lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1ccccc1/C=C/c1cc(O)c2ccccc2n1
InChIKey: NUTJRCJUMGYLIV-ZHACJKMWSA-N
Target: Dihydroorotate dehydrogenase, mitochondrial, putative (SINGLE PROTEIN), Plasmodium vivax (strain Salvador I)
UniProt: A5K1N1
Assay: Enzymatic Assays: Type 2 DHODH activity was monitored with either the direct assay measuring the formation of orotate or via a chromogen reduction assay using DCIP. Although the extinction coefficient and absorption wavelength are preferable for the chromogen reduction assay, the inorganic electron acceptor DCIP can be utilized by DHODH as the final electron acceptor in lieu of CoQn when the endogenous substrate is at a low concentration. As such, the direct assay was used to measure the binding affinity of pfDHODH to CoQD and L-DHO. The enzymatic reaction was performed by varying the L-DHO concentration (1-400 μM) or CoQD concentration (1-200 μM) while keeping the other substrate constant and in excess. Inhibition of DHODH by small molecules was evaluated using the chromogen based assay with a final substrate concentration of 200 μM L-DHO, 18 μM CoQD, and 100 μM DCIP, unless otherwise noted.
Measurement: IC50 = 5600 nM (pChEMBL 5.25)
Descriptors: MW 261.32, ALogP 4.42, HBA 2, HBD 1, PSA 33.12, QED 0.74
Compound (SMILES): CCCCCC1CCCc2c1nc1ccccc1c2O
InChIKey: BLBSNYYRLAWWDS-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (fumarate) (SINGLE PROTEIN), Saccharomyces cerevisiae S288c
UniProt: P28272
Assay: Enzymatic Assays: Type 2 DHODH activity was monitored with either the direct assay measuring the formation of orotate or via a chromogen reduction assay using DCIP. Although the extinction coefficient and absorption wavelength are preferable for the chromogen reduction assay, the inorganic electron acceptor DCIP can be utilized by DHODH as the final electron acceptor in lieu of CoQn when the endogenous substrate is at a low concentration. As such, the direct assay was used to measure the binding affinity of pfDHODH to CoQD and L-DHO. The enzymatic reaction was performed by varying the L-DHO concentration (1-400 μM) or CoQD concentration (1-200 μM) while keeping the other substrate constant and in excess. Inhibition of DHODH by small molecules was evaluated using the chromogen based assay with a final substrate concentration of 200 μM L-DHO, 18 μM CoQD, and 100 μM DCIP, unless otherwise noted.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 269.39, ALogP 4.94, HBA 2, HBD 1, PSA 33.12, QED 0.8
Compound (SMILES): CCCNC(=O)c1ccc(-n2c(C)cc3ccccc32)s1
InChIKey: OQYMMMMIAASALW-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (quinone), mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q02127
Assay: Enzymatic Assays: Type 2 DHODH activity was monitored with either the direct assay measuring the formation of orotate or via a chromogen reduction assay using DCIP. Although the extinction coefficient and absorption wavelength are preferable for the chromogen reduction assay, the inorganic electron acceptor DCIP can be utilized by DHODH as the final electron acceptor in lieu of CoQn when the endogenous substrate is at a low concentration. As such, the direct assay was used to measure the binding affinity of pfDHODH to CoQD and L-DHO. The enzymatic reaction was performed by varying the L-DHO concentration (1-400 μM) or CoQD concentration (1-200 μM) while keeping the other substrate constant and in excess. Inhibition of DHODH by small molecules was evaluated using the chromogen based assay with a final substrate concentration of 200 μM L-DHO, 18 μM CoQD, and 100 μM DCIP, unless otherwise noted.
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 298.41, ALogP 4.14, HBA 3, HBD 1, PSA 34.03, QED 0.77
Compound (SMILES): O=C(NC1CC1)c1ccc(N2CCSc3ccccc32)s1
InChIKey: RNLKPTOJCXLFDG-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (quinone), mitochondrial (SINGLE PROTEIN), Plasmodium berghei (strain Anka)
UniProt: A0A0Y9T855
Assay: Enzymatic Assays: Type 2 DHODH activity was monitored with either the direct assay measuring the formation of orotate or via a chromogen reduction assay using DCIP. Although the extinction coefficient and absorption wavelength are preferable for the chromogen reduction assay, the inorganic electron acceptor DCIP can be utilized by DHODH as the final electron acceptor in lieu of CoQn when the endogenous substrate is at a low concentration. As such, the direct assay was used to measure the binding affinity of pfDHODH to CoQD and L-DHO. The enzymatic reaction was performed by varying the L-DHO concentration (1-400 μM) or CoQD concentration (1-200 μM) while keeping the other substrate constant and in excess. Inhibition of DHODH by small molecules was evaluated using the chromogen based assay with a final substrate concentration of 200 μM L-DHO, 18 μM CoQD, and 100 μM DCIP, unless otherwise noted.
Measurement: IC50 = 380 nM (pChEMBL 6.420000076293945)
Descriptors: MW 316.45, ALogP 3.88, HBA 4, HBD 1, PSA 32.34, QED 0.93
Compound (SMILES): Clc1cnc2nc1NCc1cccc(c1)OCc1cccc(c1)N2
InChIKey: PKOKZOVQUJMMJL-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: HTRF Kinase Assay: HTRF kinase assay: 40 μL reactions were run in black 384 well polystyrene plates in assay buffer (50 mM Tris, pH 7.8, 100 mM NaCI, 0.1 mg/mL BSA, 5 mM DTT), containing 0.5 μM Biotinylated peptide substrate, 10 mM MgCl2, 90 μM ATP, and 0.25 nM enzyme for 2 hours at 25° C. Reactions were stopped by addition of 20 μL assay buffer supplemented with an additional 50 mM NaCl, 0.4 mg/mL BSA, 45 mM EDTA, 4.5 nM LANCE Eu-W1024 labeled anti-phosphotyrosine antibody and 200 nM streptavidin conjugated SureLight-allophycocyanin. Plates were read in Fusion α-FP instrument (Perkin-Elmer).
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 338.8, ALogP 4.38, HBA 5, HBD 2, PSA 59.07, QED 0.64
Compound (SMILES): Clc1cnc2nc1NCc1cccc(c1)OCCc1cccc(c1)N2
InChIKey: HOLZGQKSANGENU-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: In Vitro Kinase Assay: One or more compounds herein were tested for inhibitory activity of JAK targets according to the following in vitro assay described in Park et al., Analytical Biochemistry 1999, 269, 94-104. The catalytic domains of human JAK1 (a.a. 837-1142), JAK2 (a.a. 828-1132) and JAK3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. The ATP concentration in the reactions was 90 uM for JAK1, 30 uM for JAK2 and 3 uM for JAK3. Reactions were carried out at room temperature for 1 hr and then stopped with 20 uL 45 mM EDTA.
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 352.83, ALogP 4.42, HBA 5, HBD 2, PSA 59.07, QED 0.63
Compound (SMILES): O=S1(=O)Nc2cccc(c2)CNc2nc(ncc2Cl)Nc2cccc1c2
InChIKey: ARCKFUMURBKDRR-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: HTRF Kinase Assay: HTRF kinase assay: 40 μL reactions were run in black 384 well polystyrene plates in assay buffer (50 mM Tris, pH 7.8, 100 mM NaCI, 0.1 mg/mL BSA, 5 mM DTT), containing 0.5 μM Biotinylated peptide substrate, 10 mM MgCl2, 90 μM ATP, and 0.25 nM enzyme for 2 hours at 25° C. Reactions were stopped by addition of 20 μL assay buffer supplemented with an additional 50 mM NaCl, 0.4 mg/mL BSA, 45 mM EDTA, 4.5 nM LANCE Eu-W1024 labeled anti-phosphotyrosine antibody and 200 nM streptavidin conjugated SureLight-allophycocyanin. Plates were read in Fusion α-FP instrument (Perkin-Elmer).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 387.85, ALogP 3.6, HBA 6, HBD 3, PSA 96.01, QED 0.55
Compound (SMILES): O=C1Nc2cccc(c2)CNc2nc(ncc2Cl)Nc2cccc1c2
InChIKey: WKFDYXPIKYJBDD-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: HTRF Kinase Assay: HTRF kinase assay: 40 μL reactions were run in black 384 well polystyrene plates in assay buffer (50 mM Tris, pH 7.8, 100 mM NaCI, 0.1 mg/mL BSA, 5 mM DTT), containing 0.5 μM Biotinylated peptide substrate, 10 mM MgCl2, 90 μM ATP, and 0.25 nM enzyme for 2 hours at 25° C. Reactions were stopped by addition of 20 μL assay buffer supplemented with an additional 50 mM NaCl, 0.4 mg/mL BSA, 45 mM EDTA, 4.5 nM LANCE Eu-W1024 labeled anti-phosphotyrosine antibody and 200 nM streptavidin conjugated SureLight-allophycocyanin. Plates were read in Fusion α-FP instrument (Perkin-Elmer).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 351.8, ALogP 4.05, HBA 5, HBD 3, PSA 78.94, QED 0.57
Compound (SMILES): Clc1cnc2nc1NCc1cccc(c1)OCCCc1cccc(c1)N2
InChIKey: WILMKMPUMOSDLH-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: HTRF Kinase Assay: HTRF kinase assay: 40 μL reactions were run in black 384 well polystyrene plates in assay buffer (50 mM Tris, pH 7.8, 100 mM NaCI, 0.1 mg/mL BSA, 5 mM DTT), containing 0.5 μM Biotinylated peptide substrate, 10 mM MgCl2, 90 μM ATP, and 0.25 nM enzyme for 2 hours at 25° C. Reactions were stopped by addition of 20 μL assay buffer supplemented with an additional 50 mM NaCl, 0.4 mg/mL BSA, 45 mM EDTA, 4.5 nM LANCE Eu-W1024 labeled anti-phosphotyrosine antibody and 200 nM streptavidin conjugated SureLight-allophycocyanin. Plates were read in Fusion α-FP instrument (Perkin-Elmer).
Measurement: IC50 = 706 nM (pChEMBL 6.150000095367432)
Descriptors: MW 366.85, ALogP 4.81, HBA 5, HBD 2, PSA 59.07, QED 0.6
Compound (SMILES): C[C@H]1Nc2nc(ncc2Cl)Nc2cccc(c2)COc2cccc1c2
InChIKey: OMIMDZMFZXMMGS-GFCCVEGCSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: In Vitro Kinase Assay: One or more compounds herein were tested for inhibitory activity of JAK targets according to the following in vitro assay described in Park et al., Analytical Biochemistry 1999, 269, 94-104. The catalytic domains of human JAK1 (a.a. 837-1142), JAK2 (a.a. 828-1132) and JAK3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. The ATP concentration in the reactions was 90 uM for JAK1, 30 uM for JAK2 and 3 uM for JAK3. Reactions were carried out at room temperature for 1 hr and then stopped with 20 uL 45 mM EDTA.
Measurement: IC50 = 350 nM (pChEMBL 6.460000038146973)
Descriptors: MW 352.83, ALogP 4.94, HBA 5, HBD 2, PSA 59.07, QED 0.6
Compound (SMILES): Clc1cnc2nc1NCc1cccc(c1)OCCOc1cccc(c1)N2
InChIKey: JRMWFZSAQXNBSZ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: In Vitro Kinase Assay: One or more compounds herein were tested for inhibitory activity of JAK targets according to the following in vitro assay described in Park et al., Analytical Biochemistry 1999, 269, 94-104. The catalytic domains of human JAK1 (a.a. 837-1142), JAK2 (a.a. 828-1132) and JAK3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. The ATP concentration in the reactions was 90 uM for JAK1, 30 uM for JAK2 and 3 uM for JAK3. Reactions were carried out at room temperature for 1 hr and then stopped with 20 uL 45 mM EDTA.
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 368.82, ALogP 4.26, HBA 6, HBD 2, PSA 68.3, QED 0.62
Compound (SMILES): Clc1cnc2nc1NCCc1cccc(c1)OCc1cccc(c1)N2
InChIKey: BBVOVZFYMUEXGT-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: In Vitro Kinase Assay: One or more compounds herein were tested for inhibitory activity of JAK targets according to the following in vitro assay described in Park et al., Analytical Biochemistry 1999, 269, 94-104. The catalytic domains of human JAK1 (a.a. 837-1142), JAK2 (a.a. 828-1132) and JAK3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. The ATP concentration in the reactions was 90 uM for JAK1, 30 uM for JAK2 and 3 uM for JAK3. Reactions were carried out at room temperature for 1 hr and then stopped with 20 uL 45 mM EDTA.
Measurement: IC50 = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 352.83, ALogP 4.42, HBA 5, HBD 2, PSA 59.07, QED 0.63
Compound (SMILES): Clc1cnc2nc1NCCc1cccc(c1)OCCc1cccc(c1)N2
InChIKey: DDEPHNOBUQYIBZ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: In Vitro Kinase Assay: One or more compounds herein were tested for inhibitory activity of JAK targets according to the following in vitro assay described in Park et al., Analytical Biochemistry 1999, 269, 94-104. The catalytic domains of human JAK1 (a.a. 837-1142), JAK2 (a.a. 828-1132) and JAK3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. The ATP concentration in the reactions was 90 uM for JAK1, 30 uM for JAK2 and 3 uM for JAK3. Reactions were carried out at room temperature for 1 hr and then stopped with 20 uL 45 mM EDTA.
Measurement: IC50 = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 366.85, ALogP 4.46, HBA 5, HBD 2, PSA 59.07, QED 0.61
Compound (SMILES): Clc1cnc2nc1NCCCc1cccc(c1)OCc1cccc(c1)N2
InChIKey: PGBXYNXDKMTLPH-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: HTRF Kinase Assay: HTRF kinase assay: 40 μL reactions were run in black 384 well polystyrene plates in assay buffer (50 mM Tris, pH 7.8, 100 mM NaCI, 0.1 mg/mL BSA, 5 mM DTT), containing 0.5 μM Biotinylated peptide substrate, 10 mM MgCl2, 90 μM ATP, and 0.25 nM enzyme for 2 hours at 25° C. Reactions were stopped by addition of 20 μL assay buffer supplemented with an additional 50 mM NaCl, 0.4 mg/mL BSA, 45 mM EDTA, 4.5 nM LANCE Eu-W1024 labeled anti-phosphotyrosine antibody and 200 nM streptavidin conjugated SureLight-allophycocyanin. Plates were read in Fusion α-FP instrument (Perkin-Elmer).
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 366.85, ALogP 4.81, HBA 5, HBD 2, PSA 59.07, QED 0.6
Compound (SMILES): C[C@@H]1Nc2nc(ncc2Cl)Nc2cccc(c2)COc2cccc1c2
InChIKey: OMIMDZMFZXMMGS-LBPRGKRZSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: In Vitro Kinase Assay: One or more compounds herein were tested for inhibitory activity of JAK targets according to the following in vitro assay described in Park et al., Analytical Biochemistry 1999, 269, 94-104. The catalytic domains of human JAK1 (a.a. 837-1142), JAK2 (a.a. 828-1132) and JAK3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. The ATP concentration in the reactions was 90 uM for JAK1, 30 uM for JAK2 and 3 uM for JAK3. Reactions were carried out at room temperature for 1 hr and then stopped with 20 uL 45 mM EDTA.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 352.83, ALogP 4.94, HBA 5, HBD 2, PSA 59.07, QED 0.6
Compound (SMILES): Clc1cnc2nc1NCCc1cccc(c1)OCCCc1cccc(c1)N2
InChIKey: YCEQOGSAKUVGII-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: HTRF Kinase Assay: HTRF kinase assay: 40 μL reactions were run in black 384 well polystyrene plates in assay buffer (50 mM Tris, pH 7.8, 100 mM NaCI, 0.1 mg/mL BSA, 5 mM DTT), containing 0.5 μM Biotinylated peptide substrate, 10 mM MgCl2, 90 μM ATP, and 0.25 nM enzyme for 2 hours at 25° C. Reactions were stopped by addition of 20 μL assay buffer supplemented with an additional 50 mM NaCl, 0.4 mg/mL BSA, 45 mM EDTA, 4.5 nM LANCE Eu-W1024 labeled anti-phosphotyrosine antibody and 200 nM streptavidin conjugated SureLight-allophycocyanin. Plates were read in Fusion α-FP instrument (Perkin-Elmer).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 380.88, ALogP 4.85, HBA 5, HBD 2, PSA 59.07, QED 0.58
Compound (SMILES): Clc1cnc2nc1NCCCc1cccc(c1)OCCc1cccc(c1)N2
InChIKey: NLGCDKKLEZPXLI-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: HTRF Kinase Assay: HTRF kinase assay: 40 μL reactions were run in black 384 well polystyrene plates in assay buffer (50 mM Tris, pH 7.8, 100 mM NaCI, 0.1 mg/mL BSA, 5 mM DTT), containing 0.5 μM Biotinylated peptide substrate, 10 mM MgCl2, 90 μM ATP, and 0.25 nM enzyme for 2 hours at 25° C. Reactions were stopped by addition of 20 μL assay buffer supplemented with an additional 50 mM NaCl, 0.4 mg/mL BSA, 45 mM EDTA, 4.5 nM LANCE Eu-W1024 labeled anti-phosphotyrosine antibody and 200 nM streptavidin conjugated SureLight-allophycocyanin. Plates were read in Fusion α-FP instrument (Perkin-Elmer).
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 380.88, ALogP 4.85, HBA 5, HBD 2, PSA 59.07, QED 0.58
Compound (SMILES): Clc1cnc2nc1NCc1cc(ccc1Br)OCCCc1cccc(c1)N2
InChIKey: YYZSNJQQGCXQNG-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: HTRF Kinase Assay: HTRF kinase assay: 40 μL reactions were run in black 384 well polystyrene plates in assay buffer (50 mM Tris, pH 7.8, 100 mM NaCI, 0.1 mg/mL BSA, 5 mM DTT), containing 0.5 μM Biotinylated peptide substrate, 10 mM MgCl2, 90 μM ATP, and 0.25 nM enzyme for 2 hours at 25° C. Reactions were stopped by addition of 20 μL assay buffer supplemented with an additional 50 mM NaCl, 0.4 mg/mL BSA, 45 mM EDTA, 4.5 nM LANCE Eu-W1024 labeled anti-phosphotyrosine antibody and 200 nM streptavidin conjugated SureLight-allophycocyanin. Plates were read in Fusion α-FP instrument (Perkin-Elmer).
Measurement: IC50 = 8200 nM (pChEMBL 5.090000152587891)
Descriptors: MW 445.75, ALogP 5.57, HBA 5, HBD 2, PSA 59.07, QED 0.47
Compound (SMILES): Clc1cnc2nc1NCc1cc(ccc1-c1ccccc1)OCCCc1cccc(c1)N2
InChIKey: JHMLRNFFLKYFAU-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: In Vitro Kinase Assay: One or more compounds herein were tested for inhibitory activity of JAK targets according to the following in vitro assay described in Park et al., Analytical Biochemistry 1999, 269, 94-104. The catalytic domains of human JAK1 (a.a. 837-1142), JAK2 (a.a. 828-1132) and JAK3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. The ATP concentration in the reactions was 90 uM for JAK1, 30 uM for JAK2 and 3 uM for JAK3. Reactions were carried out at room temperature for 1 hr and then stopped with 20 uL 45 mM EDTA.
Measurement: IC50 = 41 nM (pChEMBL 7.389999866485596)
Descriptors: MW 442.95, ALogP 6.48, HBA 5, HBD 2, PSA 59.07, QED 0.35
Compound (SMILES): Clc1cnc2nc1NCc1cc(Br)cc(c1)OCCCc1cccc(c1)N2
InChIKey: IBAVCNVUPMTBKJ-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: HTRF Kinase Assay: HTRF kinase assay: 40 μL reactions were run in black 384 well polystyrene plates in assay buffer (50 mM Tris, pH 7.8, 100 mM NaCI, 0.1 mg/mL BSA, 5 mM DTT), containing 0.5 μM Biotinylated peptide substrate, 10 mM MgCl2, 90 μM ATP, and 0.25 nM enzyme for 2 hours at 25° C. Reactions were stopped by addition of 20 μL assay buffer supplemented with an additional 50 mM NaCl, 0.4 mg/mL BSA, 45 mM EDTA, 4.5 nM LANCE Eu-W1024 labeled anti-phosphotyrosine antibody and 200 nM streptavidin conjugated SureLight-allophycocyanin. Plates were read in Fusion α-FP instrument (Perkin-Elmer).
Measurement: IC50 = 280 nM (pChEMBL 6.550000190734863)
Descriptors: MW 445.75, ALogP 5.57, HBA 5, HBD 2, PSA 59.07, QED 0.47
Compound (SMILES): Nc1ccc2cc1CCc1cncc(c1)Nc1ncc(Cl)c(n1)NC2
InChIKey: FKLWUWJYBORMDH-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: HTRF Kinase Assay: HTRF kinase assay: 40 μL reactions were run in black 384 well polystyrene plates in assay buffer (50 mM Tris, pH 7.8, 100 mM NaCI, 0.1 mg/mL BSA, 5 mM DTT), containing 0.5 μM Biotinylated peptide substrate, 10 mM MgCl2, 90 μM ATP, and 0.25 nM enzyme for 2 hours at 25° C. Reactions were stopped by addition of 20 μL assay buffer supplemented with an additional 50 mM NaCl, 0.4 mg/mL BSA, 45 mM EDTA, 4.5 nM LANCE Eu-W1024 labeled anti-phosphotyrosine antibody and 200 nM streptavidin conjugated SureLight-allophycocyanin. Plates were read in Fusion α-FP instrument (Perkin-Elmer).
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 352.83, ALogP 3.56, HBA 6, HBD 3, PSA 88.75, QED 0.54
Compound (SMILES): O=C(Nc1ccc2cc1CCc1cncc(c1)Nc1ncc(Cl)c(n1)NC2)c1ccccc1
InChIKey: DZOSAHMEHFLHAZ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: In Vitro Kinase Assay: One or more compounds herein were tested for inhibitory activity of JAK targets according to the following in vitro assay described in Park et al., Analytical Biochemistry 1999, 269, 94-104. The catalytic domains of human JAK1 (a.a. 837-1142), JAK2 (a.a. 828-1132) and JAK3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. The ATP concentration in the reactions was 90 uM for JAK1, 30 uM for JAK2 and 3 uM for JAK3. Reactions were carried out at room temperature for 1 hr and then stopped with 20 uL 45 mM EDTA.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 456.94, ALogP 5.23, HBA 6, HBD 3, PSA 91.83, QED 0.38
Compound (SMILES): N#Cc1ccccc1S(=O)(=O)Nc1ccc2cc1CCc1cncc(c1)Nc1ncc(Cl)c(n1)NC2
InChIKey: AVINPMJXOWDOIE-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: HTRF Kinase Assay: HTRF kinase assay: 40 μL reactions were run in black 384 well polystyrene plates in assay buffer (50 mM Tris, pH 7.8, 100 mM NaCI, 0.1 mg/mL BSA, 5 mM DTT), containing 0.5 μM Biotinylated peptide substrate, 10 mM MgCl2, 90 μM ATP, and 0.25 nM enzyme for 2 hours at 25° C. Reactions were stopped by addition of 20 μL assay buffer supplemented with an additional 50 mM NaCl, 0.4 mg/mL BSA, 45 mM EDTA, 4.5 nM LANCE Eu-W1024 labeled anti-phosphotyrosine antibody and 200 nM streptavidin conjugated SureLight-allophycocyanin. Plates were read in Fusion α-FP instrument (Perkin-Elmer).
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 518, ALogP 4.65, HBA 8, HBD 3, PSA 132.69, QED 0.36
Compound (SMILES): Nc1nc(-n2cccn2)nc(-n2cccn2)c1Br
InChIKey: ATFXVNUWQOXRRU-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Inhibition of A2aR (unknown origin) expressed in HEK293 cells incubated overnight by dual luciferase reporter assay
Measurement: IC50 = 5.6 nM (pChEMBL 8.25)
Descriptors: MW 306.13, ALogP 1.19, HBA 7, HBD 1, PSA 87.44, QED 0.77
Compound (SMILES): O=C(O)c1nc2ccccc2n([C@H]2C[C@H]3CC[C@@H](C2)N3C23CC4CC(CC(C4)C2)C3)c1=O
InChIKey: PYJURBZJZDHCNO-ODWFAFRFSA-N
Target: Opioid growth factor receptor-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5TC84
Assay: Radioligand Binding Assay: Radioligand binding assays (screening and dose-displacement) used 0.1nM [3H]-nociceptin (NEN; 87.7 Cl/nimole) with 10-20 ug membrane protein in a final volume of 500uL binding buffer (10mM MgCl2, 1mM EDTA, 5% DMSO, 50mM HEPES, pH 7.4). Non-specific binding was determined in the presence of 10nM unlabeled nociceptin (American Peptide Company). All reactions were performed in 96-deep well polypropylene plates for 1 h at about 25C. Binding reactions were terminated by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma). Harvesting was performed using a 96-well tissue harvester (Packard) followed by three filtration washes with 500uL ice-cold binding buffer. Filter plates were subsequently dried at 50C for 2-3 hours. Fifty uL/well scintillation cocktail (BetaScint; Wallac) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki = 89.9 nM (pChEMBL 7.050000190734863)
Descriptors: MW 433.55, ALogP 4.23, HBA 5, HBD 1, PSA 75.43, QED 0.78
Compound (SMILES): O=C(CCCCCCNC(=O)c1cnc(N(c2ccccc2)c2ccccc2Cl)nc1)NO
InChIKey: VLIUIBXPEDFJRF-UHFFFAOYSA-N
Target: Histone deacetylase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56524
Assay: Inhibition of recombinant full length human HDAC4 expressed in baculovirus infected Sf9 cells using FAM-RHKK-TFAc as substrate incubated for 1.5 hrs by electrophoretic mobility shift assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 467.96, ALogP 4.79, HBA 6, HBD 3, PSA 107.45, QED 0.21
Compound (SMILES): CNC(=O)[C@@H]1NC2(CCCCC2)[C@@]2(C(=O)Nc3cc(Cl)ccc32)[C@H]1c1cccc(Cl)c1F
InChIKey: LHBZDASUSDFFIL-MFSJNOQSSA-N
Target: Protein cereblon (SINGLE PROTEIN), Homo sapiens
UniProt: Q96SW2
Assay: Binding affinity to cereblon in human RV4:11/IRMI-2 cells harboring p53 hotspot mutation Y236H/R249G assessed as cell growth inhibition measured after 4 days
Measurement: IC50 > 10 nM (pChEMBL 8)
Descriptors: MW 476.38, ALogP 4.53, HBA 3, HBD 3, PSA 70.23, QED 0.6
Compound (SMILES): Nc1nc(-n2cccn2)nc(-n2cccn2)c1Br
InChIKey: ATFXVNUWQOXRRU-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Inhibition of A2bR (unknown origin) expressed in HEK293 cells incubated overnight by dual luciferase reporter assay
Measurement: IC50 = 680 nM (pChEMBL 6.170000076293945)
Descriptors: MW 306.13, ALogP 1.19, HBA 7, HBD 1, PSA 87.44, QED 0.77
Compound (SMILES): O=C(O)c1nc2ccccc2n([C@H]2C[C@H]3CC[C@@H](C2)N3C23CC4CC(CC(C4)C2)C3)c1=O
InChIKey: PYJURBZJZDHCNO-ODWFAFRFSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Radioligand Binding Assay: Radioligand dose-displacement binding assays for u-opioid receptors used 0.2nM[3H]-diprenorphine (NEN, Boston, Mass.), with 5-20mg membrane protein/well in a final volume of 500 uL binding buffer (10mM MgCl2, 1mM EDTA, 5% DMSO, 50mM HEPES, pH 7.4). Reactions were carried out in the absence or presence of increasing concentrations of unlabeled naloxone. All reactions were conducted in 96-deep well polypropylene plates for 1-2 hr at about 25C. Binding reactions were terminated by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard, Meriden, Conn.) presoaked in 0.5% polyethylemimine using a 96-well tissue harvester (Brandel, Gaithersburg, Md.) followed by performing three filtration washes with 500uL of ice-cold binding buffer. Filter plates were subsequently dried at 50C for 2-3 hours. BetaScint scintillation cocktail (Wallac, Turku, Finland) was added (50uL/well), and plates were counted using a Packard Top-Count for 1 min/well.
Measurement: Ki = 10970 nM (pChEMBL 4.960000038146973)
Descriptors: MW 433.55, ALogP 4.23, HBA 5, HBD 1, PSA 75.43, QED 0.78
Compound (SMILES): O=C(CCCCCCNC(=O)c1cnc(N(c2ccccc2)c2ccccc2Cl)nc1)NO
InChIKey: VLIUIBXPEDFJRF-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of recombinant full length human HDAC3 expressed in SF9 baculovirus using FAM- labelled acetylated peptide as substrate measured by Electrophoretic mobility shift assay
Measurement: IC50 = 12.5 nM (pChEMBL 7.900000095367432)
Descriptors: MW 467.96, ALogP 4.79, HBA 6, HBD 3, PSA 107.45, QED 0.21
Compound (SMILES): CNC(=O)[C@@H]1NC2(CCCCC2)[C@@]2(C(=O)Nc3cc(Cl)ccc32)[C@H]1c1cccc(Cl)c1F
InChIKey: LHBZDASUSDFFIL-MFSJNOQSSA-N
Target: Protein cereblon (SINGLE PROTEIN), Homo sapiens
UniProt: Q96SW2
Assay: Binding affinity to cereblon in human MDA-MB-231 cells assessed as cell growth inhibition measured after 4 days
Measurement: IC50 > 10 nM (pChEMBL 8)
Descriptors: MW 476.38, ALogP 4.53, HBA 3, HBD 3, PSA 70.23, QED 0.6
Compound (SMILES): CCCNC(=O)c1ccc(-n2c(C)cc3ccccc32)s1
InChIKey: OQYMMMMIAASALW-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (quinone), mitochondrial (SINGLE PROTEIN), Plasmodium berghei (strain Anka)
UniProt: A0A0Y9T855
Assay: Enzymatic Assays: Type 2 DHODH activity was monitored with either the direct assay measuring the formation of orotate or via a chromogen reduction assay using DCIP. Although the extinction coefficient and absorption wavelength are preferable for the chromogen reduction assay, the inorganic electron acceptor DCIP can be utilized by DHODH as the final electron acceptor in lieu of CoQn when the endogenous substrate is at a low concentration. As such, the direct assay was used to measure the binding affinity of pfDHODH to CoQD and L-DHO. The enzymatic reaction was performed by varying the L-DHO concentration (1-400 μM) or CoQD concentration (1-200 μM) while keeping the other substrate constant and in excess. Inhibition of DHODH by small molecules was evaluated using the chromogen based assay with a final substrate concentration of 200 μM L-DHO, 18 μM CoQD, and 100 μM DCIP, unless otherwise noted.
Measurement: IC50 = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 298.41, ALogP 4.14, HBA 3, HBD 1, PSA 34.03, QED 0.77
Compound (SMILES): Nc1nc(-n2cccn2)nc(-n2cccn2)c1Br
InChIKey: ATFXVNUWQOXRRU-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Competition Radioligand Binding Assay: Competition assays were carried out by incubation of membranes from hA1 receptors transfected to CHO cells, [3H]-DPCPX as radioligand, buffer (HEPES 20 mM (pH=7.4), 10 mM MgCl2, 100 mM NaCl, 2 units/ml adenosine deaminase), and unlabelled ligand in a total volume of 0.2 ml for 60 min at 25 C. R-PIA was used to determinate non-specific binding. Filter over Schleicher&Schuell GF/52 filters (pre-soaked 0.5% polyethylenimine) in a Brandel cell harvester. Unbound radioligand was removed with (3x 250 ul) HEPES 20 mM (pH=7.4), 100 mM NaCl and 10 mM MgCl2. Competition assays were carried out by incubation of membranes from hA2a receptors transfected to HeLa cells, [3H]ZM241385 as radioligand, buffer (50 mM Tris-HCl (pH=7.4), 10 mM MgCl2, 1 mM EDTA, 2 units/ml adenosine deaminase), and unlabelled ligand in a total volume of 0.2 ml for 30 min at 25 C. NECA was used to determinate non-specific binding.
Measurement: Ki = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 306.13, ALogP 1.19, HBA 7, HBD 1, PSA 87.44, QED 0.77
Compound (SMILES): O=C(O)c1nc2ccccc2n([C@H]2C[C@H]3CC[C@@H](C2)N3C23CC4CC(CC(C4)C2)C3)c1=O
InChIKey: PYJURBZJZDHCNO-ODWFAFRFSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Radioligand Binding Assay: Radioligand dose displacement assays used 0.4-0.8nM [3H]-U69,593 (NEN; 40 Ci/mmole) with 10-20 ug membrane protein (recombinant kappa opioid receptor expressed in HEK 293 cells; in-house prep) in a final volume of 200 uL binding buffer (5% DMSO, 50mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 10 uM unlabeled naloxone or U69,593. All reactions were performed in 96-well polypropylene plates for 1 h at a temperature of about 25C. Binding reactions were determined by rapid filtration onto 96-well Unifilter GF/C filter plates (Packard) presoaked in 0.5% polyethylenimine (Sigma). Harvesting was performed using a 96-well tissue harvester (Packard) followed by five filtration washes with 200uL ice-cold binding buffer. Filter plates were subsequently dried at 50C for 1-2 hours. Fifty uL/well scintillation cocktail (MicroScint20, Packard) was added and plates were counted in a Packard Top-Count for 1 min/well.
Measurement: Ki = 3500 nM (pChEMBL 5.460000038146973)
Descriptors: MW 433.55, ALogP 4.23, HBA 5, HBD 1, PSA 75.43, QED 0.78
Compound (SMILES): O=C(CCCCCCNC(=O)c1cnc(N(c2ccccc2)c2ccccc2Cl)nc1)NO
InChIKey: VLIUIBXPEDFJRF-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombinant full length human HDAC6 expressed in SF9 baculovirus using FAM- labelled acetylated peptide as substrate measured by Electrophoretic mobility shift assay
Measurement: IC50 = 2.21 nM (pChEMBL 8.65999984741211)
Descriptors: MW 467.96, ALogP 4.79, HBA 6, HBD 3, PSA 107.45, QED 0.21
Compound (SMILES): CNC(=O)[C@@H]1NC2(CCCCC2)[C@@]2(C(=O)Nc3cc(Cl)ccc32)[C@H]1c1cccc(Cl)c1F
InChIKey: LHBZDASUSDFFIL-MFSJNOQSSA-N
Target: Protein cereblon (SINGLE PROTEIN), Homo sapiens
UniProt: Q96SW2
Assay: Binding affinity to cereblon in human MDA-MB-468 cells assessed as cell growth inhibition measured after 4 days
Measurement: IC50 > 10 nM (pChEMBL 8)
Descriptors: MW 476.38, ALogP 4.53, HBA 3, HBD 3, PSA 70.23, QED 0.6
Compound (SMILES): CCCNC(=O)c1ccc(-n2c(C)cc3ccccc32)s1
InChIKey: OQYMMMMIAASALW-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase, mitochondrial, putative (SINGLE PROTEIN), Plasmodium vivax (strain Salvador I)
UniProt: A5K1N1
Assay: Enzymatic Assays: Type 2 DHODH activity was monitored with either the direct assay measuring the formation of orotate or via a chromogen reduction assay using DCIP. Although the extinction coefficient and absorption wavelength are preferable for the chromogen reduction assay, the inorganic electron acceptor DCIP can be utilized by DHODH as the final electron acceptor in lieu of CoQn when the endogenous substrate is at a low concentration. As such, the direct assay was used to measure the binding affinity of pfDHODH to CoQD and L-DHO. The enzymatic reaction was performed by varying the L-DHO concentration (1-400 μM) or CoQD concentration (1-200 μM) while keeping the other substrate constant and in excess. Inhibition of DHODH by small molecules was evaluated using the chromogen based assay with a final substrate concentration of 200 μM L-DHO, 18 μM CoQD, and 100 μM DCIP, unless otherwise noted.
Measurement: IC50 = 420 nM (pChEMBL 6.380000114440918)
Descriptors: MW 298.41, ALogP 4.14, HBA 3, HBD 1, PSA 34.03, QED 0.77
Compound (SMILES): Nc1nc(-n2cccn2)nc(-n2cccn2)c1Br
InChIKey: ATFXVNUWQOXRRU-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: cAMP Production Assay: hese assays were performed at adenosine receptors transfected using a cAMP enzymeimmunoassay kit (Amersham Biosciences). CHO-A2A cells were seeded (10000 cells/well) in 96-well culture plates and incubated at 37 C. in an atmosphere with 5% CO2 in Dulbecco's Modified Eagle's Medium Nutrient Mixture F-12 (DMEM F-12), containing 10% Foetal Calf Serum (FCS) and 1% L-Glutamine. Cells were washed 3x with 200 ul assay medium (DMEM-F12 and 25 mM HEPES pH=7.4) and pre-incubated with assay medium containing 30 uM rolipram and test compounds at 37 C. for 15 min. 1 uM NECA was incubated for 15 min at 37 C. (total incubation time 30 min). Reaction was stopped with lysis buffer supplied in the kit and the enzymeimmunoassay was carried out for detection of intracellular cAMP at 450 nm in an Ultra Evolution detector (Tecan).
Measurement: Ki = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 306.13, ALogP 1.19, HBA 7, HBD 1, PSA 87.44, QED 0.77
Compound (SMILES): O=C(CCCCCCNC(=O)c1cnc(N(c2ccccc2)c2ccccc2Cl)nc1)NO
InChIKey: VLIUIBXPEDFJRF-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant full length human HDAC8 expressed in SF9 baculovirus using FAM- labelled acetylated peptide as substrate measured by Electrophoretic mobility shift assay
Measurement: IC50 = 171 nM (pChEMBL 6.769999980926514)
Descriptors: MW 467.96, ALogP 4.79, HBA 6, HBD 3, PSA 107.45, QED 0.21
Compound (SMILES): Nc1nc(-n2cccn2)nc(-n2cccn2)c1Br
InChIKey: ATFXVNUWQOXRRU-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Antagonist activity at adenosine A2A receptor (unknown origin)
Measurement: Ki = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 306.13, ALogP 1.19, HBA 7, HBD 1, PSA 87.44, QED 0.77
Compound (SMILES): O=C(CCCCCCNC(=O)c1cnc(N(c2ccccc2)c2ccccc2Cl)nc1)NO
InChIKey: VLIUIBXPEDFJRF-UHFFFAOYSA-N
Target: Histone deacetylase 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96DB2
Assay: Inhibition of recombinant full length human HDAC11 expressed in SF9 baculovirus using FAM- labelled acetylated peptide as substrate measured by Electrophoretic mobility shift assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 467.96, ALogP 4.79, HBA 6, HBD 3, PSA 107.45, QED 0.21
Compound (SMILES): O=C(CCCCCCNC(=O)c1cnc(N(c2ccccc2)c2ccccc2Cl)nc1)NO
InChIKey: VLIUIBXPEDFJRF-UHFFFAOYSA-N
Target: Histone deacetylase 6 (SINGLE PROTEIN), Danio rerio
UniProt: F8W4B7
Assay: Inhibition of N-terminal 6 His-SUMO tagged Zebrafish HDAC6 CD2 domain expressed in Escherichia coli BL21(DE3) RILP pretreated for 10 mins before FITC-M344 addition and measured after 10 mins by fluorescence polarization competition assay
Measurement: IC50 = 154 nM (pChEMBL 6.809999942779541)
Descriptors: MW 467.96, ALogP 4.79, HBA 6, HBD 3, PSA 107.45, QED 0.21
Compound (SMILES): O=C(CCCCCCNC(=O)c1cnc(N(c2ccccc2)c2ccccc2Cl)nc1)NO
InChIKey: VLIUIBXPEDFJRF-UHFFFAOYSA-N
Target: Histone deacetylase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56524
Assay: Inhibition of HDAC4 (unknown origin) using MAZ-1675 as substrate preincubated for 10 mins followed by substrate addition by microtiter plate reader assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 467.96, ALogP 4.79, HBA 6, HBD 3, PSA 107.45, QED 0.21
Compound (SMILES): O=C(CCCCCCNC(=O)c1cnc(N(c2ccccc2)c2ccccc2Cl)nc1)NO
InChIKey: VLIUIBXPEDFJRF-UHFFFAOYSA-N
Target: Histone deacetylase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQL6
Assay: Inhibition of HDAC5 (unknown origin) using MAZ-1675 as substrate preincubated for 10 mins followed by substrate addition by microtiter plate reader assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 467.96, ALogP 4.79, HBA 6, HBD 3, PSA 107.45, QED 0.21
Compound (SMILES): O=C(CCCCCCNC(=O)c1cnc(N(c2ccccc2)c2ccccc2Cl)nc1)NO
InChIKey: VLIUIBXPEDFJRF-UHFFFAOYSA-N
Target: Histone deacetylase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8WUI4
Assay: Inhibition of HDAC7 (unknown origin) using MAZ-1675 as substrate preincubated for 10 mins followed by substrate addition by microtiter plate reader assay
Measurement: IC50 = 7300 nM (pChEMBL 5.139999866485596)
Descriptors: MW 467.96, ALogP 4.79, HBA 6, HBD 3, PSA 107.45, QED 0.21
Compound (SMILES): O=C(CCCCCCNC(=O)c1cnc(N(c2ccccc2)c2ccccc2Cl)nc1)NO
InChIKey: VLIUIBXPEDFJRF-UHFFFAOYSA-N
Target: Histone deacetylase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKV0
Assay: Inhibition of HDAC9 (unknown origin) using MAZ-1675 as substrate preincubated for 10 mins followed by substrate addition by microtiter plate reader assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 467.96, ALogP 4.79, HBA 6, HBD 3, PSA 107.45, QED 0.21
Compound (SMILES): O=C(CCCCCCNC(=O)c1cnc(N(c2ccccc2)c2ccccc2Cl)nc1)NO
InChIKey: VLIUIBXPEDFJRF-UHFFFAOYSA-N
Target: Histone deacetylase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQL6
Assay: Inhibition of HDAC5 (unknown origin) using MAZ-1675 as substrate preincubated for 10 mins followed by substrate addition and shaken for 60 secs and measured over 30 mins
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 467.96, ALogP 4.79, HBA 6, HBD 3, PSA 107.45, QED 0.21
Compound (SMILES): O=C(CCCCCCNC(=O)c1cnc(N(c2ccccc2)c2ccccc2Cl)nc1)NO
InChIKey: VLIUIBXPEDFJRF-UHFFFAOYSA-N
Target: Histone deacetylase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8WUI4
Assay: Inhibition of HDAC7 (unknown origin) using MAZ-1675 as substrate preincubated for 10 mins followed by substrate addition and shaken for 60 secs and measured over 30 mins
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 467.96, ALogP 4.79, HBA 6, HBD 3, PSA 107.45, QED 0.21
Compound (SMILES): O=C(CCCCCCNC(=O)c1cnc(N(c2ccccc2)c2ccccc2Cl)nc1)NO
InChIKey: VLIUIBXPEDFJRF-UHFFFAOYSA-N
Target: Histone deacetylase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKV0
Assay: Inhibition of HDAC9 (unknown origin) using MAZ-1675 as substrate preincubated for 10 mins followed by substrate addition and shaken for 60 secs and measured over 30 mins
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 467.96, ALogP 4.79, HBA 6, HBD 3, PSA 107.45, QED 0.21
Compound (SMILES): O=C(CCCCCCNC(=O)c1cnc(N(c2ccccc2)c2ccccc2Cl)nc1)NO
InChIKey: VLIUIBXPEDFJRF-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin) using FTS as substrate preincubated for 10 mins followed by substrate addition and shaken for 60 secs and measured over 30 mins
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 467.96, ALogP 4.79, HBA 6, HBD 3, PSA 107.45, QED 0.21
Compound (SMILES): O=C(CCCCCCNC(=O)c1cnc(N(c2ccccc2)c2ccccc2Cl)nc1)NO
InChIKey: VLIUIBXPEDFJRF-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of HDAC2 (unknown origin) using FTS as substrate preincubated for 10 mins followed by substrate addition and shaken for 60 secs and measured over 30 mins
Measurement: IC50 = 45 nM (pChEMBL 7.349999904632568)
Descriptors: MW 467.96, ALogP 4.79, HBA 6, HBD 3, PSA 107.45, QED 0.21
Compound (SMILES): O=C(CCCCCCNC(=O)c1cnc(N(c2ccccc2)c2ccccc2Cl)nc1)NO
InChIKey: VLIUIBXPEDFJRF-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of HDAC3 (unknown origin) using FTS as substrate preincubated for 10 mins followed by substrate addition and shaken for 60 secs and measured over 30 mins
Measurement: IC50 = 46 nM (pChEMBL 7.340000152587891)
Descriptors: MW 467.96, ALogP 4.79, HBA 6, HBD 3, PSA 107.45, QED 0.21
Compound (SMILES): O=C(CCCCCCNC(=O)c1cnc(N(c2ccccc2)c2ccccc2Cl)nc1)NO
InChIKey: VLIUIBXPEDFJRF-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of HDAC8 (unknown origin) using MAZ-1675 as substrate preincubated for 10 mins followed by substrate addition and shaken for 60 secs and measured over 30 mins
Measurement: IC50 = 137 nM (pChEMBL 6.860000133514404)
Descriptors: MW 467.96, ALogP 4.79, HBA 6, HBD 3, PSA 107.45, QED 0.21
Compound (SMILES): O=C(CCCCCCNC(=O)c1cnc(N(c2ccccc2)c2ccccc2Cl)nc1)NO
InChIKey: VLIUIBXPEDFJRF-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of full length human recombinant HDAC2 expressed in Sf9 baculovirus system using FAM-labeled acetylated peptide as substrate by measuring fluorescence intensity by EMSA method
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 467.96, ALogP 4.79, HBA 6, HBD 3, PSA 107.45, QED 0.21
Compound (SMILES): O=C(CCCCCCNC(=O)c1cnc(N(c2ccccc2)c2ccccc2Cl)nc1)NO
InChIKey: VLIUIBXPEDFJRF-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of full length human HDAC6 using FAM-labeled acetylated peptide as substrate by electrophoretic mobility shift assay
Measurement: IC50 = 2200 nM (pChEMBL 5.659999847412109)
Descriptors: MW 467.96, ALogP 4.79, HBA 6, HBD 3, PSA 107.45, QED 0.21
Compound (SMILES): Cc1cccc2cc(Cn3nc(I)c4c(N)ncnc43)n(C(C)C)c(=O)c12
InChIKey: IRINYVMOBLZBRN-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of recombinant human C-terminal His6-tagged p110gamma expressed in insect cells using phosphatidylinositol as substrate in presence of gamma-32P-ATP after 5 mins by thin layer chromatographic method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 474.31, ALogP 3.27, HBA 7, HBD 1, PSA 91.62, QED 0.46
Compound (SMILES): O=C(NS(=O)(=O)c1ccc(NC2CCN(S(=O)(=O)c3cccc4cccnc34)CC2)c([N+](=O)[O-])c1)c1ccc(N2CCN(Cc3ccccc3-c3ccc(Cl)cc3)CC2)cc1Oc1ccccc1
InChIKey: RKIHOVNIMDBFJX-UHFFFAOYSA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Mus musculus
UniProt: Q64373
Assay: Time Resolved-Fluorescence Resonance Energy Transfer (TR-FRET) Assay: The inhibition constant (Ki) is the dissociation constant of an enzyme-inhibitor complex or a protein/small molecule complex, wherein the small molecule is inhibiting binding of one protein to another protein or peptide. Where the Ki for a compound is represented as > (greater than) a certain numerical value, it is intended to mean that the binding affinity value (e.g., for Bcl-XL) is greater than the limits of detection of the assay used. Where the binding selectivity ratio for a compound is represented as > (greater than) a certain numerical value, it is intended to mean that the selectivity of a particular compound for Bcl-2 over Bcl-XL is at least as great as the number indicated. Where the Ki for a compound is represented as < (less than) a certain numerical value, it is intended to mean that the binding affinity value (e.g., for Bcl-2) is lower than the limit of detection of the assay used. Inhibition constants were determined using Wang's equation (Wang Z-X).
Measurement: Ki > 660 nM (pChEMBL 6.179999828338623)
Descriptors: MW 972.55, ALogP 8.96, HBA 12, HBD 2, PSA 184.39, QED 0.08
Compound (SMILES): COc1cc(OC)c(C)c(N(CCNC(C)C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: WSXFENUDJHHXRN-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of FGFR3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 = 6918.31 nM (pChEMBL 5.159999847412109)
Descriptors: MW 460.58, ALogP 4.49, HBA 8, HBD 1, PSA 77.33, QED 0.39