part number PV 3975). As substrate for the kinase reaction the biotinylated peptide biotin-Ahx-KKLNRTLSFAEPG (C-terminus in amide form) was used which can be purchased e.g. from the company Biosynthan GmbH (Berlin-Buch, Germany). For the assay 50 nl of a 100 fold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384 well microtiter plate (Greiner Bio-One, Frickenhausen, Germany), 2 μl of a solution of Akt2 in assay buffer [50 mM TRIS/HCl pH 7.5, 5 mM MgCl2, 1 mM dithiothreitol, 0.02% (v/v) Triton X-100 (Sigma)] were added and the mixture was incubated for 15 min at 22° C. to allow pre-binding of the test compounds to the enzyme before the start of the kinase reaction. Then the kinase reaction was started by the addition of 3 μl of a solution of adenosine-tri-phosphate (ATP, 16.7 μM=>final conc. in the 5 μl assay volume is 10 μM) and substrate (1.67 μM=>final conc. in the 5 μl assay volume is 1 μM) in assay buffer and the resulting mixture was incubated for a reaction time of 60 min at 22° C. The concentration of Akt2 in the assay was adjusted depending of the activity of the enzyme lot and was chosen appropriate to have the assay in the linear range, typical enzyme concentrations were in the range of about 0.2 ng/μl (final conc. in the 5 μl assay volume). The reaction was stopped by the addition of 5 μl of a solution of HTRF detection reagents (200 nM streptavidine-XL665 [Cisbio] and 1.5 nM anti-phosho-Serine antibody [Millipore, cat. #35-001] and 0.75 nM LANCE Eu-W 1024 labeled anti-mouse IgG antibody [Perkin Elmer]) in an aqueous EDTA-solution (100 mM EDTA, 0.1% (w/v) bovine serum albumin in 50 mM HEPES/NaOH pH 7.5). The resulting mixture was incubated 1 h at 22° C. to allow the binding of the biotinylated phosphorylated peptide to the streptavidine-XL665 and the antibodies.
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 383.46, ALogP 3.5, HBA 5, HBD 2, PSA 99.3, QED 0.56
Compound (SMILES): CCCCCCCC(=O)Nc1cc(NC(=N)N)cc(C(=O)NCC(=O)NC[C@H](NC(=O)[C@@H]2CCCN2S(=O)(=O)c2ccccc2)C(=O)O)c1
InChIKey: YFKSRHSJFVAXDN-UIOOFZCWSA-N
Target: Integrin alpha-5/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P08648
Assay: Inhibition of alpha5beta1 integrin in human SW480 cells assessed as inhibition of cell adhesion to fibronectin incubated for 60 mins by crystal violet staining based analysis
Measurement: IC50 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 700.82, ALogP 1.56, HBA 8, HBD 8, PSA 252.98, QED 0.06
Compound (SMILES): CNC(=O)CN(Cc1ccccc1OC(F)F)C(=O)c1cc(C(=O)N2CCCC2)[nH]n1
InChIKey: MVIQAXPKPANAOP-UHFFFAOYSA-N
Target: TAK1/TAB1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O43318
Assay: Inhibition of recombinant human full-length His-tagged TAK1-TAB1 fusion protein (437 to 504 residues) expressed in baculovirus expression system using fluorescein-MAP2K1 as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins in presence of ATP by lanthascreen TR-FRET assay
Measurement: IC50 = 59000 nM (pChEMBL 4.230000019073486)
Descriptors: MW 435.43, ALogP 1.64, HBA 5, HBD 2, PSA 107.63, QED 0.66
Compound (SMILES): C[C@@H]1COCCN1c1nc(-c2cnc(N)nc2C(F)F)nc2c1C[C@@H]1COCCN21
InChIKey: XXVSQSOIIVGFNA-GHMZBOCLSA-N
Target: mTORC1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8N122
Assay: Inhibition of mTORC1 in human A2058 cells assessed as reduction in S6 ribosomal protein phosphorylation at Ser235/236 residues incubated for 1 hr by Western blot analysis
Measurement: IC50 = 119 nM (pChEMBL 6.920000076293945)
Descriptors: MW 419.44, ALogP 1.44, HBA 9, HBD 1, PSA 102.52, QED 0.79
Compound (SMILES): CCn1c(-c2cnc(C)nc2)nc2c(-c3ccc4c(c3)[C@](C)(Cc3ccccc3)NC4=O)ncnc21
InChIKey: GSJLFWJQRGTLPZ-NDEPHWFRSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of N-terminal His6 tagged recombinant full-length human PI3Kdelta/human recombinant full-length p85alpha expressed in baculovirus infected Sf21 cells assessed as reduction in PIP3 product formation using PIP2 as substrate preincubated with enzyme for 15 mins followed by further incubation with substrate and ATP for 1 hr by HTRF assay
Measurement: IC50 = 4.5 nM (pChEMBL 8.350000381469727)
Descriptors: MW 475.56, ALogP 4.48, HBA 7, HBD 1, PSA 98.48, QED 0.4
Compound (SMILES): Cc1nn(-c2ccc([N+](=O)[O-])cn2)c2c1C(=O)CC(C)(C)C2Br
InChIKey: SACWVZGRVDPMSQ-UHFFFAOYSA-N
Target: CDK2/Cyclin A2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24941
Assay: Inhibition of human N-terminal GST-tagged CDK2 (1 to 298 residues)/Cyclin A (174 to 432 residues) expressed in Escherichia coli Turner (DE3) cells assessed as reduction in ADP formation using PKTPKKAKKL as substrate by resorufin dye based fluorescence assay
Measurement: IC50 = 3100 nM (pChEMBL 5.510000228881836)
Descriptors: MW 379.21, ALogP 3.53, HBA 6, HBD 0, PSA 90.92, QED 0.45
Compound (SMILES): O=c1[nH]cc(-c2ccccc2)c2ncc(I)n12
InChIKey: XBAODMCDUZTEEI-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24941
Assay: Inhibition of CDK2/cyclin E (unknown origin) using peptide substrate in presence of [gamma33P]ATP by image analyser
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 337.12, ALogP 2.29, HBA 3, HBD 1, PSA 50.16, QED 0.69
Compound (SMILES): CC(=O)N[C@@H]1CCC[C@H](C(=O)Nc2cc(-c3cnn4c3CCCC4O)c(Cl)cn2)C1
InChIKey: BRQSWVAJJNFGEP-IODPJOFQSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: Inhibition of recombinant full length human N-terminal GST-fused CDK9 (1 to 372 residues)/His-tagged CyclinT1 (1 to 726 residues) expressed in baculovirus infected insect cells using FITC-X-GSRTPMY-NH2 as substrate preincubated for 10 mins followed by MgCl2 addition and measured after 90 mins in presence of 5 mM ATP by mobility shift assay
Measurement: IC50 = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 431.92, ALogP 3.06, HBA 6, HBD 3, PSA 109.14, QED 0.69
Compound (SMILES): CCn1c(-c2cnc(C)nc2)nc2c(-c3cnc4c(c3)[C@](C)(NCC(C)(C)F)C(=O)N4)ncnc21
InChIKey: YYXYTTPRFNUTKT-DEOSSOPVSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of N-terminal His6 tagged recombinant full-length human PI3Kdelta/human recombinant full-length p85alpha expressed in baculovirus infected Sf21 cells assessed as reduction in PIP3 product formation using PIP2 as substrate preincubated with enzyme for 15 mins followed by further incubation with substrate and ATP for 1 hr by HTRF assay
Measurement: IC50 = 3.8 nM (pChEMBL 8.420000076293945)
Descriptors: MW 475.53, ALogP 3.18, HBA 9, HBD 2, PSA 123.4, QED 0.44
Compound (SMILES): O=C(Nc1ccc(F)cc1)c1n[nH]cc1NC(=O)c1c(F)ccc(-c2ccncc2)c1F
InChIKey: OMQDZRXQVJBWCY-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 1/cyclin B1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P14635
Assay: Inhibition of CDK1/cyclin B1 (unknown origin) using FAM-labeled peptide and ATP as substrate preincubated for 10 mins followed by substrate addition by mobility shift assay
Measurement: IC50 = 306 nM (pChEMBL 6.510000228881836)
Descriptors: MW 437.38, ALogP 4.39, HBA 4, HBD 3, PSA 99.77, QED 0.43
Compound (SMILES): Cc1ccc(NC(=O)c2ccc(C(F)(F)F)cc2)cc1-n1cc(-c2cnc3cccnn23)cn1
InChIKey: IDMLCHSTWFWJHX-UHFFFAOYSA-N
Target: Bcr/Abl fusion protein (CHIMERIC PROTEIN), Homo sapiens
UniProt: P00519
Assay: Inhibition of BCR (unknown origin)/recombinant human N-terminal His-tagged ABL1 (27 to end residues) expressed in baculovirus infected Sf9 cells using ABLtide as substrate preincubated for 30 mins followed by substrate addition and measured after 1 hr in presence of ATP by kinase-Glo luminescence assay
Measurement: IC50 = 74.1 nM (pChEMBL 7.130000114440918)
Descriptors: MW 462.44, ALogP 5.16, HBA 6, HBD 1, PSA 77.11, QED 0.4
Compound (SMILES): O=C(O)C[C@H](C(=O)N1CC[C@@H](CCc2ccc3c(n2)NCCC3)C1)c1ccc(Br)s1
InChIKey: CGDCNLRQFMWABO-PBHICJAKSA-N
Target: Integrin alpha-V/beta-3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P05106
Assay: Inhibition of integrin alphavbeta3 (unknown origin) by fluorescence polarization assay
Measurement: IC50 = 199.53 nM (pChEMBL 6.699999809265137)
Descriptors: MW 492.44, ALogP 4.3, HBA 5, HBD 2, PSA 82.53, QED 0.6
Compound (SMILES): CC(C)(C)OC(=O)N1CCC(n2cc(-c3cncc(Cl)c3N3CCC4(CCNC4=O)CC3)cn2)CC1
InChIKey: YDJXIXYVADFTGJ-UHFFFAOYSA-N
Target: CDK8/Cyclin C (PROTEIN COMPLEX), Homo sapiens
UniProt: P49336
Assay: Inhibition of CDK8/cyclin C (unknown origin) using RBER-IRStide as substrate incubated for 60 mins in presence of [gamma33P]ATP by scintillation counting method
Measurement: Ki = 700 nM (pChEMBL 6.159999847412109)
Descriptors: MW 515.06, ALogP 4.28, HBA 7, HBD 1, PSA 92.59, QED 0.66
Compound (SMILES): CNC(=O)c1ccn(-c2c(Cl)cncc2-c2ccc(-c3cnn(C)c3)cc2)c1
InChIKey: PPKCFDWJQCHYIR-UHFFFAOYSA-N
Target: CDK8/Cyclin C (PROTEIN COMPLEX), Homo sapiens
UniProt: P49336
Assay: Inhibition of CDK8/cyclin C (unknown origin) using RBER-IRStide as substrate incubated for 60 mins in presence of [gamma33P]ATP by scintillation counting method
Measurement: Ki = 2030 nM (pChEMBL 5.690000057220459)
Descriptors: MW 391.86, ALogP 3.95, HBA 5, HBD 1, PSA 64.74, QED 0.57
Compound (SMILES): Nc1ncnc2c1ncn2[C@@H]1O[C@H](CN2CCCC23CCNCC3)[C@@H](O)[C@H]1O
InChIKey: NBMHRKZWASUUCJ-LSCFUAHRSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O14744
Assay: Inhibition of full-length human N-terminal FLAG-tagged PRMT5/full length N-terminal His6-tagged MEP50 (unknown origin) expressed in baculovirus infected Sf9 insect cells assessed as reduction of S-adenosyl-L-homocysteine formation using human recombinant histone H2A (1 to 130 residues) and S-adenosyl-L-methionine as substrate after 60 mins by rapidfire mass spectrometry analysis
Measurement: IC50 = 52 nM (pChEMBL 7.28000020980835)
Descriptors: MW 389.46, ALogP -0.75, HBA 10, HBD 4, PSA 134.58, QED 0.53
Compound (SMILES): CC(=O)N[C@@H]1CCC[C@H](C(=O)Nc2cc(-c3cnn4c3NCCC4)c(Cl)cn2)C1
InChIKey: HGTYXDXGMWEQPT-UONOGXRCSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: Inhibition of recombinant full length human N-terminal GST-fused CDK9 (1 to 372 residues)/His-tagged CyclinT1 (1 to 726 residues) expressed in baculovirus infected insect cells using FITC-X-GSRTPMY-NH2 as substrate preincubated for 10 mins followed by MgCl2 addition and measured after 90 mins in presence of 5 mM ATP by mobility shift assay
Measurement: IC50 = 350 nM (pChEMBL 6.460000038146973)
Descriptors: MW 416.91, ALogP 3.05, HBA 6, HBD 3, PSA 100.94, QED 0.71
Compound (SMILES): C[C@]1(O)CCC[C@@H]1n1c(=O)c(CC(F)F)cc2cnc(NC3CCN(S(C)(=O)=O)CC3)nc21
InChIKey: GUFBYMCWKSZUBS-KKSFZXQISA-N
Target: CDK4/Cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P11802
Assay: Inhibition of non-phosphorylated CDK4/Cyclin D3 (unknown origin) assessed as reduction in production of ADP using 5-FAM-RRRFRPASPLRGPPK peptide as substrate preincubated with enzyme for 12 mins and measured after 35 mins in presence of ATP by fluorescence-based microfluidic mobility shift assay
Measurement: Ki = 0.16 nM (pChEMBL 9.800000190734863)
Descriptors: MW 485.56, ALogP 1.91, HBA 8, HBD 2, PSA 117.42, QED 0.64
Compound (SMILES): N=C(N)Nc1cc(NC(=O)CCCN)cc(C(=O)NCC(=O)NC[C@H](NC(=O)[C@@H]2CCCN2S(=O)(=O)c2ccccc2)C(=O)O)c1
InChIKey: MGRPJUCLIBBWKX-VXKWHMMOSA-N
Target: Integrin alpha-V/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P05556
Assay: Cell adhesion assay to Hamster Ovary: The blockade of integrin alpha 5 beta 1 provides a novel target for the treatment of asthma. As shown in FIGS. 1A and 1B, delivery of ATN-161, a low affinity yet specific inhibitor of alpha5beta1, reduces the magnitude of airway narrowing in vivo in mice sensitized and challenged with ovalbumin, a widely used model of allergic asthma. In the same model, it was found that mice with a specific deletion of this integrin in smooth muscle also have reduced airway narrowing. The intracellular actin-myosin cross-bridging pathway serves as a useful target. Modulating the interactions of the cell and the extracellular matrix impairs the ability of the smooth muscle to transmit tension effectively. The blockade of integrin alpha 5 beta 1 was tested in vitro with human cell lines as well as in vivo with a mouse model of airway hyperresponsiveness. Novel compounds as described herein, and identified in Table 1, have been synthesized and tested in vitro for their ability to inhibit cell adhesion mediated by alphavbeta1 (adhesion of Chinese Hamster Ovary cells transfected with human alphav to the latency associated peptide of transforming growth factor beta, a response that is entirely dependent on binding of alphavbeta1 to LAP).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 659.73, ALogP -1.06, HBA 9, HBD 9, PSA 279, QED 0.08
Compound (SMILES): COc1nc(-c2csc(Nc3c4c(nn3CCF)CCCC4)n2)ccc1-n1cnc(C)c1
InChIKey: JEIIPIFVEMKMLA-UHFFFAOYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NZ42
Assay: Modulation of gamma secretase in human SH-SY5Y cells overexpressing wild type APP751 assessed as inhibition of amyloid beta (35 to 42 residues) formation incubated for overnight by ELISA
Measurement: IC50 = 47 nM (pChEMBL 7.329999923706055)
Descriptors: MW 453.55, ALogP 4.5, HBA 9, HBD 1, PSA 82.68, QED 0.44
Compound (SMILES): Cc1cn(-c2ccc(-c3csc(Nc4cc(C(C)(C)C)nn4C)n3)cn2)cn1
InChIKey: IVXAYQRTIGYBAK-UHFFFAOYSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NZ42
Assay: Modulation of gamma secretase in human SH-SY5Y cells overexpressing wild type APP751 assessed as inhibition of amyloid beta (35 to 42 residues) formation incubated for overnight by ELISA
Measurement: IC50 = 590 nM (pChEMBL 6.230000019073486)
Descriptors: MW 393.52, ALogP 4.47, HBA 8, HBD 1, PSA 73.45, QED 0.55
Compound (SMILES): Cc1cc(N2C[C@H]3CC[C@@H](C2)[C@@H]3Nc2nc3n(n2)CCC[C@H]3Oc2cccc(Cl)c2)ncn1
InChIKey: UNTHRMMZVRJKBA-IMLKGASGSA-N
Target: Gamma-secretase (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NZ42
Assay: Inhibition of human gamma secretase assessed as reduction in Abeta42 production
Measurement: IC50 = 9.9 nM (pChEMBL 8)
Descriptors: MW 465.99, ALogP 4.27, HBA 8, HBD 1, PSA 80.99, QED 0.6
Compound (SMILES): COc1ccc(Sc2ncnc3[nH]cnc23)cc1
InChIKey: JMGCYSLZRQCADR-UHFFFAOYSA-N
Target: CDC7/DBF4 (Cell division cycle 7-related protein kinase/Activator of S phase kinase) (PROTEIN COMPLEX), Homo sapiens
UniProt: O00311
Assay: Inhibition of recombinant human CDC7/Dbf4 expressed in baculovirus infected Sf9 insect cells assessed as inhibition of fluorescein labelled substrate phosphorylation in presence of ATP measured after 60 mins by TR-FRET assay
Measurement: IC50 = 1720 nM (pChEMBL 5.760000228881836)
Descriptors: MW 258.31, ALogP 2.51, HBA 5, HBD 1, PSA 63.69, QED 0.73
Compound (SMILES): O=C(O)c1cccc(-c2cn(-c3ccc(-c4ccc5c(c4)OCCO5)cc3)nn2)c1
InChIKey: WEYBKUJHNIGCDR-UHFFFAOYSA-N
Target: ORAI1/STIM1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q96D31
Assay: Inhibition of STIM1/Orai1 (unknown origin) expressed in HEK293 cells assessed as reduction in tBHQ-induced calcium response
Measurement: IC50 = 1198 nM (pChEMBL 5.920000076293945)
Descriptors: MW 399.41, ALogP 4.07, HBA 6, HBD 1, PSA 86.47, QED 0.56
Compound (SMILES): CC[C@H]1OC(=O)[C@H](C)[C@@H](OC(=O)Cc2ccccn2)[C@H](C)[C@@H](O[C@@H]2O[C@H](C)C[C@H](N(C)C)[C@H]2O)[C@](C)(OC(=O)CCN2CCN(c3c(F)cc4c(=O)c(C(N)=O)cn(C5CC5)c4c3OC)CC2C)C[C@@H](C)CN(C)[C@H](C)[C@@H](O)[C@]1(C)O
InChIKey: KFZYYEACIBJLLW-HULVZAKVSA-N
Target: DNA gyrase (PROTEIN COMPLEX), Escherichia coli
UniProt: P0AES6
Assay: Inhibition of Escherichia coli DNA gyrase using relaxed DNA as substrate incubated for 15 mins by ethidium bromide-based agarose gel electrophoresis
Measurement: IC50 = 9600 nM (pChEMBL 5.019999980926514)
Descriptors: MW 1138.39
Compound (SMILES): COc1cc(C(=O)N2CCc3c(-c4ccccc4)cccc32)cc(OC)c1CNCCNC(C)=O
InChIKey: FGUQCNMRWWJUBY-UHFFFAOYSA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15116
Assay: Inhibition of PD-1/PDL1 interaction (unknown origin) by HTRF assay
Measurement: IC50 = 7258 nM (pChEMBL 5.139999866485596)
Descriptors: MW 473.57, ALogP 3.8, HBA 5, HBD 2, PSA 79.9, QED 0.46
Compound (SMILES): CC(=O)N[C@@H]1CCC[C@H](C(=O)Nc2cc(-c3cnn4c3CCCC4)c(F)cn2)C1
InChIKey: UKQNWDWADMKKFN-LSDHHAIUSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60563
Assay: Inhibition of recombinant full length human N-terminal GST-fused CDK9 (1 to 372 residues)/His-tagged CyclinT1 (1 to 726 residues) expressed in baculovirus infected insect cells using FITC-X-GSRTPMY-NH2 as substrate preincubated for 10 mins followed by MgCl2 addition and measured after 90 mins in presence of 5 mM ATP by mobility shift assay
Measurement: IC50 = 51 nM (pChEMBL 7.289999961853027)
Descriptors: MW 399.47, ALogP 3.05, HBA 5, HBD 2, PSA 88.91, QED 0.83