lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1c(-c2noc(=O)[nH]2)nc(-c2cncc(Cl)c2)c2c1nc(N1CCO[C@@H]3CCC[C@H]31)n2C[C@H]1CC[C@H](C)CC1
InChIKey: UITXZAZIVADQIR-LVOPCWDJSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: FRET Assay: Methods: An HDM2 FRET assay was developed to assess the compounds' inhibitory activity towards binding of p53 protein. A truncated version of HDM2 with residues 17 to 125 (containing p53 binding surface, Science (1994) 265, 346-355), with N-terminal His and Thioredoxin tag was generated in pET32a expression vector and expressed in E. coli strain BL21(DE3)Rosetta. Protein was purified using Ni-affinity chromatography, followed by size exclusion chromatography using Superdex 75 26/60 column. To assess inhibition of p53 binding to HDM2, a FITC labeled 8-mer peptide (SEQ ID NO:1: Ac-Phe-Arg-Dpr-Ac6c-(6-Br)Trp-Glu-Glu-Leu-NH2; Anal Biochem. 2004 Aug. 1; 331(1):138-46) with strong affinity towards the p53 binding pocket of HDM2 was used. The HDM2 assay buffer contained 1x Phosphate Buffered Saline (Invitrogen, Cat#14190), 0.01% BSA (Jackson ImmunoResearch, Cat#001-000-162), 0.01% Tween-20. In the 1x assay buffer recombinant HDM2 protein, peptide and Lumi-4-Tb Cryptate-conjugate mouse.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 564.09, ALogP 5.38, HBA 9, HBD 1, PSA 114.96, QED 0.34
Compound (SMILES): CN(C)c1c(C(=O)O)nc(-c2cncc(Cl)c2)c2c1nc(N1CCO[C@@H]3CCC[C@H]31)n2C[C@H]1CC[C@H](C)CC1
InChIKey: FRMLMWRFFZHYID-MCEIDBOGSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: FRET Assay: Methods: An HDM2 FRET assay was developed to assess the compounds' inhibitory activity towards binding of p53 protein. A truncated version of HDM2 with residues 17 to 125 (containing p53 binding surface, Science (1994) 265, 346-355), with N-terminal His and Thioredoxin tag was generated in pET32a expression vector and expressed in E. coli strain BL21(DE3)Rosetta. Protein was purified using Ni-affinity chromatography, followed by size exclusion chromatography using Superdex 75 26/60 column. To assess inhibition of p53 binding to HDM2, a FITC labeled 8-mer peptide (SEQ ID NO:1: Ac-Phe-Arg-Dpr-Ac6c-(6-Br)Trp-Glu-Glu-Leu-NH2; Anal Biochem. 2004 Aug. 1; 331(1):138-46) with strong affinity towards the p53 binding pocket of HDM2 was used. The HDM2 assay buffer contained 1x Phosphate Buffered Saline (Invitrogen, Cat#14190), 0.01% BSA (Jackson ImmunoResearch, Cat#001-000-162), 0.01% Tween-20. In the 1x assay buffer recombinant HDM2 protein, peptide and Lumi-4-Tb Cryptate-conjugate mouse.
Measurement: IC50 = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 553.11, ALogP 5.49, HBA 8, HBD 1, PSA 96.61, QED 0.43
Compound (SMILES): COCC(C)c1nc2cc(-c3noc(=O)[nH]3)nc(-c3cncc(Cl)c3)c2n1C(C)[C@H]1CC[C@H](C)CC1
InChIKey: BOHJWRUCGNOBMS-GQRAJKLCSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: FRET Assay: Methods: An HDM2 FRET assay was developed to assess the compounds' inhibitory activity towards binding of p53 protein. A truncated version of HDM2 with residues 17 to 125 (containing p53 binding surface, Science (1994) 265, 346-355), with N-terminal His and Thioredoxin tag was generated in pET32a expression vector and expressed in E. coli strain BL21(DE3)Rosetta. Protein was purified using Ni-affinity chromatography, followed by size exclusion chromatography using Superdex 75 26/60 column. To assess inhibition of p53 binding to HDM2, a FITC labeled 8-mer peptide (SEQ ID NO:1: Ac-Phe-Arg-Dpr-Ac6c-(6-Br)Trp-Glu-Glu-Leu-NH2; Anal Biochem. 2004 Aug. 1; 331(1):138-46) with strong affinity towards the p53 binding pocket of HDM2 was used. The HDM2 assay buffer contained 1x Phosphate Buffered Saline (Invitrogen, Cat#14190), 0.01% BSA (Jackson ImmunoResearch, Cat#001-000-162), 0.01% Tween-20.
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 511.03, ALogP 5.63, HBA 8, HBD 1, PSA 111.72, QED 0.34
Compound (SMILES): CS(=O)(=O)NC(=O)c1cc2nc(N3CCO[C@@H]4CCC[C@H]43)n(C[C@H]3CC[C@H](C)CC3)c2c(-c2cncc(Cl)c2)n1
InChIKey: FOVGPBPSNKEHGH-MCJPXMOYSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: FRET Assay: Methods: An HDM2 FRET assay was developed to assess the compounds' inhibitory activity towards binding of p53 protein. A truncated version of HDM2 with residues 17 to 125 (containing p53 binding surface, Science (1994) 265, 346-355), with N-terminal His and Thioredoxin tag was generated in pET32a expression vector and expressed in E. coli strain BL21(DE3)Rosetta. Protein was purified using Ni-affinity chromatography, followed by size exclusion chromatography using Superdex 75 26/60 column. To assess inhibition of p53 binding to HDM2, a FITC labeled 8-mer peptide (SEQ ID NO:1: Ac-Phe-Arg-Dpr-Ac6c-(6-Br)Trp-Glu-Glu-Leu-NH2; Anal Biochem. 2004 Aug. 1; 331(1):138-46) with strong affinity towards the p53 binding pocket of HDM2 was used. The HDM2 assay buffer contained 1x Phosphate Buffered Saline (Invitrogen, Cat#14190), 0.01% BSA (Jackson ImmunoResearch, Cat#001-000-162), 0.01% Tween-20.
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 587.15, ALogP 4.42, HBA 9, HBD 1, PSA 119.31, QED 0.45
Compound (SMILES): CN(C)S(=O)(=O)NC(=O)c1cc2nc(N3CCO[C@@H]4CCC[C@H]43)n(C[C@H]3CC[C@H](C)CC3)c2c(-c2cncc(Cl)c2)n1
InChIKey: IADFONFJBQGQSB-PIYXRGFCSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: FRET Assay: Methods: An HDM2 FRET assay was developed to assess the compounds' inhibitory activity towards binding of p53 protein. A truncated version of HDM2 with residues 17 to 125 (containing p53 binding surface, Science (1994) 265, 346-355), with N-terminal His and Thioredoxin tag was generated in pET32a expression vector and expressed in E. coli strain BL21(DE3)Rosetta. Protein was purified using Ni-affinity chromatography, followed by size exclusion chromatography using Superdex 75 26/60 column. To assess inhibition of p53 binding to HDM2, a FITC labeled 8-mer peptide (SEQ ID NO:1: Ac-Phe-Arg-Dpr-Ac6c-(6-Br)Trp-Glu-Glu-Leu-NH2; Anal Biochem. 2004 Aug. 1; 331(1):138-46) with strong affinity towards the p53 binding pocket of HDM2 was used. The HDM2 assay buffer contained 1x Phosphate Buffered Saline (Invitrogen, Cat#14190), 0.01% BSA (Jackson ImmunoResearch, Cat#001-000-162), 0.01% Tween-20. In the 1x assay buffer recombinant HDM2 protein, peptide and Lumi-4-Tb Cryptate-conjugate mouse.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 616.19, ALogP 4.27, HBA 9, HBD 1, PSA 122.55, QED 0.42
Compound (SMILES): CNC(=O)c1cc2nc(N3CCOC[C@H]3c3ccccc3)n(C[C@H]3CC[C@H](C)CC3)c2c(-c2cncc(Cl)c2)n1
InChIKey: WQQBXFMMYBXVRZ-IZVMNLJQSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: FRET Assay: Methods: An HDM2 FRET assay was developed to assess the compounds' inhibitory activity towards binding of p53 protein. A truncated version of HDM2 with residues 17 to 125 (containing p53 binding surface, Science (1994) 265, 346-355), with N-terminal His and Thioredoxin tag was generated in pET32a expression vector and expressed in E. coli strain BL21(DE3)Rosetta. Protein was purified using Ni-affinity chromatography, followed by size exclusion chromatography using Superdex 75 26/60 column. To assess inhibition of p53 binding to HDM2, a FITC labeled 8-mer peptide (SEQ ID NO:1: Ac-Phe-Arg-Dpr-Ac6c-(6-Br)Trp-Glu-Glu-Leu-NH2; Anal Biochem. 2004 Aug. 1; 331(1):138-46) with strong affinity towards the p53 binding pocket of HDM2 was used. The HDM2 assay buffer contained 1x Phosphate Buffered Saline (Invitrogen, Cat#14190), 0.01% BSA (Jackson ImmunoResearch, Cat#001-000-162), 0.01% Tween-20.
Measurement: IC50 = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 559.11, ALogP 5.91, HBA 7, HBD 1, PSA 85.17, QED 0.32
Compound (SMILES): CN(C)C(=O)c1cc2nc(N3CCOC[C@H]3c3ccccc3)n(C[C@H]3CC[C@H](C)CC3)c2c(-c2cncc(Cl)c2)n1
InChIKey: SPEKTYMVGNZTAL-VPYPWEPUSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: FRET Assay: Methods: An HDM2 FRET assay was developed to assess the compounds' inhibitory activity towards binding of p53 protein. A truncated version of HDM2 with residues 17 to 125 (containing p53 binding surface, Science (1994) 265, 346-355), with N-terminal His and Thioredoxin tag was generated in pET32a expression vector and expressed in E. coli strain BL21(DE3)Rosetta. Protein was purified using Ni-affinity chromatography, followed by size exclusion chromatography using Superdex 75 26/60 column. To assess inhibition of p53 binding to HDM2, a FITC labeled 8-mer peptide (SEQ ID NO:1: Ac-Phe-Arg-Dpr-Ac6c-(6-Br)Trp-Glu-Glu-Leu-NH2; Anal Biochem. 2004 Aug. 1; 331(1):138-46) with strong affinity towards the p53 binding pocket of HDM2 was used. The HDM2 assay buffer contained 1x Phosphate Buffered Saline (Invitrogen, Cat#14190), 0.01% BSA (Jackson ImmunoResearch, Cat#001-000-162), 0.01% Tween-20.
Measurement: IC50 = 175 nM (pChEMBL 6.760000228881836)
Descriptors: MW 573.14, ALogP 6.25, HBA 7, HBD 0, PSA 76.38, QED 0.27
Compound (SMILES): CS(=O)(=O)Nc1cc2nc(N3CCOC[C@H]3c3ccccc3)n(C[C@H]3CC[C@H](C)CC3)c2c(-c2cncc(Cl)c2)n1
InChIKey: JAZIYSMLAMDBQY-WOVHNISZSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: FRET Assay: Methods: An HDM2 FRET assay was developed to assess the compounds' inhibitory activity towards binding of p53 protein. A truncated version of HDM2 with residues 17 to 125 (containing p53 binding surface, Science (1994) 265, 346-355), with N-terminal His and Thioredoxin tag was generated in pET32a expression vector and expressed in E. coli strain BL21(DE3)Rosetta. Protein was purified using Ni-affinity chromatography, followed by size exclusion chromatography using Superdex 75 26/60 column. To assess inhibition of p53 binding to HDM2, a FITC labeled 8-mer peptide (SEQ ID NO:1: Ac-Phe-Arg-Dpr-Ac6c-(6-Br)Trp-Glu-Glu-Leu-NH2; Anal Biochem. 2004 Aug. 1; 331(1):138-46) with strong affinity towards the p53 binding pocket of HDM2 was used. The HDM2 assay buffer contained 1x Phosphate Buffered Saline (Invitrogen, Cat#14190), 0.01% BSA (Jackson ImmunoResearch, Cat#001-000-162), 0.01% Tween-20.
Measurement: IC50 = 122 nM (pChEMBL 6.909999847412109)
Descriptors: MW 595.17, ALogP 5.92, HBA 8, HBD 1, PSA 102.24, QED 0.28
Compound (SMILES): C[C@H]1CC[C@H](Cn2c(N3CCC[C@H]3C(F)(F)F)nc3cc(-c4nnn[nH]4)nc(-c4cncc(Cl)c4)c32)CC1
InChIKey: LXGNSQRNDPXXEN-AVYPCKFXSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: FRET Assay: Methods: An HDM2 FRET assay was developed to assess the compounds' inhibitory activity towards binding of p53 protein. A truncated version of HDM2 with residues 17 to 125 (containing p53 binding surface, Science (1994) 265, 346-355), with N-terminal His and Thioredoxin tag was generated in pET32a expression vector and expressed in E. coli strain BL21(DE3)Rosetta. Protein was purified using Ni-affinity chromatography, followed by size exclusion chromatography using Superdex 75 26/60 column. To assess inhibition of p53 binding to HDM2, a FITC labeled 8-mer peptide (SEQ ID NO:1: Ac-Phe-Arg-Dpr-Ac6c-(6-Br)Trp-Glu-Glu-Leu-NH2; Anal Biochem. 2004 Aug. 1; 331(1):138-46) with strong affinity towards the p53 binding pocket of HDM2 was used. The HDM2 assay buffer contained 1x Phosphate Buffered Saline (Invitrogen, Cat#14190), 0.01% BSA (Jackson ImmunoResearch, Cat#001-000-162), 0.01% Tween-20.
Measurement: IC50 < 1 nM (pChEMBL 9)
Descriptors: MW 546, ALogP 5.68, HBA 8, HBD 1, PSA 101.3, QED 0.34
Compound (SMILES): Cn1[nH]c(-c2cc3nc(N4CCC[C@H]4CF)n(C[C@H]4CC[C@H](C)CC4)c3c(-c3cncc(Cl)c3)n2)nc1=O
InChIKey: SBGYEFPPMMJYBQ-ZWOKBUDYSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: FRET Assay: Methods: An HDM2 FRET assay was developed to assess the compounds' inhibitory activity towards binding of p53 protein. A truncated version of HDM2 with residues 17 to 125 (containing p53 binding surface, Science (1994) 265, 346-355), with N-terminal His and Thioredoxin tag was generated in pET32a expression vector and expressed in E. coli strain BL21(DE3)Rosetta. Protein was purified using Ni-affinity chromatography, followed by size exclusion chromatography using Superdex 75 26/60 column. To assess inhibition of p53 binding to HDM2, a FITC labeled 8-mer peptide (SEQ ID NO:1: Ac-Phe-Arg-Dpr-Ac6c-(6-Br)Trp-Glu-Glu-Leu-NH2; Anal Biochem. 2004 Aug. 1; 331(1):138-46) with strong affinity towards the p53 binding pocket of HDM2 was used. The HDM2 assay buffer contained 1x Phosphate Buffered Saline (Invitrogen, Cat#14190), 0.01% BSA (Jackson ImmunoResearch, Cat#001-000-162), 0.01% Tween-20.
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 539.06, ALogP 5, HBA 8, HBD 1, PSA 97.52, QED 0.37
Compound (SMILES): C[C@H]1CC[C@H](Cn2c(N3CCC[C@H]3CF)nc3cc(-c4n[nH]c(=O)[nH]4)nc(-c4cncc(Cl)c4)c32)CC1
InChIKey: BKANZFXGMQIDPN-BXWFABGCSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: FRET Assay: Methods: An HDM2 FRET assay was developed to assess the compounds' inhibitory activity towards binding of p53 protein. A truncated version of HDM2 with residues 17 to 125 (containing p53 binding surface, Science (1994) 265, 346-355), with N-terminal His and Thioredoxin tag was generated in pET32a expression vector and expressed in E. coli strain BL21(DE3)Rosetta. Protein was purified using Ni-affinity chromatography, followed by size exclusion chromatography using Superdex 75 26/60 column. To assess inhibition of p53 binding to HDM2, a FITC labeled 8-mer peptide (SEQ ID NO:1: Ac-Phe-Arg-Dpr-Ac6c-(6-Br)Trp-Glu-Glu-Leu-NH2; Anal Biochem. 2004 Aug. 1; 331(1):138-46) with strong affinity towards the p53 binding pocket of HDM2 was used. The HDM2 assay buffer contained 1x Phosphate Buffered Saline (Invitrogen, Cat#14190), 0.01% BSA (Jackson ImmunoResearch, Cat#001-000-162), 0.01% Tween-20.
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 525.03, ALogP 4.99, HBA 7, HBD 2, PSA 108.38, QED 0.37
Compound (SMILES): C[C@H]1CC[C@H](Cn2c(N3CCO[C@@H]4CCC[C@H]43)nc3cc(-c4nnn[nH]4)nc(-c4cncc(Cl)c4)c32)CC1
InChIKey: PZTUOKVCYNWBOF-IEGYKGNPSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: FRET Assay: Methods: An HDM2 FRET assay was developed to assess the compounds' inhibitory activity towards binding of p53 protein. A truncated version of HDM2 with residues 17 to 125 (containing p53 binding surface, Science (1994) 265, 346-355), with N-terminal His and Thioredoxin tag was generated in pET32a expression vector and expressed in E. coli strain BL21(DE3)Rosetta. Protein was purified using Ni-affinity chromatography, followed by size exclusion chromatography using Superdex 75 26/60 column. To assess inhibition of p53 binding to HDM2, a FITC labeled 8-mer peptide (SEQ ID NO:1: Ac-Phe-Arg-Dpr-Ac6c-(6-Br)Trp-Glu-Glu-Leu-NH2; Anal Biochem. 2004 Aug. 1; 331(1):138-46) with strong affinity towards the p53 binding pocket of HDM2 was used. The HDM2 assay buffer contained 1x Phosphate Buffered Saline (Invitrogen, Cat#14190), 0.01% BSA (Jackson ImmunoResearch, Cat#001-000-162), 0.01% Tween-20.
Measurement: IC50 < 1 nM (pChEMBL 9)
Descriptors: MW 534.07, ALogP 4.91, HBA 9, HBD 1, PSA 110.53, QED 0.38
Compound (SMILES): COC(=O)c1cc2nc(N3CCOC[C@H]3c3ccccc3)n(C[C@H]3CC[C@H](C)CC3)c2c(-c2cncc(Cl)c2)n1
InChIKey: SYNFYBFKFDFYHY-IZVMNLJQSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: FRET Assay: Methods: An HDM2 FRET assay was developed to assess the compounds' inhibitory activity towards binding of p53 protein. A truncated version of HDM2 with residues 17 to 125 (containing p53 binding surface, Science (1994) 265, 346-355), with N-terminal His and Thioredoxin tag was generated in pET32a expression vector and expressed in E. coli strain BL21(DE3)Rosetta. Protein was purified using Ni-affinity chromatography, followed by size exclusion chromatography using Superdex 75 26/60 column. To assess inhibition of p53 binding to HDM2, a FITC labeled 8-mer peptide (SEQ ID NO:1: Ac-Phe-Arg-Dpr-Ac6c-(6-Br)Trp-Glu-Glu-Leu-NH2; Anal Biochem. 2004 Aug. 1; 331(1):138-46) with strong affinity towards the p53 binding pocket of HDM2 was used. The HDM2 assay buffer contained 1x Phosphate Buffered Saline (Invitrogen, Cat#14190), 0.01% BSA (Jackson ImmunoResearch, Cat#001-000-162), 0.01% Tween-20.
Measurement: IC50 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 560.1, ALogP 6.34, HBA 8, HBD 0, PSA 82.37, QED 0.25
Compound (SMILES): CCON(c1nc2cc(-c3noc(=O)[nH]3)nc(-c3cncc(Cl)c3)c2n1C(C)[C@H]1CC[C@H](C)CC1)C1CC1
InChIKey: ZSUPCYDBQJNTGJ-XUWMOKQASA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: FRET Assay: Methods: An HDM2 FRET assay was developed to assess the compounds' inhibitory activity towards binding of p53 protein. A truncated version of HDM2 with residues 17 to 125 (containing p53 binding surface, Science (1994) 265, 346-355), with N-terminal His and Thioredoxin tag was generated in pET32a expression vector and expressed in E. coli strain BL21(DE3)Rosetta. Protein was purified using Ni-affinity chromatography, followed by size exclusion chromatography using Superdex 75 26/60 column. To assess inhibition of p53 binding to HDM2, a FITC labeled 8-mer peptide (SEQ ID NO:1: Ac-Phe-Arg-Dpr-Ac6c-(6-Br)Trp-Glu-Glu-Leu-NH2; Anal Biochem. 2004 Aug. 1; 331(1):138-46) with strong affinity towards the p53 binding pocket of HDM2 was used. The HDM2 assay buffer contained 1x Phosphate Buffered Saline (Invitrogen, Cat#14190), 0.01% BSA (Jackson ImmunoResearch, Cat#001-000-162), 0.01% Tween-20.
Measurement: IC50 < 1 nM (pChEMBL 9)
Descriptors: MW 538.05, ALogP 5.8, HBA 9, HBD 1, PSA 114.96, QED 0.28
Compound (SMILES): CCOC(c1nc2cc(-c3noc(=O)[nH]3)nc(-c3cncc(Cl)c3)c2n1C(C)[C@H]1CC[C@H](C)CC1)C1CC1
InChIKey: PJGMHURMTNPVFZ-RNFMHXQYSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: FRET Assay: Methods: An HDM2 FRET assay was developed to assess the compounds' inhibitory activity towards binding of p53 protein. A truncated version of HDM2 with residues 17 to 125 (containing p53 binding surface, Science (1994) 265, 346-355), with N-terminal His and Thioredoxin tag was generated in pET32a expression vector and expressed in E. coli strain BL21(DE3)Rosetta. Protein was purified using Ni-affinity chromatography, followed by size exclusion chromatography using Superdex 75 26/60 column. To assess inhibition of p53 binding to HDM2, a FITC labeled 8-mer peptide (SEQ ID NO:1: Ac-Phe-Arg-Dpr-Ac6c-(6-Br)Trp-Glu-Glu-Leu-NH2; Anal Biochem. 2004 Aug. 1; 331(1):138-46) with strong affinity towards the p53 binding pocket of HDM2 was used. The HDM2 assay buffer contained 1x Phosphate Buffered Saline (Invitrogen, Cat#14190), 0.01% BSA (Jackson ImmunoResearch, Cat#001-000-162), 0.01% Tween-20.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 537.06, ALogP 6.36, HBA 8, HBD 1, PSA 111.72, QED 0.28
Compound (SMILES): CCOC(C)c1nc2cc(-c3noc(=O)[nH]3)nc(-c3cncc(Cl)c3)c2n1C(C)[C@H]1CC[C@H](C)CC1
InChIKey: DQEAMAGOZZSBEV-GQRAJKLCSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: FRET Assay: Methods: An HDM2 FRET assay was developed to assess the compounds' inhibitory activity towards binding of p53 protein. A truncated version of HDM2 with residues 17 to 125 (containing p53 binding surface, Science (1994) 265, 346-355), with N-terminal His and Thioredoxin tag was generated in pET32a expression vector and expressed in E. coli strain BL21(DE3)Rosetta. Protein was purified using Ni-affinity chromatography, followed by size exclusion chromatography using Superdex 75 26/60 column. To assess inhibition of p53 binding to HDM2, a FITC labeled 8-mer peptide (SEQ ID NO:1: Ac-Phe-Arg-Dpr-Ac6c-(6-Br)Trp-Glu-Glu-Leu-NH2; Anal Biochem. 2004 Aug. 1; 331(1):138-46) with strong affinity towards the p53 binding pocket of HDM2 was used. The HDM2 assay buffer contained 1x Phosphate Buffered Saline (Invitrogen, Cat#14190), 0.01% BSA (Jackson ImmunoResearch, Cat#001-000-162), 0.01% Tween-20.
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 511.03, ALogP 5.97, HBA 8, HBD 1, PSA 111.72, QED 0.33
Compound (SMILES): CCOC(COC)c1nc2cc(-c3noc(=O)[nH]3)nc(-c3cncc(Cl)c3)c2n1C(C)[C@H]1CC[C@H](C)CC1
InChIKey: XEXOJNYQMHVNNX-KSUCGMBASA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: FRET Assay: Methods: An HDM2 FRET assay was developed to assess the compounds' inhibitory activity towards binding of p53 protein. A truncated version of HDM2 with residues 17 to 125 (containing p53 binding surface, Science (1994) 265, 346-355), with N-terminal His and Thioredoxin tag was generated in pET32a expression vector and expressed in E. coli strain BL21(DE3)Rosetta. Protein was purified using Ni-affinity chromatography, followed by size exclusion chromatography using Superdex 75 26/60 column. To assess inhibition of p53 binding to HDM2, a FITC labeled 8-mer peptide (SEQ ID NO:1: Ac-Phe-Arg-Dpr-Ac6c-(6-Br)Trp-Glu-Glu-Leu-NH2; Anal Biochem. 2004 Aug. 1; 331(1):138-46) with strong affinity towards the p53 binding pocket of HDM2 was used. The HDM2 assay buffer contained 1x Phosphate Buffered Saline (Invitrogen, Cat#14190), 0.01% BSA (Jackson ImmunoResearch, Cat#001-000-162), 0.01% Tween-20.
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 541.05, ALogP 5.6, HBA 9, HBD 1, PSA 120.95, QED 0.29
Compound (SMILES): CCON(COC)c1nc2cc(-c3noc(=O)[nH]3)nc(-c3cncc(Cl)c3)c2n1C(C)[C@H]1CC[C@H](C)CC1
InChIKey: AQPWEKIFXPEUBY-XUWMOKQASA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: FRET Assay: Methods: An HDM2 FRET assay was developed to assess the compounds' inhibitory activity towards binding of p53 protein. A truncated version of HDM2 with residues 17 to 125 (containing p53 binding surface, Science (1994) 265, 346-355), with N-terminal His and Thioredoxin tag was generated in pET32a expression vector and expressed in E. coli strain BL21(DE3)Rosetta. Protein was purified using Ni-affinity chromatography, followed by size exclusion chromatography using Superdex 75 26/60 column. To assess inhibition of p53 binding to HDM2, a FITC labeled 8-mer peptide (SEQ ID NO:1: Ac-Phe-Arg-Dpr-Ac6c-(6-Br)Trp-Glu-Glu-Leu-NH2; Anal Biochem. 2004 Aug. 1; 331(1):138-46) with strong affinity towards the p53 binding pocket of HDM2 was used. The HDM2 assay buffer contained 1x Phosphate Buffered Saline (Invitrogen, Cat#14190), 0.01% BSA (Jackson ImmunoResearch, Cat#001-000-162), 0.01% Tween-20.
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 542.04, ALogP 5.24, HBA 10, HBD 1, PSA 124.19, QED 0.22
Compound (SMILES): CC([C@H]1CC[C@H](C)CC1)n1c(N2CCN(C(=O)C3(F)CC3)C[C@H]2C)nc2cc(-c3noc(=O)[nH]3)nc(-c3cncc(Cl)c3)c21
InChIKey: HKXVEJYALGEOSJ-LAURYZNVSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: FRET Assay: Methods: An HDM2 FRET assay was developed to assess the compounds' inhibitory activity towards binding of p53 protein. A truncated version of HDM2 with residues 17 to 125 (containing p53 binding surface, Science (1994) 265, 346-355), with N-terminal His and Thioredoxin tag was generated in pET32a expression vector and expressed in E. coli strain BL21(DE3)Rosetta. Protein was purified using Ni-affinity chromatography, followed by size exclusion chromatography using Superdex 75 26/60 column. To assess inhibition of p53 binding to HDM2, a FITC labeled 8-mer peptide (SEQ ID NO:1: Ac-Phe-Arg-Dpr-Ac6c-(6-Br)Trp-Glu-Glu-Leu-NH2; Anal Biochem. 2004 Aug. 1; 331(1):138-46) with strong affinity towards the p53 binding pocket of HDM2 was used. The HDM2 assay buffer contained 1x Phosphate Buffered Saline (Invitrogen, Cat#14190), 0.01% BSA (Jackson ImmunoResearch, Cat#001-000-162), 0.01% Tween-20.
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 623.13, ALogP 5.42, HBA 9, HBD 1, PSA 126.04, QED 0.3
Compound (SMILES): O=c1[nH]c(-c2cc3nc(N4CCO[C@@H]5CCC[C@H]54)n(Cc4ccc(C(F)(F)F)cc4)c3c(-c3cncc(Cl)c3)n2)no1
InChIKey: BRSDRQCFISXLFK-FGZHOGPDSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: FRET Assay: Methods: An HDM2 FRET assay was developed to assess the compounds' inhibitory activity towards binding of p53 protein. A truncated version of HDM2 with residues 17 to 125 (containing p53 binding surface, Science (1994) 265, 346-355), with N-terminal His and Thioredoxin tag was generated in pET32a expression vector and expressed in E. coli strain BL21(DE3)Rosetta. Protein was purified using Ni-affinity chromatography, followed by size exclusion chromatography using Superdex 75 26/60 column. To assess inhibition of p53 binding to HDM2, a FITC labeled 8-mer peptide (SEQ ID NO:1: Ac-Phe-Arg-Dpr-Ac6c-(6-Br)Trp-Glu-Glu-Leu-NH2; Anal Biochem. 2004 Aug. 1; 331(1):138-46) with strong affinity towards the p53 binding pocket of HDM2 was used. The HDM2 assay buffer contained 1x Phosphate Buffered Saline (Invitrogen, Cat#14190), 0.01% BSA (Jackson ImmunoResearch, Cat#001-000-162), 0.01% Tween-20.
Measurement: IC50 = 39 nM (pChEMBL 7.409999847412109)
Descriptors: MW 597.99, ALogP 5.31, HBA 9, HBD 1, PSA 114.96, QED 0.29
Compound (SMILES): CC[C@H]1CC[C@H](Cn2c(N3CCO[C@@H]4CCC[C@H]43)nc3cc(-c4noc(=O)[nH]4)nc(-c4cncc(Cl)c4)c32)CC1
InChIKey: DOLNTHQVJXBLGG-MCJPXMOYSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: FRET Assay: Methods: An HDM2 FRET assay was developed to assess the compounds' inhibitory activity towards binding of p53 protein. A truncated version of HDM2 with residues 17 to 125 (containing p53 binding surface, Science (1994) 265, 346-355), with N-terminal His and Thioredoxin tag was generated in pET32a expression vector and expressed in E. coli strain BL21(DE3)Rosetta. Protein was purified using Ni-affinity chromatography, followed by size exclusion chromatography using Superdex 75 26/60 column. To assess inhibition of p53 binding to HDM2, a FITC labeled 8-mer peptide (SEQ ID NO:1: Ac-Phe-Arg-Dpr-Ac6c-(6-Br)Trp-Glu-Glu-Leu-NH2; Anal Biochem. 2004 Aug. 1; 331(1):138-46) with strong affinity towards the p53 binding pocket of HDM2 was used. The HDM2 assay buffer contained 1x Phosphate Buffered Saline (Invitrogen, Cat#14190), 0.01% BSA (Jackson ImmunoResearch, Cat#001-000-162), 0.01% Tween-20.
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 564.09, ALogP 5.46, HBA 9, HBD 1, PSA 114.96, QED 0.33
Compound (SMILES): CC(NC(=O)c1cc2cccc(N3CCN(CCc4ccccn4)CC3)c2o1)c1ccnn1C
InChIKey: XOVZEOLIOJODHZ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1B (SINGLE PROTEIN), Cricetulus griseus
UniProt: P46636
Assay: Inhibition Assay: Assays that were used to measure affinity of the compounds of the present invention for 5-HT1A and 5-HT1B receptors are described in J. Recept Signal Transduct. Res. 22:483-495 (2002) and Naunyn-Schmiedeberg's Arch Pharmacol. 356:328-334 (1997) and incorporated by reference herein. These assays were be used with some modifications:For the binding assay stably transfected chinese hamster ovary (CHO) cell lines expressing 5-HT1A receptors or 5-HT1B receptors were harvested by centrifugation at 300x g for 10 min and resuspended in 10 mM Tris-HCl, 5 mM EDTA at pH 7.4. The cells were pooled, recentrifuged and resuspended before homogenisation using a Dounce homogeniser ("type B"). Cell membranes were centrifuged at 48 000x g for 10 min and then resuspended in harvesting buffer using an Ultra-Turrax T8 (IKA Labortechnik, Germany), aliquots were stored frozen in -70 C.Frozen membrane preparations were thawed, homogenized with an Ultra-Turrax and mixed with SPA beads.
Measurement: Ki = 280 nM (pChEMBL 6.550000190734863)
Descriptors: MW 458.57, ALogP 3.42, HBA 7, HBD 1, PSA 79.43, QED 0.46
Compound (SMILES): Cc1ccc(C(C)NC(=O)c2cc3cccc(N4CCN(CCc5ccccn5)CC4)c3o2)cn1
InChIKey: ONWPRCYUJMNGHK-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor (SINGLE PROTEIN), Cricetulus griseus
UniProt: G3I1B6
Assay: Inhibition Assay: Assays that were used to measure affinity of the compounds of the present invention for 5-HT1A and 5-HT1B receptors are described in J. Recept Signal Transduct. Res. 22:483-495 (2002) and Naunyn-Schmiedeberg's Arch Pharmacol. 356:328-334 (1997) and incorporated by reference herein. These assays were be used with some modifications:For the binding assay stably transfected chinese hamster ovary (CHO) cell lines expressing 5-HT1A receptors or 5-HT1B receptors were harvested by centrifugation at 300x g for 10 min and resuspended in 10 mM Tris-HCl, 5 mM EDTA at pH 7.4. The cells were pooled, recentrifuged and resuspended before homogenisation using a Dounce homogeniser ("type B"). Cell membranes were centrifuged at 48 000x g for 10 min and then resuspended in harvesting buffer using an Ultra-Turrax T8 (IKA Labortechnik, Germany), aliquots were stored frozen in -70 C.Frozen membrane preparations were thawed, homogenized with an Ultra-Turrax and mixed with SPA beads.
Measurement: Ki = 2.1 nM (pChEMBL 8.680000305175781)
Descriptors: MW 469.59, ALogP 4.39, HBA 6, HBD 1, PSA 74.5, QED 0.43
Compound (SMILES): Cc1ncc(CNC(=O)c2cc3cccc(N4CCN(CCc5ccccn5)CC4)c3o2)cn1
InChIKey: MZZSMGOVCAPEFV-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1B (SINGLE PROTEIN), Cricetulus griseus
UniProt: P46636
Assay: Inhibition Assay: Assays that were used to measure affinity of the compounds of the present invention for 5-HT1A and 5-HT1B receptors are described in J. Recept Signal Transduct. Res. 22:483-495 (2002) and Naunyn-Schmiedeberg's Arch Pharmacol. 356:328-334 (1997) and incorporated by reference herein. These assays were be used with some modifications:For the binding assay stably transfected chinese hamster ovary (CHO) cell lines expressing 5-HT1A receptors or 5-HT1B receptors were harvested by centrifugation at 300x g for 10 min and resuspended in 10 mM Tris-HCl, 5 mM EDTA at pH 7.4. The cells were pooled, recentrifuged and resuspended before homogenisation using a Dounce homogeniser ("type B"). Cell membranes were centrifuged at 48 000x g for 10 min and then resuspended in harvesting buffer using an Ultra-Turrax T8 (IKA Labortechnik, Germany), aliquots were stored frozen in -70 C.Frozen membrane preparations were thawed, homogenized with an Ultra-Turrax and mixed with SPA beads.
Measurement: Ki = 38 nM (pChEMBL 7.420000076293945)
Descriptors: MW 456.55, ALogP 3.22, HBA 7, HBD 1, PSA 87.39, QED 0.46
Compound (SMILES): O=C(NCc1cccnc1)c1cc2cccc(N3CCN(CCc4ccccn4)CC3)c2o1
InChIKey: HWPOSMAVWYGBQQ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1B (SINGLE PROTEIN), Cricetulus griseus
UniProt: P46636
Assay: Inhibition Assay: Assays that were used to measure affinity of the compounds of the present invention for 5-HT1A and 5-HT1B receptors are described in J. Recept Signal Transduct. Res. 22:483-495 (2002) and Naunyn-Schmiedeberg's Arch Pharmacol. 356:328-334 (1997) and incorporated by reference herein. These assays were be used with some modifications:For the binding assay stably transfected chinese hamster ovary (CHO) cell lines expressing 5-HT1A receptors or 5-HT1B receptors were harvested by centrifugation at 300x g for 10 min and resuspended in 10 mM Tris-HCl, 5 mM EDTA at pH 7.4. The cells were pooled, recentrifuged and resuspended before homogenisation using a Dounce homogeniser ("type B"). Cell membranes were centrifuged at 48 000x g for 10 min and then resuspended in harvesting buffer using an Ultra-Turrax T8 (IKA Labortechnik, Germany), aliquots were stored frozen in -70 C.Frozen membrane preparations were thawed, homogenized with an Ultra-Turrax and mixed with SPA beads.
Measurement: Ki = 34 nM (pChEMBL 7.46999979019165)
Descriptors: MW 441.54, ALogP 3.52, HBA 6, HBD 1, PSA 74.5, QED 0.47
Compound (SMILES): O=C(c1cc2cccc(N3CCN(CCc4ccccn4)CC3)c2o1)N1CC(Oc2cccnc2)C1
InChIKey: KYRROGZKWQXONT-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1B (SINGLE PROTEIN), Cricetulus griseus
UniProt: P46636
Assay: Inhibition Assay: Assays that were used to measure affinity of the compounds of the present invention for 5-HT1A and 5-HT1B receptors are described in J. Recept Signal Transduct. Res. 22:483-495 (2002) and Naunyn-Schmiedeberg's Arch Pharmacol. 356:328-334 (1997) and incorporated by reference herein. These assays were be used with some modifications:For the binding assay stably transfected chinese hamster ovary (CHO) cell lines expressing 5-HT1A receptors or 5-HT1B receptors were harvested by centrifugation at 300x g for 10 min and resuspended in 10 mM Tris-HCl, 5 mM EDTA at pH 7.4. The cells were pooled, recentrifuged and resuspended before homogenisation using a Dounce homogeniser ("type B"). Cell membranes were centrifuged at 48 000x g for 10 min and then resuspended in harvesting buffer using an Ultra-Turrax T8 (IKA Labortechnik, Germany), aliquots were stored frozen in -70 C.Frozen membrane preparations were thawed, homogenized with an Ultra-Turrax and mixed with SPA beads.
Measurement: Ki = 0.46 nM (pChEMBL 9.34000015258789)
Descriptors: MW 483.57, ALogP 3.49, HBA 7, HBD 0, PSA 74.94, QED 0.4
Compound (SMILES): O=C(NCc1cccc(O)c1)c1cc2cccc(N3CCN(CCc4ccccn4)CC3)c2o1
InChIKey: PAQCZDXYXLCTFI-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1B (SINGLE PROTEIN), Cricetulus griseus
UniProt: P46636
Assay: Inhibition Assay: Assays that were used to measure affinity of the compounds of the present invention for 5-HT1A and 5-HT1B receptors are described in J. Recept Signal Transduct. Res. 22:483-495 (2002) and Naunyn-Schmiedeberg's Arch Pharmacol. 356:328-334 (1997) and incorporated by reference herein. These assays were be used with some modifications:For the binding assay stably transfected chinese hamster ovary (CHO) cell lines expressing 5-HT1A receptors or 5-HT1B receptors were harvested by centrifugation at 300x g for 10 min and resuspended in 10 mM Tris-HCl, 5 mM EDTA at pH 7.4. The cells were pooled, recentrifuged and resuspended before homogenisation using a Dounce homogeniser ("type B"). Cell membranes were centrifuged at 48 000x g for 10 min and then resuspended in harvesting buffer using an Ultra-Turrax T8 (IKA Labortechnik, Germany), aliquots were stored frozen in -70 C.Frozen membrane preparations were thawed, homogenized with an Ultra-Turrax and mixed with SPA beads.
Measurement: Ki = 3.5 nM (pChEMBL 8.460000038146973)
Descriptors: MW 456.55, ALogP 3.83, HBA 6, HBD 2, PSA 81.84, QED 0.44
Compound (SMILES): CC(=O)N1CCc2cc(CCN3CCN(c4cccc5cc(C(=O)N(C)C)oc45)CC3)ccc21
InChIKey: CDVRIIKHWVFVFT-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1B (SINGLE PROTEIN), Cricetulus griseus
UniProt: P46636
Assay: Inhibition Assay: Assays that were used to measure affinity of the compounds of the present invention for 5-HT1A and 5-HT1B receptors are described in J. Recept Signal Transduct. Res. 22:483-495 (2002) and Naunyn-Schmiedeberg's Arch Pharmacol. 356:328-334 (1997) and incorporated by reference herein. These assays were be used with some modifications:For the binding assay stably transfected chinese hamster ovary (CHO) cell lines expressing 5-HT1A receptors or 5-HT1B receptors were harvested by centrifugation at 300x g for 10 min and resuspended in 10 mM Tris-HCl, 5 mM EDTA at pH 7.4. The cells were pooled, recentrifuged and resuspended before homogenisation using a Dounce homogeniser ("type B"). Cell membranes were centrifuged at 48 000x g for 10 min and then resuspended in harvesting buffer using an Ultra-Turrax T8 (IKA Labortechnik, Germany), aliquots were stored frozen in -70 C.Frozen membrane preparations were thawed, homogenized with an Ultra-Turrax and mixed with SPA beads.
Measurement: Ki = 1.6 nM (pChEMBL 8.800000190734863)
Descriptors: MW 460.58, ALogP 3.41, HBA 5, HBD 0, PSA 60.24, QED 0.58
Compound (SMILES): COc1ccnc(CCN2CCN(c3cccc4cc(C(=O)N(C)C)oc34)CC2)c1
InChIKey: CAXWOPIXKUGWBU-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor (SINGLE PROTEIN), Cricetulus griseus
UniProt: G3I1B6
Assay: Inhibition Assay: Assays that were used to measure affinity of the compounds of the present invention for 5-HT1A and 5-HT1B receptors are described in J. Recept Signal Transduct. Res. 22:483-495 (2002) and Naunyn-Schmiedeberg's Arch Pharmacol. 356:328-334 (1997) and incorporated by reference herein. These assays were be used with some modifications:For the binding assay stably transfected chinese hamster ovary (CHO) cell lines expressing 5-HT1A receptors or 5-HT1B receptors were harvested by centrifugation at 300x g for 10 min and resuspended in 10 mM Tris-HCl, 5 mM EDTA at pH 7.4. The cells were pooled, recentrifuged and resuspended before homogenisation using a Dounce homogeniser ("type B"). Cell membranes were centrifuged at 48 000x g for 10 min and then resuspended in harvesting buffer using an Ultra-Turrax T8 (IKA Labortechnik, Germany), aliquots were stored frozen in -70 C.Frozen membrane preparations were thawed, homogenized with an Ultra-Turrax and mixed with SPA beads.
Measurement: Ki = 0.32 nM (pChEMBL 9.489999771118164)
Descriptors: MW 408.5, ALogP 2.9, HBA 6, HBD 0, PSA 62.05, QED 0.63
Compound (SMILES): Cc1ccc(CCN2CCN(c3cccc4cc(C(=O)N(C)C)oc34)CC2)nc1
InChIKey: UYRNUFWWRJXIHU-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor (SINGLE PROTEIN), Cricetulus griseus
UniProt: G3I1B6
Assay: Inhibition Assay: Assays that were used to measure affinity of the compounds of the present invention for 5-HT1A and 5-HT1B receptors are described in J. Recept Signal Transduct. Res. 22:483-495 (2002) and Naunyn-Schmiedeberg's Arch Pharmacol. 356:328-334 (1997) and incorporated by reference herein. These assays were be used with some modifications:For the binding assay stably transfected chinese hamster ovary (CHO) cell lines expressing 5-HT1A receptors or 5-HT1B receptors were harvested by centrifugation at 300x g for 10 min and resuspended in 10 mM Tris-HCl, 5 mM EDTA at pH 7.4. The cells were pooled, recentrifuged and resuspended before homogenisation using a Dounce homogeniser ("type B"). Cell membranes were centrifuged at 48 000x g for 10 min and then resuspended in harvesting buffer using an Ultra-Turrax T8 (IKA Labortechnik, Germany), aliquots were stored frozen in -70 C.Frozen membrane preparations were thawed, homogenized with an Ultra-Turrax and mixed with SPA beads.
Measurement: Ki = 0.14 nM (pChEMBL 9.850000381469727)
Descriptors: MW 392.5, ALogP 3.2, HBA 5, HBD 0, PSA 52.82, QED 0.67
Compound (SMILES): CN(C)C(=O)c1cc2cccc(N3CCN(CCc4cc(C#N)ccn4)CC3)c2o1
InChIKey: FVKDRXNFIUNQBF-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1B (SINGLE PROTEIN), Cricetulus griseus
UniProt: P46636
Assay: Inhibition Assay: Assays that were used to measure affinity of the compounds of the present invention for 5-HT1A and 5-HT1B receptors are described in J. Recept Signal Transduct. Res. 22:483-495 (2002) and Naunyn-Schmiedeberg's Arch Pharmacol. 356:328-334 (1997) and incorporated by reference herein. These assays were be used with some modifications:For the binding assay stably transfected chinese hamster ovary (CHO) cell lines expressing 5-HT1A receptors or 5-HT1B receptors were harvested by centrifugation at 300x g for 10 min and resuspended in 10 mM Tris-HCl, 5 mM EDTA at pH 7.4. The cells were pooled, recentrifuged and resuspended before homogenisation using a Dounce homogeniser ("type B"). Cell membranes were centrifuged at 48 000x g for 10 min and then resuspended in harvesting buffer using an Ultra-Turrax T8 (IKA Labortechnik, Germany), aliquots were stored frozen in -70 C.Frozen membrane preparations were thawed, homogenized with an Ultra-Turrax and mixed with SPA beads.
Measurement: Ki = 73 nM (pChEMBL 7.139999866485596)
Descriptors: MW 403.49, ALogP 2.77, HBA 6, HBD 0, PSA 76.61, QED 0.65
Compound (SMILES): CN(C)C(=O)c1cc2cccc(N3CCN(CCc4cccc(C(F)(F)F)n4)CC3)c2o1
InChIKey: KIBCJAHEQRCNSO-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1B (SINGLE PROTEIN), Cricetulus griseus
UniProt: P46636
Assay: Inhibition Assay: Assays that were used to measure affinity of the compounds of the present invention for 5-HT1A and 5-HT1B receptors are described in J. Recept Signal Transduct. Res. 22:483-495 (2002) and Naunyn-Schmiedeberg's Arch Pharmacol. 356:328-334 (1997) and incorporated by reference herein. These assays were be used with some modifications:For the binding assay stably transfected chinese hamster ovary (CHO) cell lines expressing 5-HT1A receptors or 5-HT1B receptors were harvested by centrifugation at 300x g for 10 min and resuspended in 10 mM Tris-HCl, 5 mM EDTA at pH 7.4. The cells were pooled, recentrifuged and resuspended before homogenisation using a Dounce homogeniser ("type B"). Cell membranes were centrifuged at 48 000x g for 10 min and then resuspended in harvesting buffer using an Ultra-Turrax T8 (IKA Labortechnik, Germany), aliquots were stored frozen in -70 C.Frozen membrane preparations were thawed, homogenized with an Ultra-Turrax and mixed with SPA beads.
Measurement: Ki = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 446.47, ALogP 3.91, HBA 5, HBD 0, PSA 52.82, QED 0.59
Compound (SMILES): CC(=O)c1ccc(CCN2CCN(c3cccc4cc(C(=O)N(C)C)oc34)CC2)nc1
InChIKey: YJUZOTSZKOCVNL-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor (SINGLE PROTEIN), Cricetulus griseus
UniProt: G3I1B6
Assay: Inhibition Assay: Assays that were used to measure affinity of the compounds of the present invention for 5-HT1A and 5-HT1B receptors are described in J. Recept Signal Transduct. Res. 22:483-495 (2002) and Naunyn-Schmiedeberg's Arch Pharmacol. 356:328-334 (1997) and incorporated by reference herein. These assays were be used with some modifications:For the binding assay stably transfected chinese hamster ovary (CHO) cell lines expressing 5-HT1A receptors or 5-HT1B receptors were harvested by centrifugation at 300x g for 10 min and resuspended in 10 mM Tris-HCl, 5 mM EDTA at pH 7.4. The cells were pooled, recentrifuged and resuspended before homogenisation using a Dounce homogeniser ("type B"). Cell membranes were centrifuged at 48 000x g for 10 min and then resuspended in harvesting buffer using an Ultra-Turrax T8 (IKA Labortechnik, Germany), aliquots were stored frozen in -70 C.Frozen membrane preparations were thawed, homogenized with an Ultra-Turrax and mixed with SPA beads.
Measurement: Ki = 0.33 nM (pChEMBL 9.479999542236328)
Descriptors: MW 420.51, ALogP 3.1, HBA 6, HBD 0, PSA 69.89, QED 0.57
Compound (SMILES): CC(=O)Nc1ccc(CCN2CCN(c3cccc4cc(C(=O)N(C)C)oc34)CC2)nc1
InChIKey: WJWJXULJOUOQIG-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1B (SINGLE PROTEIN), Cricetulus griseus
UniProt: P46636
Assay: Inhibition Assay: Assays that were used to measure affinity of the compounds of the present invention for 5-HT1A and 5-HT1B receptors are described in J. Recept Signal Transduct. Res. 22:483-495 (2002) and Naunyn-Schmiedeberg's Arch Pharmacol. 356:328-334 (1997) and incorporated by reference herein. These assays were be used with some modifications:For the binding assay stably transfected chinese hamster ovary (CHO) cell lines expressing 5-HT1A receptors or 5-HT1B receptors were harvested by centrifugation at 300x g for 10 min and resuspended in 10 mM Tris-HCl, 5 mM EDTA at pH 7.4. The cells were pooled, recentrifuged and resuspended before homogenisation using a Dounce homogeniser ("type B"). Cell membranes were centrifuged at 48 000x g for 10 min and then resuspended in harvesting buffer using an Ultra-Turrax T8 (IKA Labortechnik, Germany), aliquots were stored frozen in -70 C.Frozen membrane preparations were thawed, homogenized with an Ultra-Turrax and mixed with SPA beads.
Measurement: Ki = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 435.53, ALogP 2.85, HBA 6, HBD 1, PSA 81.92, QED 0.64
Compound (SMILES): COc1cccc(CCN2CCN(c3cccc4cc(C(=O)N5CCC5)oc34)CC2)n1
InChIKey: CIWOESWFVHEUMU-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1B (SINGLE PROTEIN), Cricetulus griseus
UniProt: P46636
Assay: Inhibition Assay: Assays that were used to measure affinity of the compounds of the present invention for 5-HT1A and 5-HT1B receptors are described in J. Recept Signal Transduct. Res. 22:483-495 (2002) and Naunyn-Schmiedeberg's Arch Pharmacol. 356:328-334 (1997) and incorporated by reference herein. These assays were be used with some modifications:For the binding assay stably transfected chinese hamster ovary (CHO) cell lines expressing 5-HT1A receptors or 5-HT1B receptors were harvested by centrifugation at 300x g for 10 min and resuspended in 10 mM Tris-HCl, 5 mM EDTA at pH 7.4. The cells were pooled, recentrifuged and resuspended before homogenisation using a Dounce homogeniser ("type B"). Cell membranes were centrifuged at 48 000x g for 10 min and then resuspended in harvesting buffer using an Ultra-Turrax T8 (IKA Labortechnik, Germany), aliquots were stored frozen in -70 C.Frozen membrane preparations were thawed, homogenized with an Ultra-Turrax and mixed with SPA beads.
Measurement: Ki = 2.4 nM (pChEMBL 8.619999885559082)
Descriptors: MW 420.51, ALogP 3.05, HBA 6, HBD 0, PSA 62.05, QED 0.61
Compound (SMILES): COc1cccc(CCN2CCN(c3cccc4cc(C(=O)N(C)C)oc34)CC2)n1
InChIKey: VINCURCLBWSXBM-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1B (SINGLE PROTEIN), Cricetulus griseus
UniProt: P46636
Assay: Inhibition Assay: Assays that were used to measure affinity of the compounds of the present invention for 5-HT1A and 5-HT1B receptors are described in J. Recept Signal Transduct. Res. 22:483-495 (2002) and Naunyn-Schmiedeberg's Arch Pharmacol. 356:328-334 (1997) and incorporated by reference herein. These assays were be used with some modifications:For the binding assay stably transfected chinese hamster ovary (CHO) cell lines expressing 5-HT1A receptors or 5-HT1B receptors were harvested by centrifugation at 300x g for 10 min and resuspended in 10 mM Tris-HCl, 5 mM EDTA at pH 7.4. The cells were pooled, recentrifuged and resuspended before homogenisation using a Dounce homogeniser ("type B"). Cell membranes were centrifuged at 48 000x g for 10 min and then resuspended in harvesting buffer using an Ultra-Turrax T8 (IKA Labortechnik, Germany), aliquots were stored frozen in -70 C.Frozen membrane preparations were thawed, homogenized with an Ultra-Turrax and mixed with SPA beads.
Measurement: Ki = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 408.5, ALogP 2.9, HBA 6, HBD 0, PSA 62.05, QED 0.63
Compound (SMILES): CN(C)C(=O)c1cc2cccc(N3CCN(CCc4ccc(F)cn4)CC3)c2o1
InChIKey: JYXZCGMXPABTBZ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor (SINGLE PROTEIN), Cricetulus griseus
UniProt: G3I1B6
Assay: Inhibition Assay: Assays that were used to measure affinity of the compounds of the present invention for 5-HT1A and 5-HT1B receptors are described in J. Recept Signal Transduct. Res. 22:483-495 (2002) and Naunyn-Schmiedeberg's Arch Pharmacol. 356:328-334 (1997) and incorporated by reference herein. These assays were be used with some modifications:For the binding assay stably transfected chinese hamster ovary (CHO) cell lines expressing 5-HT1A receptors or 5-HT1B receptors were harvested by centrifugation at 300x g for 10 min and resuspended in 10 mM Tris-HCl, 5 mM EDTA at pH 7.4. The cells were pooled, recentrifuged and resuspended before homogenisation using a Dounce homogeniser ("type B"). Cell membranes were centrifuged at 48 000x g for 10 min and then resuspended in harvesting buffer using an Ultra-Turrax T8 (IKA Labortechnik, Germany), aliquots were stored frozen in -70 C.Frozen membrane preparations were thawed, homogenized with an Ultra-Turrax and mixed with SPA beads.
Measurement: Ki = 0.22 nM (pChEMBL 9.65999984741211)
Descriptors: MW 396.47, ALogP 3.03, HBA 5, HBD 0, PSA 52.82, QED 0.66