lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): NC(=O)c1nc(Nc2ccc3ccccc3c2)sc1NC(=O)c1ccc(CN2CCC(N)CC2)cc1
InChIKey: VTYBXTOFABINOL-UHFFFAOYSA-N
Target: TRAF2 and NCK-interacting protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKE5
Assay: Kinase Assay: The kinase assays were conducted in a 20 μl volume using 384-well plates (Greiner). The reaction mixture consists of compound or vehicle (1% DMSO), 0.08 ng/μl TNIK_N, 1 μM FITC-labeled substrate peptides, including ε-aminocaproic acid and 7 amino acids (described as SEQ ID NO. 3 in "Kinase assay of TEST EXAMPLE 1" of WO 2010/064111(P.31)), 20 mM Hepes, pH 7.5, 0.01% Triton X-100, 5 mM MgCl2, 25 μM ATP and 2 mM DTT. As blank, TNIK_N was excluded from the reaction mixture of vehicle (1% DMSO). The kinase reaction was carried out 1 h at room temperature and terminated by addition of 60 μl of the termination buffer (127 mM Hepes, pH 7.5, 26.7 mM EDTA, 0.01% Triton X-100, 1% DMSO and 0.13% Coating Reagent 3 (Caliper Life Sciences)). The amount of unphosphorylated and phosphorylated FITC-labeled substrate peptides was detected by Mobility Shift Micro Fluidic Technology (Caliper LC3000 System, Caliper Life Sciences).
Measurement: IC50 = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 500.63, ALogP 4.31, HBA 7, HBD 4, PSA 126.37, QED 0.3
Compound (SMILES): NC(=O)c1nc(Nc2ccc3ccccc3c2)sc1NC(=O)C#CCCO
InChIKey: JCFCCHWJZKIJAL-UHFFFAOYSA-N
Target: TRAF2 and NCK-interacting protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKE5
Assay: Kinase Assay: The kinase assays were conducted in a 20 μl volume using 384-well plates (Greiner). The reaction mixture consists of compound or vehicle (1% DMSO), 0.08 ng/μl TNIK_N, 1 μM FITC-labeled substrate peptides, including ε-aminocaproic acid and 7 amino acids (described as SEQ ID NO. 3 in "Kinase assay of TEST EXAMPLE 1" of WO 2010/064111(P.31)), 20 mM Hepes, pH 7.5, 0.01% Triton X-100, 5 mM MgCl2, 25 μM ATP and 2 mM DTT. As blank, TNIK_N was excluded from the reaction mixture of vehicle (1% DMSO). The kinase reaction was carried out 1 h at room temperature and terminated by addition of 60 μl of the termination buffer (127 mM Hepes, pH 7.5, 26.7 mM EDTA, 0.01% Triton X-100, 1% DMSO and 0.13% Coating Reagent 3 (Caliper Life Sciences)). The amount of unphosphorylated and phosphorylated FITC-labeled substrate peptides was detected by Mobility Shift Micro Fluidic Technology (Caliper LC3000 System, Caliper Life Sciences).
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 380.43, ALogP 2.46, HBA 6, HBD 4, PSA 117.34, QED 0.51
Compound (SMILES): NC(=O)c1nc(Nc2ccc3ccccc3c2)sc1NC(=O)c1ccc(Cc2nn[nH]n2)cc1
InChIKey: LYCJUVASGNNBSC-UHFFFAOYSA-N
Target: TRAF2 and NCK-interacting protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKE5
Assay: Kinase Assay: The kinase assays were conducted in a 20 μl volume using 384-well plates (Greiner). The reaction mixture consists of compound or vehicle (1% DMSO), 0.08 ng/μl TNIK_N, 1 μM FITC-labeled substrate peptides, including ε-aminocaproic acid and 7 amino acids (described as SEQ ID NO. 3 in "Kinase assay of TEST EXAMPLE 1" of WO 2010/064111(P.31)), 20 mM Hepes, pH 7.5, 0.01% Triton X-100, 5 mM MgCl2, 25 μM ATP and 2 mM DTT. As blank, TNIK_N was excluded from the reaction mixture of vehicle (1% DMSO). The kinase reaction was carried out 1 h at room temperature and terminated by addition of 60 μl of the termination buffer (127 mM Hepes, pH 7.5, 26.7 mM EDTA, 0.01% Triton X-100, 1% DMSO and 0.13% Coating Reagent 3 (Caliper Life Sciences)). The amount of unphosphorylated and phosphorylated FITC-labeled substrate peptides was detected by Mobility Shift Micro Fluidic Technology (Caliper LC3000 System, Caliper Life Sciences).
Measurement: IC50 = 2.9 nM (pChEMBL 8.539999961853027)
Descriptors: MW 470.52, ALogP 3.5, HBA 8, HBD 4, PSA 151.57, QED 0.28
Compound (SMILES): NC(=O)c1nc(Nc2ccc3ccccc3c2)sc1NC(=O)c1ccc(Cn2cccn2)cc1
InChIKey: COPOQFFEIJXCCX-UHFFFAOYSA-N
Target: TRAF2 and NCK-interacting protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKE5
Assay: Kinase Assay: The kinase assays were conducted in a 20 μl volume using 384-well plates (Greiner). The reaction mixture consists of compound or vehicle (1% DMSO), 0.08 ng/μl TNIK_N, 1 μM FITC-labeled substrate peptides, including ε-aminocaproic acid and 7 amino acids (described as SEQ ID NO. 3 in "Kinase assay of TEST EXAMPLE 1" of WO 2010/064111(P.31)), 20 mM Hepes, pH 7.5, 0.01% Triton X-100, 5 mM MgCl2, 25 μM ATP and 2 mM DTT. As blank, TNIK_N was excluded from the reaction mixture of vehicle (1% DMSO). The kinase reaction was carried out 1 h at room temperature and terminated by addition of 60 μl of the termination buffer (127 mM Hepes, pH 7.5, 26.7 mM EDTA, 0.01% Triton X-100, 1% DMSO and 0.13% Coating Reagent 3 (Caliper Life Sciences)). The amount of unphosphorylated and phosphorylated FITC-labeled substrate peptides was detected by Mobility Shift Micro Fluidic Technology (Caliper LC3000 System, Caliper Life Sciences).
Measurement: IC50 = 10.3 nM (pChEMBL 7.989999771118164)
Descriptors: MW 468.54, ALogP 4.64, HBA 7, HBD 3, PSA 114.93, QED 0.32
Compound (SMILES): NC(=O)c1nc(Nc2ccc3ccccc3c2)sc1NC(=O)C#CCCCn1cncn1
InChIKey: RGXVGKCMCNJIBL-UHFFFAOYSA-N
Target: TRAF2 and NCK-interacting protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKE5
Assay: Kinase Assay: The kinase assays were conducted in a 20 μl volume using 384-well plates (Greiner). The reaction mixture consists of compound or vehicle (1% DMSO), 0.08 ng/μl TNIK_N, 1 μM FITC-labeled substrate peptides, including ε-aminocaproic acid and 7 amino acids (described as SEQ ID NO. 3 in "Kinase assay of TEST EXAMPLE 1" of WO 2010/064111(P.31)), 20 mM Hepes, pH 7.5, 0.01% Triton X-100, 5 mM MgCl2, 25 μM ATP and 2 mM DTT. As blank, TNIK_N was excluded from the reaction mixture of vehicle (1% DMSO). The kinase reaction was carried out 1 h at room temperature and terminated by addition of 60 μl of the termination buffer (127 mM Hepes, pH 7.5, 26.7 mM EDTA, 0.01% Triton X-100, 1% DMSO and 0.13% Coating Reagent 3 (Caliper Life Sciences)). The amount of unphosphorylated and phosphorylated FITC-labeled substrate peptides was detected by Mobility Shift Micro Fluidic Technology (Caliper LC3000 System, Caliper Life Sciences).
Measurement: IC50 = 10.7 nM (pChEMBL 7.96999979019165)
Descriptors: MW 445.51, ALogP 3.15, HBA 8, HBD 3, PSA 127.82, QED 0.3
Compound (SMILES): NC(=O)c1nc(Nc2ccc3ccccc3c2)sc1NC(=O)C#CCCCn1ccnc1
InChIKey: JFZHXKPFKIUXIX-UHFFFAOYSA-N
Target: TRAF2 and NCK-interacting protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKE5
Assay: Kinase Assay: The kinase assays were conducted in a 20 μl volume using 384-well plates (Greiner). The reaction mixture consists of compound or vehicle (1% DMSO), 0.08 ng/μl TNIK_N, 1 μM FITC-labeled substrate peptides, including ε-aminocaproic acid and 7 amino acids (described as SEQ ID NO. 3 in "Kinase assay of TEST EXAMPLE 1" of WO 2010/064111(P.31)), 20 mM Hepes, pH 7.5, 0.01% Triton X-100, 5 mM MgCl2, 25 μM ATP and 2 mM DTT. As blank, TNIK_N was excluded from the reaction mixture of vehicle (1% DMSO). The kinase reaction was carried out 1 h at room temperature and terminated by addition of 60 μl of the termination buffer (127 mM Hepes, pH 7.5, 26.7 mM EDTA, 0.01% Triton X-100, 1% DMSO and 0.13% Coating Reagent 3 (Caliper Life Sciences)). The amount of unphosphorylated and phosphorylated FITC-labeled substrate peptides was detected by Mobility Shift Micro Fluidic Technology (Caliper LC3000 System, Caliper Life Sciences).
Measurement: IC50 = 9.7 nM (pChEMBL 8.010000228881836)
Descriptors: MW 444.52, ALogP 3.76, HBA 7, HBD 3, PSA 114.93, QED 0.3
Compound (SMILES): NC(=O)c1nc(Nc2ccc3ccccc3c2)sc1NC(=O)c1ccc(Cn2ccnc2[N+](=O)[O-])cc1
InChIKey: BVCAMMFFQYWHOG-UHFFFAOYSA-N
Target: TRAF2 and NCK-interacting protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKE5
Assay: Kinase Assay: The kinase assays were conducted in a 20 μl volume using 384-well plates (Greiner). The reaction mixture consists of compound or vehicle (1% DMSO), 0.08 ng/μl TNIK_N, 1 μM FITC-labeled substrate peptides, including ε-aminocaproic acid and 7 amino acids (described as SEQ ID NO. 3 in "Kinase assay of TEST EXAMPLE 1" of WO 2010/064111(P.31)), 20 mM Hepes, pH 7.5, 0.01% Triton X-100, 5 mM MgCl2, 25 μM ATP and 2 mM DTT. As blank, TNIK_N was excluded from the reaction mixture of vehicle (1% DMSO). The kinase reaction was carried out 1 h at room temperature and terminated by addition of 60 μl of the termination buffer (127 mM Hepes, pH 7.5, 26.7 mM EDTA, 0.01% Triton X-100, 1% DMSO and 0.13% Coating Reagent 3 (Caliper Life Sciences)). The amount of unphosphorylated and phosphorylated FITC-labeled substrate peptides was detected by Mobility Shift Micro Fluidic Technology (Caliper LC3000 System, Caliper Life Sciences).
Measurement: IC50 = 9.5 nM (pChEMBL 8.020000457763672)
Descriptors: MW 513.54, ALogP 4.54, HBA 9, HBD 3, PSA 158.07, QED 0.2
Compound (SMILES): Cc1nccn1Cc1ccc(C(=O)Nc2sc(Nc3ccc4ccccc4c3)nc2C(N)=O)cc1
InChIKey: BDXUSEPHZGIROK-UHFFFAOYSA-N
Target: TRAF2 and NCK-interacting protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKE5
Assay: Kinase Assay: The kinase assays were conducted in a 20 μl volume using 384-well plates (Greiner). The reaction mixture consists of compound or vehicle (1% DMSO), 0.08 ng/μl TNIK_N, 1 μM FITC-labeled substrate peptides, including ε-aminocaproic acid and 7 amino acids (described as SEQ ID NO. 3 in "Kinase assay of TEST EXAMPLE 1" of WO 2010/064111(P.31)), 20 mM Hepes, pH 7.5, 0.01% Triton X-100, 5 mM MgCl2, 25 μM ATP and 2 mM DTT. As blank, TNIK_N was excluded from the reaction mixture of vehicle (1% DMSO). The kinase reaction was carried out 1 h at room temperature and terminated by addition of 60 μl of the termination buffer (127 mM Hepes, pH 7.5, 26.7 mM EDTA, 0.01% Triton X-100, 1% DMSO and 0.13% Coating Reagent 3 (Caliper Life Sciences)). The amount of unphosphorylated and phosphorylated FITC-labeled substrate peptides was detected by Mobility Shift Micro Fluidic Technology (Caliper LC3000 System, Caliper Life Sciences).
Measurement: IC50 = 2.3 nM (pChEMBL 8.640000343322754)
Descriptors: MW 482.57, ALogP 4.94, HBA 7, HBD 3, PSA 114.93, QED 0.3
Compound (SMILES): Cc1cn(Cc2ccc(C(=O)Nc3sc(Nc4ccc5ccccc5c4)nc3C(N)=O)cc2)cn1
InChIKey: LCWYRNCEBNJVLN-UHFFFAOYSA-N
Target: TRAF2 and NCK-interacting protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKE5
Assay: Kinase Assay: The kinase assays were conducted in a 20 μl volume using 384-well plates (Greiner). The reaction mixture consists of compound or vehicle (1% DMSO), 0.08 ng/μl TNIK_N, 1 μM FITC-labeled substrate peptides, including ε-aminocaproic acid and 7 amino acids (described as SEQ ID NO. 3 in "Kinase assay of TEST EXAMPLE 1" of WO 2010/064111(P.31)), 20 mM Hepes, pH 7.5, 0.01% Triton X-100, 5 mM MgCl2, 25 μM ATP and 2 mM DTT. As blank, TNIK_N was excluded from the reaction mixture of vehicle (1% DMSO). The kinase reaction was carried out 1 h at room temperature and terminated by addition of 60 μl of the termination buffer (127 mM Hepes, pH 7.5, 26.7 mM EDTA, 0.01% Triton X-100, 1% DMSO and 0.13% Coating Reagent 3 (Caliper Life Sciences)). The amount of unphosphorylated and phosphorylated FITC-labeled substrate peptides was detected by Mobility Shift Micro Fluidic Technology (Caliper LC3000 System, Caliper Life Sciences).
Measurement: IC50 = 3.1 nM (pChEMBL 8.510000228881836)
Descriptors: MW 482.57, ALogP 4.94, HBA 7, HBD 3, PSA 114.93, QED 0.3
Compound (SMILES): NC(=O)c1nc(Nc2ccc3ccccc3c2)sc1NC(=O)c1ccc(Cn2cnc([N+](=O)[O-])c2)cc1
InChIKey: UMEDGXJLECGVPB-UHFFFAOYSA-N
Target: TRAF2 and NCK-interacting protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKE5
Assay: Kinase Assay: The kinase assays were conducted in a 20 μl volume using 384-well plates (Greiner). The reaction mixture consists of compound or vehicle (1% DMSO), 0.08 ng/μl TNIK_N, 1 μM FITC-labeled substrate peptides, including ε-aminocaproic acid and 7 amino acids (described as SEQ ID NO. 3 in "Kinase assay of TEST EXAMPLE 1" of WO 2010/064111(P.31)), 20 mM Hepes, pH 7.5, 0.01% Triton X-100, 5 mM MgCl2, 25 μM ATP and 2 mM DTT. As blank, TNIK_N was excluded from the reaction mixture of vehicle (1% DMSO). The kinase reaction was carried out 1 h at room temperature and terminated by addition of 60 μl of the termination buffer (127 mM Hepes, pH 7.5, 26.7 mM EDTA, 0.01% Triton X-100, 1% DMSO and 0.13% Coating Reagent 3 (Caliper Life Sciences)). The amount of unphosphorylated and phosphorylated FITC-labeled substrate peptides was detected by Mobility Shift Micro Fluidic Technology (Caliper LC3000 System, Caliper Life Sciences).
Measurement: IC50 = 5.9 nM (pChEMBL 8.229999542236328)
Descriptors: MW 513.54, ALogP 4.54, HBA 9, HBD 3, PSA 158.07, QED 0.2
Compound (SMILES): NC(=O)c1nc(Nc2ccc3ccccc3c2)sc1NC(=O)c1ccc(Cn2cnc([N+](=O)[O-])n2)cc1
InChIKey: JSUIYBNOOSGNKO-UHFFFAOYSA-N
Target: TRAF2 and NCK-interacting protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKE5
Assay: Kinase Assay: The kinase assays were conducted in a 20 μl volume using 384-well plates (Greiner). The reaction mixture consists of compound or vehicle (1% DMSO), 0.08 ng/μl TNIK_N, 1 μM FITC-labeled substrate peptides, including ε-aminocaproic acid and 7 amino acids (described as SEQ ID NO. 3 in "Kinase assay of TEST EXAMPLE 1" of WO 2010/064111(P.31)), 20 mM Hepes, pH 7.5, 0.01% Triton X-100, 5 mM MgCl2, 25 μM ATP and 2 mM DTT. As blank, TNIK_N was excluded from the reaction mixture of vehicle (1% DMSO). The kinase reaction was carried out 1 h at room temperature and terminated by addition of 60 μl of the termination buffer (127 mM Hepes, pH 7.5, 26.7 mM EDTA, 0.01% Triton X-100, 1% DMSO and 0.13% Coating Reagent 3 (Caliper Life Sciences)). The amount of unphosphorylated and phosphorylated FITC-labeled substrate peptides was detected by Mobility Shift Micro Fluidic Technology (Caliper LC3000 System, Caliper Life Sciences).
Measurement: IC50 = 14.8 nM (pChEMBL 7.829999923706055)
Descriptors: MW 514.53, ALogP 3.94, HBA 10, HBD 3, PSA 170.96, QED 0.21
Compound (SMILES): Cc1nnnn1Cc1ccc(C(=O)Nc2sc(Nc3ccc4ccccc4c3)nc2C(N)=O)cc1
InChIKey: NSLPRQHZCSDDQJ-UHFFFAOYSA-N
Target: TRAF2 and NCK-interacting protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKE5
Assay: Kinase Assay: The kinase assays were conducted in a 20 μl volume using 384-well plates (Greiner). The reaction mixture consists of compound or vehicle (1% DMSO), 0.08 ng/μl TNIK_N, 1 μM FITC-labeled substrate peptides, including ε-aminocaproic acid and 7 amino acids (described as SEQ ID NO. 3 in "Kinase assay of TEST EXAMPLE 1" of WO 2010/064111(P.31)), 20 mM Hepes, pH 7.5, 0.01% Triton X-100, 5 mM MgCl2, 25 μM ATP and 2 mM DTT. As blank, TNIK_N was excluded from the reaction mixture of vehicle (1% DMSO). The kinase reaction was carried out 1 h at room temperature and terminated by addition of 60 μl of the termination buffer (127 mM Hepes, pH 7.5, 26.7 mM EDTA, 0.01% Triton X-100, 1% DMSO and 0.13% Coating Reagent 3 (Caliper Life Sciences)). The amount of unphosphorylated and phosphorylated FITC-labeled substrate peptides was detected by Mobility Shift Micro Fluidic Technology (Caliper LC3000 System, Caliper Life Sciences).
Measurement: IC50 = 7.1 nM (pChEMBL 8.149999618530273)
Descriptors: MW 484.55, ALogP 3.73, HBA 9, HBD 3, PSA 140.71, QED 0.32
Compound (SMILES): NC(=O)c1nc(Nc2ccc3ccccc3c2)sc1NC(=O)c1ccc(Cn2cnc(CO)c2)cc1
InChIKey: FLVOIUFCXVTLRR-UHFFFAOYSA-N
Target: TRAF2 and NCK-interacting protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKE5
Assay: Kinase Assay: The kinase assays were conducted in a 20 μl volume using 384-well plates (Greiner). The reaction mixture consists of compound or vehicle (1% DMSO), 0.08 ng/μl TNIK_N, 1 μM FITC-labeled substrate peptides, including ε-aminocaproic acid and 7 amino acids (described as SEQ ID NO. 3 in "Kinase assay of TEST EXAMPLE 1" of WO 2010/064111(P.31)), 20 mM Hepes, pH 7.5, 0.01% Triton X-100, 5 mM MgCl2, 25 μM ATP and 2 mM DTT. As blank, TNIK_N was excluded from the reaction mixture of vehicle (1% DMSO). The kinase reaction was carried out 1 h at room temperature and terminated by addition of 60 μl of the termination buffer (127 mM Hepes, pH 7.5, 26.7 mM EDTA, 0.01% Triton X-100, 1% DMSO and 0.13% Coating Reagent 3 (Caliper Life Sciences)). The amount of unphosphorylated and phosphorylated FITC-labeled substrate peptides was detected by Mobility Shift Micro Fluidic Technology (Caliper LC3000 System, Caliper Life Sciences).
Measurement: IC50 = 3.5 nM (pChEMBL 8.460000038146973)
Descriptors: MW 498.57, ALogP 4.13, HBA 8, HBD 4, PSA 135.16, QED 0.25
Compound (SMILES): COc1ccc2cc(Nc3nc(C(N)=O)c(NC(=O)c4ccc(Cn5ccnc5)cc4)s3)ccc2c1
InChIKey: MJNSLBDLFKVOOY-UHFFFAOYSA-N
Target: TRAF2 and NCK-interacting protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKE5
Assay: Kinase Assay: The kinase assays were conducted in a 20 μl volume using 384-well plates (Greiner). The reaction mixture consists of compound or vehicle (1% DMSO), 0.08 ng/μl TNIK_N, 1 μM FITC-labeled substrate peptides, including ε-aminocaproic acid and 7 amino acids (described as SEQ ID NO. 3 in "Kinase assay of TEST EXAMPLE 1" of WO 2010/064111(P.31)), 20 mM Hepes, pH 7.5, 0.01% Triton X-100, 5 mM MgCl2, 25 μM ATP and 2 mM DTT. As blank, TNIK_N was excluded from the reaction mixture of vehicle (1% DMSO). The kinase reaction was carried out 1 h at room temperature and terminated by addition of 60 μl of the termination buffer (127 mM Hepes, pH 7.5, 26.7 mM EDTA, 0.01% Triton X-100, 1% DMSO and 0.13% Coating Reagent 3 (Caliper Life Sciences)). The amount of unphosphorylated and phosphorylated FITC-labeled substrate peptides was detected by Mobility Shift Micro Fluidic Technology (Caliper LC3000 System, Caliper Life Sciences).
Measurement: IC50 = 6.1 nM (pChEMBL 8.210000038146973)
Descriptors: MW 498.57, ALogP 4.64, HBA 8, HBD 3, PSA 124.16, QED 0.29
Compound (SMILES): NC(=O)c1nc(Nc2ccc3cc(F)ccc3c2)sc1NC(=O)c1ccc(Cn2ccnc2)cc1
InChIKey: DEPXFCIIACMQTF-UHFFFAOYSA-N
Target: TRAF2 and NCK-interacting protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKE5
Assay: Kinase Assay: The kinase assays were conducted in a 20 μl volume using 384-well plates (Greiner). The reaction mixture consists of compound or vehicle (1% DMSO), 0.08 ng/μl TNIK_N, 1 μM FITC-labeled substrate peptides, including ε-aminocaproic acid and 7 amino acids (described as SEQ ID NO. 3 in "Kinase assay of TEST EXAMPLE 1" of WO 2010/064111(P.31)), 20 mM Hepes, pH 7.5, 0.01% Triton X-100, 5 mM MgCl2, 25 μM ATP and 2 mM DTT. As blank, TNIK_N was excluded from the reaction mixture of vehicle (1% DMSO). The kinase reaction was carried out 1 h at room temperature and terminated by addition of 60 μl of the termination buffer (127 mM Hepes, pH 7.5, 26.7 mM EDTA, 0.01% Triton X-100, 1% DMSO and 0.13% Coating Reagent 3 (Caliper Life Sciences)). The amount of unphosphorylated and phosphorylated FITC-labeled substrate peptides was detected by Mobility Shift Micro Fluidic Technology (Caliper LC3000 System, Caliper Life Sciences).
Measurement: IC50 = 10.1 nM (pChEMBL 8)
Descriptors: MW 486.53, ALogP 4.78, HBA 7, HBD 3, PSA 114.93, QED 0.31
Compound (SMILES): NC(=O)c1nc(Nc2ccc3ncccc3c2)sc1NC(=O)c1ccc(Cn2ccnc2)cc1
InChIKey: NTLIJPXQZBGNJO-UHFFFAOYSA-N
Target: TRAF2 and NCK-interacting protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKE5
Assay: Kinase Assay: The kinase assays were conducted in a 20 μl volume using 384-well plates (Greiner). The reaction mixture consists of compound or vehicle (1% DMSO), 0.08 ng/μl TNIK_N, 1 μM FITC-labeled substrate peptides, including ε-aminocaproic acid and 7 amino acids (described as SEQ ID NO. 3 in "Kinase assay of TEST EXAMPLE 1" of WO 2010/064111(P.31)), 20 mM Hepes, pH 7.5, 0.01% Triton X-100, 5 mM MgCl2, 25 μM ATP and 2 mM DTT. As blank, TNIK_N was excluded from the reaction mixture of vehicle (1% DMSO). The kinase reaction was carried out 1 h at room temperature and terminated by addition of 60 μl of the termination buffer (127 mM Hepes, pH 7.5, 26.7 mM EDTA, 0.01% Triton X-100, 1% DMSO and 0.13% Coating Reagent 3 (Caliper Life Sciences)). The amount of unphosphorylated and phosphorylated FITC-labeled substrate peptides was detected by Mobility Shift Micro Fluidic Technology (Caliper LC3000 System, Caliper Life Sciences).
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 469.53, ALogP 4.03, HBA 8, HBD 3, PSA 127.82, QED 0.33
Compound (SMILES): NC(=O)c1nc(Nc2ccc3ccccc3c2)sc1NC(=O)c1ccc(Cn2ccnc2)s1
InChIKey: YXTXPQJQEZSINU-UHFFFAOYSA-N
Target: TRAF2 and NCK-interacting protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKE5
Assay: Kinase Assay: The kinase assays were conducted in a 20 μl volume using 384-well plates (Greiner). The reaction mixture consists of compound or vehicle (1% DMSO), 0.08 ng/μl TNIK_N, 1 μM FITC-labeled substrate peptides, including ε-aminocaproic acid and 7 amino acids (described as SEQ ID NO. 3 in "Kinase assay of TEST EXAMPLE 1" of WO 2010/064111(P.31)), 20 mM Hepes, pH 7.5, 0.01% Triton X-100, 5 mM MgCl2, 25 μM ATP and 2 mM DTT. As blank, TNIK_N was excluded from the reaction mixture of vehicle (1% DMSO). The kinase reaction was carried out 1 h at room temperature and terminated by addition of 60 μl of the termination buffer (127 mM Hepes, pH 7.5, 26.7 mM EDTA, 0.01% Triton X-100, 1% DMSO and 0.13% Coating Reagent 3 (Caliper Life Sciences)). The amount of unphosphorylated and phosphorylated FITC-labeled substrate peptides was detected by Mobility Shift Micro Fluidic Technology (Caliper LC3000 System, Caliper Life Sciences).
Measurement: IC50 = 7.7 nM (pChEMBL 8.109999656677246)
Descriptors: MW 474.57, ALogP 4.7, HBA 8, HBD 3, PSA 114.93, QED 0.32
Compound (SMILES): NC(=O)c1nc(Nc2ccc3ccccc3c2)sc1NC(=O)c1ccc(CN2C(=O)CSC2=O)cc1
InChIKey: RSPQQLDEVYQIIA-UHFFFAOYSA-N
Target: TRAF2 and NCK-interacting protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKE5
Assay: Kinase Assay: The kinase assays were conducted in a 20 μl volume using 384-well plates (Greiner). The reaction mixture consists of compound or vehicle (1% DMSO), 0.08 ng/μl TNIK_N, 1 μM FITC-labeled substrate peptides, including ε-aminocaproic acid and 7 amino acids (described as SEQ ID NO. 3 in "Kinase assay of TEST EXAMPLE 1" of WO 2010/064111(P.31)), 20 mM Hepes, pH 7.5, 0.01% Triton X-100, 5 mM MgCl2, 25 μM ATP and 2 mM DTT. As blank, TNIK_N was excluded from the reaction mixture of vehicle (1% DMSO). The kinase reaction was carried out 1 h at room temperature and terminated by addition of 60 μl of the termination buffer (127 mM Hepes, pH 7.5, 26.7 mM EDTA, 0.01% Triton X-100, 1% DMSO and 0.13% Coating Reagent 3 (Caliper Life Sciences)). The amount of unphosphorylated and phosphorylated FITC-labeled substrate peptides was detected by Mobility Shift Micro Fluidic Technology (Caliper LC3000 System, Caliper Life Sciences).
Measurement: IC50 = 15.9 nM (pChEMBL 7.800000190734863)
Descriptors: MW 517.59, ALogP 4.59, HBA 8, HBD 3, PSA 134.49, QED 0.33
Compound (SMILES): NC(=O)c1nc(Nc2cccc3ncccc23)sc1NC(=O)c1ccc(Cn2ccnc2)cc1
InChIKey: JGPTUBGWBPWAKX-UHFFFAOYSA-N
Target: TRAF2 and NCK-interacting protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKE5
Assay: Kinase Assay: The kinase assays were conducted in a 20 μl volume using 384-well plates (Greiner). The reaction mixture consists of compound or vehicle (1% DMSO), 0.08 ng/μl TNIK_N, 1 μM FITC-labeled substrate peptides, including ε-aminocaproic acid and 7 amino acids (described as SEQ ID NO. 3 in "Kinase assay of TEST EXAMPLE 1" of WO 2010/064111(P.31)), 20 mM Hepes, pH 7.5, 0.01% Triton X-100, 5 mM MgCl2, 25 μM ATP and 2 mM DTT. As blank, TNIK_N was excluded from the reaction mixture of vehicle (1% DMSO). The kinase reaction was carried out 1 h at room temperature and terminated by addition of 60 μl of the termination buffer (127 mM Hepes, pH 7.5, 26.7 mM EDTA, 0.01% Triton X-100, 1% DMSO and 0.13% Coating Reagent 3 (Caliper Life Sciences)). The amount of unphosphorylated and phosphorylated FITC-labeled substrate peptides was detected by Mobility Shift Micro Fluidic Technology (Caliper LC3000 System, Caliper Life Sciences).
Measurement: IC50 = 4.8 nM (pChEMBL 8.319999694824219)
Descriptors: MW 469.53, ALogP 4.03, HBA 8, HBD 3, PSA 127.82, QED 0.33
Compound (SMILES): NC(=O)c1nc(Nc2ccnc3ccccc23)sc1NC(=O)c1ccc(Cn2ccnc2)cc1
InChIKey: FRQNWLUZUQPLBF-UHFFFAOYSA-N
Target: TRAF2 and NCK-interacting protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKE5
Assay: Kinase Assay: The kinase assays were conducted in a 20 μl volume using 384-well plates (Greiner). The reaction mixture consists of compound or vehicle (1% DMSO), 0.08 ng/μl TNIK_N, 1 μM FITC-labeled substrate peptides, including ε-aminocaproic acid and 7 amino acids (described as SEQ ID NO. 3 in "Kinase assay of TEST EXAMPLE 1" of WO 2010/064111(P.31)), 20 mM Hepes, pH 7.5, 0.01% Triton X-100, 5 mM MgCl2, 25 μM ATP and 2 mM DTT. As blank, TNIK_N was excluded from the reaction mixture of vehicle (1% DMSO). The kinase reaction was carried out 1 h at room temperature and terminated by addition of 60 μl of the termination buffer (127 mM Hepes, pH 7.5, 26.7 mM EDTA, 0.01% Triton X-100, 1% DMSO and 0.13% Coating Reagent 3 (Caliper Life Sciences)). The amount of unphosphorylated and phosphorylated FITC-labeled substrate peptides was detected by Mobility Shift Micro Fluidic Technology (Caliper LC3000 System, Caliper Life Sciences).
Measurement: IC50 = 26.5 nM (pChEMBL 7.579999923706055)
Descriptors: MW 469.53, ALogP 4.03, HBA 8, HBD 3, PSA 127.82, QED 0.33
Compound (SMILES): Cc1noc(Cc2ccc(C(=O)Nc3sc(Nc4ccc5ccccc5c4)nc3C(N)=O)cc2)n1
InChIKey: QBECQMWVMHVBBS-UHFFFAOYSA-N
Target: TRAF2 and NCK-interacting protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKE5
Assay: Kinase Assay: The kinase assays were conducted in a 20 μl volume using 384-well plates (Greiner). The reaction mixture consists of compound or vehicle (1% DMSO), 0.08 ng/μl TNIK_N, 1 μM FITC-labeled substrate peptides, including ε-aminocaproic acid and 7 amino acids (described as SEQ ID NO. 3 in "Kinase assay of TEST EXAMPLE 1" of WO 2010/064111(P.31)), 20 mM Hepes, pH 7.5, 0.01% Triton X-100, 5 mM MgCl2, 25 μM ATP and 2 mM DTT. As blank, TNIK_N was excluded from the reaction mixture of vehicle (1% DMSO). The kinase reaction was carried out 1 h at room temperature and terminated by addition of 60 μl of the termination buffer (127 mM Hepes, pH 7.5, 26.7 mM EDTA, 0.01% Triton X-100, 1% DMSO and 0.13% Coating Reagent 3 (Caliper Life Sciences)). The amount of unphosphorylated and phosphorylated FITC-labeled substrate peptides was detected by Mobility Shift Micro Fluidic Technology (Caliper LC3000 System, Caliper Life Sciences).
Measurement: IC50 = 18.5 nM (pChEMBL 7.730000019073486)
Descriptors: MW 484.54, ALogP 4.67, HBA 8, HBD 3, PSA 136.03, QED 0.31
Compound (SMILES): Cc1nnc(Cc2ccc(C(=O)Nc3sc(Nc4ccc5ccccc5c4)nc3C(N)=O)cc2)o1
InChIKey: RVPBQJLBHLGXSN-UHFFFAOYSA-N
Target: TRAF2 and NCK-interacting protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKE5
Assay: Kinase Assay: The kinase assays were conducted in a 20 μl volume using 384-well plates (Greiner). The reaction mixture consists of compound or vehicle (1% DMSO), 0.08 ng/μl TNIK_N, 1 μM FITC-labeled substrate peptides, including ε-aminocaproic acid and 7 amino acids (described as SEQ ID NO. 3 in "Kinase assay of TEST EXAMPLE 1" of WO 2010/064111(P.31)), 20 mM Hepes, pH 7.5, 0.01% Triton X-100, 5 mM MgCl2, 25 μM ATP and 2 mM DTT. As blank, TNIK_N was excluded from the reaction mixture of vehicle (1% DMSO). The kinase reaction was carried out 1 h at room temperature and terminated by addition of 60 μl of the termination buffer (127 mM Hepes, pH 7.5, 26.7 mM EDTA, 0.01% Triton X-100, 1% DMSO and 0.13% Coating Reagent 3 (Caliper Life Sciences)). The amount of unphosphorylated and phosphorylated FITC-labeled substrate peptides was detected by Mobility Shift Micro Fluidic Technology (Caliper LC3000 System, Caliper Life Sciences).
Measurement: IC50 = 6.2 nM (pChEMBL 8.210000038146973)
Descriptors: MW 484.54, ALogP 4.67, HBA 8, HBD 3, PSA 136.03, QED 0.31
Compound (SMILES): NC(=O)c1nc(Nc2ccc3ccccc3c2)sc1NC(=O)c1csc(Cn2ccnc2)c1
InChIKey: LJWPEEQDLHTOKE-UHFFFAOYSA-N
Target: TRAF2 and NCK-interacting protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKE5
Assay: Kinase Assay: The kinase assays were conducted in a 20 μl volume using 384-well plates (Greiner). The reaction mixture consists of compound or vehicle (1% DMSO), 0.08 ng/μl TNIK_N, 1 μM FITC-labeled substrate peptides, including ε-aminocaproic acid and 7 amino acids (described as SEQ ID NO. 3 in "Kinase assay of TEST EXAMPLE 1" of WO 2010/064111(P.31)), 20 mM Hepes, pH 7.5, 0.01% Triton X-100, 5 mM MgCl2, 25 μM ATP and 2 mM DTT. As blank, TNIK_N was excluded from the reaction mixture of vehicle (1% DMSO). The kinase reaction was carried out 1 h at room temperature and terminated by addition of 60 μl of the termination buffer (127 mM Hepes, pH 7.5, 26.7 mM EDTA, 0.01% Triton X-100, 1% DMSO and 0.13% Coating Reagent 3 (Caliper Life Sciences)). The amount of unphosphorylated and phosphorylated FITC-labeled substrate peptides was detected by Mobility Shift Micro Fluidic Technology (Caliper LC3000 System, Caliper Life Sciences).
Measurement: IC50 = 8.7 nM (pChEMBL 8.0600004196167)
Descriptors: MW 474.57, ALogP 4.7, HBA 8, HBD 3, PSA 114.93, QED 0.32
Compound (SMILES): NC(=O)c1nc(Nc2cccc3cccnc23)sc1NC(=O)c1ccc(Cn2ccnc2)cc1
InChIKey: WUMVHCACJJYRGU-UHFFFAOYSA-N
Target: TRAF2 and NCK-interacting protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKE5
Assay: Kinase Assay: The kinase assays were conducted in a 20 μl volume using 384-well plates (Greiner). The reaction mixture consists of compound or vehicle (1% DMSO), 0.08 ng/μl TNIK_N, 1 μM FITC-labeled substrate peptides, including ε-aminocaproic acid and 7 amino acids (described as SEQ ID NO. 3 in "Kinase assay of TEST EXAMPLE 1" of WO 2010/064111(P.31)), 20 mM Hepes, pH 7.5, 0.01% Triton X-100, 5 mM MgCl2, 25 μM ATP and 2 mM DTT. As blank, TNIK_N was excluded from the reaction mixture of vehicle (1% DMSO). The kinase reaction was carried out 1 h at room temperature and terminated by addition of 60 μl of the termination buffer (127 mM Hepes, pH 7.5, 26.7 mM EDTA, 0.01% Triton X-100, 1% DMSO and 0.13% Coating Reagent 3 (Caliper Life Sciences)). The amount of unphosphorylated and phosphorylated FITC-labeled substrate peptides was detected by Mobility Shift Micro Fluidic Technology (Caliper LC3000 System, Caliper Life Sciences).
Measurement: IC50 = 5.5 nM (pChEMBL 8.260000228881836)
Descriptors: MW 469.53, ALogP 4.03, HBA 8, HBD 3, PSA 127.82, QED 0.33
Compound (SMILES): NC(=O)c1nc(Nc2ccc3ccccc3c2)sc1NC(=O)c1ccc(Cn2cc(CO)nn2)cc1
InChIKey: HZZCXBALRJDSNS-UHFFFAOYSA-N
Target: TRAF2 and NCK-interacting protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKE5
Assay: Kinase Assay: The kinase assays were conducted in a 20 μl volume using 384-well plates (Greiner). The reaction mixture consists of compound or vehicle (1% DMSO), 0.08 ng/μl TNIK_N, 1 μM FITC-labeled substrate peptides, including ε-aminocaproic acid and 7 amino acids (described as SEQ ID NO. 3 in "Kinase assay of TEST EXAMPLE 1" of WO 2010/064111(P.31)), 20 mM Hepes, pH 7.5, 0.01% Triton X-100, 5 mM MgCl2, 25 μM ATP and 2 mM DTT. As blank, TNIK_N was excluded from the reaction mixture of vehicle (1% DMSO). The kinase reaction was carried out 1 h at room temperature and terminated by addition of 60 μl of the termination buffer (127 mM Hepes, pH 7.5, 26.7 mM EDTA, 0.01% Triton X-100, 1% DMSO and 0.13% Coating Reagent 3 (Caliper Life Sciences)). The amount of unphosphorylated and phosphorylated FITC-labeled substrate peptides was detected by Mobility Shift Micro Fluidic Technology (Caliper LC3000 System, Caliper Life Sciences).
Measurement: IC50 = 5.3 nM (pChEMBL 8.279999732971191)
Descriptors: MW 499.56, ALogP 3.52, HBA 9, HBD 4, PSA 148.05, QED 0.26
Compound (SMILES): NC(=O)c1nc(Nc2ccc3ccc(F)cc3c2)sc1NC(=O)c1ccc(Cn2ccnc2)cc1
InChIKey: BERTVBSXZCQFSW-UHFFFAOYSA-N
Target: TRAF2 and NCK-interacting protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKE5
Assay: Kinase Assay: The kinase assays were conducted in a 20 μl volume using 384-well plates (Greiner). The reaction mixture consists of compound or vehicle (1% DMSO), 0.08 ng/μl TNIK_N, 1 μM FITC-labeled substrate peptides, including ε-aminocaproic acid and 7 amino acids (described as SEQ ID NO. 3 in "Kinase assay of TEST EXAMPLE 1" of WO 2010/064111(P.31)), 20 mM Hepes, pH 7.5, 0.01% Triton X-100, 5 mM MgCl2, 25 μM ATP and 2 mM DTT. As blank, TNIK_N was excluded from the reaction mixture of vehicle (1% DMSO). The kinase reaction was carried out 1 h at room temperature and terminated by addition of 60 μl of the termination buffer (127 mM Hepes, pH 7.5, 26.7 mM EDTA, 0.01% Triton X-100, 1% DMSO and 0.13% Coating Reagent 3 (Caliper Life Sciences)). The amount of unphosphorylated and phosphorylated FITC-labeled substrate peptides was detected by Mobility Shift Micro Fluidic Technology (Caliper LC3000 System, Caliper Life Sciences).
Measurement: IC50 = 8.4 nM (pChEMBL 8.079999923706055)
Descriptors: MW 486.53, ALogP 4.78, HBA 7, HBD 3, PSA 114.93, QED 0.31
Compound (SMILES): COC1C[C@H](OCc2ccccc2)C[C@@H](/C=C/c2c(-c3ccc(F)cc3)nc(N(C)S(C)(=O)=O)nc2C(C)C)O1
InChIKey: GOSFJIQQWKZQRI-OZFVRTCJSA-N
Target: 3-hydroxy-3-methylglutaryl-coenzyme A reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P04035
Assay: Reductase Assay : The following procedure was followed using a HMG-CoA Reductase assay kit obtained from Sigma-Aldrich (catalogue number CS1090). The assay is based on the spectrophotometric measurement of the decrease in absorbance at 340 nm of NADPH in solution. A decrease in absorbance is caused by the oxidation of NADPH by the catalytic subunit of HMGR in the presence of the substrate HMG-CoA. Effective inhibition of the HMG-CoA leads to a reduction in oxidation of NADPH which in turn leads to a smaller reduction in the absorbance at 340 nm over time.
Measurement: IC50 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 569.7, ALogP 5.55, HBA 7, HBD 0, PSA 90.85, QED 0.32
Compound (SMILES): Cn1cc(-c2ccc(N3CCC(N4CCc5ccc(CO)cc54)CC3)nn2)cn1
InChIKey: PEQAVOGGCFURJQ-UHFFFAOYSA-N
Target: Stearoyl-CoA desaturase (SINGLE PROTEIN), Homo sapiens
UniProt: O00767
Assay: Enzymatic Assay: The SCD1 enzymatic assay was done in a volume of 50 μL using 10 μg of RLM (prepared as described above) in a 96-well polypropylene plate (enzyme reaction buffer contains 0.1 M K-Phosphate Buffer, 10 mM ATP, 6 mM MgCl2. 1 mM CoA, 1 mM β-NADH, 1.6 mM L-glutathione, 20 μM Stearoyl-CoA). Stearoyl-[9,10-3H]-CoA (ARC-0390, 1 mCi/mL, 60 Ci/mmol,) was added at a final concentration of 2 μCi/mL. Test compound was then added to the reaction mixture at the selected concentration. After incubation at room temperature for 2 hours, 5 μL 1 N HCl was added to stop the reaction, followed by addition of 25 μL of 10% charcoal. The reaction mixture was then transferred to 96-well Multiscreen plate (Millipore, Cat#MSFCN6B50). [3H2O] was collected into Opti-plate (PE, Cat#6005290) by centrifuge, at 1,000 rpm for 2 minutes. 150 μL Microscint 40 (PE, cat #6013641) was then added to each well and counted on Topcount for [3H] counts per minute (cpm).
Measurement: IC50 = 394 nM (pChEMBL 6.409999847412109)
Descriptors: MW 390.49, ALogP 2.4, HBA 7, HBD 1, PSA 70.31, QED 0.74
Compound (SMILES): Cc1cn(-c2ccc(N3CCC(N4CCc5ccccc54)CC3)nn2)cn1
InChIKey: VONRSHIJPODIKL-UHFFFAOYSA-N
Target: Stearoyl-CoA desaturase (SINGLE PROTEIN), Homo sapiens
UniProt: O00767
Assay: Enzymatic Assay: The SCD1 enzymatic assay was done in a volume of 50 μL using 10 μg of RLM (prepared as described above) in a 96-well polypropylene plate (enzyme reaction buffer contains 0.1 M K-Phosphate Buffer, 10 mM ATP, 6 mM MgCl2. 1 mM CoA, 1 mM β-NADH, 1.6 mM L-glutathione, 20 μM Stearoyl-CoA). Stearoyl-[9,10-3H]-CoA (ARC-0390, 1 mCi/mL, 60 Ci/mmol,) was added at a final concentration of 2 μCi/mL. Test compound was then added to the reaction mixture at the selected concentration. After incubation at room temperature for 2 hours, 5 μL 1 N HCl was added to stop the reaction, followed by addition of 25 μL of 10% charcoal. The reaction mixture was then transferred to 96-well Multiscreen plate (Millipore, Cat#MSFCN6B50). [3H2O] was collected into Opti-plate (PE, Cat#6005290) by centrifuge, at 1,000 rpm for 2 minutes. 150 μL Microscint 40 (PE, cat #6013641) was then added to each well and counted on Topcount for [3H] counts per minute (cpm).
Measurement: IC50 = 76 nM (pChEMBL 7.119999885559082)
Descriptors: MW 360.47, ALogP 3, HBA 6, HBD 0, PSA 50.08, QED 0.72
Compound (SMILES): Cc1nsc(-c2ccc(N3CCC(c4noc5ccc(F)cc45)CC3)nn2)n1
InChIKey: FYZPOAFODMHPSO-UHFFFAOYSA-N
Target: Stearoyl-CoA desaturase (SINGLE PROTEIN), Homo sapiens
UniProt: O00767
Assay: Enzymatic Assay: The SCD1 enzymatic assay was done in a volume of 50 μL using 10 μg of RLM (prepared as described above) in a 96-well polypropylene plate (enzyme reaction buffer contains 0.1 M K-Phosphate Buffer, 10 mM ATP, 6 mM MgCl2. 1 mM CoA, 1 mM β-NADH, 1.6 mM L-glutathione, 20 μM Stearoyl-CoA). Stearoyl-[9,10-3H]-CoA (ARC-0390, 1 mCi/mL, 60 Ci/mmol,) was added at a final concentration of 2 μCi/mL. Test compound was then added to the reaction mixture at the selected concentration. After incubation at room temperature for 2 hours, 5 μL 1 N HCl was added to stop the reaction, followed by addition of 25 μL of 10% charcoal. The reaction mixture was then transferred to 96-well Multiscreen plate (Millipore, Cat#MSFCN6B50). [3H2O] was collected into Opti-plate (PE, Cat#6005290) by centrifuge, at 1,000 rpm for 2 minutes. 150 μL Microscint 40 (PE, cat #6013641) was then added to each well and counted on Topcount for [3H] counts per minute (cpm).
Measurement: IC50 = 68 nM (pChEMBL 7.170000076293945)
Descriptors: MW 396.45, ALogP 3.97, HBA 8, HBD 0, PSA 80.83, QED 0.52
Compound (SMILES): Cc1nsc(-c2ccc(N3CCC(n4ccc5ccccc54)CC3)nn2)n1
InChIKey: SHLKRAJIHVATIE-UHFFFAOYSA-N
Target: Stearoyl-CoA desaturase (SINGLE PROTEIN), Homo sapiens
UniProt: O00767
Assay: Enzymatic Assay: The SCD1 enzymatic assay was done in a volume of 50 μL using 10 μg of RLM (prepared as described above) in a 96-well polypropylene plate (enzyme reaction buffer contains 0.1 M K-Phosphate Buffer, 10 mM ATP, 6 mM MgCl2. 1 mM CoA, 1 mM β-NADH, 1.6 mM L-glutathione, 20 μM Stearoyl-CoA). Stearoyl-[9,10-3H]-CoA (ARC-0390, 1 mCi/mL, 60 Ci/mmol,) was added at a final concentration of 2 μCi/mL. Test compound was then added to the reaction mixture at the selected concentration. After incubation at room temperature for 2 hours, 5 μL 1 N HCl was added to stop the reaction, followed by addition of 25 μL of 10% charcoal. The reaction mixture was then transferred to 96-well Multiscreen plate (Millipore, Cat#MSFCN6B50). [3H2O] was collected into Opti-plate (PE, Cat#6005290) by centrifuge, at 1,000 rpm for 2 minutes. 150 μL Microscint 40 (PE, cat #6013641) was then added to each well and counted on Topcount for [3H] counts per minute (cpm).
Measurement: IC50 = 34 nM (pChEMBL 7.46999979019165)
Descriptors: MW 376.49, ALogP 4.1, HBA 7, HBD 0, PSA 59.73, QED 0.54
Compound (SMILES): Cc1nsc(-c2ccc(N3CCC(N4CCc5ccccc54)CC3)nn2)n1
InChIKey: ZIZNVIXVYYAVOC-UHFFFAOYSA-N
Target: Stearoyl-CoA desaturase (SINGLE PROTEIN), Homo sapiens
UniProt: O00767
Assay: Enzymatic Assay: The SCD1 enzymatic assay was done in a volume of 50 μL using 10 μg of RLM (prepared as described above) in a 96-well polypropylene plate (enzyme reaction buffer contains 0.1 M K-Phosphate Buffer, 10 mM ATP, 6 mM MgCl2. 1 mM CoA, 1 mM β-NADH, 1.6 mM L-glutathione, 20 μM Stearoyl-CoA). Stearoyl-[9,10-3H]-CoA (ARC-0390, 1 mCi/mL, 60 Ci/mmol,) was added at a final concentration of 2 μCi/mL. Test compound was then added to the reaction mixture at the selected concentration. After incubation at room temperature for 2 hours, 5 μL 1 N HCl was added to stop the reaction, followed by addition of 25 μL of 10% charcoal. The reaction mixture was then transferred to 96-well Multiscreen plate (Millipore, Cat#MSFCN6B50). [3H2O] was collected into Opti-plate (PE, Cat#6005290) by centrifuge, at 1,000 rpm for 2 minutes. 150 μL Microscint 40 (PE, cat #6013641) was then added to each well and counted on Topcount for [3H] counts per minute (cpm).
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 378.51, ALogP 3.34, HBA 7, HBD 0, PSA 58.04, QED 0.7
Compound (SMILES): Fc1ccc2onc(C3CCN(c4ccc(-c5cccnc5)nn4)CC3)c2c1
InChIKey: PKTVBMJHJKUWKY-UHFFFAOYSA-N
Target: Stearoyl-CoA desaturase (SINGLE PROTEIN), Homo sapiens
UniProt: O00767
Assay: Enzymatic Assay: The SCD1 enzymatic assay was done in a volume of 50 μL using 10 μg of RLM (prepared as described above) in a 96-well polypropylene plate (enzyme reaction buffer contains 0.1 M K-Phosphate Buffer, 10 mM ATP, 6 mM MgCl2. 1 mM CoA, 1 mM β-NADH, 1.6 mM L-glutathione, 20 μM Stearoyl-CoA). Stearoyl-[9,10-3H]-CoA (ARC-0390, 1 mCi/mL, 60 Ci/mmol,) was added at a final concentration of 2 μCi/mL. Test compound was then added to the reaction mixture at the selected concentration. After incubation at room temperature for 2 hours, 5 μL 1 N HCl was added to stop the reaction, followed by addition of 25 μL of 10% charcoal. The reaction mixture was then transferred to 96-well Multiscreen plate (Millipore, Cat#MSFCN6B50). [3H2O] was collected into Opti-plate (PE, Cat#6005290) by centrifuge, at 1,000 rpm for 2 minutes. 150 μL Microscint 40 (PE, cat #6013641) was then added to each well and counted on Topcount for [3H] counts per minute (cpm).
Measurement: IC50 = 165 nM (pChEMBL 6.78000020980835)
Descriptors: MW 375.41, ALogP 4.2, HBA 6, HBD 0, PSA 67.94, QED 0.53
Compound (SMILES): CCn1cc(-c2ccc(N3CCC(c4noc5ccc(F)cc45)CC3)nn2)cn1
InChIKey: ZTKDFCKKQLEJNQ-UHFFFAOYSA-N
Target: Stearoyl-CoA desaturase (SINGLE PROTEIN), Homo sapiens
UniProt: O00767
Assay: Enzymatic Assay: The SCD1 enzymatic assay was done in a volume of 50 μL using 10 μg of RLM (prepared as described above) in a 96-well polypropylene plate (enzyme reaction buffer contains 0.1 M K-Phosphate Buffer, 10 mM ATP, 6 mM MgCl2. 1 mM CoA, 1 mM β-NADH, 1.6 mM L-glutathione, 20 μM Stearoyl-CoA). Stearoyl-[9,10-3H]-CoA (ARC-0390, 1 mCi/mL, 60 Ci/mmol,) was added at a final concentration of 2 μCi/mL. Test compound was then added to the reaction mixture at the selected concentration. After incubation at room temperature for 2 hours, 5 μL 1 N HCl was added to stop the reaction, followed by addition of 25 μL of 10% charcoal. The reaction mixture was then transferred to 96-well Multiscreen plate (Millipore, Cat#MSFCN6B50). [3H2O] was collected into Opti-plate (PE, Cat#6005290) by centrifuge, at 1,000 rpm for 2 minutes. 150 μL Microscint 40 (PE, cat #6013641) was then added to each well and counted on Topcount for [3H] counts per minute (cpm).
Measurement: IC50 = 70 nM (pChEMBL 7.159999847412109)
Descriptors: MW 392.44, ALogP 4.02, HBA 7, HBD 0, PSA 72.87, QED 0.52
Compound (SMILES): Cc1nnc(-c2ccc(N3CCC(c4noc5ccc(F)cc45)CC3)nn2)o1
InChIKey: YRYCVYQUTHYAMW-UHFFFAOYSA-N
Target: Stearoyl-CoA desaturase (SINGLE PROTEIN), Homo sapiens
UniProt: O00767
Assay: Enzymatic Assay: The SCD1 enzymatic assay was done in a volume of 50 μL using 10 μg of RLM (prepared as described above) in a 96-well polypropylene plate (enzyme reaction buffer contains 0.1 M K-Phosphate Buffer, 10 mM ATP, 6 mM MgCl2. 1 mM CoA, 1 mM β-NADH, 1.6 mM L-glutathione, 20 μM Stearoyl-CoA). Stearoyl-[9,10-3H]-CoA (ARC-0390, 1 mCi/mL, 60 Ci/mmol,) was added at a final concentration of 2 μCi/mL. Test compound was then added to the reaction mixture at the selected concentration. After incubation at room temperature for 2 hours, 5 μL 1 N HCl was added to stop the reaction, followed by addition of 25 μL of 10% charcoal. The reaction mixture was then transferred to 96-well Multiscreen plate (Millipore, Cat#MSFCN6B50). [3H2O] was collected into Opti-plate (PE, Cat#6005290) by centrifuge, at 1,000 rpm for 2 minutes. 150 μL Microscint 40 (PE, cat #6013641) was then added to each well and counted on Topcount for [3H] counts per minute (cpm).
Measurement: IC50 = 315 nM (pChEMBL 6.5)
Descriptors: MW 380.38, ALogP 3.5, HBA 8, HBD 0, PSA 93.97, QED 0.53
Compound (SMILES): OCc1nnc(-c2ccc(N3CCC(c4noc5ccc(F)cc45)CC3)nn2)o1
InChIKey: CTCYFGZXOIZJMH-UHFFFAOYSA-N
Target: Stearoyl-CoA desaturase (SINGLE PROTEIN), Homo sapiens
UniProt: O00767
Assay: Enzymatic Assay: The SCD1 enzymatic assay was done in a volume of 50 μL using 10 μg of RLM (prepared as described above) in a 96-well polypropylene plate (enzyme reaction buffer contains 0.1 M K-Phosphate Buffer, 10 mM ATP, 6 mM MgCl2. 1 mM CoA, 1 mM β-NADH, 1.6 mM L-glutathione, 20 μM Stearoyl-CoA). Stearoyl-[9,10-3H]-CoA (ARC-0390, 1 mCi/mL, 60 Ci/mmol,) was added at a final concentration of 2 μCi/mL. Test compound was then added to the reaction mixture at the selected concentration. After incubation at room temperature for 2 hours, 5 μL 1 N HCl was added to stop the reaction, followed by addition of 25 μL of 10% charcoal. The reaction mixture was then transferred to 96-well Multiscreen plate (Millipore, Cat#MSFCN6B50). [3H2O] was collected into Opti-plate (PE, Cat#6005290) by centrifuge, at 1,000 rpm for 2 minutes. 150 μL Microscint 40 (PE, cat #6013641) was then added to each well and counted on Topcount for [3H] counts per minute (cpm).
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 396.38, ALogP 2.68, HBA 9, HBD 1, PSA 114.2, QED 0.56
Compound (SMILES): Cc1csc(-c2ccc(N3CCC(c4noc5ccc(F)cc45)CC3)nn2)n1
InChIKey: CIBPNAWYMVRORE-UHFFFAOYSA-N
Target: Stearoyl-CoA desaturase (SINGLE PROTEIN), Homo sapiens
UniProt: O00767
Assay: Enzymatic Assay: The SCD1 enzymatic assay was done in a volume of 50 μL using 10 μg of RLM (prepared as described above) in a 96-well polypropylene plate (enzyme reaction buffer contains 0.1 M K-Phosphate Buffer, 10 mM ATP, 6 mM MgCl2. 1 mM CoA, 1 mM β-NADH, 1.6 mM L-glutathione, 20 μM Stearoyl-CoA). Stearoyl-[9,10-3H]-CoA (ARC-0390, 1 mCi/mL, 60 Ci/mmol,) was added at a final concentration of 2 μCi/mL. Test compound was then added to the reaction mixture at the selected concentration. After incubation at room temperature for 2 hours, 5 μL 1 N HCl was added to stop the reaction, followed by addition of 25 μL of 10% charcoal. The reaction mixture was then transferred to 96-well Multiscreen plate (Millipore, Cat#MSFCN6B50). [3H2O] was collected into Opti-plate (PE, Cat#6005290) by centrifuge, at 1,000 rpm for 2 minutes. 150 μL Microscint 40 (PE, cat #6013641) was then added to each well and counted on Topcount for [3H] counts per minute (cpm).
Measurement: IC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 395.46, ALogP 4.57, HBA 7, HBD 0, PSA 67.94, QED 0.51
Compound (SMILES): Cc1ccc(-c2ccc(N3CCC(c4noc5ccc(F)cc45)CC3)nn2)cn1
InChIKey: JFEHBZBLMMENQT-UHFFFAOYSA-N
Target: Stearoyl-CoA desaturase (SINGLE PROTEIN), Homo sapiens
UniProt: O00767
Assay: Enzymatic Assay: The SCD1 enzymatic assay was done in a volume of 50 μL using 10 μg of RLM (prepared as described above) in a 96-well polypropylene plate (enzyme reaction buffer contains 0.1 M K-Phosphate Buffer, 10 mM ATP, 6 mM MgCl2. 1 mM CoA, 1 mM β-NADH, 1.6 mM L-glutathione, 20 μM Stearoyl-CoA). Stearoyl-[9,10-3H]-CoA (ARC-0390, 1 mCi/mL, 60 Ci/mmol,) was added at a final concentration of 2 μCi/mL. Test compound was then added to the reaction mixture at the selected concentration. After incubation at room temperature for 2 hours, 5 μL 1 N HCl was added to stop the reaction, followed by addition of 25 μL of 10% charcoal. The reaction mixture was then transferred to 96-well Multiscreen plate (Millipore, Cat#MSFCN6B50). [3H2O] was collected into Opti-plate (PE, Cat#6005290) by centrifuge, at 1,000 rpm for 2 minutes. 150 μL Microscint 40 (PE, cat #6013641) was then added to each well and counted on Topcount for [3H] counts per minute (cpm).
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 389.43, ALogP 4.51, HBA 6, HBD 0, PSA 67.94, QED 0.51