lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CCN(CCO)C1CCN(c2ccc(Nc3ncc4c5ccncc5n(C5CCCC5)c4n3)nc2)CC1
InChIKey: JJJVFTNNFDYRFZ-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00534
Assay: In Vitro Assay: The Cdk4 and Cdk6 inhibitory activity of the compounds is measured with a kinase inhibition assay using recombinant Cdk4/CyclinD1 or Cdk6/CyclinD3 protein complexes. The protein substrate used in the assay is the retinoblastoma protein (Rb). The kinase reactions are carried out in a 96-well filter plate (MSDV N6B50, Millipore). Compounds are serially diluted in kinase buffer (20 mM Tris-HCl, pH 7.4, 50 mM NaCl, 1 mM DTT, 1 mg/ml BSA) and added to the reaction mixture containing 2.5 ng/ml Cdk4/CyclinD1 or Cdk6/CyclinD3, 25 μM ATP, 10 μCi/ml [33P]-ATP, 0.1 μg/ml Rb in the kinase buffer. The mixture is incubated at room temperature for 1 hour and the proteins precipitated with an equal volume of 20% TCA. The plates are washed with 10% TCA according to the manufacturer's instruction and dried at room temperature. The amount of the phosphorylated Rb is determined with a TopCount (PerkinElmer).
Measurement: IC50 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 500.65, ALogP 4.52, HBA 9, HBD 2, PSA 95.23, QED 0.36
Compound (SMILES): OC1CN(C2CCN(c3ccc(Nc4ncc5c6ccncc6n(C6CCCC6)c5n4)nc3)CC2)C1
InChIKey: VKWVMZJDIBGOSR-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00534
Assay: In Vitro Assay: The Cdk4 and Cdk6 inhibitory activity of the compounds is measured with a kinase inhibition assay using recombinant Cdk4/CyclinD1 or Cdk6/CyclinD3 protein complexes. The protein substrate used in the assay is the retinoblastoma protein (Rb). The kinase reactions are carried out in a 96-well filter plate (MSDV N6B50, Millipore). Compounds are serially diluted in kinase buffer (20 mM Tris-HCl, pH 7.4, 50 mM NaCl, 1 mM DTT, 1 mg/ml BSA) and added to the reaction mixture containing 2.5 ng/ml Cdk4/CyclinD1 or Cdk6/CyclinD3, 25 μM ATP, 10 μCi/ml [33P]-ATP, 0.1 μg/ml Rb in the kinase buffer. The mixture is incubated at room temperature for 1 hour and the proteins precipitated with an equal volume of 20% TCA. The plates are washed with 10% TCA according to the manufacturer's instruction and dried at room temperature. The amount of the phosphorylated Rb is determined with a TopCount (PerkinElmer).
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 484.61, ALogP 3.88, HBA 9, HBD 2, PSA 95.23, QED 0.44
Compound (SMILES): C[C@@H](CO)NC1CCN(c2ccc(Nc3ncc4c5ccncc5n(C5CCCC5)c4n3)nc2)CC1
InChIKey: SISAEGSKELJSQO-SFHVURJKSA-N
Target: Cyclin-dependent kinase 6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00534
Assay: In Vitro Assay: The Cdk4 and Cdk6 inhibitory activity of the compounds is measured with a kinase inhibition assay using recombinant Cdk4/CyclinD1 or Cdk6/CyclinD3 protein complexes. The protein substrate used in the assay is the retinoblastoma protein (Rb). The kinase reactions are carried out in a 96-well filter plate (MSDV N6B50, Millipore). Compounds are serially diluted in kinase buffer (20 mM Tris-HCl, pH 7.4, 50 mM NaCl, 1 mM DTT, 1 mg/ml BSA) and added to the reaction mixture containing 2.5 ng/ml Cdk4/CyclinD1 or Cdk6/CyclinD3, 25 μM ATP, 10 μCi/ml [33P]-ATP, 0.1 μg/ml Rb in the kinase buffer. The mixture is incubated at room temperature for 1 hour and the proteins precipitated with an equal volume of 20% TCA. The plates are washed with 10% TCA according to the manufacturer's instruction and dried at room temperature. The amount of the phosphorylated Rb is determined with a TopCount (PerkinElmer).
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 486.62, ALogP 4.17, HBA 9, HBD 3, PSA 104.02, QED 0.36
Compound (SMILES): COC(=O)CNC1CCN(c2ccc(Nc3ncc4c5ccncc5n(C5CCCC5)c4n3)nn2)CC1
InChIKey: GKYNYPYSGJOBRE-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00534
Assay: In Vitro Assay: The Cdk4 and Cdk6 inhibitory activity of the compounds is measured with a kinase inhibition assay using recombinant Cdk4/CyclinD1 or Cdk6/CyclinD3 protein complexes. The protein substrate used in the assay is the retinoblastoma protein (Rb). The kinase reactions are carried out in a 96-well filter plate (MSDV N6B50, Millipore). Compounds are serially diluted in kinase buffer (20 mM Tris-HCl, pH 7.4, 50 mM NaCl, 1 mM DTT, 1 mg/ml BSA) and added to the reaction mixture containing 2.5 ng/ml Cdk4/CyclinD1 or Cdk6/CyclinD3, 25 μM ATP, 10 μCi/ml [33P]-ATP, 0.1 μg/ml Rb in the kinase buffer. The mixture is incubated at room temperature for 1 hour and the proteins precipitated with an equal volume of 20% TCA. The plates are washed with 10% TCA according to the manufacturer's instruction and dried at room temperature. The amount of the phosphorylated Rb is determined with a TopCount (PerkinElmer).
Measurement: IC50 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 501.6, ALogP 3.36, HBA 11, HBD 2, PSA 122.98, QED 0.36
Compound (SMILES): O=C(O)CNC1CCN(c2ccc(Nc3ncc4c5ccncc5n(C5CCCC5)c4n3)nc2)CC1
InChIKey: ZRBMKKBZXGSURN-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00534
Assay: In Vitro Assay: The Cdk4 and Cdk6 inhibitory activity of the compounds is measured with a kinase inhibition assay using recombinant Cdk4/CyclinD1 or Cdk6/CyclinD3 protein complexes. The protein substrate used in the assay is the retinoblastoma protein (Rb). The kinase reactions are carried out in a 96-well filter plate (MSDV N6B50, Millipore). Compounds are serially diluted in kinase buffer (20 mM Tris-HCl, pH 7.4, 50 mM NaCl, 1 mM DTT, 1 mg/ml BSA) and added to the reaction mixture containing 2.5 ng/ml Cdk4/CyclinD1 or Cdk6/CyclinD3, 25 μM ATP, 10 μCi/ml [33P]-ATP, 0.1 μg/ml Rb in the kinase buffer. The mixture is incubated at room temperature for 1 hour and the proteins precipitated with an equal volume of 20% TCA. The plates are washed with 10% TCA according to the manufacturer's instruction and dried at room temperature. The amount of the phosphorylated Rb is determined with a TopCount (PerkinElmer).
Measurement: IC50 = 5.1 nM (pChEMBL 8.289999961853027)
Descriptors: MW 486.58, ALogP 3.88, HBA 9, HBD 3, PSA 121.09, QED 0.36
Compound (SMILES): O=C(O)CNC1CCN(c2ccc(Nc3ncc4c5ccncc5n(C5CCCC5)c4n3)nn2)CC1
InChIKey: NROJANSVZVKJQE-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00534
Assay: In Vitro Assay: The Cdk4 and Cdk6 inhibitory activity of the compounds is measured with a kinase inhibition assay using recombinant Cdk4/CyclinD1 or Cdk6/CyclinD3 protein complexes. The protein substrate used in the assay is the retinoblastoma protein (Rb). The kinase reactions are carried out in a 96-well filter plate (MSDV N6B50, Millipore). Compounds are serially diluted in kinase buffer (20 mM Tris-HCl, pH 7.4, 50 mM NaCl, 1 mM DTT, 1 mg/ml BSA) and added to the reaction mixture containing 2.5 ng/ml Cdk4/CyclinD1 or Cdk6/CyclinD3, 25 μM ATP, 10 μCi/ml [33P]-ATP, 0.1 μg/ml Rb in the kinase buffer. The mixture is incubated at room temperature for 1 hour and the proteins precipitated with an equal volume of 20% TCA. The plates are washed with 10% TCA according to the manufacturer's instruction and dried at room temperature. The amount of the phosphorylated Rb is determined with a TopCount (PerkinElmer).
Measurement: IC50 = 5.7 nM (pChEMBL 8.239999771118164)
Descriptors: MW 487.57, ALogP 3.27, HBA 10, HBD 3, PSA 133.98, QED 0.36
Compound (SMILES): CN(C)CCN(C)C1CCN(c2ccc(Nc3ncc4c5ccncc5n(C5CCCC5)c4n3)nn2)CC1
InChIKey: XUPRCCLLUPDTDK-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00534
Assay: In Vitro Assay: The Cdk4 and Cdk6 inhibitory activity of the compounds is measured with a kinase inhibition assay using recombinant Cdk4/CyclinD1 or Cdk6/CyclinD3 protein complexes. The protein substrate used in the assay is the retinoblastoma protein (Rb). The kinase reactions are carried out in a 96-well filter plate (MSDV N6B50, Millipore). Compounds are serially diluted in kinase buffer (20 mM Tris-HCl, pH 7.4, 50 mM NaCl, 1 mM DTT, 1 mg/ml BSA) and added to the reaction mixture containing 2.5 ng/ml Cdk4/CyclinD1 or Cdk6/CyclinD3, 25 μM ATP, 10 μCi/ml [33P]-ATP, 0.1 μg/ml Rb in the kinase buffer. The mixture is incubated at room temperature for 1 hour and the proteins precipitated with an equal volume of 20% TCA. The plates are washed with 10% TCA according to the manufacturer's instruction and dried at room temperature. The amount of the phosphorylated Rb is determined with a TopCount (PerkinElmer).
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 514.68, ALogP 4.09, HBA 10, HBD 1, PSA 91.13, QED 0.37
Compound (SMILES): CN(C)CCNC1CCN(c2ccc(Nc3ncc4c5ccncc5n(C5CCCC5)c4n3)nn2)CC1
InChIKey: DPIODVZRGWTHFY-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P11802
Assay: In Vitro Assay: The Cdk4 and Cdk6 inhibitory activity of the compounds is measured with a kinase inhibition assay using recombinant Cdk4/CyclinD1 or Cdk6/CyclinD3 protein complexes. The protein substrate used in the assay is the retinoblastoma protein (Rb). The kinase reactions are carried out in a 96-well filter plate (MSDV N6B50, Millipore). Compounds are serially diluted in kinase buffer (20 mM Tris-HCl, pH 7.4, 50 mM NaCl, 1 mM DTT, 1 mg/ml BSA) and added to the reaction mixture containing 2.5 ng/ml Cdk4/CyclinD1 or Cdk6/CyclinD3, 25 μM ATP, 10 μCi/ml [33P]-ATP, 0.1 μg/ml Rb in the kinase buffer. The mixture is incubated at room temperature for 1 hour and the proteins precipitated with an equal volume of 20% TCA. The plates are washed with 10% TCA according to the manufacturer's instruction and dried at room temperature. The amount of the phosphorylated Rb is determined with a TopCount (PerkinElmer).
Measurement: IC50 = 4.9 nM (pChEMBL 8.3100004196167)
Descriptors: MW 500.66, ALogP 3.75, HBA 10, HBD 2, PSA 99.92, QED 0.37
Compound (SMILES): OC[C@@H](O)CNC1CCN(c2ccc(Nc3ncc4c5ccncc5n(C5CCCC5)c4n3)nn2)CC1
InChIKey: MLLWORSXSDVTQA-IBGZPJMESA-N
Target: Cyclin-dependent kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P11802
Assay: In Vitro Assay: The Cdk4 and Cdk6 inhibitory activity of the compounds is measured with a kinase inhibition assay using recombinant Cdk4/CyclinD1 or Cdk6/CyclinD3 protein complexes. The protein substrate used in the assay is the retinoblastoma protein (Rb). The kinase reactions are carried out in a 96-well filter plate (MSDV N6B50, Millipore). Compounds are serially diluted in kinase buffer (20 mM Tris-HCl, pH 7.4, 50 mM NaCl, 1 mM DTT, 1 mg/ml BSA) and added to the reaction mixture containing 2.5 ng/ml Cdk4/CyclinD1 or Cdk6/CyclinD3, 25 μM ATP, 10 μCi/ml [33P]-ATP, 0.1 μg/ml Rb in the kinase buffer. The mixture is incubated at room temperature for 1 hour and the proteins precipitated with an equal volume of 20% TCA. The plates are washed with 10% TCA according to the manufacturer's instruction and dried at room temperature. The amount of the phosphorylated Rb is determined with a TopCount (PerkinElmer).
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 503.61, ALogP 2.54, HBA 11, HBD 4, PSA 137.14, QED 0.28
Compound (SMILES): CN(C)[C@@H]1CN(c2ccc(Nc3ncc4c5ccncc5n(C5CCCC5)c4n3)nn2)CC[C@H]1O
InChIKey: XNFJUHZLDMOZHP-NHCUHLMSSA-N
Target: Cyclin-dependent kinase 6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00534
Assay: In Vitro Assay: The Cdk4 and Cdk6 inhibitory activity of the compounds is measured with a kinase inhibition assay using recombinant Cdk4/CyclinD1 or Cdk6/CyclinD3 protein complexes. The protein substrate used in the assay is the retinoblastoma protein (Rb). The kinase reactions are carried out in a 96-well filter plate (MSDV N6B50, Millipore). Compounds are serially diluted in kinase buffer (20 mM Tris-HCl, pH 7.4, 50 mM NaCl, 1 mM DTT, 1 mg/ml BSA) and added to the reaction mixture containing 2.5 ng/ml Cdk4/CyclinD1 or Cdk6/CyclinD3, 25 μM ATP, 10 μCi/ml [33P]-ATP, 0.1 μg/ml Rb in the kinase buffer. The mixture is incubated at room temperature for 1 hour and the proteins precipitated with an equal volume of 20% TCA. The plates are washed with 10% TCA according to the manufacturer's instruction and dried at room temperature. The amount of the phosphorylated Rb is determined with a TopCount (PerkinElmer).
Measurement: IC50 = 41 nM (pChEMBL 7.389999866485596)
Descriptors: MW 473.59, ALogP 3.13, HBA 10, HBD 2, PSA 108.12, QED 0.45
Compound (SMILES): CN(C)C1CN(c2ccc(Nc3ncc4c5ccncc5n(C5CCCC5)c4n3)nn2)CCC1O
InChIKey: XNFJUHZLDMOZHP-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00534
Assay: In Vitro Assay: The Cdk4 and Cdk6 inhibitory activity of the compounds is measured with a kinase inhibition assay using recombinant Cdk4/CyclinD1 or Cdk6/CyclinD3 protein complexes. The protein substrate used in the assay is the retinoblastoma protein (Rb). The kinase reactions are carried out in a 96-well filter plate (MSDV N6B50, Millipore). Compounds are serially diluted in kinase buffer (20 mM Tris-HCl, pH 7.4, 50 mM NaCl, 1 mM DTT, 1 mg/ml BSA) and added to the reaction mixture containing 2.5 ng/ml Cdk4/CyclinD1 or Cdk6/CyclinD3, 25 μM ATP, 10 μCi/ml [33P]-ATP, 0.1 μg/ml Rb in the kinase buffer. The mixture is incubated at room temperature for 1 hour and the proteins precipitated with an equal volume of 20% TCA. The plates are washed with 10% TCA according to the manufacturer's instruction and dried at room temperature. The amount of the phosphorylated Rb is determined with a TopCount (PerkinElmer).
Measurement: IC50 = 13.3 nM (pChEMBL 7.880000114440918)
Descriptors: MW 473.59, ALogP 3.13, HBA 10, HBD 2, PSA 108.12, QED 0.45
Compound (SMILES): CC(=O)NCCc1c[nH]c2ccc(OC(=O)NCCCCCCCNc3c4c(nc5ccccc35)CCCC4)cc12
InChIKey: AKQSCHLJARNVMJ-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition Assay: The biological activity of the compounds of general formula (I) towards the cholinesterase inhibition was evaluated using Ellman's method (Ellman, G. L.; Courtney, K. D.; Anders, B.; Featherstone, R. M. Biochem. Pharmacol. 1961, 7, 88-95).This method of evaluation of the cholinesterase inhibitors activity is based on the fact that acetyl/butyrylcholinesterase interacts with the inhibitor, which prevents the acetyl/butyrylcholine hydrolysis. The inhibitor causes the enzyme activity drop which is dependent on the inhibitor concentration. The enzyme unbound with the inhibitor is able to hydrolyze acetyl/butyrylthiocholine (ASCh/BSCh). The amount of the hydrolyzed ASCh/BSCh is measured indirectly, by quantification of the product of its reaction with DTNB (5,5Ã¢Â²-dithio-bis-2-nitrobenzoic acid). Ellman's method relies therefore on the spectrophotometric quantification of product of the reaction between acylthiocholine and DTNB.
Measurement: IC50 = 0.25 nM (pChEMBL 9.600000381469727)
Descriptors: MW 555.72, ALogP 6.42, HBA 5, HBD 4, PSA 108.14, QED 0.14
Compound (SMILES): CC(=O)NCCc1c[nH]c2ccc(OC(=O)NCCNc3c4c(nc5ccccc35)CCCC4)cc12
InChIKey: WSXAJVAWKDKQHT-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition Assay: The biological activity of the compounds of general formula (I) towards the cholinesterase inhibition was evaluated using Ellman's method (Ellman, G. L.; Courtney, K. D.; Anders, B.; Featherstone, R. M. Biochem. Pharmacol. 1961, 7, 88-95).This method of evaluation of the cholinesterase inhibitors activity is based on the fact that acetyl/butyrylcholinesterase interacts with the inhibitor, which prevents the acetyl/butyrylcholine hydrolysis. The inhibitor causes the enzyme activity drop which is dependent on the inhibitor concentration. The enzyme unbound with the inhibitor is able to hydrolyze acetyl/butyrylthiocholine (ASCh/BSCh). The amount of the hydrolyzed ASCh/BSCh is measured indirectly, by quantification of the product of its reaction with DTNB (5,5Ã¢Â²-dithio-bis-2-nitrobenzoic acid). Ellman's method relies therefore on the spectrophotometric quantification of product of the reaction between acylthiocholine and DTNB.
Measurement: IC50 = 4.28 nM (pChEMBL 8.369999885559082)
Descriptors: MW 485.59, ALogP 4.47, HBA 5, HBD 4, PSA 108.14, QED 0.28
Compound (SMILES): CC(=O)NCCc1c[nH]c2ccc(OC(=O)NCCCCCCNc3c4c(nc5ccccc35)CCCC4)cc12
InChIKey: JTODDVDFMYBPGG-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition Assay: The biological activity of the compounds of general formula (I) towards the cholinesterase inhibition was evaluated using Ellman's method (Ellman, G. L.; Courtney, K. D.; Anders, B.; Featherstone, R. M. Biochem. Pharmacol. 1961, 7, 88-95).This method of evaluation of the cholinesterase inhibitors activity is based on the fact that acetyl/butyrylcholinesterase interacts with the inhibitor, which prevents the acetyl/butyrylcholine hydrolysis. The inhibitor causes the enzyme activity drop which is dependent on the inhibitor concentration. The enzyme unbound with the inhibitor is able to hydrolyze acetyl/butyrylthiocholine (ASCh/BSCh). The amount of the hydrolyzed ASCh/BSCh is measured indirectly, by quantification of the product of its reaction with DTNB (5,5Ã¢Â²-dithio-bis-2-nitrobenzoic acid). Ellman's method relies therefore on the spectrophotometric quantification of product of the reaction between acylthiocholine and DTNB.
Measurement: IC50 = 2.04 nM (pChEMBL 8.6899995803833)
Descriptors: MW 541.7, ALogP 6.03, HBA 5, HBD 4, PSA 108.14, QED 0.16
Compound (SMILES): CC(=O)NCCc1c[nH]c2ccc(OC(=O)NCCCCCCCNc3c4c(nc5cc(Cl)ccc35)CCCC4)cc12
InChIKey: HMTBXSCYSXEFRI-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition Assay: The biological activity of the compounds of general formula (I) towards the cholinesterase inhibition was evaluated using Ellman's method (Ellman, G. L.; Courtney, K. D.; Anders, B.; Featherstone, R. M. Biochem. Pharmacol. 1961, 7, 88-95).This method of evaluation of the cholinesterase inhibitors activity is based on the fact that acetyl/butyrylcholinesterase interacts with the inhibitor, which prevents the acetyl/butyrylcholine hydrolysis. The inhibitor causes the enzyme activity drop which is dependent on the inhibitor concentration. The enzyme unbound with the inhibitor is able to hydrolyze acetyl/butyrylthiocholine (ASCh/BSCh). The amount of the hydrolyzed ASCh/BSCh is measured indirectly, by quantification of the product of its reaction with DTNB (5,5Ã¢Â²-dithio-bis-2-nitrobenzoic acid). Ellman's method relies therefore on the spectrophotometric quantification of product of the reaction between acylthiocholine and DTNB.
Measurement: IC50 = 0.38 nM (pChEMBL 9.420000076293945)
Descriptors: MW 590.17, ALogP 7.08, HBA 5, HBD 4, PSA 108.14, QED 0.12
Compound (SMILES): CC(=O)NCCc1c[nH]c2ccc(OC(=O)NCCNc3c4c(nc5cc(Cl)ccc35)CCCC4)cc12
InChIKey: RISDMIZNEKTMBT-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition Assay: The biological activity of the compounds of general formula (I) towards the cholinesterase inhibition was evaluated using Ellman's method (Ellman, G. L.; Courtney, K. D.; Anders, B.; Featherstone, R. M. Biochem. Pharmacol. 1961, 7, 88-95).This method of evaluation of the cholinesterase inhibitors activity is based on the fact that acetyl/butyrylcholinesterase interacts with the inhibitor, which prevents the acetyl/butyrylcholine hydrolysis. The inhibitor causes the enzyme activity drop which is dependent on the inhibitor concentration. The enzyme unbound with the inhibitor is able to hydrolyze acetyl/butyrylthiocholine (ASCh/BSCh). The amount of the hydrolyzed ASCh/BSCh is measured indirectly, by quantification of the product of its reaction with DTNB (5,5Ã¢Â²-dithio-bis-2-nitrobenzoic acid). Ellman's method relies therefore on the spectrophotometric quantification of product of the reaction between acylthiocholine and DTNB.
Measurement: IC50 = 34.5 nM (pChEMBL 7.460000038146973)
Descriptors: MW 520.03, ALogP 5.13, HBA 5, HBD 4, PSA 108.14, QED 0.24
Compound (SMILES): CC(=O)O[C@@]12CCN(C(C)=O)[C@@H]1N(C(C)=O)c1ccc(OC(=O)NCCCCCCNc3c4c(nc5ccccc35)CCCC4)cc12
InChIKey: JCZCGQLHQOCURC-QZCRLSDHSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition Assay: The biological activity of the compounds of general formula (I) towards the cholinesterase inhibition was evaluated using Ellman's method (Ellman, G. L.; Courtney, K. D.; Anders, B.; Featherstone, R. M. Biochem. Pharmacol. 1961, 7, 88-95).This method of evaluation of the cholinesterase inhibitors activity is based on the fact that acetyl/butyrylcholinesterase interacts with the inhibitor, which prevents the acetyl/butyrylcholine hydrolysis. The inhibitor causes the enzyme activity drop which is dependent on the inhibitor concentration. The enzyme unbound with the inhibitor is able to hydrolyze acetyl/butyrylthiocholine (ASCh/BSCh). The amount of the hydrolyzed ASCh/BSCh is measured indirectly, by quantification of the product of its reaction with DTNB (5,5Ã¢Â²-dithio-bis-2-nitrobenzoic acid). Ellman's method relies therefore on the spectrophotometric quantification of product of the reaction between acylthiocholine and DTNB.
Measurement: IC50 = 3.15 nM (pChEMBL 8.5)
Descriptors: MW 641.77, ALogP 5.58, HBA 8, HBD 2, PSA 130.17, QED 0.22
Compound (SMILES): CC(=O)NCCc1c[nH]c2ccc(OC(=O)NCCCNc3c4c(nc5ccccc35)CCCC4)cc12
InChIKey: AFGFYJJNRLVSLM-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition Assay: The biological activity of the compounds of general formula (I) towards the cholinesterase inhibition was evaluated using Ellman's method (Ellman, G. L.; Courtney, K. D.; Anders, B.; Featherstone, R. M. Biochem. Pharmacol. 1961, 7, 88-95).This method of evaluation of the cholinesterase inhibitors activity is based on the fact that acetyl/butyrylcholinesterase interacts with the inhibitor, which prevents the acetyl/butyrylcholine hydrolysis. The inhibitor causes the enzyme activity drop which is dependent on the inhibitor concentration. The enzyme unbound with the inhibitor is able to hydrolyze acetyl/butyrylthiocholine (ASCh/BSCh). The amount of the hydrolyzed ASCh/BSCh is measured indirectly, by quantification of the product of its reaction with DTNB (5,5Ã¢Â²-dithio-bis-2-nitrobenzoic acid). Ellman's method relies therefore on the spectrophotometric quantification of product of the reaction between acylthiocholine and DTNB.
Measurement: IC50 = 269.68 nM (pChEMBL 6.570000171661377)
Descriptors: MW 499.62, ALogP 4.86, HBA 5, HBD 4, PSA 108.14, QED 0.25
Compound (SMILES): CC(=O)NCCc1c[nH]c2ccc(OC(=O)NCCCCNc3c4c(nc5ccccc35)CCCC4)cc12
InChIKey: APIRGAOTKZFKAS-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition Assay: The biological activity of the compounds of general formula (I) towards the cholinesterase inhibition was evaluated using Ellman's method (Ellman, G. L.; Courtney, K. D.; Anders, B.; Featherstone, R. M. Biochem. Pharmacol. 1961, 7, 88-95).This method of evaluation of the cholinesterase inhibitors activity is based on the fact that acetyl/butyrylcholinesterase interacts with the inhibitor, which prevents the acetyl/butyrylcholine hydrolysis. The inhibitor causes the enzyme activity drop which is dependent on the inhibitor concentration. The enzyme unbound with the inhibitor is able to hydrolyze acetyl/butyrylthiocholine (ASCh/BSCh). The amount of the hydrolyzed ASCh/BSCh is measured indirectly, by quantification of the product of its reaction with DTNB (5,5Ã¢Â²-dithio-bis-2-nitrobenzoic acid). Ellman's method relies therefore on the spectrophotometric quantification of product of the reaction between acylthiocholine and DTNB.
Measurement: IC50 = 15.49 nM (pChEMBL 7.809999942779541)
Descriptors: MW 513.64, ALogP 5.25, HBA 5, HBD 4, PSA 108.14, QED 0.22
Compound (SMILES): CC(=O)NCCc1c[nH]c2ccc(OC(=O)NCCCCCNc3c4c(nc5ccccc35)CCCC4)cc12
InChIKey: DZVVTCMRQZXZRQ-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition Assay: The biological activity of the compounds of general formula (I) towards the cholinesterase inhibition was evaluated using Ellman's method (Ellman, G. L.; Courtney, K. D.; Anders, B.; Featherstone, R. M. Biochem. Pharmacol. 1961, 7, 88-95).This method of evaluation of the cholinesterase inhibitors activity is based on the fact that acetyl/butyrylcholinesterase interacts with the inhibitor, which prevents the acetyl/butyrylcholine hydrolysis. The inhibitor causes the enzyme activity drop which is dependent on the inhibitor concentration. The enzyme unbound with the inhibitor is able to hydrolyze acetyl/butyrylthiocholine (ASCh/BSCh). The amount of the hydrolyzed ASCh/BSCh is measured indirectly, by quantification of the product of its reaction with DTNB (5,5Ã¢Â²-dithio-bis-2-nitrobenzoic acid). Ellman's method relies therefore on the spectrophotometric quantification of product of the reaction between acylthiocholine and DTNB.
Measurement: IC50 = 186.44 nM (pChEMBL 6.730000019073486)
Descriptors: MW 527.67, ALogP 5.64, HBA 5, HBD 4, PSA 108.14, QED 0.19
Compound (SMILES): CC(=O)NCCc1c[nH]c2ccc(OC(=O)NCCCCCCCCNc3c4c(nc5ccccc35)CCCC4)cc12
InChIKey: HYWHYYQDFBRNJV-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition Assay: The biological activity of the compounds of general formula (I) towards the cholinesterase inhibition was evaluated using Ellman's method (Ellman, G. L.; Courtney, K. D.; Anders, B.; Featherstone, R. M. Biochem. Pharmacol. 1961, 7, 88-95).This method of evaluation of the cholinesterase inhibitors activity is based on the fact that acetyl/butyrylcholinesterase interacts with the inhibitor, which prevents the acetyl/butyrylcholine hydrolysis. The inhibitor causes the enzyme activity drop which is dependent on the inhibitor concentration. The enzyme unbound with the inhibitor is able to hydrolyze acetyl/butyrylthiocholine (ASCh/BSCh). The amount of the hydrolyzed ASCh/BSCh is measured indirectly, by quantification of the product of its reaction with DTNB (5,5Ã¢Â²-dithio-bis-2-nitrobenzoic acid). Ellman's method relies therefore on the spectrophotometric quantification of product of the reaction between acylthiocholine and DTNB.
Measurement: IC50 = 0.25 nM (pChEMBL 9.600000381469727)
Descriptors: MW 569.75, ALogP 6.81, HBA 5, HBD 4, PSA 108.14, QED 0.12
Compound (SMILES): CC(=O)NCCc1c[nH]c2ccc(OC(=O)NCCCCCCCNc3c4c(nc5ccc(Cl)cc35)CCCC4)cc12
InChIKey: UTQFNPJLIOYJFL-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition Assay: The biological activity of the compounds of general formula (I) towards the cholinesterase inhibition was evaluated using Ellman's method (Ellman, G. L.; Courtney, K. D.; Anders, B.; Featherstone, R. M. Biochem. Pharmacol. 1961, 7, 88-95).This method of evaluation of the cholinesterase inhibitors activity is based on the fact that acetyl/butyrylcholinesterase interacts with the inhibitor, which prevents the acetyl/butyrylcholine hydrolysis. The inhibitor causes the enzyme activity drop which is dependent on the inhibitor concentration. The enzyme unbound with the inhibitor is able to hydrolyze acetyl/butyrylthiocholine (ASCh/BSCh). The amount of the hydrolyzed ASCh/BSCh is measured indirectly, by quantification of the product of its reaction with DTNB (5,5Ã¢Â²-dithio-bis-2-nitrobenzoic acid). Ellman's method relies therefore on the spectrophotometric quantification of product of the reaction between acylthiocholine and DTNB.
Measurement: IC50 = 0.88 nM (pChEMBL 9.0600004196167)
Descriptors: MW 590.17, ALogP 7.08, HBA 5, HBD 4, PSA 108.14, QED 0.12
Compound (SMILES): CC(=O)NCCc1c[nH]c2ccc(OC(=O)NCCNc3c4c(nc5ccc(Cl)cc35)CCCC4)cc12
InChIKey: MBBVMMONYFBGOE-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition Assay: The biological activity of the compounds of general formula (I) towards the cholinesterase inhibition was evaluated using Ellman's method (Ellman, G. L.; Courtney, K. D.; Anders, B.; Featherstone, R. M. Biochem. Pharmacol. 1961, 7, 88-95).This method of evaluation of the cholinesterase inhibitors activity is based on the fact that acetyl/butyrylcholinesterase interacts with the inhibitor, which prevents the acetyl/butyrylcholine hydrolysis. The inhibitor causes the enzyme activity drop which is dependent on the inhibitor concentration. The enzyme unbound with the inhibitor is able to hydrolyze acetyl/butyrylthiocholine (ASCh/BSCh). The amount of the hydrolyzed ASCh/BSCh is measured indirectly, by quantification of the product of its reaction with DTNB (5,5Ã¢Â²-dithio-bis-2-nitrobenzoic acid). Ellman's method relies therefore on the spectrophotometric quantification of product of the reaction between acylthiocholine and DTNB.
Measurement: IC50 = 8.2 nM (pChEMBL 8.09000015258789)
Descriptors: MW 520.03, ALogP 5.13, HBA 5, HBD 4, PSA 108.14, QED 0.24
Compound (SMILES): CC(=O)NCCc1c[nH]c2ccc(OC(=O)NCCCCCCCCCCNc3c4c(nc5ccccc35)CCCC4)cc12
InChIKey: KMMFIXOTKGBTSZ-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition Assay: The biological activity of the compounds of general formula (I) towards the cholinesterase inhibition was evaluated using Ellman's method (Ellman, G. L.; Courtney, K. D.; Anders, B.; Featherstone, R. M. Biochem. Pharmacol. 1961, 7, 88-95).This method of evaluation of the cholinesterase inhibitors activity is based on the fact that acetyl/butyrylcholinesterase interacts with the inhibitor, which prevents the acetyl/butyrylcholine hydrolysis. The inhibitor causes the enzyme activity drop which is dependent on the inhibitor concentration. The enzyme unbound with the inhibitor is able to hydrolyze acetyl/butyrylthiocholine (ASCh/BSCh). The amount of the hydrolyzed ASCh/BSCh is measured indirectly, by quantification of the product of its reaction with DTNB (5,5Ã¢Â²-dithio-bis-2-nitrobenzoic acid). Ellman's method relies therefore on the spectrophotometric quantification of product of the reaction between acylthiocholine and DTNB.
Measurement: IC50 = 1.18 nM (pChEMBL 8.930000305175781)
Descriptors: MW 597.8, ALogP 7.59, HBA 5, HBD 4, PSA 108.14, QED 0.1
Compound (SMILES): CC(=O)NCCc1c[nH]c2ccc(OC(=O)NCCCCCCCCCCCCNc3c4c(nc5ccccc35)CCCC4)cc12
InChIKey: CPSSIDMPFSBMRO-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition Assay: The biological activity of the compounds of general formula (I) towards the cholinesterase inhibition was evaluated using Ellman's method (Ellman, G. L.; Courtney, K. D.; Anders, B.; Featherstone, R. M. Biochem. Pharmacol. 1961, 7, 88-95).This method of evaluation of the cholinesterase inhibitors activity is based on the fact that acetyl/butyrylcholinesterase interacts with the inhibitor, which prevents the acetyl/butyrylcholine hydrolysis. The inhibitor causes the enzyme activity drop which is dependent on the inhibitor concentration. The enzyme unbound with the inhibitor is able to hydrolyze acetyl/butyrylthiocholine (ASCh/BSCh). The amount of the hydrolyzed ASCh/BSCh is measured indirectly, by quantification of the product of its reaction with DTNB (5,5Ã¢Â²-dithio-bis-2-nitrobenzoic acid). Ellman's method relies therefore on the spectrophotometric quantification of product of the reaction between acylthiocholine and DTNB.
Measurement: IC50 = 0.24 nM (pChEMBL 9.619999885559082)
Descriptors: MW 625.86, ALogP 8.38, HBA 5, HBD 4, PSA 108.14, QED 0.08
Compound (SMILES): CC(=O)NCCc1c[nH]c2ccc(OC(=O)NCCCCCCCCCCNc3c4c(nc5ccc(Cl)cc35)CCCC4)cc12
InChIKey: XVXDTYXMYWAMAF-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition Assay: The biological activity of the compounds of general formula (I) towards the cholinesterase inhibition was evaluated using Ellman's method (Ellman, G. L.; Courtney, K. D.; Anders, B.; Featherstone, R. M. Biochem. Pharmacol. 1961, 7, 88-95).This method of evaluation of the cholinesterase inhibitors activity is based on the fact that acetyl/butyrylcholinesterase interacts with the inhibitor, which prevents the acetyl/butyrylcholine hydrolysis. The inhibitor causes the enzyme activity drop which is dependent on the inhibitor concentration. The enzyme unbound with the inhibitor is able to hydrolyze acetyl/butyrylthiocholine (ASCh/BSCh). The amount of the hydrolyzed ASCh/BSCh is measured indirectly, by quantification of the product of its reaction with DTNB (5,5Ã¢Â²-dithio-bis-2-nitrobenzoic acid). Ellman's method relies therefore on the spectrophotometric quantification of product of the reaction between acylthiocholine and DTNB.
Measurement: IC50 = 1.43 nM (pChEMBL 8.850000381469727)
Descriptors: MW 632.25, ALogP 8.25, HBA 5, HBD 4, PSA 108.14, QED 0.09
Compound (SMILES): CC(=O)NCCc1c[nH]c2ccc(OC(=O)NCCCCCCCCCCNc3c4c(nc5cc(Cl)ccc35)CCCC4)cc12
InChIKey: SPEKQSDIHIDYJX-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition Assay: The biological activity of the compounds of general formula (I) towards the cholinesterase inhibition was evaluated using Ellman's method (Ellman, G. L.; Courtney, K. D.; Anders, B.; Featherstone, R. M. Biochem. Pharmacol. 1961, 7, 88-95).This method of evaluation of the cholinesterase inhibitors activity is based on the fact that acetyl/butyrylcholinesterase interacts with the inhibitor, which prevents the acetyl/butyrylcholine hydrolysis. The inhibitor causes the enzyme activity drop which is dependent on the inhibitor concentration. The enzyme unbound with the inhibitor is able to hydrolyze acetyl/butyrylthiocholine (ASCh/BSCh). The amount of the hydrolyzed ASCh/BSCh is measured indirectly, by quantification of the product of its reaction with DTNB (5,5Ã¢Â²-dithio-bis-2-nitrobenzoic acid). Ellman's method relies therefore on the spectrophotometric quantification of product of the reaction between acylthiocholine and DTNB.
Measurement: IC50 = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 632.25, ALogP 8.25, HBA 5, HBD 4, PSA 108.14, QED 0.09
Compound (SMILES): CC(=O)NCCc1c[nH]c2ccc(OC(=O)NCCCCCCCCCCCCNc3c4c(nc5cc(Cl)ccc35)CCCC4)cc12
InChIKey: FDPFEWCMKUTRHJ-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition Assay: The biological activity of the compounds of general formula (I) towards the cholinesterase inhibition was evaluated using Ellman's method (Ellman, G. L.; Courtney, K. D.; Anders, B.; Featherstone, R. M. Biochem. Pharmacol. 1961, 7, 88-95).This method of evaluation of the cholinesterase inhibitors activity is based on the fact that acetyl/butyrylcholinesterase interacts with the inhibitor, which prevents the acetyl/butyrylcholine hydrolysis. The inhibitor causes the enzyme activity drop which is dependent on the inhibitor concentration. The enzyme unbound with the inhibitor is able to hydrolyze acetyl/butyrylthiocholine (ASCh/BSCh). The amount of the hydrolyzed ASCh/BSCh is measured indirectly, by quantification of the product of its reaction with DTNB (5,5Ã¢Â²-dithio-bis-2-nitrobenzoic acid). Ellman's method relies therefore on the spectrophotometric quantification of product of the reaction between acylthiocholine and DTNB.
Measurement: IC50 = 1.31 nM (pChEMBL 8.880000114440918)
Descriptors: MW 660.3, ALogP 9.03, HBA 5, HBD 4, PSA 108.14, QED 0.08
Compound (SMILES): CC(=O)NCCc1c[nH]c2ccc(OC(=O)NCCCCCCCCCCCCNc3c4c(nc5ccc(Cl)cc35)CCCC4)cc12
InChIKey: JUBDOIQNUNJQNE-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition Assay: The biological activity of the compounds of general formula (I) towards the cholinesterase inhibition was evaluated using Ellman's method (Ellman, G. L.; Courtney, K. D.; Anders, B.; Featherstone, R. M. Biochem. Pharmacol. 1961, 7, 88-95).This method of evaluation of the cholinesterase inhibitors activity is based on the fact that acetyl/butyrylcholinesterase interacts with the inhibitor, which prevents the acetyl/butyrylcholine hydrolysis. The inhibitor causes the enzyme activity drop which is dependent on the inhibitor concentration. The enzyme unbound with the inhibitor is able to hydrolyze acetyl/butyrylthiocholine (ASCh/BSCh). The amount of the hydrolyzed ASCh/BSCh is measured indirectly, by quantification of the product of its reaction with DTNB (5,5Ã¢Â²-dithio-bis-2-nitrobenzoic acid). Ellman's method relies therefore on the spectrophotometric quantification of product of the reaction between acylthiocholine and DTNB.
Measurement: IC50 = 0.78 nM (pChEMBL 9.109999656677246)
Descriptors: MW 660.3, ALogP 9.03, HBA 5, HBD 4, PSA 108.14, QED 0.08
Compound (SMILES): CC(C)S(=O)(=O)c1ccc(-c2cnc(N)c(-c3cc(-c4ccc([C@@H]5COCCN5)cc4)no3)n2)cc1
InChIKey: IXGKDJWUPZRAPM-QHCPKHFHSA-N
Target: Serine/threonine-protein kinase ATR (SINGLE PROTEIN), Homo sapiens
UniProt: Q13535
Assay: ATR Inhibition Assay: Assays were carried out in a mixture of 50 mM Tris/HCl (pH 7.5), 10 mM MgCl2 and 1 mM DTT. Final substrate concentrations were 10 μM [γ-33P]ATP (3mCi 33P ATP/mmol ATP, Perkin Elmer) and 800 μM target peptide (ASELPASQPQPFSAKKK). Assays were carried out at 25° C. in the presence of 5 nM full-length ATR. An assay stock buffer solution was prepared containing all of the reagents listed above, with the exception of ATP and the test compound of interest. 13.5 μL of the stock solution was placed in a 96 well plate followed by addition of 2 μL of DMSO stock containing serial dilutions of the test compound (typically starting from a final concentration of 15 μM with 3-fold serial dilutions) in duplicate (final DMSO concentration 7%). The plate was pre-incubated for 10 minutes at 25° C. and the reaction initiated by addition of 15 μL [γ-33P]ATP (final concentration 10 μM). The reaction was stopped after 24 hours by the addition of 30 μL 0.1M phosphoric acid containing 2 mM ATP. A multiscreen phosphocellulose filter 96-well plate (Millipore, Cat no. MAPHN0B50) was pretreated with 100 μL 0.2M phosphoric acid prior to the addition of 45 μL of the stopped assay mixture. The plate was washed with 5×200 μL 0.2M phosphoric acid. After drying, 100 μL Optiphase 'SuperMix' liquid scintillation cocktail (Perkin Elmer) was added to the well prior to scintillation counting (1450 Microbeta Liquid Scintillation Counter, Wallac).
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 505.6, ALogP 3.89, HBA 9, HBD 2, PSA 133.23, QED 0.4
Compound (SMILES): Cc1cccc(C(=O)N2C[C@H](Oc3cc(C#N)ccn3)CC[C@H]2C)c1-n1nccn1
InChIKey: QACHRKPZIJHNHU-SJLPKXTDSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Radioligand Binding Assay: The inhibition constant (Ki) is determined using a radioligand binding assay (described in Bergman et. al. Bioorg. Med. Chem. Lett. 2008, 18, 1425-1430).
Measurement: Ki = 669 nM (pChEMBL 6.170000076293945)
Descriptors: MW 402.46, ALogP 2.91, HBA 7, HBD 0, PSA 96.93, QED 0.67
Compound (SMILES): Cc1cccc(-n2nccn2)c1C(=O)N1C[C@H](Oc2cc(C#N)ccn2)CC[C@H]1C
InChIKey: GQCLNKPNLVDVKR-SJLPKXTDSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P56719
Assay: FLIPR Ca2+ Flux Assay: Chinese hamster ovary (CHO) cells expressing the rat orexin-1 receptor or the human orexin-2 receptor, are grown in Iscove's modified DMEM containing 2 mM L-glutamine, 0.5 g/ml G418, 1% hypoxanthine-thymidine supplement, 100 U/ml penicillin, 100 ug/ml streptomycin and 10% heat-inactivated fetal calf serum (FCS). The cells are seeded at 20,000 cells/well into Becton-Dickinson black 384-well clear bottom sterile plates coated with poly-D-lysine. All reagents were from GIBCO-Invitrogen Corp. The seeded plates are incubated overnight at 37° C. and 5% CO2. Ala-6,12 human orexin-A as the agonist is prepared as a 1 mM stock solution in 1% bovine serum albumin (BSA) and diluted in assay buffer (HBSS containing 20 mM HEPES, 0.1% BSA and 2.5 mM probenecid, pH7.4) for use in the assay at a final concentration of 70 pM. Test compounds are prepared as 10 mM stock solution in DMSO, then diluted in 384-well plates, first in DMSO, then assay buffer. On the day of the assay, cells are washed 3 times with 100 ul assay buffer and then incubated for 60 min (37° C., 5% CO2) in 60 ul assay buffer containing 1 uM Fluo-4AM ester, 0.02% pluronic acid, and 1% BSA. The dye loading solution is then aspirated and cells are washed 3 times with 100 ul assay buffer. 30 ul of that same buffer is left in each well. Within the Fluorescent Imaging Plate Reader (FLIPR, Molecular Devices), test compounds are added to the plate in a volume of 25 ul, incubated for 5 min and finally 25 ul of agonist is added. Fluorescence is measured for each well at 1 second intervals for 5 minutes and the height of each fluorescence peak is compared to the height of the fluorescence peak induced by 70 pM Ala-6,12 orexin-A with buffer in place of antagonist.
Measurement: IC50 = 29 nM (pChEMBL 7.539999961853027)
Descriptors: MW 402.46, ALogP 2.91, HBA 7, HBD 0, PSA 96.93, QED 0.67
Compound (SMILES): C[C@@H]1CC[C@@H](Oc2cc(C#N)ccn2)CN1C(=O)c1cccc(F)c1-n1nccn1
InChIKey: GCPJITKYQCWZPV-GDBMZVCRSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Radioligand Binding Assay: The inhibition constant (Ki) is determined using a radioligand binding assay (described in Bergman et. al. Bioorg. Med. Chem. Lett. 2008, 18, 1425-1430).
Measurement: Ki = 1900 nM (pChEMBL 5.71999979019165)
Descriptors: MW 406.42, ALogP 2.75, HBA 7, HBD 0, PSA 96.93, QED 0.66
Compound (SMILES): C[C@@H]1CC[C@@H](Oc2cc(C#N)ccn2)CN1C(=O)c1cc(Cl)ccc1-n1nccn1
InChIKey: XNQHPHHSLRWILW-RHSMWYFYSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Radioligand Binding Assay: The inhibition constant (Ki) is determined using a radioligand binding assay (described in Bergman et. al. Bioorg. Med. Chem. Lett. 2008, 18, 1425-1430).
Measurement: Ki = 57 nM (pChEMBL 7.239999771118164)
Descriptors: MW 422.88, ALogP 3.26, HBA 7, HBD 0, PSA 96.93, QED 0.64
Compound (SMILES): C[C@@H]1CC[C@@H](Oc2cc(C#N)ccn2)CN1C(=O)c1ccc(F)cc1-n1nccn1
InChIKey: XADMHFYHZAIOGX-RHSMWYFYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P56718
Assay: FLIPR Ca2+ Flux Assay: Chinese hamster ovary (CHO) cells expressing the rat orexin-1 receptor or the human orexin-2 receptor, are grown in Iscove's modified DMEM containing 2 mM L-glutamine, 0.5 g/ml G418, 1% hypoxanthine-thymidine supplement, 100 U/ml penicillin, 100 ug/ml streptomycin and 10% heat-inactivated fetal calf serum (FCS). The cells are seeded at 20,000 cells/well into Becton-Dickinson black 384-well clear bottom sterile plates coated with poly-D-lysine. All reagents were from GIBCO-Invitrogen Corp. The seeded plates are incubated overnight at 37° C. and 5% CO2. Ala-6,12 human orexin-A as the agonist is prepared as a 1 mM stock solution in 1% bovine serum albumin (BSA) and diluted in assay buffer (HBSS containing 20 mM HEPES, 0.1% BSA and 2.5 mM probenecid, pH7.4) for use in the assay at a final concentration of 70 pM. Test compounds are prepared as 10 mM stock solution in DMSO, then diluted in 384-well plates, first in DMSO, then assay buffer. On the day of the assay, cells are washed 3 times with 100 ul assay buffer and then incubated for 60 min (37° C., 5% CO2) in 60 ul assay buffer containing 1 uM Fluo-4AM ester, 0.02% pluronic acid, and 1% BSA. The dye loading solution is then aspirated and cells are washed 3 times with 100 ul assay buffer. 30 ul of that same buffer is left in each well. Within the Fluorescent Imaging Plate Reader (FLIPR, Molecular Devices), test compounds are added to the plate in a volume of 25 ul, incubated for 5 min and finally 25 ul of agonist is added. Fluorescence is measured for each well at 1 second intervals for 5 minutes and the height of each fluorescence peak is compared to the height of the fluorescence peak induced by 70 pM Ala-6,12 orexin-A with buffer in place of antagonist.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 406.42, ALogP 2.75, HBA 7, HBD 0, PSA 96.93, QED 0.66
Compound (SMILES): Cc1ccc(C(=O)N2C[C@H](Oc3cc(C#N)ccn3)CC[C@H]2C)c(-n2nccn2)c1
InChIKey: HVKZCWBOKSNHRN-SJLPKXTDSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P56719
Assay: FLIPR Ca2+ Flux Assay: Chinese hamster ovary (CHO) cells expressing the rat orexin-1 receptor or the human orexin-2 receptor, are grown in Iscove's modified DMEM containing 2 mM L-glutamine, 0.5 g/ml G418, 1% hypoxanthine-thymidine supplement, 100 U/ml penicillin, 100 ug/ml streptomycin and 10% heat-inactivated fetal calf serum (FCS). The cells are seeded at 20,000 cells/well into Becton-Dickinson black 384-well clear bottom sterile plates coated with poly-D-lysine. All reagents were from GIBCO-Invitrogen Corp. The seeded plates are incubated overnight at 37° C. and 5% CO2. Ala-6,12 human orexin-A as the agonist is prepared as a 1 mM stock solution in 1% bovine serum albumin (BSA) and diluted in assay buffer (HBSS containing 20 mM HEPES, 0.1% BSA and 2.5 mM probenecid, pH7.4) for use in the assay at a final concentration of 70 pM. Test compounds are prepared as 10 mM stock solution in DMSO, then diluted in 384-well plates, first in DMSO, then assay buffer. On the day of the assay, cells are washed 3 times with 100 ul assay buffer and then incubated for 60 min (37° C., 5% CO2) in 60 ul assay buffer containing 1 uM Fluo-4AM ester, 0.02% pluronic acid, and 1% BSA. The dye loading solution is then aspirated and cells are washed 3 times with 100 ul assay buffer. 30 ul of that same buffer is left in each well. Within the Fluorescent Imaging Plate Reader (FLIPR, Molecular Devices), test compounds are added to the plate in a volume of 25 ul, incubated for 5 min and finally 25 ul of agonist is added. Fluorescence is measured for each well at 1 second intervals for 5 minutes and the height of each fluorescence peak is compared to the height of the fluorescence peak induced by 70 pM Ala-6,12 orexin-A with buffer in place of antagonist.
Measurement: IC50 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 402.46, ALogP 2.91, HBA 7, HBD 0, PSA 96.93, QED 0.67
Compound (SMILES): C[C@@H]1CC[C@@H](Oc2cc(C#N)ccn2)CN1C(=O)c1ccsc1-n1nccn1
InChIKey: CFLCOSGEEDANMY-UKRRQHHQSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P56719
Assay: FLIPR Ca2+ Flux Assay: Chinese hamster ovary (CHO) cells expressing the rat orexin-1 receptor or the human orexin-2 receptor, are grown in Iscove's modified DMEM containing 2 mM L-glutamine, 0.5 g/ml G418, 1% hypoxanthine-thymidine supplement, 100 U/ml penicillin, 100 ug/ml streptomycin and 10% heat-inactivated fetal calf serum (FCS). The cells are seeded at 20,000 cells/well into Becton-Dickinson black 384-well clear bottom sterile plates coated with poly-D-lysine. All reagents were from GIBCO-Invitrogen Corp. The seeded plates are incubated overnight at 37° C. and 5% CO2. Ala-6,12 human orexin-A as the agonist is prepared as a 1 mM stock solution in 1% bovine serum albumin (BSA) and diluted in assay buffer (HBSS containing 20 mM HEPES, 0.1% BSA and 2.5 mM probenecid, pH7.4) for use in the assay at a final concentration of 70 pM. Test compounds are prepared as 10 mM stock solution in DMSO, then diluted in 384-well plates, first in DMSO, then assay buffer. On the day of the assay, cells are washed 3 times with 100 ul assay buffer and then incubated for 60 min (37° C., 5% CO2) in 60 ul assay buffer containing 1 uM Fluo-4AM ester, 0.02% pluronic acid, and 1% BSA. The dye loading solution is then aspirated and cells are washed 3 times with 100 ul assay buffer. 30 ul of that same buffer is left in each well. Within the Fluorescent Imaging Plate Reader (FLIPR, Molecular Devices), test compounds are added to the plate in a volume of 25 ul, incubated for 5 min and finally 25 ul of agonist is added. Fluorescence is measured for each well at 1 second intervals for 5 minutes and the height of each fluorescence peak is compared to the height of the fluorescence peak induced by 70 pM Ala-6,12 orexin-A with buffer in place of antagonist.
Measurement: IC50 = 29 nM (pChEMBL 7.539999961853027)
Descriptors: MW 394.46, ALogP 2.67, HBA 8, HBD 0, PSA 96.93, QED 0.67