lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): N#Cc1cnc2ccc(-c3c(-c4ccc(F)c(Cl)c4)ncn3CCO)nn12
InChIKey: VZZBCNXVZFAIQX-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of recombinant CYP2C9 (unknown origin)
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 382.79, ALogP 2.92, HBA 7, HBD 1, PSA 92.03, QED 0.59
Compound (SMILES): C=CC(=O)N[C@H]1CCOC[C@H]1Nc1ncc2cc(-c3c(Cl)c(OC)cc(OC)c3Cl)ccc2n1
InChIKey: MGZKYOAQVGSSGC-DLBZAZTESA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human liver microsomes
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 503.39, ALogP 4.49, HBA 7, HBD 2, PSA 94.6, QED 0.46
Compound (SMILES): C=CC(=O)N(C)CCOc1c(N)ncnc1-c1cc(F)cc(NC(=O)c2ccc(C3CC3)cc2F)c1C
InChIKey: CUABMPOJOBCXJI-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ITK/TSK (SINGLE PROTEIN), Homo sapiens
UniProt: Q08881
Assay: Binding affinity to DNA-tagged recombinant ITK (unknown origin) measured after 1 hr by biotinylated-ligand affinity bead-based qPCR analysis
Measurement: Kd > 10000 nM (pChEMBL 5)
Descriptors: MW 507.54, ALogP 4.47, HBA 6, HBD 2, PSA 110.44, QED 0.41
Compound (SMILES): Clc1nc(NCc2ccccn2)c2c(-c3ccccc3)cccc2n1
InChIKey: JSYVMXAHYRRFOQ-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24864
Assay: Caliper Kinase Assay: The analyses were performed in U-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 (20 mM HEPES pH 7.4, 10 mM MgCl2, 0.015% Brij35 and 4 mM DTT). The reaction was initiated by the combination of purified protein kinase with substrates and test compounds. The reaction was incubated at room temperature for 60 min. and terminated by adding 30 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 vehicle-only reactions for 0% inhibition. The ATP was used at a final concentration equivalent to the Km and the peptide substrate concentration was 1.5 μM. Dose response curves were generated to determine the concentration required to inhibit 50% of kinase activity (IC50). Compounds were dissolved at 10 mM in dimethylsulfoxide (DMSO) and evaluated at eleven concentrations.
Measurement: IC50 = 50000 nM (pChEMBL 4.300000190734863)
Descriptors: MW 346.82, ALogP 4.96, HBA 4, HBD 1, PSA 50.7, QED 0.53
Compound (SMILES): Cc1cccc(Cn2nc(C)c3c(NC(=O)c4csc5c(N)ncnc45)cccc32)n1
InChIKey: KZVIZFHCMVWFNT-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of recombinant human N-terminal His6-tagged KDR (790 to end residues) expressed in baculovirus infected Sf21 insect cells using MBP as substrate in presence of [gamma-33P]-ATP or [gamma-32P]-ATP
Measurement: IC50 = 527 nM (pChEMBL 6.28000020980835)
Descriptors: MW 429.51, ALogP 3.94, HBA 8, HBD 2, PSA 111.61, QED 0.45
Compound (SMILES): COc1ccc2c(c1OC)-c1ccc(Br)c3c1[C@H](C2)N(C)CC3
InChIKey: QCXMWEJEZDJYLD-HNNXBMFYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Antagonist activity at C-terminal RLuc8-fused D2 long receptor (unknown origin) transfected in human HEK293T cells co-expressing N-terminal Venus-tagged beta-arrestin2 assessed as increase in beta-arrestin2 recruitment measured after 5 mins in presence of coelenterazine H by BRET assay
Measurement: IC50 = 1949.84 nM (pChEMBL 5.710000038146973)
Descriptors: MW 374.28, ALogP 4.22, HBA 3, HBD 0, PSA 21.7, QED 0.79
Compound (SMILES): NS(=O)(=O)c1cc(C(=O)NCCCC(=O)O)c(SC2CCCCC2)cc1Cl
InChIKey: QBFWPSYDISFIKC-UHFFFAOYSA-N
Target: Carbonic anhydrase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9ULX7
Assay: Binding affinity to recombinant human carbonic anhydrase 14 expressed in Escherichia coli expression system assessed as observed dissociation constant fluorescent thermal shift assay
Measurement: Kd = 1.8 nM (pChEMBL 8.739999771118164)
Descriptors: MW 434.97, ALogP 3.01, HBA 5, HBD 3, PSA 126.56, QED 0.54
Compound (SMILES): Cc1cc2ncnn2cc1Nc1ncc2c(n1)n([C@H]1CC[C@@](C)(O)CC1)c(=O)n2C
InChIKey: FAPBUMXELNHUHE-NXHRWCDGSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Aurora-A, Aurora-B, JAK1, JAK2, JAK3 Enzyme Assays: The inhibitory activity of compounds against AURKA, AURKB, JAK1, JAK2 and JAK3 was determined in Z'-LYTE® assays run by ThermoFisher Scientific as part of their SelectScreen® Biochemical Kinase Profiling Service. The Z'-LYTE® biochemical assay format employs a fluorescence-based, coupled-enzyme format and is based on the differential sensitivity of phosphorylated and non-phosphorylated peptides to proteolytic cleavage. The peptide substrate is labeled with two fluorophoresone at each endthat make up a FRET pair. In the primary reaction, the kinase transfers the gamma-phosphate of ATP to a single tyrosine, serine or threonine residue in a synthetic FRET-peptide. In the secondary reaction, a site-specific protease recognises and cleaves non-phosphorylated FRET-peptides. Phosphorylation of FRET-peptides suppresses cleavage by the Development Reagent. Cleavage disrupts FRET between the donor (i.e., coumarin) and acceptor (i.e., fluorescein) fluorophores on the FRET-peptide, whereas uncleaved, phosphorylated FRET-peptides maintain FRET. A ratiometric method, which calculates the ratio (the Emission Ratio) of donor emission to acceptor emission after excitation of the donor fluorophore at 400 nm, is used to quantitate reaction progress. Both cleaved and uncleaved FRET-peptides contribute to the fluorescence signals and therefore to the Emission Ratio. The extent of phosphorylation of the FRET-peptide can be calculated from the Emission Ratio. The Emission Ratio will remain low if the FRET-peptide is phosphorylated (i.e., no kinase inhibition) and will be high if the FRET-peptide is non-phosphorylated (i.e., kinase inhibition).10 point three-fold dilution compound concentration-response curves, with a top concentration of 10 μM were generated from 10 mM stocks of compound solubilised in DMSO. All assays were performed in black, non-binding, low volume Corning 384-well plates (cat. #4514, Corning), in a total reaction volume of 10 μL and 1% (v/v) final DMSO concentration. 2.4 μL Kinase Buffer (50 mM HEPES pH 7.5, 0.01% BRIJ-35, 10 mM MgCl2, 1 mM EGTA), 5 μL 2× Peptide/Kinase mixture (detailed below for each kinase) and 2.5 μL 4×ATP Solution (prepared in Kinase Buffer) were added separately to the compound plates, placed on a plate shaker for 30 sec, and then incubated for 60 mins at room temperature. The kinase reaction was then quenched by the addition of 5 μL of Development Reagent (ThermoFisher Scientific proprietary). Assay plates were placed on a plate shaker for 30 sec, incubated for 60 mins at room temperature, and then read using a fluorescence plate reader. IC50 values were calculated using XLfit software (IDBS Ltd, Surrey, UK), with the curve fit to model number 205 (sigmoidal dose-response model).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 408.47, ALogP 2.09, HBA 10, HBD 2, PSA 115.16, QED 0.53
Compound (SMILES): CCCCN(CCCC)C(=O)CN1C[C@@H](c2cc(OC)c3c(c2)OCO3)[C@H](C(=O)O)[C@H]1CC(C)(C)CCC
InChIKey: OAEWNSKRLBVVBV-OBTVHEKISA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: GPCRScan assay: inhibition of KOR
Measurement: Ki = 2818.38 nM (pChEMBL 5.550000190734863)
Descriptors: MW 532.72, ALogP 5.54, HBA 6, HBD 1, PSA 88.54, QED 0.32
Compound (SMILES): Cc1c(C2(C(F)(F)F)CC2)nc(C2CC2)n1-c1c(Cl)ccc(N2CC3(CC(C(=O)O)C3)C2)c1Cl
InChIKey: ATOAVZQFLCOJQE-UHFFFAOYSA-N
Target: Progesterone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06401
Assay: Inhibition of Gal4-tagged PR LBD (unknown origin) by cell based luciferase reporter gene assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 514.38, ALogP 6.26, HBA 4, HBD 1, PSA 58.36, QED 0.51
Compound (SMILES): NS(=O)(=O)c1cc(C(=O)NCCO)c(S(=O)(=O)Cc2ccccc2)cc1Br
InChIKey: PYLVVDNHUGVMGF-UHFFFAOYSA-N
Target: Carbonic anhydrase 13 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N1Q1
Assay: Binding affinity to recombinant human carbonic anhydrase 13 expressed in Escherichia coli expression system assessed as observed dissociation constant fluorescent thermal shift assay
Measurement: Kd = 140 nM (pChEMBL 6.849999904632568)
Descriptors: MW 477.36, ALogP 0.79, HBA 6, HBD 3, PSA 143.63, QED 0.54
Compound (SMILES): COC(=O)CCCNC(=O)c1cc(S(N)(=O)=O)c(Cl)cc1S(=O)(=O)C1CCCCC1
InChIKey: OJCBLUGIJDOTFF-UHFFFAOYSA-N
Target: Carbonic anhydrase 13 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N1Q1
Assay: Binding affinity to recombinant human carbonic anhydrase 13 expressed in Escherichia coli expression system assessed as observed dissociation constant fluorescent thermal shift assay
Measurement: Kd = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 480.99, ALogP 1.78, HBA 7, HBD 2, PSA 149.7, QED 0.42
Compound (SMILES): O[C@]1(C(F)(F)F)CCCC[C@H]1Nc1ccc(F)cc1
InChIKey: IESAJAZKMLPVIB-VXGBXAGGSA-N
Target: Transient receptor potential cation channel subfamily A member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75762
Assay: Ephys (human TRPA1)
Measurement: IC50 = 82 nM (pChEMBL 7.090000152587891)
Descriptors: MW 277.26, ALogP 3.47, HBA 2, HBD 2, PSA 32.26, QED 0.81
Compound (SMILES): CC(C)c1cc(C(=O)N(C)c2ccc(NC(=O)CCCCCCC(=O)NO)cc2)c(O)cc1O
InChIKey: NRTQVEBKTMOYBI-UHFFFAOYSA-N
Target: Histone deacetylase 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96DB2
Assay: Inhibition of human recombinant N-terminal Streptavidin2-tagged HDAC11 (1 to 347 residues) expressed in baculovirus infected insect cells using Boc-Lys(TFA)-AMC as substrate after 60 mins by fluorescence assay
Measurement: IC50 = 3610 nM (pChEMBL 5.440000057220459)
Descriptors: MW 471.55, ALogP 4.28, HBA 6, HBD 5, PSA 139.2, QED 0.19
Compound (SMILES): N#Cc1cnc2ccc(-c3c(-c4ccc(F)c(Cl)c4)ncn3CCO)nn12
InChIKey: VZZBCNXVZFAIQX-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of recombinant CYP2C19 (unknown origin)
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 382.79, ALogP 2.92, HBA 7, HBD 1, PSA 92.03, QED 0.59
Compound (SMILES): C=CC(=O)N[C@H]1CCOC[C@H]1Nc1ncc2cc(-c3c(Cl)c(OC)cc(OC)c3Cl)ccc2n1
InChIKey: MGZKYOAQVGSSGC-DLBZAZTESA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 503.39, ALogP 4.49, HBA 7, HBD 2, PSA 94.6, QED 0.46
Compound (SMILES): C=CC(=O)N(C)CCOc1c(N)ncnc1-c1cc(F)cc(NC(=O)c2ccc(C3CC3)cc2F)c1C
InChIKey: CUABMPOJOBCXJI-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Binding affinity to DNA-tagged recombinant EGFR (unknown origin) measured after 1 hr by biotinylated-ligand affinity bead-based qPCR analysis
Measurement: Kd > 10000 nM (pChEMBL 5)
Descriptors: MW 507.54, ALogP 4.47, HBA 6, HBD 2, PSA 110.44, QED 0.41
Compound (SMILES): Clc1nc(NCc2ccccn2)c2c(-c3ccccc3)cccc2n1
InChIKey: JSYVMXAHYRRFOQ-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00535
Assay: Caliper Kinase Assay: The analyses were performed in U-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 (20 mM HEPES pH 7.4, 10 mM MgCl2, 0.015% Brij35 and 4 mM DTT). The reaction was initiated by the combination of purified protein kinase with substrates and test compounds. The reaction was incubated at room temperature for 60 min. and terminated by adding 30 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 vehicle-only reactions for 0% inhibition. The ATP was used at a final concentration equivalent to the Km and the peptide substrate concentration was 1.5 μM. Dose response curves were generated to determine the concentration required to inhibit 50% of kinase activity (IC50). Compounds were dissolved at 10 mM in dimethylsulfoxide (DMSO) and evaluated at eleven concentrations.
Measurement: IC50 = 50000 nM (pChEMBL 4.300000190734863)
Descriptors: MW 346.82, ALogP 4.96, HBA 4, HBD 1, PSA 50.7, QED 0.53
Compound (SMILES): Cc1cccc(Cn2nc(C)c3c(NC(=O)c4csc5c(N)ncnc45)cccc32)n1
InChIKey: KZVIZFHCMVWFNT-UHFFFAOYSA-N
Target: Maternal embryonic leucine zipper kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q14680
Assay: Inhibition of recombinant human N-terminal GST-tagged MELK (1 to 340 residues) expressed in baculovirus infected Sf21 insect cells using KKLNRTLSFAEPG as substrate in presence of [gamma-33P]-ATP or [gamma-32P]-ATP
Measurement: IC50 = 258 nM (pChEMBL 6.590000152587891)
Descriptors: MW 429.51, ALogP 3.94, HBA 8, HBD 2, PSA 111.61, QED 0.45
Compound (SMILES): COc1ccc2c(c1OC)-c1ccc(Br)c3c1[C@H](C2)N(C)CC3
InChIKey: QCXMWEJEZDJYLD-HNNXBMFYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Antagonist activity at C-terminal RLuc8-fused D2 long receptor (unknown origin) transfected in human HEK293T cells co-expressing N-terminal Venus-tagged beta-arrestin2 assessed as increase in beta-arrestin2 recruitment measured after 5 mins in presence of coelenterazine H by BRET assay
Measurement: IC50 = 1957 nM (pChEMBL 5.710000038146973)
Descriptors: MW 374.28, ALogP 4.22, HBA 3, HBD 0, PSA 21.7, QED 0.79
Compound (SMILES): NS(=O)(=O)c1cc(C(=O)NCCCC(=O)O)c(SC2CCCCC2)cc1Cl
InChIKey: QBFWPSYDISFIKC-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Binding affinity to recombinant human carbonic anhydrase 1 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay
Measurement: Kd = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 434.97, ALogP 3.01, HBA 5, HBD 3, PSA 126.56, QED 0.54
Compound (SMILES): Cc1cc2ncnn2cc1Nc1ncc2c(n1)n([C@H]1CC[C@@](C)(O)CC1)c(=O)n2C
InChIKey: FAPBUMXELNHUHE-NXHRWCDGSA-N
Target: Aurora kinase A (SINGLE PROTEIN), Homo sapiens
UniProt: O14965
Assay: Aurora-A, Aurora-B, JAK1, JAK2, JAK3 Enzyme Assays: The inhibitory activity of compounds against AURKA, AURKB, JAK1, JAK2 and JAK3 was determined in Z'-LYTE® assays run by ThermoFisher Scientific as part of their SelectScreen® Biochemical Kinase Profiling Service. The Z'-LYTE® biochemical assay format employs a fluorescence-based, coupled-enzyme format and is based on the differential sensitivity of phosphorylated and non-phosphorylated peptides to proteolytic cleavage. The peptide substrate is labeled with two fluorophoresone at each endthat make up a FRET pair. In the primary reaction, the kinase transfers the gamma-phosphate of ATP to a single tyrosine, serine or threonine residue in a synthetic FRET-peptide. In the secondary reaction, a site-specific protease recognises and cleaves non-phosphorylated FRET-peptides. Phosphorylation of FRET-peptides suppresses cleavage by the Development Reagent. Cleavage disrupts FRET between the donor (i.e., coumarin) and acceptor (i.e., fluorescein) fluorophores on the FRET-peptide, whereas uncleaved, phosphorylated FRET-peptides maintain FRET. A ratiometric method, which calculates the ratio (the Emission Ratio) of donor emission to acceptor emission after excitation of the donor fluorophore at 400 nm, is used to quantitate reaction progress. Both cleaved and uncleaved FRET-peptides contribute to the fluorescence signals and therefore to the Emission Ratio. The extent of phosphorylation of the FRET-peptide can be calculated from the Emission Ratio. The Emission Ratio will remain low if the FRET-peptide is phosphorylated (i.e., no kinase inhibition) and will be high if the FRET-peptide is non-phosphorylated (i.e., kinase inhibition).10 point three-fold dilution compound concentration-response curves, with a top concentration of 10 μM were generated from 10 mM stocks of compound solubilised in DMSO. All assays were performed in black, non-binding, low volume Corning 384-well plates (cat. #4514, Corning), in a total reaction volume of 10 μL and 1% (v/v) final DMSO concentration. 2.4 μL Kinase Buffer (50 mM HEPES pH 7.5, 0.01% BRIJ-35, 10 mM MgCl2, 1 mM EGTA), 5 μL 2× Peptide/Kinase mixture (detailed below for each kinase) and 2.5 μL 4×ATP Solution (prepared in Kinase Buffer) were added separately to the compound plates, placed on a plate shaker for 30 sec, and then incubated for 60 mins at room temperature. The kinase reaction was then quenched by the addition of 5 μL of Development Reagent (ThermoFisher Scientific proprietary). Assay plates were placed on a plate shaker for 30 sec, incubated for 60 mins at room temperature, and then read using a fluorescence plate reader. IC50 values were calculated using XLfit software (IDBS Ltd, Surrey, UK), with the curve fit to model number 205 (sigmoidal dose-response model).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 408.47, ALogP 2.09, HBA 10, HBD 2, PSA 115.16, QED 0.53
Compound (SMILES): CCCCN(CCCC)C(=O)CN1C[C@@H](c2cc(OC)c3c(c2)OCO3)[C@H](C(=O)O)[C@H]1CC(C)(C)CCC
InChIKey: OAEWNSKRLBVVBV-OBTVHEKISA-N
Target: Alpha-2B adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P18089
Assay: GPCRScan assay: inhibition of Alpha2B
Measurement: Ki = 4643.5 nM (pChEMBL 5.329999923706055)
Descriptors: MW 532.72, ALogP 5.54, HBA 6, HBD 1, PSA 88.54, QED 0.32
Compound (SMILES): Cc1c(C2(C(F)(F)F)CC2)nc(C2CC2)n1-c1c(Cl)ccc(N2CC3(CC(C(=O)O)C3)C2)c1Cl
InChIKey: ATOAVZQFLCOJQE-UHFFFAOYSA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Inhibition of Gal4-tagged PXR LBD (unknown origin) by cell based luciferase reporter gene assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 514.38, ALogP 6.26, HBA 4, HBD 1, PSA 58.36, QED 0.51
Compound (SMILES): NS(=O)(=O)c1cc(C(=O)NCCO)c(S(=O)(=O)Cc2ccccc2)cc1Br
InChIKey: PYLVVDNHUGVMGF-UHFFFAOYSA-N
Target: Carbonic anhydrase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9ULX7
Assay: Binding affinity to recombinant human carbonic anhydrase 14 expressed in Escherichia coli expression system assessed as observed dissociation constant fluorescent thermal shift assay
Measurement: Kd = 63 nM (pChEMBL 7.199999809265137)
Descriptors: MW 477.36, ALogP 0.79, HBA 6, HBD 3, PSA 143.63, QED 0.54
Compound (SMILES): COC(=O)CCCNC(=O)c1cc(S(N)(=O)=O)c(Cl)cc1S(=O)(=O)C1CCCCC1
InChIKey: OJCBLUGIJDOTFF-UHFFFAOYSA-N
Target: Carbonic anhydrase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9ULX7
Assay: Binding affinity to recombinant human carbonic anhydrase 14 expressed in Escherichia coli expression system assessed as observed dissociation constant fluorescent thermal shift assay
Measurement: Kd = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 480.99, ALogP 1.78, HBA 7, HBD 2, PSA 149.7, QED 0.42
Compound (SMILES): O[C@]1(C(F)(F)F)CCCC[C@H]1Nc1ccc(F)cc1
InChIKey: IESAJAZKMLPVIB-VXGBXAGGSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NER1
Assay: TRP selectivity screen (TRPV1)
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 277.26, ALogP 3.47, HBA 2, HBD 2, PSA 32.26, QED 0.81
Compound (SMILES): CC(C)c1cc(C(=O)N(C)c2ccc(NC(=O)CCCCCCC(=O)NO)cc2)c(O)cc1O
InChIKey: NRTQVEBKTMOYBI-UHFFFAOYSA-N
Target: NAD-dependent protein deacetylase sirtuin-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96EB6
Assay: Inhibition of human recombinant N-terminal His-tagged SIRT1 (1 to 747 residues) expressed in Escherichia coli using Ac-RHK-K(Ac)-AMC as substrate after 30 mins in presence of NAD+ by fluorimetry analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 471.55, ALogP 4.28, HBA 6, HBD 5, PSA 139.2, QED 0.19
Compound (SMILES): N#Cc1cnc2ccc(-c3c(-c4ccc(F)c(Cl)c4)ncn3CCO)nn12
InChIKey: VZZBCNXVZFAIQX-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of recombinant CYP2D6 (unknown origin)
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 382.79, ALogP 2.92, HBA 7, HBD 1, PSA 92.03, QED 0.59
Compound (SMILES): C=CC(=O)N[C@H]1CCOC[C@H]1Nc1ncc2cc(-c3c(Cl)c(OC)cc(OC)c3Cl)ccc2n1
InChIKey: MGZKYOAQVGSSGC-DLBZAZTESA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using Midazolam as substrate
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 503.39, ALogP 4.49, HBA 7, HBD 2, PSA 94.6, QED 0.46
Compound (SMILES): C=CC(=O)N(C)CCOc1c(N)ncnc1-c1cc(F)cc(NC(=O)c2ccc(C3CC3)cc2F)c1C
InChIKey: CUABMPOJOBCXJI-UHFFFAOYSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: Binding affinity to DNA-tagged recombinant ERBB2 (unknown origin) measured after 1 hr by biotinylated-ligand affinity bead-based qPCR analysis
Measurement: Kd > 10000 nM (pChEMBL 5)
Descriptors: MW 507.54, ALogP 4.47, HBA 6, HBD 2, PSA 110.44, QED 0.41
Compound (SMILES): Clc1nc(NCc2ccccn2)c2c(-c3ccccc3)cccc2n1
InChIKey: JSYVMXAHYRRFOQ-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 5/CDK5 activator 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15078
Assay: Caliper Kinase Assay: The analyses were performed in U-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 (20 mM HEPES pH 7.4, 10 mM MgCl2, 0.015% Brij35 and 4 mM DTT). The reaction was initiated by the combination of purified protein kinase with substrates and test compounds. The reaction was incubated at room temperature for 60 min. and terminated by adding 30 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 vehicle-only reactions for 0% inhibition. The ATP was used at a final concentration equivalent to the Km and the peptide substrate concentration was 1.5 μM. Dose response curves were generated to determine the concentration required to inhibit 50% of kinase activity (IC50). Compounds were dissolved at 10 mM in dimethylsulfoxide (DMSO) and evaluated at eleven concentrations.
Measurement: IC50 = 50000 nM (pChEMBL 4.300000190734863)
Descriptors: MW 346.82, ALogP 4.96, HBA 4, HBD 1, PSA 50.7, QED 0.53
Compound (SMILES): Cc1cccc(Cn2nc(C)c3c(NC(=O)c4csc5c(N)ncnc45)cccc32)n1
InChIKey: KZVIZFHCMVWFNT-UHFFFAOYSA-N
Target: Angiopoietin-1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q02763
Assay: Inhibition of recombinant human N-terminal His6-tagged Tie2 (771 to end residues) expressed in baculovirus infected Sf21 insect cells using Poly (Glu4-Tyr) (4:1) as substrate in presence of [gamma-33P]-ATP or [gamma-32P]-ATP
Measurement: IC50 = 208 nM (pChEMBL 6.679999828338623)
Descriptors: MW 429.51, ALogP 3.94, HBA 8, HBD 2, PSA 111.61, QED 0.45
Compound (SMILES): COc1ccc2c(c1OC)-c1ccc(Br)c3c1[C@H](C2)N(C)CC3
InChIKey: QCXMWEJEZDJYLD-HNNXBMFYSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Antagonist activity at D1R (unknown origin) transfected in human HEK293T cells assessed as increase in cAMP accumulation incubated for 2 hrs by cAMP Glo-sensor assay
Measurement: IC50 = 7413.1 nM (pChEMBL 5.130000114440918)
Descriptors: MW 374.28, ALogP 4.22, HBA 3, HBD 0, PSA 21.7, QED 0.79
Compound (SMILES): NS(=O)(=O)c1cc(C(=O)NCCCC(=O)O)c(SC2CCCCC2)cc1Cl
InChIKey: QBFWPSYDISFIKC-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Binding affinity to recombinant human carbonic anhydrase 2 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay
Measurement: Kd = 0.06 nM (pChEMBL 10.220000267028809)
Descriptors: MW 434.97, ALogP 3.01, HBA 5, HBD 3, PSA 126.56, QED 0.54
Compound (SMILES): Cc1cc2ncnn2cc1Nc1ncc2c(n1)n([C@H]1CC[C@@](C)(O)CC1)c(=O)n2C
InChIKey: FAPBUMXELNHUHE-NXHRWCDGSA-N
Target: Aurora kinase B (SINGLE PROTEIN), Homo sapiens
UniProt: Q96GD4
Assay: Aurora-A, Aurora-B, JAK1, JAK2, JAK3 Enzyme Assays: The inhibitory activity of compounds against AURKA, AURKB, JAK1, JAK2 and JAK3 was determined in Z'-LYTE® assays run by ThermoFisher Scientific as part of their SelectScreen® Biochemical Kinase Profiling Service. The Z'-LYTE® biochemical assay format employs a fluorescence-based, coupled-enzyme format and is based on the differential sensitivity of phosphorylated and non-phosphorylated peptides to proteolytic cleavage. The peptide substrate is labeled with two fluorophoresone at each endthat make up a FRET pair. In the primary reaction, the kinase transfers the gamma-phosphate of ATP to a single tyrosine, serine or threonine residue in a synthetic FRET-peptide. In the secondary reaction, a site-specific protease recognises and cleaves non-phosphorylated FRET-peptides. Phosphorylation of FRET-peptides suppresses cleavage by the Development Reagent. Cleavage disrupts FRET between the donor (i.e., coumarin) and acceptor (i.e., fluorescein) fluorophores on the FRET-peptide, whereas uncleaved, phosphorylated FRET-peptides maintain FRET. A ratiometric method, which calculates the ratio (the Emission Ratio) of donor emission to acceptor emission after excitation of the donor fluorophore at 400 nm, is used to quantitate reaction progress. Both cleaved and uncleaved FRET-peptides contribute to the fluorescence signals and therefore to the Emission Ratio. The extent of phosphorylation of the FRET-peptide can be calculated from the Emission Ratio. The Emission Ratio will remain low if the FRET-peptide is phosphorylated (i.e., no kinase inhibition) and will be high if the FRET-peptide is non-phosphorylated (i.e., kinase inhibition).10 point three-fold dilution compound concentration-response curves, with a top concentration of 10 μM were generated from 10 mM stocks of compound solubilised in DMSO. All assays were performed in black, non-binding, low volume Corning 384-well plates (cat. #4514, Corning), in a total reaction volume of 10 μL and 1% (v/v) final DMSO concentration. 2.4 μL Kinase Buffer (50 mM HEPES pH 7.5, 0.01% BRIJ-35, 10 mM MgCl2, 1 mM EGTA), 5 μL 2× Peptide/Kinase mixture (detailed below for each kinase) and 2.5 μL 4×ATP Solution (prepared in Kinase Buffer) were added separately to the compound plates, placed on a plate shaker for 30 sec, and then incubated for 60 mins at room temperature. The kinase reaction was then quenched by the addition of 5 μL of Development Reagent (ThermoFisher Scientific proprietary). Assay plates were placed on a plate shaker for 30 sec, incubated for 60 mins at room temperature, and then read using a fluorescence plate reader. IC50 values were calculated using XLfit software (IDBS Ltd, Surrey, UK), with the curve fit to model number 205 (sigmoidal dose-response model).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 408.47, ALogP 2.09, HBA 10, HBD 2, PSA 115.16, QED 0.53
Compound (SMILES): CCCCN(CCCC)C(=O)CN1C[C@@H](c2cc(OC)c3c(c2)OCO3)[C@H](C(=O)O)[C@H]1CC(C)(C)CCC
InChIKey: OAEWNSKRLBVVBV-OBTVHEKISA-N
Target: Alpha-2B adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P18089
Assay: GPCRScan assay: inhibition of Alpha2B
Measurement: Ki = 4168.69 nM (pChEMBL 5.380000114440918)
Descriptors: MW 532.72, ALogP 5.54, HBA 6, HBD 1, PSA 88.54, QED 0.32
Compound (SMILES): Cc1c(C2(C(F)(F)F)CC2)nc(C2CC2)n1-c1c(Cl)ccc(N2CC3(CC(C(=O)O)C3)C2)c1Cl
InChIKey: ATOAVZQFLCOJQE-UHFFFAOYSA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Inhibition of Gal4-tagged GR LBD (unknown origin) by cell based luciferase reporter gene assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 514.38, ALogP 6.26, HBA 4, HBD 1, PSA 58.36, QED 0.51
Compound (SMILES): NS(=O)(=O)c1cc(C(=O)NCCO)c(S(=O)(=O)Cc2ccccc2)cc1Br
InChIKey: PYLVVDNHUGVMGF-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Binding affinity to recombinant human carbonic anhydrase 1 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay
Measurement: Kd = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 477.36, ALogP 0.79, HBA 6, HBD 3, PSA 143.63, QED 0.54
Compound (SMILES): COC(=O)CCCNC(=O)c1cc(S(N)(=O)=O)c(Cl)cc1S(=O)(=O)C1CCCCC1
InChIKey: OJCBLUGIJDOTFF-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Binding affinity to recombinant human carbonic anhydrase 1 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay
Measurement: Kd = 99 nM (pChEMBL 7)
Descriptors: MW 480.99, ALogP 1.78, HBA 7, HBD 2, PSA 149.7, QED 0.42
Compound (SMILES): O[C@]1(C(F)(F)F)CCCC[C@H]1Nc1ccc(F)cc1
InChIKey: IESAJAZKMLPVIB-VXGBXAGGSA-N
Target: Transient receptor potential cation channel subfamily V member 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HBA0
Assay: TRP selectivity screen (TRPV4)
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 277.26, ALogP 3.47, HBA 2, HBD 2, PSA 32.26, QED 0.81
Compound (SMILES): N#Cc1cnc2ccc(-c3c(-c4ccc(F)c(Cl)c4)ncn3CCO)nn12
InChIKey: VZZBCNXVZFAIQX-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of recombinant CYP3A4 (unknown origin)
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 382.79, ALogP 2.92, HBA 7, HBD 1, PSA 92.03, QED 0.59
Compound (SMILES): C=CC(=O)N[C@H]1CCOC[C@H]1Nc1ncc2cc(-c3c(Cl)c(OC)cc(OC)c3Cl)ccc2n1
InChIKey: MGZKYOAQVGSSGC-DLBZAZTESA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 503.39, ALogP 4.49, HBA 7, HBD 2, PSA 94.6, QED 0.46
Compound (SMILES): C=CC(=O)N(C)CCOc1c(N)ncnc1-c1cc(F)cc(NC(=O)c2ccc(C3CC3)cc2F)c1C
InChIKey: CUABMPOJOBCXJI-UHFFFAOYSA-N
Target: Receptor tyrosine-protein kinase erbB-4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15303
Assay: Binding affinity to DNA-tagged recombinant ERBB4 (unknown origin) measured after 1 hr by biotinylated-ligand affinity bead-based qPCR analysis
Measurement: Kd > 10000 nM (pChEMBL 5)
Descriptors: MW 507.54, ALogP 4.47, HBA 6, HBD 2, PSA 110.44, QED 0.41
Compound (SMILES): Clc1nc(NCc2ccccn2)c2c(-c3ccccc3)cccc2n1
InChIKey: JSYVMXAHYRRFOQ-UHFFFAOYSA-N
Target: Casein kinase I isoform alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P48729
Assay: Caliper Kinase Assay: The analyses were performed in U-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 (20 mM HEPES pH 7.4, 10 mM MgCl2, 0.015% Brij35 and 4 mM DTT). The reaction was initiated by the combination of purified protein kinase with substrates and test compounds. The reaction was incubated at room temperature for 60 min. and terminated by adding 30 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 vehicle-only reactions for 0% inhibition. The ATP was used at a final concentration equivalent to the Km and the peptide substrate concentration was 1.5 μM. Dose response curves were generated to determine the concentration required to inhibit 50% of kinase activity (IC50). Compounds were dissolved at 10 mM in dimethylsulfoxide (DMSO) and evaluated at eleven concentrations.
Measurement: IC50 = 50000 nM (pChEMBL 4.300000190734863)
Descriptors: MW 346.82, ALogP 4.96, HBA 4, HBD 1, PSA 50.7, QED 0.53
Compound (SMILES): COc1ccc2c(c1OC)-c1ccc(Br)c3c1[C@H](C2)N(C)CC3
InChIKey: QCXMWEJEZDJYLD-HNNXBMFYSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Antagonist activity at D1R (unknown origin) transfected in human HEK293T cells assessed as increase in cAMP accumulation incubated for 2 hrs by cAMP Glo-sensor assay
Measurement: IC50 = 7461 nM (pChEMBL 5.130000114440918)
Descriptors: MW 374.28, ALogP 4.22, HBA 3, HBD 0, PSA 21.7, QED 0.79
Compound (SMILES): NS(=O)(=O)c1cc(C(=O)NCCCC(=O)O)c(SC2CCCCC2)cc1Cl
InChIKey: QBFWPSYDISFIKC-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Binding affinity to recombinant human carbonic anhydrase 4 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay
Measurement: Kd = 0.35 nM (pChEMBL 9.460000038146973)
Descriptors: MW 434.97, ALogP 3.01, HBA 5, HBD 3, PSA 126.56, QED 0.54
Compound (SMILES): CCCCN(CCCC)C(=O)CN1C[C@@H](c2cc(OC)c3c(c2)OCO3)[C@H](C(=O)O)[C@H]1CC(C)(C)CCC
InChIKey: OAEWNSKRLBVVBV-OBTVHEKISA-N
Target: Alpha-2C adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P18825
Assay: GPCRScan assay: inhibition of Alpha2C
Measurement: Ki = 5766 nM (pChEMBL 5.239999771118164)
Descriptors: MW 532.72, ALogP 5.54, HBA 6, HBD 1, PSA 88.54, QED 0.32
Compound (SMILES): Cc1c(C2(C(F)(F)F)CC2)nc(C2CC2)n1-c1c(Cl)ccc(N2CC3(CC(C(=O)O)C3)C2)c1Cl
InChIKey: ATOAVZQFLCOJQE-UHFFFAOYSA-N
Target: Vitamin D3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P11473
Assay: Inhibition of Gal4-tagged VDR LBD (unknown origin) by cell based luciferase reporter gene assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 514.38, ALogP 6.26, HBA 4, HBD 1, PSA 58.36, QED 0.51
Compound (SMILES): NS(=O)(=O)c1cc(C(=O)NCCO)c(S(=O)(=O)Cc2ccccc2)cc1Br
InChIKey: PYLVVDNHUGVMGF-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Binding affinity to recombinant human carbonic anhydrase 2 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay
Measurement: Kd = 1.5 nM (pChEMBL 8.819999694824219)
Descriptors: MW 477.36, ALogP 0.79, HBA 6, HBD 3, PSA 143.63, QED 0.54
Compound (SMILES): COC(=O)CCCNC(=O)c1cc(S(N)(=O)=O)c(Cl)cc1S(=O)(=O)C1CCCCC1
InChIKey: OJCBLUGIJDOTFF-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Binding affinity to recombinant human carbonic anhydrase 2 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay
Measurement: Kd = 0.11 nM (pChEMBL 9.960000038146973)
Descriptors: MW 480.99, ALogP 1.78, HBA 7, HBD 2, PSA 149.7, QED 0.42
Compound (SMILES): O[C@]1(C(F)(F)F)CCCC[C@H]1Nc1ccc(F)cc1
InChIKey: IESAJAZKMLPVIB-VXGBXAGGSA-N
Target: Short transient receptor potential channel 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13507
Assay: TRP selectivity screen (TRPC3)
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 277.26, ALogP 3.47, HBA 2, HBD 2, PSA 32.26, QED 0.81
Compound (SMILES): N#Cc1cnc2ccc(-c3c(-c4ccc(F)c(Cl)c4)ncn3CCO)nn12
InChIKey: VZZBCNXVZFAIQX-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by electrophysiology analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 382.79, ALogP 2.92, HBA 7, HBD 1, PSA 92.03, QED 0.59
Compound (SMILES): C=CC(=O)N[C@H]1CCOC[C@H]1Nc1ncc2cc(-c3c(Cl)c(OC)cc(OC)c3Cl)ccc2n1
InChIKey: MGZKYOAQVGSSGC-DLBZAZTESA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG channel assessed as prolongation of QT interval by patch clamp method
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 503.39, ALogP 4.49, HBA 7, HBD 2, PSA 94.6, QED 0.46
Compound (SMILES): C=CC(=O)N(C)CCOc1c(N)ncnc1-c1cc(F)cc(NC(=O)c2ccc(C3CC3)cc2F)c1C
InChIKey: CUABMPOJOBCXJI-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Binding affinity to DNA-tagged recombinant JAK3 (unknown origin) measured after 1 hr by biotinylated-ligand affinity bead-based qPCR analysis
Measurement: Kd > 10000 nM (pChEMBL 5)
Descriptors: MW 507.54, ALogP 4.47, HBA 6, HBD 2, PSA 110.44, QED 0.41
Compound (SMILES): Clc1nc(NCc2ccccn2)c2c(-c3ccccc3)cccc2n1
InChIKey: JSYVMXAHYRRFOQ-UHFFFAOYSA-N
Target: Casein kinase II subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P68400
Assay: Caliper Kinase Assay: The analyses were performed in U-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 (20 mM HEPES pH 7.4, 10 mM MgCl2, 0.015% Brij35 and 4 mM DTT). The reaction was initiated by the combination of purified protein kinase with substrates and test compounds. The reaction was incubated at room temperature for 60 min. and terminated by adding 30 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 vehicle-only reactions for 0% inhibition. The ATP was used at a final concentration equivalent to the Km and the peptide substrate concentration was 1.5 μM. Dose response curves were generated to determine the concentration required to inhibit 50% of kinase activity (IC50). Compounds were dissolved at 10 mM in dimethylsulfoxide (DMSO) and evaluated at eleven concentrations.
Measurement: IC50 = 50000 nM (pChEMBL 4.300000190734863)
Descriptors: MW 346.82, ALogP 4.96, HBA 4, HBD 1, PSA 50.7, QED 0.53
Compound (SMILES): COc1ccc2c(c1OC)-c1ccc(Br)c3c1[C@H](C2)N(C)CC3
InChIKey: QCXMWEJEZDJYLD-HNNXBMFYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Antagonist activity at D2 long receptor (unknown origin) transfected in human HEK293T cells assessed as increase in cAMP accumulation incubated for 2 hrs by cAMP Glo-sensor assay
Measurement: IC50 = 8912.51 nM (pChEMBL 5.050000190734863)
Descriptors: MW 374.28, ALogP 4.22, HBA 3, HBD 0, PSA 21.7, QED 0.79
Compound (SMILES): NS(=O)(=O)c1cc(C(=O)NCCCC(=O)O)c(SC2CCCCC2)cc1Cl
InChIKey: QBFWPSYDISFIKC-UHFFFAOYSA-N
Target: Carbonic anhydrase 5A, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P35218
Assay: Binding affinity to recombinant human carbonic anhydrase 5a expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay
Measurement: Kd = 1.6 nM (pChEMBL 8.800000190734863)
Descriptors: MW 434.97, ALogP 3.01, HBA 5, HBD 3, PSA 126.56, QED 0.54
Compound (SMILES): CCCCN(CCCC)C(=O)CN1C[C@@H](c2cc(OC)c3c(c2)OCO3)[C@H](C(=O)O)[C@H]1CC(C)(C)CCC
InChIKey: OAEWNSKRLBVVBV-OBTVHEKISA-N
Target: Alpha-2C adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P18825
Assay: GPCRScan assay: inhibition of Alpha2C
Measurement: Ki = 6309.57 nM (pChEMBL 5.199999809265137)
Descriptors: MW 532.72, ALogP 5.54, HBA 6, HBD 1, PSA 88.54, QED 0.32
Compound (SMILES): Cc1c(C2(C(F)(F)F)CC2)nc(C2CC2)n1-c1c(Cl)ccc(N2CC3(CC(C(=O)O)C3)C2)c1Cl
InChIKey: ATOAVZQFLCOJQE-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inhibition of human GAL4-DBD fused RORgammat LBD expressed in human Jurkat cells assessed as inhibition of receptor transactivation after 24 hrs by luciferase reporter gene assay
Measurement: IC50 = 151 nM (pChEMBL 6.820000171661377)
Descriptors: MW 514.38, ALogP 6.26, HBA 4, HBD 1, PSA 58.36, QED 0.51
Compound (SMILES): NS(=O)(=O)c1cc(C(=O)NCCO)c(S(=O)(=O)Cc2ccccc2)cc1Br
InChIKey: PYLVVDNHUGVMGF-UHFFFAOYSA-N
Target: Carbonic anhydrase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P07451
Assay: Binding affinity to recombinant human carbonic anhydrase 3 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay
Measurement: Kd = 440 nM (pChEMBL 6.360000133514404)
Descriptors: MW 477.36, ALogP 0.79, HBA 6, HBD 3, PSA 143.63, QED 0.54
Compound (SMILES): COC(=O)CCCNC(=O)c1cc(S(N)(=O)=O)c(Cl)cc1S(=O)(=O)C1CCCCC1
InChIKey: OJCBLUGIJDOTFF-UHFFFAOYSA-N
Target: Carbonic anhydrase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P07451
Assay: Binding affinity to recombinant human carbonic anhydrase 3 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay
Measurement: Kd = 910 nM (pChEMBL 6.039999961853027)
Descriptors: MW 480.99, ALogP 1.78, HBA 7, HBD 2, PSA 149.7, QED 0.42
Compound (SMILES): O[C@]1(C(F)(F)F)CCCC[C@H]1Nc1ccc(F)cc1
InChIKey: IESAJAZKMLPVIB-VXGBXAGGSA-N
Target: Short transient receptor potential channel 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UL62
Assay: TRP selectivity screen (TRPC5)
Measurement: IC50 = 5600 nM (pChEMBL 5.25)
Descriptors: MW 277.26, ALogP 3.47, HBA 2, HBD 2, PSA 32.26, QED 0.81
Compound (SMILES): N#Cc1cnc2ccc(-c3c(-c4ccc(F)c(Cl)c4)ncn3CCO)nn12
InChIKey: VZZBCNXVZFAIQX-UHFFFAOYSA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Activation of PXR (unknown origin)
Measurement: EC50 > 24000 nM (pChEMBL 4.619999885559082)
Descriptors: MW 382.79, ALogP 2.92, HBA 7, HBD 1, PSA 92.03, QED 0.59
Compound (SMILES): C=CC(=O)N[C@H]1CCOC[C@H]1Nc1ncc2cc(-c3c(Cl)c(OC)cc(OC)c3Cl)ccc2n1
InChIKey: MGZKYOAQVGSSGC-DLBZAZTESA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of FGFR4 (unknown origin) by Z'-LYTE kinase assay
Measurement: IC50 = 53 nM (pChEMBL 7.28000020980835)
Descriptors: MW 503.39, ALogP 4.49, HBA 7, HBD 2, PSA 94.6, QED 0.46
Compound (SMILES): C=CC(=O)N(C)CCOc1c(N)ncnc1-c1cc(F)cc(NC(=O)c2ccc(C3CC3)cc2F)c1C
InChIKey: CUABMPOJOBCXJI-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by Qpatch clamp method
Measurement: IC50 = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 507.54, ALogP 4.47, HBA 6, HBD 2, PSA 110.44, QED 0.41
Compound (SMILES): Clc1nc(NCc2ccccn2)c2c(-c3ccccc3)cccc2n1
InChIKey: JSYVMXAHYRRFOQ-UHFFFAOYSA-N
Target: Casein kinase II subunit alpha' (SINGLE PROTEIN), Homo sapiens
UniProt: P19784
Assay: Caliper Kinase Assay: The analyses were performed in U-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 (20 mM HEPES pH 7.4, 10 mM MgCl2, 0.015% Brij35 and 4 mM DTT). The reaction was initiated by the combination of purified protein kinase with substrates and test compounds. The reaction was incubated at room temperature for 60 min. and terminated by adding 30 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 vehicle-only reactions for 0% inhibition. The ATP was used at a final concentration equivalent to the Km and the peptide substrate concentration was 1.5 μM. Dose response curves were generated to determine the concentration required to inhibit 50% of kinase activity (IC50). Compounds were dissolved at 10 mM in dimethylsulfoxide (DMSO) and evaluated at eleven concentrations.
Measurement: IC50 = 25520 nM (pChEMBL 4.590000152587891)
Descriptors: MW 346.82, ALogP 4.96, HBA 4, HBD 1, PSA 50.7, QED 0.53
Compound (SMILES): COc1ccc2c(c1OC)-c1ccc(Br)c3c1[C@H](C2)N(C)CC3
InChIKey: QCXMWEJEZDJYLD-HNNXBMFYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Antagonist activity at D2 long receptor (unknown origin) transfected in human HEK293T cells assessed as increase in cAMP accumulation incubated for 2 hrs by cAMP Glo-sensor assay
Measurement: IC50 = 8900 nM (pChEMBL 5.050000190734863)
Descriptors: MW 374.28, ALogP 4.22, HBA 3, HBD 0, PSA 21.7, QED 0.79
Compound (SMILES): NS(=O)(=O)c1cc(C(=O)NCCCC(=O)O)c(SC2CCCCC2)cc1Cl
InChIKey: QBFWPSYDISFIKC-UHFFFAOYSA-N
Target: Carbonic anhydrase 5B, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2D0
Assay: Binding affinity to recombinant human carbonic anhydrase 5b expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay
Measurement: Kd = 0.16 nM (pChEMBL 9.800000190734863)
Descriptors: MW 434.97, ALogP 3.01, HBA 5, HBD 3, PSA 126.56, QED 0.54
Compound (SMILES): CCCCN(CCCC)C(=O)CN1C[C@@H](c2cc(OC)c3c(c2)OCO3)[C@H](C(=O)O)[C@H]1CC(C)(C)CCC
InChIKey: OAEWNSKRLBVVBV-OBTVHEKISA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99720
Assay: GPCRScan assay: inhibition of Sigma 1
Measurement: Ki = 298 nM (pChEMBL 6.53000020980835)
Descriptors: MW 532.72, ALogP 5.54, HBA 6, HBD 1, PSA 88.54, QED 0.32
Compound (SMILES): NS(=O)(=O)c1cc(C(=O)NCCO)c(S(=O)(=O)Cc2ccccc2)cc1Br
InChIKey: PYLVVDNHUGVMGF-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Binding affinity to recombinant human carbonic anhydrase 4 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay
Measurement: Kd = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 477.36, ALogP 0.79, HBA 6, HBD 3, PSA 143.63, QED 0.54
Compound (SMILES): COC(=O)CCCNC(=O)c1cc(S(N)(=O)=O)c(Cl)cc1S(=O)(=O)C1CCCCC1
InChIKey: OJCBLUGIJDOTFF-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Binding affinity to recombinant human carbonic anhydrase 4 expressed in Escherichia coli expression system assessed as kinetic dissociation constant fluorescent thermal shift assay
Measurement: Kd = 1.6 nM (pChEMBL 8.800000190734863)
Descriptors: MW 480.99, ALogP 1.78, HBA 7, HBD 2, PSA 149.7, QED 0.42
Compound (SMILES): O[C@]1(C(F)(F)F)CCCC[C@H]1Nc1ccc(F)cc1
InChIKey: IESAJAZKMLPVIB-VXGBXAGGSA-N
Target: Short transient receptor potential channel 6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y210
Assay: TRP selectivity screen (TRPC6)
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 277.26, ALogP 3.47, HBA 2, HBD 2, PSA 32.26, QED 0.81
Compound (SMILES): N#Cc1cnc2ccc(-c3c(-c4ccc(F)c(Cl)c4)ncn3CCO)nn12
InChIKey: VZZBCNXVZFAIQX-UHFFFAOYSA-N
Target: TGF-beta receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P36897
Assay: Inhibition of TGFBR1 in human whole blood assessed as apparent inhibition constant by measuring reduction in TGFbeta-induced SMAD phosphorylation
Measurement: Ki = 0.8 nM (pChEMBL 9.100000381469727)
Descriptors: MW 382.79, ALogP 2.92, HBA 7, HBD 1, PSA 92.03, QED 0.59
Compound (SMILES): C=CC(=O)N[C@H]1CCOC[C@H]1Nc1ncc2cc(-c3c(Cl)c(OC)cc(OC)c3Cl)ccc2n1
InChIKey: MGZKYOAQVGSSGC-DLBZAZTESA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of FGFR1 (unknown origin) by Z'-LYTE kinase assay
Measurement: IC50 = 1837 nM (pChEMBL 5.739999771118164)
Descriptors: MW 503.39, ALogP 4.49, HBA 7, HBD 2, PSA 94.6, QED 0.46
Compound (SMILES): C=CC(=O)N(C)CCOc1c(N)ncnc1-c1cc(F)cc(NC(=O)c2ccc(C3CC3)cc2F)c1C
InChIKey: CUABMPOJOBCXJI-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK in human basophils assessed as reduction in anti-IgE mouse IgG1 antibody Le2-stimulated CD63 expression on basophil preincubated for 30 mins in presence of IgE antibody B11 followed by anti-IgE mouse IgG1 antibody Le2 stimulation and measured after 15 mins by flow cytometry
Measurement: IC50 = 67 nM (pChEMBL 7.170000076293945)
Descriptors: MW 507.54, ALogP 4.47, HBA 6, HBD 2, PSA 110.44, QED 0.41