lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CCN(C)c1nccc2ccc(C(=O)N3CCC4(CC3)Cc3cn(C(C)(C)C)nc3C(=O)N4)cc12
InChIKey: WQPBWBWGQVPSAJ-UHFFFAOYSA-N
Target: Acetyl-CoA carboxylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13085
Assay: Inhibition Assay: Preparation of rhACC1. Two liters of SF9 cells, infected with recombinant baculovirus containing full length human ACC1 cDNA, were suspended in ice-cold lysis buffer (25 mM Tris, pH 7.5; 150 mM NaCl; 10% glycerol; 5 mM imidazole (EMD Bioscience; Gibbstown, N.J.); 2 mM TCEP (BioVectra; Charlottetown, Canada); Benzonase nuclease (10000 U/100 g cell paste; Novagen; Madison, Wis.); EDTA-free protease inhibitor cocktail (1 tab/50 mL; Roche Diagnostics; Mannheim, Germany). Cells were lysed by 3 cycles of freeze-thaw and centrifuged at 40,000xg for 40 minutes (4 C.). Supernatant was directly loaded onto a HisTrap FF crude column (GE Healthcare; Piscataway, N.J.) and eluted with an imidazole gradient up to 0.5 M over 20 column volumes (CV). ACC1-containing fractions were pooled and diluted 1:5 with 25 mM Tris, pH 7.5, 2 mM TCEP, 10% glycerol and direct loaded onto a CaptoQ (GE Healthcare) column and eluted with an NaCl gradient up to 1 M over 20 CV's.
Measurement: IC50 = 332 nM (pChEMBL 6.480000019073486)
Descriptors: MW 474.61, ALogP 3.6, HBA 6, HBD 1, PSA 83.36, QED 0.63
Compound (SMILES): CC(C)(C)n1cc2c(n1)C(=O)NC1(CCN(C(=O)c3ccc4ccnc(NC5CCC5)c4c3)CC1)C2
InChIKey: SVJMQTWPWZNLBJ-UHFFFAOYSA-N
Target: Acetyl-CoA carboxylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13085
Assay: Inhibition Assay: Preparation of rhACC1. Two liters of SF9 cells, infected with recombinant baculovirus containing full length human ACC1 cDNA, were suspended in ice-cold lysis buffer (25 mM Tris, pH 7.5; 150 mM NaCl; 10% glycerol; 5 mM imidazole (EMD Bioscience; Gibbstown, N.J.); 2 mM TCEP (BioVectra; Charlottetown, Canada); Benzonase nuclease (10000 U/100 g cell paste; Novagen; Madison, Wis.); EDTA-free protease inhibitor cocktail (1 tab/50 mL; Roche Diagnostics; Mannheim, Germany). Cells were lysed by 3 cycles of freeze-thaw and centrifuged at 40,000xg for 40 minutes (4 C.). Supernatant was directly loaded onto a HisTrap FF crude column (GE Healthcare; Piscataway, N.J.) and eluted with an imidazole gradient up to 0.5 M over 20 column volumes (CV). ACC1-containing fractions were pooled and diluted 1:5 with 25 mM Tris, pH 7.5, 2 mM TCEP, 10% glycerol and direct loaded onto a CaptoQ (GE Healthcare) column and eluted with an NaCl gradient up to 1 M over 20 CV's.
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 486.62, ALogP 4.11, HBA 6, HBD 2, PSA 92.15, QED 0.58
Compound (SMILES): CCCNc1nccc2ccc(C(=O)N3CCC4(CC3)Cc3cn(C(C)(C)C)nc3C(=O)N4)cc12
InChIKey: VFVIIGJPUABWCI-UHFFFAOYSA-N
Target: Acetyl-CoA carboxylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13085
Assay: Inhibition Assay: Preparation of rhACC1. Two liters of SF9 cells, infected with recombinant baculovirus containing full length human ACC1 cDNA, were suspended in ice-cold lysis buffer (25 mM Tris, pH 7.5; 150 mM NaCl; 10% glycerol; 5 mM imidazole (EMD Bioscience; Gibbstown, N.J.); 2 mM TCEP (BioVectra; Charlottetown, Canada); Benzonase nuclease (10000 U/100 g cell paste; Novagen; Madison, Wis.); EDTA-free protease inhibitor cocktail (1 tab/50 mL; Roche Diagnostics; Mannheim, Germany). Cells were lysed by 3 cycles of freeze-thaw and centrifuged at 40,000xg for 40 minutes (4 C.). Supernatant was directly loaded onto a HisTrap FF crude column (GE Healthcare; Piscataway, N.J.) and eluted with an imidazole gradient up to 0.5 M over 20 column volumes (CV). ACC1-containing fractions were pooled and diluted 1:5 with 25 mM Tris, pH 7.5, 2 mM TCEP, 10% glycerol and direct loaded onto a CaptoQ (GE Healthcare) column and eluted with an NaCl gradient up to 1 M over 20 CV's.
Measurement: IC50 = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 474.61, ALogP 3.97, HBA 6, HBD 2, PSA 92.15, QED 0.6
Compound (SMILES): COCCNc1nccc2ccc(C(=O)N3CCC4(CC3)Cc3cn(C(C)(C)C)nc3C(=O)N4)cc12
InChIKey: ZDKJQHUUQXEHKB-UHFFFAOYSA-N
Target: Acetyl-CoA carboxylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13085
Assay: Inhibition Assay: Preparation of rhACC1. Two liters of SF9 cells, infected with recombinant baculovirus containing full length human ACC1 cDNA, were suspended in ice-cold lysis buffer (25 mM Tris, pH 7.5; 150 mM NaCl; 10% glycerol; 5 mM imidazole (EMD Bioscience; Gibbstown, N.J.); 2 mM TCEP (BioVectra; Charlottetown, Canada); Benzonase nuclease (10000 U/100 g cell paste; Novagen; Madison, Wis.); EDTA-free protease inhibitor cocktail (1 tab/50 mL; Roche Diagnostics; Mannheim, Germany). Cells were lysed by 3 cycles of freeze-thaw and centrifuged at 40,000xg for 40 minutes (4 C.). Supernatant was directly loaded onto a HisTrap FF crude column (GE Healthcare; Piscataway, N.J.) and eluted with an imidazole gradient up to 0.5 M over 20 column volumes (CV). ACC1-containing fractions were pooled and diluted 1:5 with 25 mM Tris, pH 7.5, 2 mM TCEP, 10% glycerol and direct loaded onto a CaptoQ (GE Healthcare) column and eluted with an NaCl gradient up to 1 M over 20 CV's.
Measurement: IC50 = 47 nM (pChEMBL 7.329999923706055)
Descriptors: MW 490.61, ALogP 3.21, HBA 7, HBD 2, PSA 101.38, QED 0.53
Compound (SMILES): CCNc1nccc2ccc(C(=O)N3CCC4(CC3)Cc3cn(C(C)(C)C)nc3C(=O)N4)cc12
InChIKey: NSIHEYUUBXTPNJ-UHFFFAOYSA-N
Target: Acetyl-CoA carboxylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13085
Assay: Inhibition Assay: Preparation of rhACC1. Two liters of SF9 cells, infected with recombinant baculovirus containing full length human ACC1 cDNA, were suspended in ice-cold lysis buffer (25 mM Tris, pH 7.5; 150 mM NaCl; 10% glycerol; 5 mM imidazole (EMD Bioscience; Gibbstown, N.J.); 2 mM TCEP (BioVectra; Charlottetown, Canada); Benzonase nuclease (10000 U/100 g cell paste; Novagen; Madison, Wis.); EDTA-free protease inhibitor cocktail (1 tab/50 mL; Roche Diagnostics; Mannheim, Germany). Cells were lysed by 3 cycles of freeze-thaw and centrifuged at 40,000xg for 40 minutes (4 C.). Supernatant was directly loaded onto a HisTrap FF crude column (GE Healthcare; Piscataway, N.J.) and eluted with an imidazole gradient up to 0.5 M over 20 column volumes (CV). ACC1-containing fractions were pooled and diluted 1:5 with 25 mM Tris, pH 7.5, 2 mM TCEP, 10% glycerol and direct loaded onto a CaptoQ (GE Healthcare) column and eluted with an NaCl gradient up to 1 M over 20 CV's.
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 460.58, ALogP 3.58, HBA 6, HBD 2, PSA 92.15, QED 0.62
Compound (SMILES): CC(C)(C)n1cc2c(n1)C(=O)NC1(CCN(C(=O)c3ccc4ccnc(NC5COC5)c4c3)CC1)C2
InChIKey: SRVCROCNLPGHTR-UHFFFAOYSA-N
Target: Acetyl-CoA carboxylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13085
Assay: Inhibition Assay: Preparation of rhACC1. Two liters of SF9 cells, infected with recombinant baculovirus containing full length human ACC1 cDNA, were suspended in ice-cold lysis buffer (25 mM Tris, pH 7.5; 150 mM NaCl; 10% glycerol; 5 mM imidazole (EMD Bioscience; Gibbstown, N.J.); 2 mM TCEP (BioVectra; Charlottetown, Canada); Benzonase nuclease (10000 U/100 g cell paste; Novagen; Madison, Wis.); EDTA-free protease inhibitor cocktail (1 tab/50 mL; Roche Diagnostics; Mannheim, Germany). Cells were lysed by 3 cycles of freeze-thaw and centrifuged at 40,000xg for 40 minutes (4 C.). Supernatant was directly loaded onto a HisTrap FF crude column (GE Healthcare; Piscataway, N.J.) and eluted with an imidazole gradient up to 0.5 M over 20 column volumes (CV). ACC1-containing fractions were pooled and diluted 1:5 with 25 mM Tris, pH 7.5, 2 mM TCEP, 10% glycerol and direct loaded onto a CaptoQ (GE Healthcare) column and eluted with an NaCl gradient up to 1 M over 20 CV's.
Measurement: IC50 = 494 nM (pChEMBL 6.309999942779541)
Descriptors: MW 488.59, ALogP 2.96, HBA 7, HBD 2, PSA 101.38, QED 0.59
Compound (SMILES): CC(C)(C)n1cc2c(n1)C(=O)NC1(CCN(C(=O)c3ccc4ccc(NCC(F)(F)F)nc4c3)CC1)C2
InChIKey: TZHCIALBUATQPF-UHFFFAOYSA-N
Target: Acetyl-CoA carboxylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13085
Assay: Inhibition Assay: Preparation of rhACC1. Two liters of SF9 cells, infected with recombinant baculovirus containing full length human ACC1 cDNA, were suspended in ice-cold lysis buffer (25 mM Tris, pH 7.5; 150 mM NaCl; 10% glycerol; 5 mM imidazole (EMD Bioscience; Gibbstown, N.J.); 2 mM TCEP (BioVectra; Charlottetown, Canada); Benzonase nuclease (10000 U/100 g cell paste; Novagen; Madison, Wis.); EDTA-free protease inhibitor cocktail (1 tab/50 mL; Roche Diagnostics; Mannheim, Germany). Cells were lysed by 3 cycles of freeze-thaw and centrifuged at 40,000xg for 40 minutes (4 C.). Supernatant was directly loaded onto a HisTrap FF crude column (GE Healthcare; Piscataway, N.J.) and eluted with an imidazole gradient up to 0.5 M over 20 column volumes (CV). ACC1-containing fractions were pooled and diluted 1:5 with 25 mM Tris, pH 7.5, 2 mM TCEP, 10% glycerol and direct loaded onto a CaptoQ (GE Healthcare) column and eluted with an NaCl gradient up to 1 M over 20 CV's.
Measurement: IC50 = 6.5 nM (pChEMBL 8.1899995803833)
Descriptors: MW 514.55, ALogP 4.12, HBA 6, HBD 2, PSA 92.15, QED 0.55
Compound (SMILES): CC(F)(F)CNc1ccc2ccc(C(=O)N3CCC4(CC3)Cc3cn(C(C)(C)C)nc3C(=O)N4)cc2n1
InChIKey: ZPKCBNMIGGUGFB-UHFFFAOYSA-N
Target: Acetyl-CoA carboxylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13085
Assay: Inhibition Assay: Preparation of rhACC1. Two liters of SF9 cells, infected with recombinant baculovirus containing full length human ACC1 cDNA, were suspended in ice-cold lysis buffer (25 mM Tris, pH 7.5; 150 mM NaCl; 10% glycerol; 5 mM imidazole (EMD Bioscience; Gibbstown, N.J.); 2 mM TCEP (BioVectra; Charlottetown, Canada); Benzonase nuclease (10000 U/100 g cell paste; Novagen; Madison, Wis.); EDTA-free protease inhibitor cocktail (1 tab/50 mL; Roche Diagnostics; Mannheim, Germany). Cells were lysed by 3 cycles of freeze-thaw and centrifuged at 40,000xg for 40 minutes (4 C.). Supernatant was directly loaded onto a HisTrap FF crude column (GE Healthcare; Piscataway, N.J.) and eluted with an imidazole gradient up to 0.5 M over 20 column volumes (CV). ACC1-containing fractions were pooled and diluted 1:5 with 25 mM Tris, pH 7.5, 2 mM TCEP, 10% glycerol and direct loaded onto a CaptoQ (GE Healthcare) column and eluted with an NaCl gradient up to 1 M over 20 CV's.
Measurement: IC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 510.59, ALogP 4.21, HBA 6, HBD 2, PSA 92.15, QED 0.55
Compound (SMILES): O=C([C@@H](O)c1ccccc1)N1CCC(c2ccc(O)cc2O)CC1
InChIKey: OWXMQAXKEFBWGA-SFHVURJKSA-N
Target: 5,6-dihydroxyindole-2-carboxylic acid oxidase (SINGLE PROTEIN), Mus musculus
UniProt: P07147
Assay: Inhibition Assay: The activity of the inhibitors is measured using a lysate of B16F1 cells (murine melanoma line). In the presence of the L-tyrosine substrate, the tyrosinase present in these cells catalyses the hydroxylation of L-tyrosine to give L-DOPA and then the oxidation of the L-DOPA to give dopaquinone. In the presence of MBTH (3-methyl-2-benzothiazolinone hydrazone), the dopaquinone is trapped so as to form a pink complex which absorbs at 520 nm.The B16F1 cells are cultured in DMEM medium+10% foetal calf serum+10-9 M alpha -MSH for 4 days at 37 C. under 7% CO2. They are treated with trypsin, washed in PBS, counted and pelleted. The pellet is taken up at 107 cells/ml in lysis buffer (10 mM sodium phosphate, pH 6.8-1% Igepal) and the suspension is treated with ultrasound for 10 seconds. After centrifugation for 30 minutes at 4000 rpm, the supernatant obtained constitutes the cell lysate used as tyrosinase source in the enzymatic assay. The assays are carried out in duplicate in 384-well plates.
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 327.38, ALogP 2.54, HBA 4, HBD 3, PSA 81, QED 0.81
Compound (SMILES): C[C@H](NC(=O)N1CCC(c2ccc(O)cc2O)CC1)c1ccccc1
InChIKey: KUXDGHCRTSGFPG-AWEZNQCLSA-N
Target: 5,6-dihydroxyindole-2-carboxylic acid oxidase (SINGLE PROTEIN), Mus musculus
UniProt: P07147
Assay: Inhibition Assay: The activity of the inhibitors is measured using a lysate of B16F1 cells (murine melanoma line). In the presence of the L-tyrosine substrate, the tyrosinase present in these cells catalyses the hydroxylation of L-tyrosine to give L-DOPA and then the oxidation of the L-DOPA to give dopaquinone. In the presence of MBTH (3-methyl-2-benzothiazolinone hydrazone), the dopaquinone is trapped so as to form a pink complex which absorbs at 520 nm.The B16F1 cells are cultured in DMEM medium+10% foetal calf serum+10-9 M alpha -MSH for 4 days at 37 C. under 7% CO2. They are treated with trypsin, washed in PBS, counted and pelleted. The pellet is taken up at 107 cells/ml in lysis buffer (10 mM sodium phosphate, pH 6.8-1% Igepal) and the suspension is treated with ultrasound for 10 seconds. After centrifugation for 30 minutes at 4000 rpm, the supernatant obtained constitutes the cell lysate used as tyrosinase source in the enzymatic assay. The assays are carried out in duplicate in 384-well plates.
Measurement: IC50 = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 340.42, ALogP 3.75, HBA 3, HBD 3, PSA 72.8, QED 0.8
Compound (SMILES): O=C(Nc1ccc(-n2nc(C3CC3)cc2C2CC2)cc1)c1ccc2nn[nH]c2c1
InChIKey: HFJSXSSYTIJJEV-UHFFFAOYSA-N
Target: Calcium release-activated calcium channel protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96D31
Assay: Inhibition Assay: Inhibition of CRAC channels was determined following thapsigargin (Sigma, Cat # T9033) induced endoplasmic calcium release in Jurkat cells. (see Yasurio Yonetoky et. al Bio. & Med. Chem. 14 (2006) 4750-4760). Cells were centrifuged and resuspended in equal volumes f Ca2+ and Mg2+ free Hanks buffer and Fluo-8 NW dye (ABD Bioquest, Inc., Sunnyvale, Calif.) loading solution at 2x105 cells/100 ul/well in 96-well black plate. Plate is incubated at 37 C./5% CO2 for 30 mM followed by further 15 mM incubation at room temperature. Test compounds (DMSO stocks diluted in Ca2+ and Mg2+ free Hanks buffer) at desired concentrations were added to the wells and incubated for 15 mM. Thapsigargin (1 uM final concentration) was added to the wells and incubated for 15 min to inhibit the Sarco-endoplasmic reticulum Ca2+ ATPase pump thereby depleting endoplasmic calcium and raising cytosolic calcium concentrations. Store-operated calcium entry was initiated by adding extracellular Ca2+.
Measurement: IC50 = 182.5 nM (pChEMBL 6.739999771118164)
Descriptors: MW 384.44, ALogP 4.15, HBA 5, HBD 2, PSA 88.49, QED 0.54
Compound (SMILES): O=C(Cn1cnc2ccccc21)Nc1ccc(-n2nc(C3CC3)cc2C2CC2)cc1
InChIKey: MAJKGCYRUWETGW-UHFFFAOYSA-N
Target: Calcium release-activated calcium channel protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96D31
Assay: Inhibition Assay: Inhibition of CRAC channels was determined following thapsigargin (Sigma, Cat # T9033) induced endoplasmic calcium release in Jurkat cells. (see Yasurio Yonetoky et. al Bio. & Med. Chem. 14 (2006) 4750-4760). Cells were centrifuged and resuspended in equal volumes f Ca2+ and Mg2+ free Hanks buffer and Fluo-8 NW dye (ABD Bioquest, Inc., Sunnyvale, Calif.) loading solution at 2x105 cells/100 ul/well in 96-well black plate. Plate is incubated at 37 C./5% CO2 for 30 mM followed by further 15 mM incubation at room temperature. Test compounds (DMSO stocks diluted in Ca2+ and Mg2+ free Hanks buffer) at desired concentrations were added to the wells and incubated for 15 mM. Thapsigargin (1 uM final concentration) was added to the wells and incubated for 15 min to inhibit the Sarco-endoplasmic reticulum Ca2+ ATPase pump thereby depleting endoplasmic calcium and raising cytosolic calcium concentrations. Store-operated calcium entry was initiated by adding extracellular Ca2+.
Measurement: IC50 = 383.1 nM (pChEMBL 6.420000076293945)
Descriptors: MW 397.48, ALogP 4.62, HBA 5, HBD 1, PSA 64.74, QED 0.52
Compound (SMILES): O=C(Cn1nnc2ccccc21)Nc1ccc(-n2nc(C3CC3)cc2C2CC2)cc1
InChIKey: WAJHNVZTIHWGQY-UHFFFAOYSA-N
Target: Calcium release-activated calcium channel protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96D31
Assay: Inhibition Assay: Inhibition of CRAC channels was determined following thapsigargin (Sigma, Cat # T9033) induced endoplasmic calcium release in Jurkat cells. (see Yasurio Yonetoky et. al Bio. & Med. Chem. 14 (2006) 4750-4760). Cells were centrifuged and resuspended in equal volumes f Ca2+ and Mg2+ free Hanks buffer and Fluo-8 NW dye (ABD Bioquest, Inc., Sunnyvale, Calif.) loading solution at 2x105 cells/100 ul/well in 96-well black plate. Plate is incubated at 37 C./5% CO2 for 30 mM followed by further 15 mM incubation at room temperature. Test compounds (DMSO stocks diluted in Ca2+ and Mg2+ free Hanks buffer) at desired concentrations were added to the wells and incubated for 15 mM. Thapsigargin (1 uM final concentration) was added to the wells and incubated for 15 min to inhibit the Sarco-endoplasmic reticulum Ca2+ ATPase pump thereby depleting endoplasmic calcium and raising cytosolic calcium concentrations. Store-operated calcium entry was initiated by adding extracellular Ca2+.
Measurement: IC50 = 51.31 nM (pChEMBL 7.289999961853027)
Descriptors: MW 398.47, ALogP 4.01, HBA 6, HBD 1, PSA 77.63, QED 0.53
Compound (SMILES): O=C(Cc1ccc2ncccc2c1)Nc1ccc(-n2nc(C3CC3)cc2C2CC2)cc1
InChIKey: VMPRVBMCLLMYRA-UHFFFAOYSA-N
Target: Calcium release-activated calcium channel protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96D31
Assay: Inhibition Assay: Inhibition of CRAC channels was determined following thapsigargin (Sigma, Cat # T9033) induced endoplasmic calcium release in Jurkat cells. (see Yasurio Yonetoky et. al Bio. & Med. Chem. 14 (2006) 4750-4760). Cells were centrifuged and resuspended in equal volumes f Ca2+ and Mg2+ free Hanks buffer and Fluo-8 NW dye (ABD Bioquest, Inc., Sunnyvale, Calif.) loading solution at 2x105 cells/100 ul/well in 96-well black plate. Plate is incubated at 37 C./5% CO2 for 30 mM followed by further 15 mM incubation at room temperature. Test compounds (DMSO stocks diluted in Ca2+ and Mg2+ free Hanks buffer) at desired concentrations were added to the wells and incubated for 15 mM. Thapsigargin (1 uM final concentration) was added to the wells and incubated for 15 min to inhibit the Sarco-endoplasmic reticulum Ca2+ ATPase pump thereby depleting endoplasmic calcium and raising cytosolic calcium concentrations. Store-operated calcium entry was initiated by adding extracellular Ca2+.
Measurement: IC50 = 146.7 nM (pChEMBL 6.829999923706055)
Descriptors: MW 408.51, ALogP 5.36, HBA 4, HBD 1, PSA 59.81, QED 0.47
Compound (SMILES): O=C(Cc1ccc2ncccc2c1)Nc1ccc(-n2nc(C3CC3)cc2C2CC2)c(F)c1
InChIKey: ZZIHFXTVTKGFQN-UHFFFAOYSA-N
Target: Calcium release-activated calcium channel protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96D31
Assay: Inhibition Assay: Inhibition of CRAC channels was determined following thapsigargin (Sigma, Cat # T9033) induced endoplasmic calcium release in Jurkat cells. (see Yasurio Yonetoky et. al Bio. & Med. Chem. 14 (2006) 4750-4760). Cells were centrifuged and resuspended in equal volumes f Ca2+ and Mg2+ free Hanks buffer and Fluo-8 NW dye (ABD Bioquest, Inc., Sunnyvale, Calif.) loading solution at 2x105 cells/100 ul/well in 96-well black plate. Plate is incubated at 37 C./5% CO2 for 30 mM followed by further 15 mM incubation at room temperature. Test compounds (DMSO stocks diluted in Ca2+ and Mg2+ free Hanks buffer) at desired concentrations were added to the wells and incubated for 15 mM. Thapsigargin (1 uM final concentration) was added to the wells and incubated for 15 min to inhibit the Sarco-endoplasmic reticulum Ca2+ ATPase pump thereby depleting endoplasmic calcium and raising cytosolic calcium concentrations. Store-operated calcium entry was initiated by adding extracellular Ca2+.
Measurement: IC50 = 263.2 nM (pChEMBL 6.579999923706055)
Descriptors: MW 426.5, ALogP 5.5, HBA 4, HBD 1, PSA 59.81, QED 0.44
Compound (SMILES): O=C(Nc1ccc(-n2nc(C(F)(F)F)cc2C2CC2)cc1)c1ccc2ncccc2c1
InChIKey: CIWBOSXDTXNQJQ-UHFFFAOYSA-N
Target: Calcium release-activated calcium channel protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96D31
Assay: Inhibition Assay: Inhibition of CRAC channels was determined following thapsigargin (Sigma, Cat # T9033) induced endoplasmic calcium release in Jurkat cells. (see Yasurio Yonetoky et. al Bio. & Med. Chem. 14 (2006) 4750-4760). Cells were centrifuged and resuspended in equal volumes f Ca2+ and Mg2+ free Hanks buffer and Fluo-8 NW dye (ABD Bioquest, Inc., Sunnyvale, Calif.) loading solution at 2x105 cells/100 ul/well in 96-well black plate. Plate is incubated at 37 C./5% CO2 for 30 mM followed by further 15 mM incubation at room temperature. Test compounds (DMSO stocks diluted in Ca2+ and Mg2+ free Hanks buffer) at desired concentrations were added to the wells and incubated for 15 mM. Thapsigargin (1 uM final concentration) was added to the wells and incubated for 15 min to inhibit the Sarco-endoplasmic reticulum Ca2+ ATPase pump thereby depleting endoplasmic calcium and raising cytosolic calcium concentrations. Store-operated calcium entry was initiated by adding extracellular Ca2+.
Measurement: IC50 = 86.12 nM (pChEMBL 7.070000171661377)
Descriptors: MW 422.41, ALogP 5.57, HBA 4, HBD 1, PSA 59.81, QED 0.47
Compound (SMILES): O=C(Nc1ccc(-n2nc(C(F)(F)F)cc2C2CC2)cc1)c1ccc2nccnc2c1
InChIKey: JHUUUHBVXPRICU-UHFFFAOYSA-N
Target: Calcium release-activated calcium channel protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96D31
Assay: Inhibition Assay: Inhibition of CRAC channels was determined following thapsigargin (Sigma, Cat # T9033) induced endoplasmic calcium release in Jurkat cells. (see Yasurio Yonetoky et. al Bio. & Med. Chem. 14 (2006) 4750-4760). Cells were centrifuged and resuspended in equal volumes f Ca2+ and Mg2+ free Hanks buffer and Fluo-8 NW dye (ABD Bioquest, Inc., Sunnyvale, Calif.) loading solution at 2x105 cells/100 ul/well in 96-well black plate. Plate is incubated at 37 C./5% CO2 for 30 mM followed by further 15 mM incubation at room temperature. Test compounds (DMSO stocks diluted in Ca2+ and Mg2+ free Hanks buffer) at desired concentrations were added to the wells and incubated for 15 mM. Thapsigargin (1 uM final concentration) was added to the wells and incubated for 15 min to inhibit the Sarco-endoplasmic reticulum Ca2+ ATPase pump thereby depleting endoplasmic calcium and raising cytosolic calcium concentrations. Store-operated calcium entry was initiated by adding extracellular Ca2+.
Measurement: IC50 = 53.36 nM (pChEMBL 7.269999980926514)
Descriptors: MW 423.4, ALogP 4.96, HBA 5, HBD 1, PSA 72.7, QED 0.5
Compound (SMILES): O=C(Cn1nnc2ccccc21)Nc1ccc(-n2nc(C(F)(F)F)cc2C2CC2)cc1
InChIKey: APTPBHDTLDJGDO-UHFFFAOYSA-N
Target: Calcium release-activated calcium channel protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96D31
Assay: Inhibition Assay: Inhibition of CRAC channels was determined following thapsigargin (Sigma, Cat # T9033) induced endoplasmic calcium release in Jurkat cells. (see Yasurio Yonetoky et. al Bio. & Med. Chem. 14 (2006) 4750-4760). Cells were centrifuged and resuspended in equal volumes f Ca2+ and Mg2+ free Hanks buffer and Fluo-8 NW dye (ABD Bioquest, Inc., Sunnyvale, Calif.) loading solution at 2x105 cells/100 ul/well in 96-well black plate. Plate is incubated at 37 C./5% CO2 for 30 mM followed by further 15 mM incubation at room temperature. Test compounds (DMSO stocks diluted in Ca2+ and Mg2+ free Hanks buffer) at desired concentrations were added to the wells and incubated for 15 mM. Thapsigargin (1 uM final concentration) was added to the wells and incubated for 15 min to inhibit the Sarco-endoplasmic reticulum Ca2+ ATPase pump thereby depleting endoplasmic calcium and raising cytosolic calcium concentrations. Store-operated calcium entry was initiated by adding extracellular Ca2+.
Measurement: IC50 = 39.17 nM (pChEMBL 7.409999847412109)
Descriptors: MW 426.4, ALogP 4.15, HBA 6, HBD 1, PSA 77.63, QED 0.52
Compound (SMILES): O=C(Cn1nc2ccccc2n1)Nc1ccc(-n2nc(C(F)(F)F)cc2C2CC2)cc1
InChIKey: ZUDNUHAUOQUVAS-UHFFFAOYSA-N
Target: Calcium release-activated calcium channel protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96D31
Assay: Inhibition Assay: Inhibition of CRAC channels was determined following thapsigargin (Sigma, Cat # T9033) induced endoplasmic calcium release in Jurkat cells. (see Yasurio Yonetoky et. al Bio. & Med. Chem. 14 (2006) 4750-4760). Cells were centrifuged and resuspended in equal volumes f Ca2+ and Mg2+ free Hanks buffer and Fluo-8 NW dye (ABD Bioquest, Inc., Sunnyvale, Calif.) loading solution at 2x105 cells/100 ul/well in 96-well black plate. Plate is incubated at 37 C./5% CO2 for 30 mM followed by further 15 mM incubation at room temperature. Test compounds (DMSO stocks diluted in Ca2+ and Mg2+ free Hanks buffer) at desired concentrations were added to the wells and incubated for 15 mM. Thapsigargin (1 uM final concentration) was added to the wells and incubated for 15 min to inhibit the Sarco-endoplasmic reticulum Ca2+ ATPase pump thereby depleting endoplasmic calcium and raising cytosolic calcium concentrations. Store-operated calcium entry was initiated by adding extracellular Ca2+.
Measurement: IC50 = 139 nM (pChEMBL 6.860000133514404)
Descriptors: MW 426.4, ALogP 4.15, HBA 6, HBD 1, PSA 77.63, QED 0.52
Compound (SMILES): O=C(Cn1nnc2ccccc21)Nc1ccc(-n2nc(C(F)(F)F)cc2C2CC2)c(F)c1
InChIKey: FCYGSKMUVGDGHQ-UHFFFAOYSA-N
Target: Calcium release-activated calcium channel protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96D31
Assay: Inhibition Assay: Inhibition of CRAC channels was determined following thapsigargin (Sigma, Cat # T9033) induced endoplasmic calcium release in Jurkat cells. (see Yasurio Yonetoky et. al Bio. & Med. Chem. 14 (2006) 4750-4760). Cells were centrifuged and resuspended in equal volumes f Ca2+ and Mg2+ free Hanks buffer and Fluo-8 NW dye (ABD Bioquest, Inc., Sunnyvale, Calif.) loading solution at 2x105 cells/100 ul/well in 96-well black plate. Plate is incubated at 37 C./5% CO2 for 30 mM followed by further 15 mM incubation at room temperature. Test compounds (DMSO stocks diluted in Ca2+ and Mg2+ free Hanks buffer) at desired concentrations were added to the wells and incubated for 15 mM. Thapsigargin (1 uM final concentration) was added to the wells and incubated for 15 min to inhibit the Sarco-endoplasmic reticulum Ca2+ ATPase pump thereby depleting endoplasmic calcium and raising cytosolic calcium concentrations. Store-operated calcium entry was initiated by adding extracellular Ca2+.
Measurement: IC50 = 160.5 nM (pChEMBL 6.789999961853027)
Descriptors: MW 444.39, ALogP 4.29, HBA 6, HBD 1, PSA 77.63, QED 0.47
Compound (SMILES): CCN(C(=O)OC(C)OC(=O)c1ccc(NC(=O)[C@@H]2N[C@@H](CC(C)(C)C)[C@](C#N)(c3ccc(Cl)cc3F)[C@H]2c2cccc(Cl)c2F)c(OC)c1)C(C)C
InChIKey: VAMATPCODPZMHW-WNCLNVGJSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: Homogeneous Time-Resolved Fluorescence (HTRF) Assay: The ability of the compounds to inhibit the interaction between p53 and MDM2 proteins was measured by an HTRF (homogeneous time-resolved fluorescence) assay in which recombinant GST-tagged MDM2 binds to a peptide that resembles the MDM2-interacting region of p53 (Lane et al.). Binding of GST-MDM2 protein and p53-peptide (biotinylated on its N-terminal end) is registered by the FRET (fluorescence resonance energy transfer) between Europium (Eu)-labeled anti-GST antibody and streptavidin-conjugated Allophycocyanin (APC).Test is performed in black flat-bottom 384-well plates (Costar) in a total volume of 40 uL containing 90 nM biotinylate peptide, 160 ng/ml GST-MDM2, 20 nM streptavidin-APC (PerkinElmerWallac), 2 nM Eu-labeled anti-GST-antibody (PerkinElmerWallac), 0.02% bovine serum albumin (BSA), 1 mM dithiothreitol (DTT) and 20 mM Tris-borate saline (TBS) buffer as follows: Add 10 uL of GST-MDM2 (640 ng/ml working solution) in reaction buffer to each well.
Measurement: IC50 = 29.6 nM (pChEMBL 7.53000020980835)
Descriptors: MW 773.71, ALogP 8.61, HBA 8, HBD 2, PSA 129.99, QED 0.15
Compound (SMILES): C[C@@H]1CN(CC(=O)N2CC(C)(C)c3cc(F)c(S(=O)(=O)C4CC4)cc32)CCN1
InChIKey: XJYFGQOEXRUCHZ-CYBMUJFWSA-N
Target: Baculoviral IAP repeat-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13490
Assay: In vitro Competitive Displacement Binding Assays : Modified SMAC peptides and compounds were tested for their ability to displace the fluorescent tracer from either XIAP, clAP-1 or clAP-2. BIR3 domains of clAP-1 , clAP-2 and XIAP were incubated with test compounds or SMAC based peptides and their respective peptide probes (Peptide Protein Research) in assay buffer (50mM Hepes pH 7.5, 0.025% Tween-20, 0.01 % BSA, and 1 mM DTT). Positive controls consisted of BIR3 proteins and tracer (no inhibition) and negative controls contained tracer only (100% inhibition). The samples were incubated at room temperature for 1 hr (XIAP and clAP-2) or 3hrs (clAP-1 ) prior to being read in the BMG Pherastar in Fluorescence Polarization mode (FP 485nm, 520nm, 520nm).
Measurement: IC50 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 409.53, ALogP 1.68, HBA 5, HBD 1, PSA 69.72, QED 0.82
Compound (SMILES): COC[C@H]1CN[C@H](C)CN1CC(=O)N1CC(C)(C)c2cc(F)c(S(=O)(=O)c3ccccc3)cc21
InChIKey: WJDBJZDNVPMKPZ-QZTJIDSGSA-N
Target: Baculoviral IAP repeat-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13490
Assay: In vitro Competitive Displacement Binding Assays : Modified SMAC peptides and compounds were tested for their ability to displace the fluorescent tracer from either XIAP, clAP-1 or clAP-2. BIR3 domains of clAP-1 , clAP-2 and XIAP were incubated with test compounds or SMAC based peptides and their respective peptide probes (Peptide Protein Research) in assay buffer (50mM Hepes pH 7.5, 0.025% Tween-20, 0.01 % BSA, and 1 mM DTT). Positive controls consisted of BIR3 proteins and tracer (no inhibition) and negative controls contained tracer only (100% inhibition). The samples were incubated at room temperature for 1 hr (XIAP and clAP-2) or 3hrs (clAP-1 ) prior to being read in the BMG Pherastar in Fluorescence Polarization mode (FP 485nm, 520nm, 520nm).
Measurement: IC50 = 45 nM (pChEMBL 7.349999904632568)
Descriptors: MW 489.61, ALogP 2.59, HBA 6, HBD 1, PSA 78.95, QED 0.67
Compound (SMILES): CCS(=O)(=O)c1ccc2c(c1)N(C(=O)CN1C[C@@H](C)NC[C@@H]1COC)CC2(C)C
InChIKey: DWJVIDCLWYONHB-HZPDHXFCSA-N
Target: E3 ubiquitin-protein ligase XIAP (SINGLE PROTEIN), Homo sapiens
UniProt: P98170
Assay: In vitro Competitive Displacement Binding Assays : Modified SMAC peptides and compounds were tested for their ability to displace the fluorescent tracer from either XIAP, clAP-1 or clAP-2. BIR3 domains of clAP-1 , clAP-2 and XIAP were incubated with test compounds or SMAC based peptides and their respective peptide probes (Peptide Protein Research) in assay buffer (50mM Hepes pH 7.5, 0.025% Tween-20, 0.01 % BSA, and 1 mM DTT). Positive controls consisted of BIR3 proteins and tracer (no inhibition) and negative controls contained tracer only (100% inhibition). The samples were incubated at room temperature for 1 hr (XIAP and clAP-2) or 3hrs (clAP-1 ) prior to being read in the BMG Pherastar in Fluorescence Polarization mode (FP 485nm, 520nm, 520nm).
Measurement: IC50 = 310 nM (pChEMBL 6.510000228881836)
Descriptors: MW 423.58, ALogP 1.41, HBA 6, HBD 1, PSA 78.95, QED 0.75
Compound (SMILES): COC[C@H]1CN[C@H](C)CN1CC(=O)N1CC(C)(C)c2cc(F)c(S(=O)(=O)c3ccc(OC)cc3)cc21
InChIKey: BJRXCNCEVXIGOC-QZTJIDSGSA-N
Target: E3 ubiquitin-protein ligase XIAP (SINGLE PROTEIN), Homo sapiens
UniProt: P98170
Assay: In vitro Competitive Displacement Binding Assays : Modified SMAC peptides and compounds were tested for their ability to displace the fluorescent tracer from either XIAP, clAP-1 or clAP-2. BIR3 domains of clAP-1 , clAP-2 and XIAP were incubated with test compounds or SMAC based peptides and their respective peptide probes (Peptide Protein Research) in assay buffer (50mM Hepes pH 7.5, 0.025% Tween-20, 0.01 % BSA, and 1 mM DTT). Positive controls consisted of BIR3 proteins and tracer (no inhibition) and negative controls contained tracer only (100% inhibition). The samples were incubated at room temperature for 1 hr (XIAP and clAP-2) or 3hrs (clAP-1 ) prior to being read in the BMG Pherastar in Fluorescence Polarization mode (FP 485nm, 520nm, 520nm).
Measurement: IC50 = 84 nM (pChEMBL 7.079999923706055)
Descriptors: MW 519.64, ALogP 2.6, HBA 7, HBD 1, PSA 88.18, QED 0.6
Compound (SMILES): CNS(=O)(=O)c1ccc2c(c1)N(C(=O)CN1C[C@@H](C)NC[C@@H]1COC)CC2(C)C
InChIKey: HXQIIVPOPMPNIB-HUUCEWRRSA-N
Target: E3 ubiquitin-protein ligase XIAP (SINGLE PROTEIN), Homo sapiens
UniProt: P98170
Assay: In vitro Competitive Displacement Binding Assays : Modified SMAC peptides and compounds were tested for their ability to displace the fluorescent tracer from either XIAP, clAP-1 or clAP-2. BIR3 domains of clAP-1 , clAP-2 and XIAP were incubated with test compounds or SMAC based peptides and their respective peptide probes (Peptide Protein Research) in assay buffer (50mM Hepes pH 7.5, 0.025% Tween-20, 0.01 % BSA, and 1 mM DTT). Positive controls consisted of BIR3 proteins and tracer (no inhibition) and negative controls contained tracer only (100% inhibition). The samples were incubated at room temperature for 1 hr (XIAP and clAP-2) or 3hrs (clAP-1 ) prior to being read in the BMG Pherastar in Fluorescence Polarization mode (FP 485nm, 520nm, 520nm).
Measurement: IC50 = 220 nM (pChEMBL 6.659999847412109)
Descriptors: MW 424.57, ALogP 0.53, HBA 6, HBD 2, PSA 90.98, QED 0.69
Compound (SMILES): COC[C@H]1CN[C@H](C)CN1CC(=O)N1CC(C)(C)c2ccc(S(=O)(=O)CC(C)C)cc21
InChIKey: DHAXEIHOHLUHRE-QZTJIDSGSA-N
Target: Baculoviral IAP repeat-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13490
Assay: In vitro Competitive Displacement Binding Assays : Modified SMAC peptides and compounds were tested for their ability to displace the fluorescent tracer from either XIAP, clAP-1 or clAP-2. BIR3 domains of clAP-1 , clAP-2 and XIAP were incubated with test compounds or SMAC based peptides and their respective peptide probes (Peptide Protein Research) in assay buffer (50mM Hepes pH 7.5, 0.025% Tween-20, 0.01 % BSA, and 1 mM DTT). Positive controls consisted of BIR3 proteins and tracer (no inhibition) and negative controls contained tracer only (100% inhibition). The samples were incubated at room temperature for 1 hr (XIAP and clAP-2) or 3hrs (clAP-1 ) prior to being read in the BMG Pherastar in Fluorescence Polarization mode (FP 485nm, 520nm, 520nm).
Measurement: IC50 = 140 nM (pChEMBL 6.849999904632568)
Descriptors: MW 451.63, ALogP 2.05, HBA 6, HBD 1, PSA 78.95, QED 0.68
Compound (SMILES): COC[C@H]1CN[C@H](C)CN1CC(=O)N1CC(C)(C)c2cc(OC)ncc21
InChIKey: MVERELJNWTTZKZ-ZIAGYGMSSA-N
Target: E3 ubiquitin-protein ligase XIAP (SINGLE PROTEIN), Homo sapiens
UniProt: P98170
Assay: In vitro Competitive Displacement Binding Assays : Modified SMAC peptides and compounds were tested for their ability to displace the fluorescent tracer from either XIAP, clAP-1 or clAP-2. BIR3 domains of clAP-1 , clAP-2 and XIAP were incubated with test compounds or SMAC based peptides and their respective peptide probes (Peptide Protein Research) in assay buffer (50mM Hepes pH 7.5, 0.025% Tween-20, 0.01 % BSA, and 1 mM DTT). Positive controls consisted of BIR3 proteins and tracer (no inhibition) and negative controls contained tracer only (100% inhibition). The samples were incubated at room temperature for 1 hr (XIAP and clAP-2) or 3hrs (clAP-1 ) prior to being read in the BMG Pherastar in Fluorescence Polarization mode (FP 485nm, 520nm, 520nm).
Measurement: IC50 = 6000 nM (pChEMBL 5.21999979019165)
Descriptors: MW 362.47, ALogP 1.02, HBA 6, HBD 1, PSA 66.93, QED 0.84
Compound (SMILES): COC[C@H]1CN[C@H](C)CN1CC(=O)N1CC(C)(C)c2cc(=O)n(Cc3ccccc3)cc21
InChIKey: RGEBRWNXQGHJQN-UYAOXDASSA-N
Target: Baculoviral IAP repeat-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13490
Assay: In vitro Competitive Displacement Binding Assays : Modified SMAC peptides and compounds were tested for their ability to displace the fluorescent tracer from either XIAP, clAP-1 or clAP-2. BIR3 domains of clAP-1 , clAP-2 and XIAP were incubated with test compounds or SMAC based peptides and their respective peptide probes (Peptide Protein Research) in assay buffer (50mM Hepes pH 7.5, 0.025% Tween-20, 0.01 % BSA, and 1 mM DTT). Positive controls consisted of BIR3 proteins and tracer (no inhibition) and negative controls contained tracer only (100% inhibition). The samples were incubated at room temperature for 1 hr (XIAP and clAP-2) or 3hrs (clAP-1 ) prior to being read in the BMG Pherastar in Fluorescence Polarization mode (FP 485nm, 520nm, 520nm).
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 438.57, ALogP 1.83, HBA 6, HBD 1, PSA 66.81, QED 0.75
Compound (SMILES): COC[C@H]1CN[C@H](C)CN1CC(=O)N1CC(C)(C)c2ccc(S(=O)(=O)N(C)C)cc21
InChIKey: ONWOSPHYIWOIBO-HZPDHXFCSA-N
Target: Baculoviral IAP repeat-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13490
Assay: In vitro Competitive Displacement Binding Assays : Modified SMAC peptides and compounds were tested for their ability to displace the fluorescent tracer from either XIAP, clAP-1 or clAP-2. BIR3 domains of clAP-1 , clAP-2 and XIAP were incubated with test compounds or SMAC based peptides and their respective peptide probes (Peptide Protein Research) in assay buffer (50mM Hepes pH 7.5, 0.025% Tween-20, 0.01 % BSA, and 1 mM DTT). Positive controls consisted of BIR3 proteins and tracer (no inhibition) and negative controls contained tracer only (100% inhibition). The samples were incubated at room temperature for 1 hr (XIAP and clAP-2) or 3hrs (clAP-1 ) prior to being read in the BMG Pherastar in Fluorescence Polarization mode (FP 485nm, 520nm, 520nm).
Measurement: IC50 = 1200 nM (pChEMBL 5.920000076293945)
Descriptors: MW 438.59, ALogP 0.87, HBA 6, HBD 1, PSA 82.19, QED 0.71
Compound (SMILES): COC[C@H]1CN[C@H](C)CN1CC(=O)N1CC(C)(C)c2ccc(S(=O)(=O)NC(C)C)cc21
InChIKey: LUGRFLHMNYMZEF-IAGOWNOFSA-N
Target: E3 ubiquitin-protein ligase XIAP (SINGLE PROTEIN), Homo sapiens
UniProt: P98170
Assay: In vitro Competitive Displacement Binding Assays : Modified SMAC peptides and compounds were tested for their ability to displace the fluorescent tracer from either XIAP, clAP-1 or clAP-2. BIR3 domains of clAP-1 , clAP-2 and XIAP were incubated with test compounds or SMAC based peptides and their respective peptide probes (Peptide Protein Research) in assay buffer (50mM Hepes pH 7.5, 0.025% Tween-20, 0.01 % BSA, and 1 mM DTT). Positive controls consisted of BIR3 proteins and tracer (no inhibition) and negative controls contained tracer only (100% inhibition). The samples were incubated at room temperature for 1 hr (XIAP and clAP-2) or 3hrs (clAP-1 ) prior to being read in the BMG Pherastar in Fluorescence Polarization mode (FP 485nm, 520nm, 520nm).
Measurement: IC50 = 280 nM (pChEMBL 6.550000190734863)
Descriptors: MW 452.62, ALogP 1.31, HBA 6, HBD 2, PSA 90.98, QED 0.65
Compound (SMILES): COC[C@H]1CN[C@H](C)CN1CC(=O)N1CC(C)(C)c2ccc(S(=O)(=O)Cc3ccccc3)cc21
InChIKey: UDYYPLCSNYIPHQ-TZIWHRDSSA-N
Target: Baculoviral IAP repeat-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13490
Assay: In vitro Competitive Displacement Binding Assays : Modified SMAC peptides and compounds were tested for their ability to displace the fluorescent tracer from either XIAP, clAP-1 or clAP-2. BIR3 domains of clAP-1 , clAP-2 and XIAP were incubated with test compounds or SMAC based peptides and their respective peptide probes (Peptide Protein Research) in assay buffer (50mM Hepes pH 7.5, 0.025% Tween-20, 0.01 % BSA, and 1 mM DTT). Positive controls consisted of BIR3 proteins and tracer (no inhibition) and negative controls contained tracer only (100% inhibition). The samples were incubated at room temperature for 1 hr (XIAP and clAP-2) or 3hrs (clAP-1 ) prior to being read in the BMG Pherastar in Fluorescence Polarization mode (FP 485nm, 520nm, 520nm).
Measurement: IC50 = 820 nM (pChEMBL 6.090000152587891)
Descriptors: MW 485.65, ALogP 2.59, HBA 6, HBD 1, PSA 78.95, QED 0.65
Compound (SMILES): COC[C@H]1CN[C@H](C)CN1CC(=O)N1CC2(CN(C(C)=O)C2)c2ccc(Cl)cc21
InChIKey: HUSMWCNFOBDGSL-RHSMWYFYSA-N
Target: Baculoviral IAP repeat-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13490
Assay: In vitro Competitive Displacement Binding Assays : Modified SMAC peptides and compounds were tested for their ability to displace the fluorescent tracer from either XIAP, clAP-1 or clAP-2. BIR3 domains of clAP-1 , clAP-2 and XIAP were incubated with test compounds or SMAC based peptides and their respective peptide probes (Peptide Protein Research) in assay buffer (50mM Hepes pH 7.5, 0.025% Tween-20, 0.01 % BSA, and 1 mM DTT). Positive controls consisted of BIR3 proteins and tracer (no inhibition) and negative controls contained tracer only (100% inhibition). The samples were incubated at room temperature for 1 hr (XIAP and clAP-2) or 3hrs (clAP-1 ) prior to being read in the BMG Pherastar in Fluorescence Polarization mode (FP 485nm, 520nm, 520nm).
Measurement: IC50 = 540 nM (pChEMBL 6.269999980926514)
Descriptors: MW 420.94, ALogP 1.1, HBA 5, HBD 1, PSA 65.12, QED 0.79
Compound (SMILES): COC[C@H]1CN[C@H](C)CN1CC(=O)N1CC(C)(C)c2cnc(CC(C)C)cc21
InChIKey: MIGMYZOQSOKYEJ-SJLPKXTDSA-N
Target: Baculoviral IAP repeat-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13490
Assay: In vitro Competitive Displacement Binding Assays : Modified SMAC peptides and compounds were tested for their ability to displace the fluorescent tracer from either XIAP, clAP-1 or clAP-2. BIR3 domains of clAP-1 , clAP-2 and XIAP were incubated with test compounds or SMAC based peptides and their respective peptide probes (Peptide Protein Research) in assay buffer (50mM Hepes pH 7.5, 0.025% Tween-20, 0.01 % BSA, and 1 mM DTT). Positive controls consisted of BIR3 proteins and tracer (no inhibition) and negative controls contained tracer only (100% inhibition). The samples were incubated at room temperature for 1 hr (XIAP and clAP-2) or 3hrs (clAP-1 ) prior to being read in the BMG Pherastar in Fluorescence Polarization mode (FP 485nm, 520nm, 520nm).
Measurement: IC50 = 310 nM (pChEMBL 6.510000228881836)
Descriptors: MW 388.56, ALogP 2.21, HBA 5, HBD 1, PSA 57.7, QED 0.81
Compound (SMILES): COC[C@H]1CN[C@H](C)CN1CC(=O)N1CC(C)(C)c2cnc(Oc3ccccc3)cc21
InChIKey: QSUMXZDTSNYFJY-QZTJIDSGSA-N
Target: E3 ubiquitin-protein ligase XIAP (SINGLE PROTEIN), Homo sapiens
UniProt: P98170
Assay: In vitro Competitive Displacement Binding Assays : Modified SMAC peptides and compounds were tested for their ability to displace the fluorescent tracer from either XIAP, clAP-1 or clAP-2. BIR3 domains of clAP-1 , clAP-2 and XIAP were incubated with test compounds or SMAC based peptides and their respective peptide probes (Peptide Protein Research) in assay buffer (50mM Hepes pH 7.5, 0.025% Tween-20, 0.01 % BSA, and 1 mM DTT). Positive controls consisted of BIR3 proteins and tracer (no inhibition) and negative controls contained tracer only (100% inhibition). The samples were incubated at room temperature for 1 hr (XIAP and clAP-2) or 3hrs (clAP-1 ) prior to being read in the BMG Pherastar in Fluorescence Polarization mode (FP 485nm, 520nm, 520nm).
Measurement: IC50 = 390 nM (pChEMBL 6.409999847412109)
Descriptors: MW 424.55, ALogP 2.81, HBA 6, HBD 1, PSA 66.93, QED 0.77
Compound (SMILES): COC[C@H]1CN[C@H](C)CN1CC(=O)N1CC(C)(C)c2cnc(CCC(C)C)cc21
InChIKey: SFRBIHGATTUURB-IEBWSBKVSA-N
Target: Baculoviral IAP repeat-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13490
Assay: In vitro Competitive Displacement Binding Assays : Modified SMAC peptides and compounds were tested for their ability to displace the fluorescent tracer from either XIAP, clAP-1 or clAP-2. BIR3 domains of clAP-1 , clAP-2 and XIAP were incubated with test compounds or SMAC based peptides and their respective peptide probes (Peptide Protein Research) in assay buffer (50mM Hepes pH 7.5, 0.025% Tween-20, 0.01 % BSA, and 1 mM DTT). Positive controls consisted of BIR3 proteins and tracer (no inhibition) and negative controls contained tracer only (100% inhibition). The samples were incubated at room temperature for 1 hr (XIAP and clAP-2) or 3hrs (clAP-1 ) prior to being read in the BMG Pherastar in Fluorescence Polarization mode (FP 485nm, 520nm, 520nm).
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 402.58, ALogP 2.6, HBA 5, HBD 1, PSA 57.7, QED 0.76
Compound (SMILES): COC[C@H]1CN[C@H](C)CN1CC(=O)N1CC2(CN(C(C)=O)C2)c2ccc(Cc3ccccc3)cc21
InChIKey: IRVKITYLCGOXFW-HYBUGGRVSA-N
Target: E3 ubiquitin-protein ligase XIAP (SINGLE PROTEIN), Homo sapiens
UniProt: P98170
Assay: In vitro Competitive Displacement Binding Assays : Modified SMAC peptides and compounds were tested for their ability to displace the fluorescent tracer from either XIAP, clAP-1 or clAP-2. BIR3 domains of clAP-1 , clAP-2 and XIAP were incubated with test compounds or SMAC based peptides and their respective peptide probes (Peptide Protein Research) in assay buffer (50mM Hepes pH 7.5, 0.025% Tween-20, 0.01 % BSA, and 1 mM DTT). Positive controls consisted of BIR3 proteins and tracer (no inhibition) and negative controls contained tracer only (100% inhibition). The samples were incubated at room temperature for 1 hr (XIAP and clAP-2) or 3hrs (clAP-1 ) prior to being read in the BMG Pherastar in Fluorescence Polarization mode (FP 485nm, 520nm, 520nm).
Measurement: IC50 = 64 nM (pChEMBL 7.190000057220459)
Descriptors: MW 476.62, ALogP 2.03, HBA 5, HBD 1, PSA 65.12, QED 0.69
Compound (SMILES): COC[C@H]1CN[C@H](C)CN1CC(=O)N1CC(C)(C)c2cnc(Cc3ccccc3F)cc21
InChIKey: HMBHEQGPDBVRRL-YLJYHZDGSA-N
Target: Baculoviral IAP repeat-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13490
Assay: In vitro Competitive Displacement Binding Assays : Modified SMAC peptides and compounds were tested for their ability to displace the fluorescent tracer from either XIAP, clAP-1 or clAP-2. BIR3 domains of clAP-1 , clAP-2 and XIAP were incubated with test compounds or SMAC based peptides and their respective peptide probes (Peptide Protein Research) in assay buffer (50mM Hepes pH 7.5, 0.025% Tween-20, 0.01 % BSA, and 1 mM DTT). Positive controls consisted of BIR3 proteins and tracer (no inhibition) and negative controls contained tracer only (100% inhibition). The samples were incubated at room temperature for 1 hr (XIAP and clAP-2) or 3hrs (clAP-1 ) prior to being read in the BMG Pherastar in Fluorescence Polarization mode (FP 485nm, 520nm, 520nm).
Measurement: IC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 440.56, ALogP 2.74, HBA 5, HBD 1, PSA 57.7, QED 0.75
Compound (SMILES): COC[C@H]1CN[C@H](C)CN1CC(=O)N1CC(C)(C)c2cnc(Cc3ccccc3Cl)cc21
InChIKey: LZQBENILDNFKLV-YLJYHZDGSA-N
Target: E3 ubiquitin-protein ligase XIAP (SINGLE PROTEIN), Homo sapiens
UniProt: P98170
Assay: In vitro Competitive Displacement Binding Assays : Modified SMAC peptides and compounds were tested for their ability to displace the fluorescent tracer from either XIAP, clAP-1 or clAP-2. BIR3 domains of clAP-1 , clAP-2 and XIAP were incubated with test compounds or SMAC based peptides and their respective peptide probes (Peptide Protein Research) in assay buffer (50mM Hepes pH 7.5, 0.025% Tween-20, 0.01 % BSA, and 1 mM DTT). Positive controls consisted of BIR3 proteins and tracer (no inhibition) and negative controls contained tracer only (100% inhibition). The samples were incubated at room temperature for 1 hr (XIAP and clAP-2) or 3hrs (clAP-1 ) prior to being read in the BMG Pherastar in Fluorescence Polarization mode (FP 485nm, 520nm, 520nm).
Measurement: IC50 = 530 nM (pChEMBL 6.28000020980835)
Descriptors: MW 457.02, ALogP 3.26, HBA 5, HBD 1, PSA 57.7, QED 0.72
Compound (SMILES): COC[C@H]1CN[C@H](C)CN1CC(=O)N1CC(C)(C)c2cnc(CC3CCCCC3)cc21
InChIKey: YDOOULBWFWNWCG-WIYYLYMNSA-N
Target: E3 ubiquitin-protein ligase XIAP (SINGLE PROTEIN), Homo sapiens
UniProt: P98170
Assay: In vitro Competitive Displacement Binding Assays : Modified SMAC peptides and compounds were tested for their ability to displace the fluorescent tracer from either XIAP, clAP-1 or clAP-2. BIR3 domains of clAP-1 , clAP-2 and XIAP were incubated with test compounds or SMAC based peptides and their respective peptide probes (Peptide Protein Research) in assay buffer (50mM Hepes pH 7.5, 0.025% Tween-20, 0.01 % BSA, and 1 mM DTT). Positive controls consisted of BIR3 proteins and tracer (no inhibition) and negative controls contained tracer only (100% inhibition). The samples were incubated at room temperature for 1 hr (XIAP and clAP-2) or 3hrs (clAP-1 ) prior to being read in the BMG Pherastar in Fluorescence Polarization mode (FP 485nm, 520nm, 520nm).
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 428.62, ALogP 3.14, HBA 5, HBD 1, PSA 57.7, QED 0.75