lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1ccc(SCc2cn3c(nc2=O)O[C@H]2C(O)[C@@H](CO)O[C@H]23)cc1
InChIKey: CWZCZCRFZVYJCR-IOJLXPLISA-N
Target: Uridine phosphorylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16831
Assay: Enzyme Assay: The aim of this study was to evaluate TK-112690 in vivo as an inhibitor of uridine phosphorylase (UPase) enzyme activity. The range of TK-112690 doses studied for ability to prevent metabolic breakdown of uridine, through the in vitro inhibition of mouse and human small intestinal UPase enzyme, was 0, 0.1, 0.5, 1, 5, 10, 50, 100, 500, 1000, 5000 and 10000 uM). Detection of UPase activity was determined by HPLC analysis using UV detection of uracil concentration (UPase catabolizes uridine into uracil and ribose-1-phosphate).The UPase enzyme material was prepared from homogenized mouse and human being small intestinal tissue. TK-112690 was dissolved in water (50 mg/ml) and analyzed for UPase inhibition in aqueous solution containing 5 mM uridine, 0.01 M Tris, 0.01 M phosphate, 1 mM EDTA, and 1 mM DTT. Reactions were performed at 37 C. at pH of 7.3.TK-11260 inhibition of mouse and human UPase was analyzed by reverse phase HPLC using UV detection.
Measurement: IC50 < 100000 nM (pChEMBL 4)
Descriptors: MW 362.41, ALogP 0.86, HBA 8, HBD 2, PSA 93.81, QED 0.78
Compound (SMILES): Cc1cn2c(nc1=O)O[C@H]1C(O)[C@@H](CO)O[C@H]12
InChIKey: WLLOAUCNUMYOQI-AOXOCZDOSA-N
Target: Uridine phosphorylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16831
Assay: Enzyme Assay: The aim of this study was to evaluate TK-112690 in vivo as an inhibitor of uridine phosphorylase (UPase) enzyme activity. The range of TK-112690 doses studied for ability to prevent metabolic breakdown of uridine, through the in vitro inhibition of mouse and human small intestinal UPase enzyme, was 0, 0.1, 0.5, 1, 5, 10, 50, 100, 500, 1000, 5000 and 10000 uM). Detection of UPase activity was determined by HPLC analysis using UV detection of uracil concentration (UPase catabolizes uridine into uracil and ribose-1-phosphate).The UPase enzyme material was prepared from homogenized mouse and human being small intestinal tissue. TK-112690 was dissolved in water (50 mg/ml) and analyzed for UPase inhibition in aqueous solution containing 5 mM uridine, 0.01 M Tris, 0.01 M phosphate, 1 mM EDTA, and 1 mM DTT. Reactions were performed at 37 C. at pH of 7.3.TK-11260 inhibition of mouse and human UPase was analyzed by reverse phase HPLC using UV detection.
Measurement: IC50 < 100000 nM (pChEMBL 4)
Descriptors: MW 240.22, ALogP -1.44, HBA 7, HBD 2, PSA 93.81, QED 0.62
Compound (SMILES): COc1cc(-c2ccccc2C)ccc1C(C)C#Cc1c(C)nc(N)nc1N
InChIKey: QLSDCZWWZVSFDC-UHFFFAOYSA-N
Target: Dihydrofolate reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P00374
Assay: Spectrophotometric Enzyme Assay: Compounds were evaluated in spectrophotometric enzyme assays using ChDHFR-TS and hDHFR. Inhibition constants (IC50) were measured (see Table 4). The lead compound, X, has an inhibition constant of 38 nM and modest selectivity (8-fold). All of the biphenyl compounds are more potent than the initial lead compound X and exhibit greater selectivity for the pathogenic enzyme. The most potent racemic compound, D(rac), a 5′-biphenyl derivative, is also the most selective of the racemic compounds (944-fold). The single R enantiomer of this 5′-biphenyl analog is the most potent (1.1 nM) and most selective (1273-fold) of all known compounds tested against the Cryptosporidium DHFR enzyme.
Measurement: IC50 = 2770 nM (pChEMBL 5.559999942779541)
Descriptors: MW 372.47, ALogP 4.09, HBA 5, HBD 2, PSA 87.05, QED 0.68
Compound (SMILES): COc1cc(-c2c(C)cccc2C)ccc1C(C)C#Cc1c(C)nc(N)nc1N
InChIKey: YFKWCAHJYXKVLT-UHFFFAOYSA-N
Target: Dihydrofolate reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P00374
Assay: Spectrophotometric Enzyme Assay: Compounds were evaluated in spectrophotometric enzyme assays using ChDHFR-TS and hDHFR. Inhibition constants (IC50) were measured (see Table 4). The lead compound, X, has an inhibition constant of 38 nM and modest selectivity (8-fold). All of the biphenyl compounds are more potent than the initial lead compound X and exhibit greater selectivity for the pathogenic enzyme. The most potent racemic compound, D(rac), a 5′-biphenyl derivative, is also the most selective of the racemic compounds (944-fold). The single R enantiomer of this 5′-biphenyl analog is the most potent (1.1 nM) and most selective (1273-fold) of all known compounds tested against the Cryptosporidium DHFR enzyme.
Measurement: IC50 = 3370 nM (pChEMBL 5.46999979019165)
Descriptors: MW 386.5, ALogP 4.4, HBA 5, HBD 2, PSA 87.05, QED 0.65
Compound (SMILES): COc1cc(-c2c(C(C)C)cccc2C(C)C)ccc1C(C)C#Cc1c(C)nc(N)nc1N
InChIKey: RUUWASGGNWMBBT-UHFFFAOYSA-N
Target: Bifunctional dihydrofolate reductase-thymidylate synthase (SINGLE PROTEIN), Cryptosporidium parvum
UniProt: Q27552
Assay: Spectrophotometric Enzyme Assay: Compounds were evaluated in spectrophotometric enzyme assays using ChDHFR-TS and hDHFR. Inhibition constants (IC50) were measured (see Table 4). The lead compound, X, has an inhibition constant of 38 nM and modest selectivity (8-fold). All of the biphenyl compounds are more potent than the initial lead compound X and exhibit greater selectivity for the pathogenic enzyme. The most potent racemic compound, D(rac), a 5′-biphenyl derivative, is also the most selective of the racemic compounds (944-fold). The single R enantiomer of this 5′-biphenyl analog is the most potent (1.1 nM) and most selective (1273-fold) of all known compounds tested against the Cryptosporidium DHFR enzyme.
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 442.61, ALogP 6.03, HBA 5, HBD 2, PSA 87.05, QED 0.47
Compound (SMILES): CCc1nc(N)nc(N)c1C#CC(C)c1cc(-c2ccccc2)ccc1OC
InChIKey: FHTSRDNJZWDVBC-UHFFFAOYSA-N
Target: Dihydrofolate reductase (SINGLE PROTEIN), Streptococcus pyogenes
UniProt: J7IFZ2
Assay: Enzyme Inhibition Assay: Heterocyclic analogs of propargyl-linked inhibitors of the third generation analogs were evaluated in enzyme inhibition assays, assessed for S. aureus and S. pyogenes inhibition, and evaluated for mammalian cell toxicity.
Measurement: IC50 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 372.47, ALogP 4.03, HBA 5, HBD 2, PSA 87.05, QED 0.68
Compound (SMILES): CCc1nc(N)nc(N)c1C#CCc1cccc(-c2ccncc2)c1
InChIKey: LMFGVRPNYCLJOJ-UHFFFAOYSA-N
Target: Dihydrofolate reductase (SINGLE PROTEIN), Streptococcus pyogenes
UniProt: J7IFZ2
Assay: Enzyme Inhibition Assay: Heterocyclic analogs of propargyl-linked inhibitors of the third generation analogs were evaluated in enzyme inhibition assays, assessed for S. aureus and S. pyogenes inhibition, and evaluated for mammalian cell toxicity.
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 329.41, ALogP 2.86, HBA 5, HBD 2, PSA 90.71, QED 0.72
Compound (SMILES): CCc1nc(N)nc(N)c1C#CCc1cccc(-c2cccnc2)c1
InChIKey: IXYIZEGMHCDBOH-UHFFFAOYSA-N
Target: Dihydrofolate reductase (SINGLE PROTEIN), Staphylococcus aureus
UniProt: P0A017
Assay: Enzyme Inhibition Assay: Heterocyclic analogs of propargyl-linked inhibitors of the third generation analogs were evaluated in enzyme inhibition assays, assessed for S. aureus and S. pyogenes inhibition, and evaluated for mammalian cell toxicity.
Measurement: IC50 = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 329.41, ALogP 2.86, HBA 5, HBD 2, PSA 90.71, QED 0.72
Compound (SMILES): CCc1nc(N)nc(N)c1C#CCc1cccc(-c2cncnc2)c1
InChIKey: UEZKDWYIIOOENX-UHFFFAOYSA-N
Target: Dihydrofolate reductase (SINGLE PROTEIN), Streptococcus pyogenes
UniProt: J7IFZ2
Assay: Enzyme Inhibition Assay: Heterocyclic analogs of propargyl-linked inhibitors of the third generation analogs were evaluated in enzyme inhibition assays, assessed for S. aureus and S. pyogenes inhibition, and evaluated for mammalian cell toxicity.
Measurement: IC50 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 330.4, ALogP 2.25, HBA 6, HBD 2, PSA 103.6, QED 0.71
Compound (SMILES): Cc1cc(-c2c(F)cc(F)cc2F)c2cc(C(=O)N=C(N)N)ccc2n1
InChIKey: DZAUWILXMWFUQY-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P47898
Assay: Binding Inhibition Assay: A solution of the compound to be tested and 100 μM 5-CT (5-carboxamidetriptamine) in DMSO was added to a 96-well plate at 2 μl/well, suspended in an incubation buffer, and a membrane from HEK293 cells for forced expressions of a human 5-HT5A receptor prepared at 200 ug/ml was added at 100 μl/well. After incubation at room temperature for 15 minutes, a [3H]5-CT solution (2 nM [3H]5-CT, incubation buffer) was added thereto at 100 μl/well.Separately, 100 μl of the solution was distributed into a liquid scintillation vial, and 2 ml of Aquasol II (registered trademark) was added thereto, followed by stirring. Then, radioactivity was measured by a liquid scintillation counter. It was incubated at 37C. for 60 minutes. The reaction mixture was sucked into 96-well GF/C filter plate that had been pre-treated with 0.2% polyethyleneimine, and washed six times with an ice-cooled, 50 mM Tris (pH 7.5) buffer. The GF/C filter plate was dried.
Measurement: Ki = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 358.32, ALogP 3.04, HBA 2, HBD 2, PSA 94.36, QED 0.54
Compound (SMILES): NC(N)=NC(=O)c1ccc2ncc(Cl)c(-c3ccc(F)cc3F)c2c1
InChIKey: PHCVAROZSLUGRS-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P47898
Assay: Binding Inhibition Assay: A solution of the compound to be tested and 100 μM 5-CT (5-carboxamidetriptamine) in DMSO was added to a 96-well plate at 2 μl/well, suspended in an incubation buffer, and a membrane from HEK293 cells for forced expressions of a human 5-HT5A receptor prepared at 200 ug/ml was added at 100 μl/well. After incubation at room temperature for 15 minutes, a [3H]5-CT solution (2 nM [3H]5-CT, incubation buffer) was added thereto at 100 μl/well.Separately, 100 μl of the solution was distributed into a liquid scintillation vial, and 2 ml of Aquasol II (registered trademark) was added thereto, followed by stirring. Then, radioactivity was measured by a liquid scintillation counter. It was incubated at 37C. for 60 minutes. The reaction mixture was sucked into 96-well GF/C filter plate that had been pre-treated with 0.2% polyethyleneimine, and washed six times with an ice-cooled, 50 mM Tris (pH 7.5) buffer. The GF/C filter plate was dried.
Measurement: Ki = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 360.75, ALogP 3.25, HBA 2, HBD 2, PSA 94.36, QED 0.54
Compound (SMILES): Cc1nc2ccc(C(=O)N=C(N)N)cc2c(-c2c(F)cc(F)cc2F)c1C
InChIKey: XAVJTAQYWJVSJU-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P47898
Assay: Binding Inhibition Assay: A solution of the compound to be tested and 100 μM 5-CT (5-carboxamidetriptamine) in DMSO was added to a 96-well plate at 2 μl/well, suspended in an incubation buffer, and a membrane from HEK293 cells for forced expressions of a human 5-HT5A receptor prepared at 200 ug/ml was added at 100 μl/well. After incubation at room temperature for 15 minutes, a [3H]5-CT solution (2 nM [3H]5-CT, incubation buffer) was added thereto at 100 μl/well.Separately, 100 μl of the solution was distributed into a liquid scintillation vial, and 2 ml of Aquasol II (registered trademark) was added thereto, followed by stirring. Then, radioactivity was measured by a liquid scintillation counter. It was incubated at 37C. for 60 minutes. The reaction mixture was sucked into 96-well GF/C filter plate that had been pre-treated with 0.2% polyethyleneimine, and washed six times with an ice-cooled, 50 mM Tris (pH 7.5) buffer. The GF/C filter plate was dried.
Measurement: Ki = 3.7 nM (pChEMBL 8.430000305175781)
Descriptors: MW 372.35, ALogP 3.35, HBA 2, HBD 2, PSA 94.36, QED 0.53
Compound (SMILES): NC(N)=NC(=O)c1ccc2c(F)cnc(-c3c(F)cccc3Cl)c2c1
InChIKey: YDOROAJJAVBIJG-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P47898
Assay: Binding Inhibition Assay: A solution of the compound to be tested and 100 μM 5-CT (5-carboxamidetriptamine) in DMSO was added to a 96-well plate at 2 μl/well, suspended in an incubation buffer, and a membrane from HEK293 cells for forced expressions of a human 5-HT5A receptor prepared at 200 ug/ml was added at 100 μl/well. After incubation at room temperature for 15 minutes, a [3H]5-CT solution (2 nM [3H]5-CT, incubation buffer) was added thereto at 100 μl/well.Separately, 100 μl of the solution was distributed into a liquid scintillation vial, and 2 ml of Aquasol II (registered trademark) was added thereto, followed by stirring. Then, radioactivity was measured by a liquid scintillation counter. It was incubated at 37C. for 60 minutes. The reaction mixture was sucked into 96-well GF/C filter plate that had been pre-treated with 0.2% polyethyleneimine, and washed six times with an ice-cooled, 50 mM Tris (pH 7.5) buffer. The GF/C filter plate was dried.
Measurement: Ki = 1.6 nM (pChEMBL 8.800000190734863)
Descriptors: MW 360.75, ALogP 3.25, HBA 2, HBD 2, PSA 94.36, QED 0.54
Compound (SMILES): NC(N)=NC(=O)c1ccc2c(F)cnc(-c3c(F)cccc3F)c2c1
InChIKey: NPYWVXJXMOTDHT-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P47898
Assay: Binding Inhibition Assay: A solution of the compound to be tested and 100 μM 5-CT (5-carboxamidetriptamine) in DMSO was added to a 96-well plate at 2 μl/well, suspended in an incubation buffer, and a membrane from HEK293 cells for forced expressions of a human 5-HT5A receptor prepared at 200 ug/ml was added at 100 μl/well. After incubation at room temperature for 15 minutes, a [3H]5-CT solution (2 nM [3H]5-CT, incubation buffer) was added thereto at 100 μl/well.Separately, 100 μl of the solution was distributed into a liquid scintillation vial, and 2 ml of Aquasol II (registered trademark) was added thereto, followed by stirring. Then, radioactivity was measured by a liquid scintillation counter. It was incubated at 37C. for 60 minutes. The reaction mixture was sucked into 96-well GF/C filter plate that had been pre-treated with 0.2% polyethyleneimine, and washed six times with an ice-cooled, 50 mM Tris (pH 7.5) buffer. The GF/C filter plate was dried.
Measurement: Ki = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 344.3, ALogP 2.73, HBA 2, HBD 2, PSA 94.36, QED 0.55
Compound (SMILES): NC(N)=NC(=O)c1ccc2c(F)cnc(-c3ccc(F)cc3Cl)c2c1
InChIKey: CRRMCGPQPIPQCJ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P47898
Assay: Binding Inhibition Assay: A solution of the compound to be tested and 100 μM 5-CT (5-carboxamidetriptamine) in DMSO was added to a 96-well plate at 2 μl/well, suspended in an incubation buffer, and a membrane from HEK293 cells for forced expressions of a human 5-HT5A receptor prepared at 200 ug/ml was added at 100 μl/well. After incubation at room temperature for 15 minutes, a [3H]5-CT solution (2 nM [3H]5-CT, incubation buffer) was added thereto at 100 μl/well.Separately, 100 μl of the solution was distributed into a liquid scintillation vial, and 2 ml of Aquasol II (registered trademark) was added thereto, followed by stirring. Then, radioactivity was measured by a liquid scintillation counter. It was incubated at 37C. for 60 minutes. The reaction mixture was sucked into 96-well GF/C filter plate that had been pre-treated with 0.2% polyethyleneimine, and washed six times with an ice-cooled, 50 mM Tris (pH 7.5) buffer. The GF/C filter plate was dried.
Measurement: Ki = 4.1 nM (pChEMBL 8.390000343322754)
Descriptors: MW 360.75, ALogP 3.25, HBA 2, HBD 2, PSA 94.36, QED 0.54
Compound (SMILES): Cc1cnc(-c2c(F)cc(F)cc2F)c2cc(C(=O)N=C(N)N)ccc12
InChIKey: NITIGSNQQNMDMF-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P47898
Assay: Binding Inhibition Assay: A solution of the compound to be tested and 100 μM 5-CT (5-carboxamidetriptamine) in DMSO was added to a 96-well plate at 2 μl/well, suspended in an incubation buffer, and a membrane from HEK293 cells for forced expressions of a human 5-HT5A receptor prepared at 200 ug/ml was added at 100 μl/well. After incubation at room temperature for 15 minutes, a [3H]5-CT solution (2 nM [3H]5-CT, incubation buffer) was added thereto at 100 μl/well.Separately, 100 μl of the solution was distributed into a liquid scintillation vial, and 2 ml of Aquasol II (registered trademark) was added thereto, followed by stirring. Then, radioactivity was measured by a liquid scintillation counter. It was incubated at 37C. for 60 minutes. The reaction mixture was sucked into 96-well GF/C filter plate that had been pre-treated with 0.2% polyethyleneimine, and washed six times with an ice-cooled, 50 mM Tris (pH 7.5) buffer. The GF/C filter plate was dried.
Measurement: Ki = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 358.32, ALogP 3.04, HBA 2, HBD 2, PSA 94.36, QED 0.54
Compound (SMILES): NC(N)=NC(=O)c1ccc2c(F)cnc(-c3c(F)cncc3F)c2c1
InChIKey: PQFJGRYHVVMYIW-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P47898
Assay: Binding Inhibition Assay: A solution of the compound to be tested and 100 μM 5-CT (5-carboxamidetriptamine) in DMSO was added to a 96-well plate at 2 μl/well, suspended in an incubation buffer, and a membrane from HEK293 cells for forced expressions of a human 5-HT5A receptor prepared at 200 ug/ml was added at 100 μl/well. After incubation at room temperature for 15 minutes, a [3H]5-CT solution (2 nM [3H]5-CT, incubation buffer) was added thereto at 100 μl/well.Separately, 100 μl of the solution was distributed into a liquid scintillation vial, and 2 ml of Aquasol II (registered trademark) was added thereto, followed by stirring. Then, radioactivity was measured by a liquid scintillation counter. It was incubated at 37C. for 60 minutes. The reaction mixture was sucked into 96-well GF/C filter plate that had been pre-treated with 0.2% polyethyleneimine, and washed six times with an ice-cooled, 50 mM Tris (pH 7.5) buffer. The GF/C filter plate was dried.
Measurement: Ki = 5.3 nM (pChEMBL 8.279999732971191)
Descriptors: MW 345.28, ALogP 2.13, HBA 3, HBD 2, PSA 107.25, QED 0.55
Compound (SMILES): COc1cccc(F)c1-c1ncc(F)c2ccc(C(=O)N=C(N)N)cc12
InChIKey: QXLNHVUUUVGLBQ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P47898
Assay: Binding Inhibition Assay: A solution of the compound to be tested and 100 μM 5-CT (5-carboxamidetriptamine) in DMSO was added to a 96-well plate at 2 μl/well, suspended in an incubation buffer, and a membrane from HEK293 cells for forced expressions of a human 5-HT5A receptor prepared at 200 ug/ml was added at 100 μl/well. After incubation at room temperature for 15 minutes, a [3H]5-CT solution (2 nM [3H]5-CT, incubation buffer) was added thereto at 100 μl/well.Separately, 100 μl of the solution was distributed into a liquid scintillation vial, and 2 ml of Aquasol II (registered trademark) was added thereto, followed by stirring. Then, radioactivity was measured by a liquid scintillation counter. It was incubated at 37C. for 60 minutes. The reaction mixture was sucked into 96-well GF/C filter plate that had been pre-treated with 0.2% polyethyleneimine, and washed six times with an ice-cooled, 50 mM Tris (pH 7.5) buffer. The GF/C filter plate was dried.
Measurement: Ki = 7.1 nM (pChEMBL 8.149999618530273)
Descriptors: MW 356.33, ALogP 2.6, HBA 3, HBD 2, PSA 103.59, QED 0.55
Compound (SMILES): NC(N)=NC(=O)c1ccc2c(F)cnc(-c3ccccc3F)c2c1
InChIKey: OXFIPEQRZBXKMG-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P47898
Assay: Binding Inhibition Assay: A solution of the compound to be tested and 100 μM 5-CT (5-carboxamidetriptamine) in DMSO was added to a 96-well plate at 2 μl/well, suspended in an incubation buffer, and a membrane from HEK293 cells for forced expressions of a human 5-HT5A receptor prepared at 200 ug/ml was added at 100 μl/well. After incubation at room temperature for 15 minutes, a [3H]5-CT solution (2 nM [3H]5-CT, incubation buffer) was added thereto at 100 μl/well.Separately, 100 μl of the solution was distributed into a liquid scintillation vial, and 2 ml of Aquasol II (registered trademark) was added thereto, followed by stirring. Then, radioactivity was measured by a liquid scintillation counter. It was incubated at 37C. for 60 minutes. The reaction mixture was sucked into 96-well GF/C filter plate that had been pre-treated with 0.2% polyethyleneimine, and washed six times with an ice-cooled, 50 mM Tris (pH 7.5) buffer. The GF/C filter plate was dried.
Measurement: Ki = 3.3 nM (pChEMBL 8.479999542236328)
Descriptors: MW 326.31, ALogP 2.59, HBA 2, HBD 2, PSA 94.36, QED 0.56
Compound (SMILES): NC(N)=NC(=O)c1ccc2c(F)cnc(-c3ccccc3Cl)c2c1
InChIKey: CURBYWXZHSUAHS-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P47898
Assay: Binding Inhibition Assay: A solution of the compound to be tested and 100 μM 5-CT (5-carboxamidetriptamine) in DMSO was added to a 96-well plate at 2 μl/well, suspended in an incubation buffer, and a membrane from HEK293 cells for forced expressions of a human 5-HT5A receptor prepared at 200 ug/ml was added at 100 μl/well. After incubation at room temperature for 15 minutes, a [3H]5-CT solution (2 nM [3H]5-CT, incubation buffer) was added thereto at 100 μl/well.Separately, 100 μl of the solution was distributed into a liquid scintillation vial, and 2 ml of Aquasol II (registered trademark) was added thereto, followed by stirring. Then, radioactivity was measured by a liquid scintillation counter. It was incubated at 37C. for 60 minutes. The reaction mixture was sucked into 96-well GF/C filter plate that had been pre-treated with 0.2% polyethyleneimine, and washed six times with an ice-cooled, 50 mM Tris (pH 7.5) buffer. The GF/C filter plate was dried.
Measurement: Ki = 3.4 nM (pChEMBL 8.470000267028809)
Descriptors: MW 342.76, ALogP 3.11, HBA 2, HBD 2, PSA 94.36, QED 0.55
Compound (SMILES): NC(N)=NC(=O)c1ccc2c(Cl)cnc(-c3c(F)cccc3F)c2c1
InChIKey: PONUYLXOKDCITA-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P47898
Assay: Binding Inhibition Assay: A solution of the compound to be tested and 100 μM 5-CT (5-carboxamidetriptamine) in DMSO was added to a 96-well plate at 2 μl/well, suspended in an incubation buffer, and a membrane from HEK293 cells for forced expressions of a human 5-HT5A receptor prepared at 200 ug/ml was added at 100 μl/well. After incubation at room temperature for 15 minutes, a [3H]5-CT solution (2 nM [3H]5-CT, incubation buffer) was added thereto at 100 μl/well.Separately, 100 μl of the solution was distributed into a liquid scintillation vial, and 2 ml of Aquasol II (registered trademark) was added thereto, followed by stirring. Then, radioactivity was measured by a liquid scintillation counter. It was incubated at 37C. for 60 minutes. The reaction mixture was sucked into 96-well GF/C filter plate that had been pre-treated with 0.2% polyethyleneimine, and washed six times with an ice-cooled, 50 mM Tris (pH 7.5) buffer. The GF/C filter plate was dried.
Measurement: Ki = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 360.75, ALogP 3.25, HBA 2, HBD 2, PSA 94.36, QED 0.54
Compound (SMILES): NC(N)=NC(=O)c1ccc2c(F)cnc(-c3c(F)cncc3Cl)c2c1
InChIKey: VYOCDNYPMYYCKI-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P47898
Assay: Binding Inhibition Assay: A solution of the compound to be tested and 100 μM 5-CT (5-carboxamidetriptamine) in DMSO was added to a 96-well plate at 2 μl/well, suspended in an incubation buffer, and a membrane from HEK293 cells for forced expressions of a human 5-HT5A receptor prepared at 200 ug/ml was added at 100 μl/well. After incubation at room temperature for 15 minutes, a [3H]5-CT solution (2 nM [3H]5-CT, incubation buffer) was added thereto at 100 μl/well.Separately, 100 μl of the solution was distributed into a liquid scintillation vial, and 2 ml of Aquasol II (registered trademark) was added thereto, followed by stirring. Then, radioactivity was measured by a liquid scintillation counter. It was incubated at 37C. for 60 minutes. The reaction mixture was sucked into 96-well GF/C filter plate that had been pre-treated with 0.2% polyethyleneimine, and washed six times with an ice-cooled, 50 mM Tris (pH 7.5) buffer. The GF/C filter plate was dried.
Measurement: Ki = 4.7 nM (pChEMBL 8.329999923706055)
Descriptors: MW 361.74, ALogP 2.64, HBA 3, HBD 2, PSA 107.25, QED 0.54
Compound (SMILES): Cc1cnc(-c2c(F)cccc2F)c2cc(C(=O)N=C(N)N)ccc12
InChIKey: MFSDVPDQRWLCTK-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P47898
Assay: Binding Inhibition Assay: A solution of the compound to be tested and 100 μM 5-CT (5-carboxamidetriptamine) in DMSO was added to a 96-well plate at 2 μl/well, suspended in an incubation buffer, and a membrane from HEK293 cells for forced expressions of a human 5-HT5A receptor prepared at 200 ug/ml was added at 100 μl/well. After incubation at room temperature for 15 minutes, a [3H]5-CT solution (2 nM [3H]5-CT, incubation buffer) was added thereto at 100 μl/well.Separately, 100 μl of the solution was distributed into a liquid scintillation vial, and 2 ml of Aquasol II (registered trademark) was added thereto, followed by stirring. Then, radioactivity was measured by a liquid scintillation counter. It was incubated at 37C. for 60 minutes. The reaction mixture was sucked into 96-well GF/C filter plate that had been pre-treated with 0.2% polyethyleneimine, and washed six times with an ice-cooled, 50 mM Tris (pH 7.5) buffer. The GF/C filter plate was dried.
Measurement: Ki = 1.9 nM (pChEMBL 8.720000267028809)
Descriptors: MW 340.33, ALogP 2.9, HBA 2, HBD 2, PSA 94.36, QED 0.55
Compound (SMILES): NC(N)=NC(=O)c1ccc2c(F)cnc(-c3ncc(F)cc3Cl)c2c1
InChIKey: SDGMYMHDNSKACE-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P47898
Assay: Binding Inhibition Assay: A solution of the compound to be tested and 100 μM 5-CT (5-carboxamidetriptamine) in DMSO was added to a 96-well plate at 2 μl/well, suspended in an incubation buffer, and a membrane from HEK293 cells for forced expressions of a human 5-HT5A receptor prepared at 200 ug/ml was added at 100 μl/well. After incubation at room temperature for 15 minutes, a [3H]5-CT solution (2 nM [3H]5-CT, incubation buffer) was added thereto at 100 μl/well.Separately, 100 μl of the solution was distributed into a liquid scintillation vial, and 2 ml of Aquasol II (registered trademark) was added thereto, followed by stirring. Then, radioactivity was measured by a liquid scintillation counter. It was incubated at 37C. for 60 minutes. The reaction mixture was sucked into 96-well GF/C filter plate that had been pre-treated with 0.2% polyethyleneimine, and washed six times with an ice-cooled, 50 mM Tris (pH 7.5) buffer. The GF/C filter plate was dried.
Measurement: Ki = 6.2 nM (pChEMBL 8.210000038146973)
Descriptors: MW 361.74, ALogP 2.64, HBA 3, HBD 2, PSA 107.25, QED 0.54
Compound (SMILES): NC(N)=NC(=O)c1ccc2c(C(F)F)cnc(-c3c(F)cccc3F)c2c1
InChIKey: IUQQTDPNDMZKFN-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P47898
Assay: Binding Inhibition Assay: A solution of the compound to be tested and 100 μM 5-CT (5-carboxamidetriptamine) in DMSO was added to a 96-well plate at 2 μl/well, suspended in an incubation buffer, and a membrane from HEK293 cells for forced expressions of a human 5-HT5A receptor prepared at 200 ug/ml was added at 100 μl/well. After incubation at room temperature for 15 minutes, a [3H]5-CT solution (2 nM [3H]5-CT, incubation buffer) was added thereto at 100 μl/well.Separately, 100 μl of the solution was distributed into a liquid scintillation vial, and 2 ml of Aquasol II (registered trademark) was added thereto, followed by stirring. Then, radioactivity was measured by a liquid scintillation counter. It was incubated at 37C. for 60 minutes. The reaction mixture was sucked into 96-well GF/C filter plate that had been pre-treated with 0.2% polyethyleneimine, and washed six times with an ice-cooled, 50 mM Tris (pH 7.5) buffer. The GF/C filter plate was dried.
Measurement: Ki = 4.6 nM (pChEMBL 8.34000015258789)
Descriptors: MW 376.31, ALogP 3.53, HBA 2, HBD 2, PSA 94.36, QED 0.42
Compound (SMILES): Cc1cnc(-c2ccccc2F)c2cc(C(=O)N=C(N)N)ccc12
InChIKey: CEIKFWBZOZKVTL-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P47898
Assay: Binding Inhibition Assay: A solution of the compound to be tested and 100 μM 5-CT (5-carboxamidetriptamine) in DMSO was added to a 96-well plate at 2 μl/well, suspended in an incubation buffer, and a membrane from HEK293 cells for forced expressions of a human 5-HT5A receptor prepared at 200 ug/ml was added at 100 μl/well. After incubation at room temperature for 15 minutes, a [3H]5-CT solution (2 nM [3H]5-CT, incubation buffer) was added thereto at 100 μl/well.Separately, 100 μl of the solution was distributed into a liquid scintillation vial, and 2 ml of Aquasol II (registered trademark) was added thereto, followed by stirring. Then, radioactivity was measured by a liquid scintillation counter. It was incubated at 37C. for 60 minutes. The reaction mixture was sucked into 96-well GF/C filter plate that had been pre-treated with 0.2% polyethyleneimine, and washed six times with an ice-cooled, 50 mM Tris (pH 7.5) buffer. The GF/C filter plate was dried.
Measurement: Ki = 1.8 nM (pChEMBL 8.739999771118164)
Descriptors: MW 322.34, ALogP 2.76, HBA 2, HBD 2, PSA 94.36, QED 0.56
Compound (SMILES): NC(N)=NC(=O)c1ccc2c(Cl)cnc(-c3ccc(F)cc3F)c2c1
InChIKey: RTCPHQATTMCCCB-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P47898
Assay: Binding Inhibition Assay: A solution of the compound to be tested and 100 μM 5-CT (5-carboxamidetriptamine) in DMSO was added to a 96-well plate at 2 μl/well, suspended in an incubation buffer, and a membrane from HEK293 cells for forced expressions of a human 5-HT5A receptor prepared at 200 ug/ml was added at 100 μl/well. After incubation at room temperature for 15 minutes, a [3H]5-CT solution (2 nM [3H]5-CT, incubation buffer) was added thereto at 100 μl/well.Separately, 100 μl of the solution was distributed into a liquid scintillation vial, and 2 ml of Aquasol II (registered trademark) was added thereto, followed by stirring. Then, radioactivity was measured by a liquid scintillation counter. It was incubated at 37C. for 60 minutes. The reaction mixture was sucked into 96-well GF/C filter plate that had been pre-treated with 0.2% polyethyleneimine, and washed six times with an ice-cooled, 50 mM Tris (pH 7.5) buffer. The GF/C filter plate was dried.
Measurement: Ki = 2.3 nM (pChEMBL 8.640000343322754)
Descriptors: MW 360.75, ALogP 3.25, HBA 2, HBD 2, PSA 94.36, QED 0.54
Compound (SMILES): Cc1cc(-c2ccccc2)ccc1CCC(C)(C(=O)NO)S(C)(=O)=O
InChIKey: IFLZWKBBDBJTAV-UHFFFAOYSA-N
Target: UDP-3-O-acyl-N-acetylglucosamine deacetylase (SINGLE PROTEIN), Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG12228)
UniProt: P47205
Assay: Enzyme Assay: IC50 determination in the LpxC enzyme assay was carried out in a similar manner to that described by Malikzay et al in the 2006 Poster, Screening LpxC (UDP-3-O(R-3-hydroxymyristoyl)-GlcNAc deacetylase) using BioTrove Rapid Fire HTS Mass Spectrometry (aNew Lead Discovery and bInflammation and Infectious Disease, cStructural Chemistry, Schering-Plough Research Institute, Kenilworth, N.J. 07033, (BioTrove, Inc. 12 Gill St., Suite 4000, Woburn, Mass. 01801). Briefly, Pseudomonas aeruginosa LpxC enzyme (0.1 nM) purified from E. coli-overexpressing bacteria was incubated at 25° C. in a final volume of 50 ul containing 0.5 uM UDP-3-O(R-3-hydroxydecanoyl)-N-acetylglucosamine, 1 mg/mL BSA, and 50 mM sodium phosphate buffer, pH 8.0 in the presence and absence of inhibitor compound. At the end of 1 hour, 5 ul of 1N HCl was added to stop the enzyme reaction; the plates were centrifuged, and then processed with the BioTrove Rapidfire HTMS Mass Spectrometry System.
Measurement: IC50 = 1.68 nM (pChEMBL 8.779999732971191)
Descriptors: MW 361.46, ALogP 2.9, HBA 4, HBD 2, PSA 83.47, QED 0.61
Compound (SMILES): CC(CCc1ccc(-c2ccccc2)cc1F)(C(=O)NO)S(C)(=O)=O
InChIKey: IQRSIWOZEFCTBQ-UHFFFAOYSA-N
Target: UDP-3-O-acyl-N-acetylglucosamine deacetylase (SINGLE PROTEIN), Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG12228)
UniProt: P47205
Assay: Enzyme Assay: IC50 determination in the LpxC enzyme assay was carried out in a similar manner to that described by Malikzay et al in the 2006 Poster, Screening LpxC (UDP-3-O(R-3-hydroxymyristoyl)-GlcNAc deacetylase) using BioTrove Rapid Fire HTS Mass Spectrometry (aNew Lead Discovery and bInflammation and Infectious Disease, cStructural Chemistry, Schering-Plough Research Institute, Kenilworth, N.J. 07033, (BioTrove, Inc. 12 Gill St., Suite 4000, Woburn, Mass. 01801). Briefly, Pseudomonas aeruginosa LpxC enzyme (0.1 nM) purified from E. coli-overexpressing bacteria was incubated at 25° C. in a final volume of 50 ul containing 0.5 uM UDP-3-O(R-3-hydroxydecanoyl)-N-acetylglucosamine, 1 mg/mL BSA, and 50 mM sodium phosphate buffer, pH 8.0 in the presence and absence of inhibitor compound. At the end of 1 hour, 5 ul of 1N HCl was added to stop the enzyme reaction; the plates were centrifuged, and then processed with the BioTrove Rapidfire HTMS Mass Spectrometry System.
Measurement: IC50 = 0.26 nM (pChEMBL 9.59000015258789)
Descriptors: MW 365.43, ALogP 2.73, HBA 4, HBD 2, PSA 83.47, QED 0.61
Compound (SMILES): Nc1ncc2c(n1)CCN(c1cncc(C(=O)Nc3cccc(C(F)(F)F)c3)c1)C2
InChIKey: MYZMNTZXXUVVOM-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Kinase Assay: Biochemical KDR kinase assays were performed in 96 well microliter plates that were coated overnight with 75 μg/well of poly-Glu-Tyr (4:1) in 10 mM Phosphate Buffered Saline (PBS), pH 7.4. The coated plates were washed with 2 mls per well PBS+0.05% Tween-20 (PBS-T), blocked by incubation with PBS containing 1% BSA, then washed with 2 mls per well PBS-T prior to starting the reaction. Reactions were carried out in 100 μL reaction volumes containing 2.7 μM ATP in kinase buffer (50 mM Hepes buffer pH 7.4, 20 mM MgCl2, 0.1 mM MnCl2 and 0.2 mM Na3VO4). Test compounds were reconstituted in 100% DMSO and added to the reaction to give a final DMSO concentration of 5%. Reactions were initiated by the addition 20 ul per well of kinase buffer containing 200-300 ng purified cytoplasmic domain KDR protein (BPS Bioscience, San Diego, Calif.). Following a 15 minute incubation at 30° C., the reactions were washed 2 mls per well PBS-T. 100 μl of a monoclonal anti-phosphotyrosine antibody-peroxidase conjugate diluted 1:10,000 in PBS-T was added to the wells for 30 minutes. Following a 2 mls per well wash with PBS-Tween-20, 100 μl of O-Phenylenediamine Dihydrochloride in phosphate-citrate buffer, containing urea hydrogen peroxide, was added to the wells for 7-10 minutes as a colorimetric substrate for the peroxidase. The reaction was terminated by the addition of 100 μl of 2.5N H2SO4 to each well and read using a microplate ELISA reader set at 492 nm.
Measurement: Ki = 584 nM (pChEMBL 6.230000019073486)
Descriptors: MW 414.39, ALogP 3.29, HBA 6, HBD 2, PSA 97.03, QED 0.68
Compound (SMILES): CC(C)c1cccc(NC(=O)c2cncc(N3CCc4nc(N)ncc4C3)c2)c1
InChIKey: YXSQFHKRJRWDHD-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Kinase Assay: Biochemical KDR kinase assays were performed in 96 well microliter plates that were coated overnight with 75 .mu.g/well of poly-Glu-Tyr (4:1) in 10 mM Phosphate Buffered Saline (PBS), pH 7.4. The coated plates were washed with 2 mLs per well PBS+0.05% Tween-20 (PBS-T), blocked by incubation with PBS containing 1% BSA, then washed with 2 mLs per well PBS-T prior to starting the reaction. Reactions were carried out in 100 .mu.L reaction volumes containing 2.7 .mu.M ATP in kinase buffer (50 mM Hepes buffer pH 7.4, 20 mM MgCl.sub.2, 0.1 mM MnCl.sub.2 and 0.2 mM Na.sub.3VO.sub.4). Test compounds were reconstituted in 100% DMSO and added to the reaction to give a final DMSO concentration of 5%. Reactions were initiated by the addition 20 ul per well of kinase buffer containing 200-300 ng purified cytoplasmic domain KDR protein (BPS Bioscience, San Diego, Calif.).
Measurement: IC50 = 149 nM (pChEMBL 6.829999923706055)
Descriptors: MW 388.48, ALogP 3.39, HBA 6, HBD 2, PSA 97.03, QED 0.71
Compound (SMILES): O=C(Nc1ccc(N2CCc3ccncc3C2)cc1)c1cccc(C(F)(F)F)c1
InChIKey: GPILFGJABMRGLK-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Kinase Assay: Biochemical KDR kinase assays were performed in 96 well microliter plates that were coated overnight with 75 .mu.g/well of poly-Glu-Tyr (4:1) in 10 mM Phosphate Buffered Saline (PBS), pH 7.4. The coated plates were washed with 2 mLs per well PBS+0.05% Tween-20 (PBS-T), blocked by incubation with PBS containing 1% BSA, then washed with 2 mLs per well PBS-T prior to starting the reaction. Reactions were carried out in 100 .mu.L reaction volumes containing 2.7 .mu.M ATP in kinase buffer (50 mM Hepes buffer pH 7.4, 20 mM MgCl.sub.2, 0.1 mM MnCl.sub.2 and 0.2 mM Na.sub.3VO.sub.4). Test compounds were reconstituted in 100% DMSO and added to the reaction to give a final DMSO concentration of 5%. Reactions were initiated by the addition 20 ul per well of kinase buffer containing 200-300 ng purified cytoplasmic domain KDR protein (BPS Bioscience, San Diego, Calif.).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 397.4, ALogP 4.92, HBA 3, HBD 1, PSA 45.23, QED 0.68
Compound (SMILES): Cc1cccc(NC(=O)Nc2ccc(N3CCc4ccncc4C3)cc2)c1
InChIKey: QBEDAVXOZVBLMC-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Kinase Assay: Biochemical KDR kinase assays were performed in 96 well microliter plates that were coated overnight with 75 .mu.g/well of poly-Glu-Tyr (4:1) in 10 mM Phosphate Buffered Saline (PBS), pH 7.4. The coated plates were washed with 2 mLs per well PBS+0.05% Tween-20 (PBS-T), blocked by incubation with PBS containing 1% BSA, then washed with 2 mLs per well PBS-T prior to starting the reaction. Reactions were carried out in 100 .mu.L reaction volumes containing 2.7 .mu.M ATP in kinase buffer (50 mM Hepes buffer pH 7.4, 20 mM MgCl.sub.2, 0.1 mM MnCl.sub.2 and 0.2 mM Na.sub.3VO.sub.4). Test compounds were reconstituted in 100% DMSO and added to the reaction to give a final DMSO concentration of 5%. Reactions were initiated by the addition 20 ul per well of kinase buffer containing 200-300 ng purified cytoplasmic domain KDR protein (BPS Bioscience, San Diego, Calif.).
Measurement: IC50 = 2200 nM (pChEMBL 5.659999847412109)
Descriptors: MW 358.45, ALogP 4.6, HBA 3, HBD 2, PSA 57.26, QED 0.72
Compound (SMILES): O=C(Nc1ccccc1)Nc1ccc(N2CCc3ccncc3C2)cc1
InChIKey: DETQEUBCKFGKNU-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Kinase Assay: Biochemical KDR kinase assays were performed in 96 well microliter plates that were coated overnight with 75 μg/well of poly-Glu-Tyr (4:1) in 10 mM Phosphate Buffered Saline (PBS), pH 7.4. The coated plates were washed with 2 mls per well PBS+0.05% Tween-20 (PBS-T), blocked by incubation with PBS containing 1% BSA, then washed with 2 mls per well PBS-T prior to starting the reaction. Reactions were carried out in 100 μL reaction volumes containing 2.7 μM ATP in kinase buffer (50 mM Hepes buffer pH 7.4, 20 mM MgCl2, 0.1 mM MnCl2 and 0.2 mM Na3VO4). Test compounds were reconstituted in 100% DMSO and added to the reaction to give a final DMSO concentration of 5%. Reactions were initiated by the addition 20 ul per well of kinase buffer containing 200-300 ng purified cytoplasmic domain KDR protein (BPS Bioscience, San Diego, Calif.). Following a 15 minute incubation at 30° C., the reactions were washed 2 mls per well PBS-T. 100 μl of a monoclonal anti-phosphotyrosine antibody-peroxidase conjugate diluted 1:10,000 in PBS-T was added to the wells for 30 minutes. Following a 2 mls per well wash with PBS-Tween-20, 100 μl of O-Phenylenediamine Dihydrochloride in phosphate-citrate buffer, containing urea hydrogen peroxide, was added to the wells for 7-10 minutes as a colorimetric substrate for the peroxidase. The reaction was terminated by the addition of 100 μl of 2.5N H2SO4 to each well and read using a microplate ELISA reader set at 492 nm.
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 344.42, ALogP 4.29, HBA 3, HBD 2, PSA 57.26, QED 0.75
Compound (SMILES): Cc1ccc(NC(=O)Nc2ccc(N3CCc4ccncc4C3)cc2)cc1
InChIKey: SFNSIRBXKCUTMM-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Kinase Assay: Biochemical KDR kinase assays were performed in 96 well microliter plates that were coated overnight with 75 .mu.g/well of poly-Glu-Tyr (4:1) in 10 mM Phosphate Buffered Saline (PBS), pH 7.4. The coated plates were washed with 2 mLs per well PBS+0.05% Tween-20 (PBS-T), blocked by incubation with PBS containing 1% BSA, then washed with 2 mLs per well PBS-T prior to starting the reaction. Reactions were carried out in 100 .mu.L reaction volumes containing 2.7 .mu.M ATP in kinase buffer (50 mM Hepes buffer pH 7.4, 20 mM MgCl.sub.2, 0.1 mM MnCl.sub.2 and 0.2 mM Na.sub.3VO.sub.4). Test compounds were reconstituted in 100% DMSO and added to the reaction to give a final DMSO concentration of 5%. Reactions were initiated by the addition 20 ul per well of kinase buffer containing 200-300 ng purified cytoplasmic domain KDR protein (BPS Bioscience, San Diego, Calif.).
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 358.45, ALogP 4.6, HBA 3, HBD 2, PSA 57.26, QED 0.72
Compound (SMILES): Cc1cccc(NC(=O)Nc2ccc(N3CCc4ccncc4C3)c(C)c2)c1
InChIKey: HMQWFQHVYCBHFE-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Kinase Assay: Biochemical KDR kinase assays were performed in 96 well microliter plates that were coated overnight with 75 .mu.g/well of poly-Glu-Tyr (4:1) in 10 mM Phosphate Buffered Saline (PBS), pH 7.4. The coated plates were washed with 2 mLs per well PBS+0.05% Tween-20 (PBS-T), blocked by incubation with PBS containing 1% BSA, then washed with 2 mLs per well PBS-T prior to starting the reaction. Reactions were carried out in 100 .mu.L reaction volumes containing 2.7 .mu.M ATP in kinase buffer (50 mM Hepes buffer pH 7.4, 20 mM MgCl.sub.2, 0.1 mM MnCl.sub.2 and 0.2 mM Na.sub.3VO.sub.4). Test compounds were reconstituted in 100% DMSO and added to the reaction to give a final DMSO concentration of 5%. Reactions were initiated by the addition 20 ul per well of kinase buffer containing 200-300 ng purified cytoplasmic domain KDR protein (BPS Bioscience, San Diego, Calif.).
Measurement: IC50 = 308 nM (pChEMBL 6.510000228881836)
Descriptors: MW 372.47, ALogP 4.91, HBA 3, HBD 2, PSA 57.26, QED 0.69
Compound (SMILES): Cc1cccc(NC(=O)Nc2ccc(N3CCc4ccncc4C3)cc2C)c1
InChIKey: IGDCJUNQEHDNIA-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Kinase Assay: Biochemical KDR kinase assays were performed in 96 well microliter plates that were coated overnight with 75 .mu.g/well of poly-Glu-Tyr (4:1) in 10 mM Phosphate Buffered Saline (PBS), pH 7.4. The coated plates were washed with 2 mLs per well PBS+0.05% Tween-20 (PBS-T), blocked by incubation with PBS containing 1% BSA, then washed with 2 mLs per well PBS-T prior to starting the reaction. Reactions were carried out in 100 .mu.L reaction volumes containing 2.7 .mu.M ATP in kinase buffer (50 mM Hepes buffer pH 7.4, 20 mM MgCl.sub.2, 0.1 mM MnCl.sub.2 and 0.2 mM Na.sub.3VO.sub.4). Test compounds were reconstituted in 100% DMSO and added to the reaction to give a final DMSO concentration of 5%. Reactions were initiated by the addition 20 ul per well of kinase buffer containing 200-300 ng purified cytoplasmic domain KDR protein (BPS Bioscience, San Diego, Calif.).
Measurement: IC50 = 454 nM (pChEMBL 6.340000152587891)
Descriptors: MW 372.47, ALogP 4.91, HBA 3, HBD 2, PSA 57.26, QED 0.69
Compound (SMILES): CC(C)c1cccc(NC(=O)c2cccc(N3CCc4ccncc4C3)c2)c1
InChIKey: RHNRCAGSWLRFCY-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Kinase Assay: Biochemical KDR kinase assays were performed in 96 well microliter plates that were coated overnight with 75 .mu.g/well of poly-Glu-Tyr (4:1) in 10 mM Phosphate Buffered Saline (PBS), pH 7.4. The coated plates were washed with 2 mLs per well PBS+0.05% Tween-20 (PBS-T), blocked by incubation with PBS containing 1% BSA, then washed with 2 mLs per well PBS-T prior to starting the reaction. Reactions were carried out in 100 .mu.L reaction volumes containing 2.7 .mu.M ATP in kinase buffer (50 mM Hepes buffer pH 7.4, 20 mM MgCl.sub.2, 0.1 mM MnCl.sub.2 and 0.2 mM Na.sub.3VO.sub.4). Test compounds were reconstituted in 100% DMSO and added to the reaction to give a final DMSO concentration of 5%. Reactions were initiated by the addition 20 ul per well of kinase buffer containing 200-300 ng purified cytoplasmic domain KDR protein (BPS Bioscience, San Diego, Calif.).
Measurement: IC50 = 39 nM (pChEMBL 7.409999847412109)
Descriptors: MW 371.48, ALogP 5.02, HBA 3, HBD 1, PSA 45.23, QED 0.7
Compound (SMILES): COC(=O)c1cncc2c1CCN(c1cccc(C(=O)Nc3cccc(C(C)C)c3)c1)C2
InChIKey: HTJCJGPUYPCIIH-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Kinase Assay: Biochemical KDR kinase assays were performed in 96 well microliter plates that were coated overnight with 75 .mu.g/well of poly-Glu-Tyr (4:1) in 10 mM Phosphate Buffered Saline (PBS), pH 7.4. The coated plates were washed with 2 mLs per well PBS+0.05% Tween-20 (PBS-T), blocked by incubation with PBS containing 1% BSA, then washed with 2 mLs per well PBS-T prior to starting the reaction. Reactions were carried out in 100 .mu.L reaction volumes containing 2.7 .mu.M ATP in kinase buffer (50 mM Hepes buffer pH 7.4, 20 mM MgCl.sub.2, 0.1 mM MnCl.sub.2 and 0.2 mM Na.sub.3VO.sub.4). Test compounds were reconstituted in 100% DMSO and added to the reaction to give a final DMSO concentration of 5%. Reactions were initiated by the addition 20 ul per well of kinase buffer containing 200-300 ng purified cytoplasmic domain KDR protein (BPS Bioscience, San Diego, Calif.).
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 429.52, ALogP 4.81, HBA 5, HBD 1, PSA 71.53, QED 0.59
Compound (SMILES): CC(C)c1cccc(NC(=O)c2cccc(N3CCc4c(cncc4C(=O)O)C3)c2)c1
InChIKey: PDGAZDOEDKXTCY-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Kinase Assay: Biochemical KDR kinase assays were performed in 96 well microliter plates that were coated overnight with 75 .mu.g/well of poly-Glu-Tyr (4:1) in 10 mM Phosphate Buffered Saline (PBS), pH 7.4. The coated plates were washed with 2 mLs per well PBS+0.05% Tween-20 (PBS-T), blocked by incubation with PBS containing 1% BSA, then washed with 2 mLs per well PBS-T prior to starting the reaction. Reactions were carried out in 100 .mu.L reaction volumes containing 2.7 .mu.M ATP in kinase buffer (50 mM Hepes buffer pH 7.4, 20 mM MgCl.sub.2, 0.1 mM MnCl.sub.2 and 0.2 mM Na.sub.3VO.sub.4). Test compounds were reconstituted in 100% DMSO and added to the reaction to give a final DMSO concentration of 5%. Reactions were initiated by the addition 20 ul per well of kinase buffer containing 200-300 ng purified cytoplasmic domain KDR protein (BPS Bioscience, San Diego, Calif.).
Measurement: IC50 = 54 nM (pChEMBL 7.269999980926514)
Descriptors: MW 415.49, ALogP 4.72, HBA 4, HBD 2, PSA 82.53, QED 0.63