lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC(C)(C)NS(=O)(=O)N1CCC[C@H](Nc2ncccc2-c2cnc3[nH]ccc3n2)C1
InChIKey: LNPNJZPJGDLRBR-AWEZNQCLSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: IC50 = 0.2215 nM (pChEMBL 9.649999618530273)
Descriptors: MW 429.55, ALogP 2.53, HBA 6, HBD 3, PSA 115.9, QED 0.57
Compound (SMILES): CSc1ncc(-c2cnc3[nH]ccc3n2)c(N[C@H]2CCCN(S(C)(=O)=O)C2)n1
InChIKey: GFZLBUBQOPALBK-NSHDSACASA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: Ki = 0.02368 nM (pChEMBL 10.630000114440918)
Descriptors: MW 419.54, ALogP 1.97, HBA 8, HBD 2, PSA 116.76, QED 0.48
Compound (SMILES): CN(C)c1ncc(-c2cnc3[nH]ccc3n2)c(N[C@H]2CCCN(S(C)(=O)=O)C2)n1
InChIKey: DZVVSKDVSJQTOZ-LBPRGKRZSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: Ki = 0.02837 nM (pChEMBL 10.550000190734863)
Descriptors: MW 416.51, ALogP 1.32, HBA 8, HBD 2, PSA 120, QED 0.64
Compound (SMILES): CN(C)c1ncc(-c2cnc3[nH]cc(C#N)c3n2)c(N[C@H]2CCCN(S(C)(=O)=O)C2)n1
InChIKey: KHSOZOOBSQCDRG-ZDUSSCGKSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: IC50 = 0.4484 nM (pChEMBL 9.350000381469727)
Descriptors: MW 441.52, ALogP 1.19, HBA 9, HBD 2, PSA 143.79, QED 0.6
Compound (SMILES): COc1ncc(-c2cnc3[nH]ccc3n2)c(N[C@H]2CCCN(S(C)(=O)=O)C2)n1
InChIKey: AVZLKLPFHIKARU-NSHDSACASA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: IC50 = 0.02712 nM (pChEMBL 10.569999694824219)
Descriptors: MW 403.47, ALogP 1.26, HBA 8, HBD 2, PSA 125.99, QED 0.65
Compound (SMILES): CS(=O)(=O)N1CCC[C@H](Nc2nc(Cl)ncc2-c2cnc3[nH]ccc3n2)C1
InChIKey: KRHZDZQVASLABQ-JTQLQIEISA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: IC50 = 0.05241 nM (pChEMBL 10.279999732971191)
Descriptors: MW 407.89, ALogP 1.9, HBA 7, HBD 2, PSA 116.76, QED 0.63
Compound (SMILES): CCOc1ncc(-c2cnc3[nH]ccc3n2)c(N[C@H]2CCCN(S(C)(=O)=O)C2)n1
InChIKey: HSAKOHADCPEPRG-LBPRGKRZSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: IC50 = 0.03263 nM (pChEMBL 10.489999771118164)
Descriptors: MW 417.5, ALogP 1.65, HBA 8, HBD 2, PSA 125.99, QED 0.62
Compound (SMILES): CSc1ncc(-c2cnc3[nH]ccc3n2)c(N[C@H]2CCCN(C(=O)CC#N)C2)n1
InChIKey: VCPJACUOLDMQIU-LBPRGKRZSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: Ki = 0.4222 nM (pChEMBL 9.369999885559082)
Descriptors: MW 408.49, ALogP 2.45, HBA 8, HBD 2, PSA 123.48, QED 0.49
Compound (SMILES): CC(C)(O)CNc1ncc(-c2cnc3[nH]ccc3n2)c(N[C@H]2CCCN(S(C)(=O)=O)C2)n1
InChIKey: VSCBPDYZLUVMLD-ZDUSSCGKSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: Ki = 0.01979 nM (pChEMBL 10.699999809265137)
Descriptors: MW 460.56, ALogP 1.43, HBA 9, HBD 4, PSA 149.02, QED 0.41
Compound (SMILES): CS(=O)(=O)N1CCC[C@H](Nc2nc(N3CCS(=O)(=O)CC3)ncc2-c2cnc3[nH]ccc3n2)C1
InChIKey: OUAVJOGPQUAXTJ-AWEZNQCLSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: IC50 = 0.04983 nM (pChEMBL 10.300000190734863)
Descriptors: MW 506.61, ALogP 0.49, HBA 10, HBD 2, PSA 154.14, QED 0.5
Compound (SMILES): COC1CCN(c2ncc(-c3cnc4[nH]ccc4n3)c(N[C@H]3CCCN(S(C)(=O)=O)C3)n2)CC1
InChIKey: HJWYZAOXQLPRRD-HNNXBMFYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: IC50 = 0.1067 nM (pChEMBL 9.970000267028809)
Descriptors: MW 486.6, ALogP 1.87, HBA 9, HBD 2, PSA 129.23, QED 0.54
Compound (SMILES): CS(=O)(=O)N1CCC[C@H](Nc2nc(NCCN)ncc2-c2cnc3[nH]ccc3n2)C1
InChIKey: XKLPKYDEDWXEAA-LBPRGKRZSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: IC50 = 0.1665 nM (pChEMBL 9.779999732971191)
Descriptors: MW 431.53, ALogP 0.62, HBA 9, HBD 4, PSA 154.81, QED 0.42
Compound (SMILES): CN1CCC(Nc2ncc(-c3cnc4[nH]ccc4n3)c(N[C@H]3CCCN(S(C)(=O)=O)C3)n2)CC1
InChIKey: GKMDQFMGAVLZKR-INIZCTEOSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: Ki = 0.01253 nM (pChEMBL 10.899999618530273)
Descriptors: MW 485.62, ALogP 1.76, HBA 9, HBD 3, PSA 132.03, QED 0.48
Compound (SMILES): CN(C)C1CCN(c2ncc(-c3cnc4[nH]ccc4n3)c(N[C@H]3CCCN(S(C)(=O)=O)C3)n2)CC1
InChIKey: WYHTYLVLSXUWPH-INIZCTEOSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: IC50 = 0.02582 nM (pChEMBL 10.59000015258789)
Descriptors: MW 499.65, ALogP 1.78, HBA 9, HBD 2, PSA 123.24, QED 0.52
Compound (SMILES): CS(=O)(=O)N1CCC[C@H](Nc2nc(C#N)ncc2-c2cnc3[nH]ccc3n2)C1
InChIKey: QFZBBBNYHMUAIF-NSHDSACASA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: IC50 = 0.1607 nM (pChEMBL 9.789999961853027)
Descriptors: MW 398.45, ALogP 1.12, HBA 8, HBD 2, PSA 140.55, QED 0.67
Compound (SMILES): CS(=O)(=O)N1CCC[C@H](Nc2nc(N3CC[C@H](O)C3)ncc2-c2cnc3[nH]ccc3n2)C1
InChIKey: SLZJYSDUTDXKHL-KBPBESRZSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: IC50 = 0.1694 nM (pChEMBL 9.770000457763672)
Descriptors: MW 458.55, ALogP 0.82, HBA 9, HBD 3, PSA 140.23, QED 0.51
Compound (SMILES): CS(=O)(=O)N1CCC[C@H](Nc2nc(N3CCN(c4ccccn4)CC3)ncc2-c2cnc3[nH]ccc3n2)C1
InChIKey: OIIBZFKNIUFBTG-SFHVURJKSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: IC50 = 0.1751 nM (pChEMBL 9.760000228881836)
Descriptors: MW 534.65, ALogP 1.97, HBA 10, HBD 2, PSA 136.13, QED 0.38
Compound (SMILES): CS(=O)(=O)N1CCC[C@H](Nc2nc(N3CCC(CC(=O)O)CC3)ncc2-c2cnc3[nH]ccc3n2)C1
InChIKey: IEZRZUHSKFJPQY-INIZCTEOSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: IC50 = 0.1131 nM (pChEMBL 9.949999809265137)
Descriptors: MW 514.61, ALogP 1.94, HBA 9, HBD 3, PSA 157.3, QED 0.43
Compound (SMILES): CS(=O)(=O)N1CCC[C@H](Nc2nc(Nc3ccncc3)ncc2-c2cnc3[nH]ccc3n2)C1
InChIKey: XNPPMSODZPSJBF-HNNXBMFYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: IC50 = 0.6379 nM (pChEMBL 9.199999809265137)
Descriptors: MW 465.54, ALogP 2.39, HBA 9, HBD 3, PSA 141.68, QED 0.39
Compound (SMILES): CN(C)CCNc1ncc(-c2cnc3[nH]ccc3n2)c(N[C@H]2CCCN(S(C)(=O)=O)C2)n1
InChIKey: ODDNPGSYZFWGMF-AWEZNQCLSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: Ki = 0.01634 nM (pChEMBL 10.789999961853027)
Descriptors: MW 459.58, ALogP 1.22, HBA 9, HBD 3, PSA 132.03, QED 0.45
Compound (SMILES): CCN1CCN(c2ncc(-c3cnc4[nH]ccc4n3)c(N[C@H]3CCCN(S(C)(=O)=O)C3)n2)CC1
InChIKey: YHQSZLMVXUELEF-INIZCTEOSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: IC50 = 0.2125 nM (pChEMBL 9.670000076293945)
Descriptors: MW 485.62, ALogP 1.39, HBA 9, HBD 2, PSA 123.24, QED 0.53
Compound (SMILES): CN(C)[C@@H]1CCN(c2ncc(-c3cnc4[nH]ccc4n3)c(N[C@H]3CCCN(S(C)(=O)=O)C3)n2)C1
InChIKey: LUXSOKJTOICWHQ-JKSUJKDBSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: IC50 = 0.02164 nM (pChEMBL 10.65999984741211)
Descriptors: MW 485.62, ALogP 1.39, HBA 9, HBD 2, PSA 123.24, QED 0.53
Compound (SMILES): C[C@H]1C[C@H](Nc2nc(N3CCN(C)CC3)ncc2-c2cnc3[nH]ccc3n2)CN(S(C)(=O)=O)C1
InChIKey: QOEZRZBVPCWVFJ-HOTGVXAUSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: IC50 = 0.2168 nM (pChEMBL 9.65999984741211)
Descriptors: MW 485.62, ALogP 1.25, HBA 9, HBD 2, PSA 123.24, QED 0.55
Compound (SMILES): CS(=O)(=O)N1C[C@@H](Nc2ncccc2-c2cnc3[nH]ccc3n2)C[C@H](C(F)(F)F)C1
InChIKey: URJSOLWSIGLZCJ-RYUDHWBXSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: IC50 = 0.391 nM (pChEMBL 9.40999984741211)
Descriptors: MW 440.45, ALogP 2.64, HBA 6, HBD 2, PSA 103.87, QED 0.65
Compound (SMILES): CC(C)CS(=O)(=O)N1C[C@@H](Nc2ncccc2-c2cnc3[nH]ccc3n2)C[C@H](C(F)(F)F)C1
InChIKey: SHSYAACXYIUJOR-GJZGRUSLSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: IC50 = 0.4635 nM (pChEMBL 9.329999923706055)
Descriptors: MW 482.53, ALogP 3.67, HBA 6, HBD 2, PSA 103.87, QED 0.56
Compound (SMILES): N#CCC1(N2CCC[C@H](Nc3ncccc3-c3cnc4[nH]ccc4n3)C2)COC1
InChIKey: IWQGAESJHGYTDV-HNNXBMFYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: Ki = 0.04998 nM (pChEMBL 10.300000190734863)
Descriptors: MW 389.46, ALogP 2.58, HBA 7, HBD 2, PSA 102.75, QED 0.69
Compound (SMILES): C[C@H]1C[C@H](Nc2ncccc2-c2cnc3[nH]ccc3n2)CN(C2(CC#N)COC2)C1
InChIKey: WRAJCGKEBIJMIV-HOTGVXAUSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: IC50 = 0.5116 nM (pChEMBL 9.289999961853027)
Descriptors: MW 403.49, ALogP 2.82, HBA 7, HBD 2, PSA 102.75, QED 0.68
Compound (SMILES): N#CCC(N1CCC[C@H](Nc2ncccc2-c2cnc3[nH]ccc3n2)C1)C(F)(F)F
InChIKey: RHVQABKELWJCNG-CWQZNGJJSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition Assay: The kinase activity of all three JAK kinases is measured using a radioactive, end-point assay and with trace amounts of 33P-ATP.
Measurement: Ki = 0.1611 nM (pChEMBL 9.789999961853027)
Descriptors: MW 415.42, ALogP 3.74, HBA 6, HBD 2, PSA 93.52, QED 0.66
Compound (SMILES): O=c1[nH]c2ccccc2n(C2CCN(C3CCCCCCC3)CC2)c1=O
InChIKey: NMRCIXCOZCASLP-UHFFFAOYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: κ-Opioid Receptor Binding Assays: κ-Opioid Receptor Binding Assay Procedures: Membranes from recombinant HEK-293 cells expressing the human kappa opioid receptor (kappa) (cloned in house) were prepared by lysing cells in ice cold hypotonic buffer (2.5 mM MgCl2, 50 mM HEPES, pH 7.4) (10 mL/10 cm dish) followed by homogenization with a tissue grinder/Teflon pestle. Membranes were collected by centrifugation at 30,000×g for 15 min at 4° C. and pellets resuspended in hypotonic buffer to a final concentration of 1-3 mg/mL.
Measurement: Ki = 167 nM (pChEMBL 6.78000020980835)
Descriptors: MW 355.48, ALogP 3.44, HBA 4, HBD 1, PSA 58.1, QED 0.84
Compound (SMILES): CC(C)C1CCC(N2CCC(n3c(=O)c(=O)[nH]c4ccccc43)CC2)CC1
InChIKey: GBRKRVVJROXVMX-UHFFFAOYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: κ-Opioid Receptor Binding Assays: κ-Opioid Receptor Binding Assay Procedures: Membranes from recombinant HEK-293 cells expressing the human kappa opioid receptor (kappa) (cloned in house) were prepared by lysing cells in ice cold hypotonic buffer (2.5 mM MgCl2, 50 mM HEPES, pH 7.4) (10 mL/10 cm dish) followed by homogenization with a tissue grinder/Teflon pestle. Membranes were collected by centrifugation at 30,000×g for 15 min at 4° C. and pellets resuspended in hypotonic buffer to a final concentration of 1-3 mg/mL.
Measurement: Ki = 880 nM (pChEMBL 6.059999942779541)
Descriptors: MW 369.51, ALogP 3.54, HBA 4, HBD 1, PSA 58.1, QED 0.84
Compound (SMILES): O=c1[nH]c2ccccc2n(C2CCN(C3Cc4cccc5cccc3c45)CC2)c1=O
InChIKey: UIPRRHHCLMYFHJ-UHFFFAOYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: κ-Opioid Receptor Binding Assays: κ-Opioid Receptor Binding Assay Procedures: Membranes from recombinant HEK-293 cells expressing the human kappa opioid receptor (kappa) (cloned in house) were prepared by lysing cells in ice cold hypotonic buffer (2.5 mM MgCl2, 50 mM HEPES, pH 7.4) (10 mL/10 cm dish) followed by homogenization with a tissue grinder/Teflon pestle. Membranes were collected by centrifugation at 30,000×g for 15 min at 4° C. and pellets resuspended in hypotonic buffer to a final concentration of 1-3 mg/mL.
Measurement: Ki = 439 nM (pChEMBL 6.360000133514404)
Descriptors: MW 397.48, ALogP 3.78, HBA 4, HBD 1, PSA 58.1, QED 0.52
Compound (SMILES): NC(=O)Cn1c(=O)c(=O)n(C2CCN(C3Cc4cccc5cccc3c45)CC2)c2ccccc21
InChIKey: YCKODQWAIKYAQB-UHFFFAOYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: κ-Opioid Receptor Binding Assays: κ-Opioid Receptor Binding Assay Procedures: Membranes from recombinant HEK-293 cells expressing the human kappa opioid receptor (kappa) (cloned in house) were prepared by lysing cells in ice cold hypotonic buffer (2.5 mM MgCl2, 50 mM HEPES, pH 7.4) (10 mL/10 cm dish) followed by homogenization with a tissue grinder/Teflon pestle. Membranes were collected by centrifugation at 30,000×g for 15 min at 4° C. and pellets resuspended in hypotonic buffer to a final concentration of 1-3 mg/mL.
Measurement: Ki = 6950 nM (pChEMBL 5.159999847412109)
Descriptors: MW 454.53, ALogP 2.74, HBA 6, HBD 1, PSA 90.33, QED 0.48
Compound (SMILES): O=C1CC(=O)N(C2CCN(C3CCCCCCC3)CC2)c2ccccc2N1
InChIKey: ZAUHABBHHZLCNE-UHFFFAOYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: κ-Opioid Receptor Binding Assays: κ-Opioid Receptor Binding Assay Procedures: Membranes from recombinant HEK-293 cells expressing the human kappa opioid receptor (kappa) (cloned in house) were prepared by lysing cells in ice cold hypotonic buffer (2.5 mM MgCl2, 50 mM HEPES, pH 7.4) (10 mL/10 cm dish) followed by homogenization with a tissue grinder/Teflon pestle. Membranes were collected by centrifugation at 30,000×g for 15 min at 4° C. and pellets resuspended in hypotonic buffer to a final concentration of 1-3 mg/mL.
Measurement: Ki = 355 nM (pChEMBL 6.449999809265137)
Descriptors: MW 369.51, ALogP 3.94, HBA 3, HBD 1, PSA 52.65, QED 0.8
Compound (SMILES): N#CCn1c(=O)c(=O)n(C2CCN(C3CCCCCCC3)CC2)c2ccccc21
InChIKey: NDTRDFOMRIWMBU-UHFFFAOYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: κ-Opioid Receptor Binding Assays: κ-Opioid Receptor Binding Assay Procedures: Membranes from recombinant HEK-293 cells expressing the human kappa opioid receptor (kappa) (cloned in house) were prepared by lysing cells in ice cold hypotonic buffer (2.5 mM MgCl2, 50 mM HEPES, pH 7.4) (10 mL/10 cm dish) followed by homogenization with a tissue grinder/Teflon pestle. Membranes were collected by centrifugation at 30,000×g for 15 min at 4° C. and pellets resuspended in hypotonic buffer to a final concentration of 1-3 mg/mL.
Measurement: Ki = 4232 nM (pChEMBL 5.369999885559082)
Descriptors: MW 394.52, ALogP 3.44, HBA 6, HBD 0, PSA 71.03, QED 0.75
Compound (SMILES): O=c1[nH]c2ncccc2n(C2CCN(C3CCCCCCC3)CC2)c1=O
InChIKey: CIMVAXZTJNDDRS-UHFFFAOYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: κ-Opioid Receptor Binding Assays: κ-Opioid Receptor Binding Assay Procedures: Membranes from recombinant HEK-293 cells expressing the human kappa opioid receptor (kappa) (cloned in house) were prepared by lysing cells in ice cold hypotonic buffer (2.5 mM MgCl2, 50 mM HEPES, pH 7.4) (10 mL/10 cm dish) followed by homogenization with a tissue grinder/Teflon pestle. Membranes were collected by centrifugation at 30,000×g for 15 min at 4° C. and pellets resuspended in hypotonic buffer to a final concentration of 1-3 mg/mL.
Measurement: Ki = 1317 nM (pChEMBL 5.880000114440918)
Descriptors: MW 356.47, ALogP 2.83, HBA 5, HBD 1, PSA 70.99, QED 0.84
Compound (SMILES): O=c1[nH]c2ccc(N3CCOCC3)cc2n(C2CCN(C3CCCCCCC3)CC2)c1=O
InChIKey: DUYDGIOXNYEFHX-UHFFFAOYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: κ-Opioid Receptor Binding Assays: κ-Opioid Receptor Binding Assay Procedures: Membranes from recombinant HEK-293 cells expressing the human kappa opioid receptor (kappa) (cloned in house) were prepared by lysing cells in ice cold hypotonic buffer (2.5 mM MgCl2, 50 mM HEPES, pH 7.4) (10 mL/10 cm dish) followed by homogenization with a tissue grinder/Teflon pestle. Membranes were collected by centrifugation at 30,000×g for 15 min at 4° C. and pellets resuspended in hypotonic buffer to a final concentration of 1-3 mg/mL.
Measurement: Ki = 559 nM (pChEMBL 6.25)
Descriptors: MW 440.59, ALogP 3.28, HBA 6, HBD 1, PSA 70.57, QED 0.74
Compound (SMILES): O=c1[nH]c2ccccc2n([C@H]2C[C@H]3CCC[C@@H](C2)N3C2CCCCCCC2)c1=O
InChIKey: QVJLNGKSPRALSV-PMOLBWCYSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: δ-Opioid Receptor Binding Assays: δ-Receptor Binding Assay Procedures: Radioligand dose-displacement assays used 0.2 nM [3H]-Naltrindole (NEN; 33.0 Ci/mmole) with 10-20 μg membrane protein (recombinant delta opioid receptor expressend in CHO-K1 cells; Perkin Elmer) in a final volume of 5004 binding buffer (5 mM MgCl2, 5% DMSO, 50 mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 25μm M unlabeled naloxone. All reactions were performed in 96-deep well polypropylene plates for 1 h at a temperature of about 25° C.
Measurement: Ki = 20800 nM (pChEMBL 4.679999828338623)
Descriptors: MW 395.55, ALogP 4.36, HBA 4, HBD 1, PSA 58.1, QED 0.77
Compound (SMILES): O=c1[nH]c2ccccc2n([C@@H]2C[C@H]3CCC[C@@H](C2)N3C2CCCCCCC2)c1=O
InChIKey: QVJLNGKSPRALSV-ACDBMABISA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: κ-Opioid Receptor Binding Assays: κ-Opioid Receptor Binding Assay Procedures: Membranes from recombinant HEK-293 cells expressing the human kappa opioid receptor (kappa) (cloned in house) were prepared by lysing cells in ice cold hypotonic buffer (2.5 mM MgCl2, 50 mM HEPES, pH 7.4) (10 mL/10 cm dish) followed by homogenization with a tissue grinder/Teflon pestle. Membranes were collected by centrifugation at 30,000×g for 15 min at 4° C. and pellets resuspended in hypotonic buffer to a final concentration of 1-3 mg/mL.
Measurement: Ki = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 395.55, ALogP 4.36, HBA 4, HBD 1, PSA 58.1, QED 0.77
Compound (SMILES): O=C1CC(=O)N(C2CCN(C3CCCCCCC3)CC2)c2cccnc2N1
InChIKey: NMGLMXRNNQARRH-UHFFFAOYSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: δ-Opioid Receptor Binding Assays: δ-Receptor Binding Assay Procedures: Radioligand dose-displacement assays used 0.2 nM [3H]-Naltrindole (NEN; 33.0 Ci/mmole) with 10-20 μg membrane protein (recombinant delta opioid receptor expressend in CHO-K1 cells; Perkin Elmer) in a final volume of 5004 binding buffer (5 mM MgCl2, 5% DMSO, 50 mM Trizma base, pH 7.4). Non-specific binding was determined in the presence of 25μm M unlabeled naloxone. All reactions were performed in 96-deep well polypropylene plates for 1 h at a temperature of about 25° C.
Measurement: Ki = 72400 nM (pChEMBL 4.139999866485596)
Descriptors: MW 370.5, ALogP 3.33, HBA 4, HBD 1, PSA 65.54, QED 0.81
Compound (SMILES): O=c1[nH]c2ccccc2n([C@H]2C[C@H]3C=C[C@@H](C2)N3C2/C=C\CCCCC2)c1=O
InChIKey: IQQOBQHEIOGKDI-IZVKAGQKSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: κ-Opioid Receptor Binding Assays: κ-Opioid Receptor Binding Assay Procedures: Membranes from recombinant HEK-293 cells expressing the human kappa opioid receptor (kappa) (cloned in house) were prepared by lysing cells in ice cold hypotonic buffer (2.5 mM MgCl2, 50 mM HEPES, pH 7.4) (10 mL/10 cm dish) followed by homogenization with a tissue grinder/Teflon pestle. Membranes were collected by centrifugation at 30,000×g for 15 min at 4° C. and pellets resuspended in hypotonic buffer to a final concentration of 1-3 mg/mL.
Measurement: Ki = 119 nM (pChEMBL 6.920000076293945)
Descriptors: MW 377.49, ALogP 3.52, HBA 4, HBD 1, PSA 58.1, QED 0.64
Compound (SMILES): O=c1[nH]c2ccccc2n([C@@H]2C[C@H]3C=C[C@@H](C2)N3C2/C=C\CCCCC2)c1=O
InChIKey: IQQOBQHEIOGKDI-VNRYDWCLSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: κ-Opioid Receptor Binding Assays: κ-Opioid Receptor Binding Assay Procedures: Membranes from recombinant HEK-293 cells expressing the human kappa opioid receptor (kappa) (cloned in house) were prepared by lysing cells in ice cold hypotonic buffer (2.5 mM MgCl2, 50 mM HEPES, pH 7.4) (10 mL/10 cm dish) followed by homogenization with a tissue grinder/Teflon pestle. Membranes were collected by centrifugation at 30,000×g for 15 min at 4° C. and pellets resuspended in hypotonic buffer to a final concentration of 1-3 mg/mL.
Measurement: Ki = 682 nM (pChEMBL 6.170000076293945)
Descriptors: MW 377.49, ALogP 3.52, HBA 4, HBD 1, PSA 58.1, QED 0.64
Compound (SMILES): CC(C)(C)C[C@H]1N[C@@H](C(=O)N[C@H]2C[C@@](C)(O)C2)[C@H](c2cccc(Cl)c2F)[C@@]12C(=O)Nc1cc(F)ccc12
InChIKey: TZQDPFTZXGEZHJ-YPZCAFDDSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: Fluorescence-polarization Binding Assay: The binding affinity of the MDM2 inhibitors was determined using an optimized, sensitive and quantitative fluorescence polarization-based (FP-based) binding assay using a recombinant human His-tagged MDM2 protein (residues 1-118) and a fluorescently tagged p53-based peptide. The design of the fluorescence probe was based upon a previously reported high-affinity p53-based peptidomimetic compound (5-FAM-βAla-βAla-Phe-Met-Aib-pTyr-(6-Cl-LTrp)-Glu-Ac3c-Leu-Asn-NH2 (SEQ ID NO: 1)) (García-Echeverría et al., J. Med. Chem. 43: 3205-3208 (2000)). This tagged peptide is called PMDM6-F. MDM2 protein was serially double diluted in a Dynex 96-well, black, round-bottom plate, and the PMDM6-F peptide was added at 1 nM concentration. The assay was performed in the buffer: 100 mM potassium phosphate, pH 7.5; 100 μg/mL bovine gamma globulin; 0.02% sodium azide, 0.01% Triton X-100) and the polarization values were measured after 3 h of incubation using an ULTRA READER (Tecan U.S. Inc).
Measurement: IC50 < 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 532.03, ALogP 4.4, HBA 4, HBD 4, PSA 90.46, QED 0.47
Compound (SMILES): CC(C)(C)C[C@@H]1N[C@@H](C(=O)N[C@H]2C[C@@](C)(O)C2)[C@H](c2cccc(F)c2F)[C@]12C(=O)Nc1cc(Cl)ccc12
InChIKey: CUMRPCQMSXHYEE-GRRGFIRHSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: Fluorescence-polarization Binding Assay: The binding affinity of the MDM2 inhibitors was determined using an optimized, sensitive and quantitative fluorescence polarization-based (FP-based) binding assay using a recombinant human His-tagged MDM2 protein (residues 1-118) and a fluorescently tagged p53-based peptide. The design of the fluorescence probe was based upon a previously reported high-affinity p53-based peptidomimetic compound (5-FAM-βAla-βAla-Phe-Met-Aib-pTyr-(6-Cl-LTrp)-Glu-Ac3c-Leu-Asn-NH2 (SEQ ID NO: 1)) (García-Echeverría et al., J. Med. Chem. 43: 3205-3208 (2000)). This tagged peptide is called PMDM6-F. MDM2 protein was serially double diluted in a Dynex 96-well, black, round-bottom plate, and the PMDM6-F peptide was added at 1 nM concentration. The assay was performed in the buffer: 100 mM potassium phosphate, pH 7.5; 100 μg/mL bovine gamma globulin; 0.02% sodium azide, 0.01% Triton X-100) and the polarization values were measured after 3 h of incubation using an ULTRA READER (Tecan U.S. Inc).
Measurement: IC50 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 532.03, ALogP 4.4, HBA 4, HBD 4, PSA 90.46, QED 0.47
Compound (SMILES): CC(C)(C)C[C@@H]1N[C@@H](C(=O)N[C@H]2C[C@@](C)(O)C2)[C@H](c2cccc(Cl)c2F)[C@]12C(=O)Nc1cc(F)c(F)cc12
InChIKey: MZLPNMUZFAVXQN-SDJDJFSXSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: Fluorescence-polarization Binding Assay: The binding affinity of the MDM2 inhibitors was determined using an optimized, sensitive and quantitative fluorescence polarization-based (FP-based) binding assay using a recombinant human His-tagged MDM2 protein (residues 1-118) and a fluorescently tagged p53-based peptide. The design of the fluorescence probe was based upon a previously reported high-affinity p53-based peptidomimetic compound (5-FAM-βAla-βAla-Phe-Met-Aib-pTyr-(6-Cl-LTrp)-Glu-Ac3c-Leu-Asn-NH2 (SEQ ID NO: 1)) (García-Echeverría et al., J. Med. Chem. 43: 3205-3208 (2000)). This tagged peptide is called PMDM6-F. MDM2 protein was serially double diluted in a Dynex 96-well, black, round-bottom plate, and the PMDM6-F peptide was added at 1 nM concentration. The assay was performed in the buffer: 100 mM potassium phosphate, pH 7.5; 100 μg/mL bovine gamma globulin; 0.02% sodium azide, 0.01% Triton X-100) and the polarization values were measured after 3 h of incubation using an ULTRA READER (Tecan U.S. Inc).
Measurement: IC50 = 35 nM (pChEMBL 7.460000038146973)
Descriptors: MW 550.02, ALogP 4.54, HBA 4, HBD 4, PSA 90.46, QED 0.45
Compound (SMILES): CC(C)(C)C[C@@H]1N[C@@H](C(=O)N[C@H]2C[C@@](C)(O)C2)[C@H](c2cccc(Cl)c2F)[C@]12C(=O)Nc1cc(Cl)c(F)cc12
InChIKey: OTLQVUTVHXHUHB-SDJDJFSXSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: Fluorescence-polarization Binding Assay: The binding affinity of the MDM2 inhibitors was determined using an optimized, sensitive and quantitative fluorescence polarization-based (FP-based) binding assay using a recombinant human His-tagged MDM2 protein (residues 1-118) and a fluorescently tagged p53-based peptide. The design of the fluorescence probe was based upon a previously reported high-affinity p53-based peptidomimetic compound (5-FAM-βAla-βAla-Phe-Met-Aib-pTyr-(6-Cl-LTrp)-Glu-Ac3c-Leu-Asn-NH2 (SEQ ID NO: 1)) (García-Echeverría et al., J. Med. Chem. 43: 3205-3208 (2000)). This tagged peptide is called PMDM6-F. MDM2 protein was serially double diluted in a Dynex 96-well, black, round-bottom plate, and the PMDM6-F peptide was added at 1 nM concentration. The assay was performed in the buffer: 100 mM potassium phosphate, pH 7.5; 100 μg/mL bovine gamma globulin; 0.02% sodium azide, 0.01% Triton X-100) and the polarization values were measured after 3 h of incubation using an ULTRA READER (Tecan U.S. Inc).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 566.48, ALogP 5.05, HBA 4, HBD 4, PSA 90.46, QED 0.42
Compound (SMILES): CC(C)(C)C[C@@H]1N[C@@H](C(=O)N[C@H]2C[C@@](C)(O)C2)[C@H](c2cccc(Cl)c2)[C@]12C(=O)Nc1cc(Cl)ccc12
InChIKey: DFNKYRCFAIHHQB-KCEIGVIJSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: Fluorescence-polarization Binding Assay: The binding affinity of the MDM2 inhibitors was determined using an optimized, sensitive and quantitative fluorescence polarization-based (FP-based) binding assay using a recombinant human His-tagged MDM2 protein (residues 1-118) and a fluorescently tagged p53-based peptide. The design of the fluorescence probe was based upon a previously reported high-affinity p53-based peptidomimetic compound (5-FAM-βAla-βAla-Phe-Met-Aib-pTyr-(6-Cl-LTrp)-Glu-Ac3c-Leu-Asn-NH2 (SEQ ID NO: 1)) (García-Echeverría et al., J. Med. Chem. 43: 3205-3208 (2000)). This tagged peptide is called PMDM6-F. MDM2 protein was serially double diluted in a Dynex 96-well, black, round-bottom plate, and the PMDM6-F peptide was added at 1 nM concentration. The assay was performed in the buffer: 100 mM potassium phosphate, pH 7.5; 100 μg/mL bovine gamma globulin; 0.02% sodium azide, 0.01% Triton X-100) and the polarization values were measured after 3 h of incubation using an ULTRA READER (Tecan U.S. Inc).
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 530.5, ALogP 4.77, HBA 4, HBD 4, PSA 90.46, QED 0.46
Compound (SMILES): CC(C)(C)C[C@@H]1N[C@@H](C(=O)N[C@H]2C[C@@](C)(O)C2)[C@H](c2cccc(Cl)c2)[C@]12C(=O)Nc1cc(Cl)c(F)cc12
InChIKey: GRCKTMFGZSJBOA-ZYCFHTJLSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: Fluorescence-polarization Binding Assay: The binding affinity of the MDM2 inhibitors was determined using an optimized, sensitive and quantitative fluorescence polarization-based (FP-based) binding assay using a recombinant human His-tagged MDM2 protein (residues 1-118) and a fluorescently tagged p53-based peptide. The design of the fluorescence probe was based upon a previously reported high-affinity p53-based peptidomimetic compound (5-FAM-βAla-βAla-Phe-Met-Aib-pTyr-(6-Cl-LTrp)-Glu-Ac3c-Leu-Asn-NH2 (SEQ ID NO: 1)) (García-Echeverría et al., J. Med. Chem. 43: 3205-3208 (2000)). This tagged peptide is called PMDM6-F. MDM2 protein was serially double diluted in a Dynex 96-well, black, round-bottom plate, and the PMDM6-F peptide was added at 1 nM concentration. The assay was performed in the buffer: 100 mM potassium phosphate, pH 7.5; 100 μg/mL bovine gamma globulin; 0.02% sodium azide, 0.01% Triton X-100) and the polarization values were measured after 3 h of incubation using an ULTRA READER (Tecan U.S. Inc).
Measurement: IC50 = 61 nM (pChEMBL 7.210000038146973)
Descriptors: MW 548.49, ALogP 4.91, HBA 4, HBD 4, PSA 90.46, QED 0.44
Compound (SMILES): O=C(c1ccccc1-c1ccccc1)N1CCC2CN(c3cnc4ccccc4n3)C2C1
InChIKey: HWBHNCKNXGKGOR-UHFFFAOYSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Radioligand Binding: HEK293 stably expressing human orexin-2 receptor (Genebank accession number NM 001526) were grown to confluency in DMEM/F12 (Gibco, Cat #11039), in DMEM, 10% FBS, 1× Pen/Strep, 1× NaPyruvate, 1×HEPES, 600 ug/ml G418 media on 150 cm2 tissue culture plates, washed with 5 mM EDTA in PBS (HyClone Dulbecco's Phosphate Buffered Saline 1× with Calcium and Magnesium, Cat #SH30264.01, hereafter referred to simply as PBS) and scraped into 50 ml tubes. After centrifugation (2K xG, 10 min at 4° C.), the supernatant was aspirated and the pellets frozen and stored at −80° C. Cells were resuspended in PBS in the presence of 1 tablet of protease inhibitor cocktail (Roche, Cat. #11836145001) per 50 mL.
Measurement: Ki = 542 nM (pChEMBL 6.269999980926514)
Descriptors: MW 420.52, ALogP 4.65, HBA 4, HBD 0, PSA 49.33, QED 0.48
Compound (SMILES): Cc1ccc([C@H](C)NC(=O)COc2cc(C)c3c(-c4ncccc4F)nn(C)c3n2)cc1
InChIKey: VHPHJZXOLJJSPJ-INIZCTEOSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Radioligand Binding Assay II : For crude cell membrane preparations, cells (CHO, Chinese hamster ovary or HEK, human embryonic kidney) expressing human orexin 1 or human orexin 2 receptors, were washed with HEPES (10 mM, pH 7.5), scraped off the culture plates with the same buffer, and centrifuged at 4 C for 5 min at 2500 x g. The cell pellet was either stored at -80 C or used directly. Before the experiments, cell membranes were re-suspended in binding assay buffer (10 mM HEPES, 0.5% (w/v) bovine serum albumin, pH 7.5) by homogenisation with a Polytron homogeniser at 50 Hz for 20 s. In competition experiments, cell homogenates (150μΙ) were incubated in assay buffer (10 mM HEPES, pH 7.5, 0.5 % (w/v) bovine serum albumin, 5 mM MgCI2, 1 mMCaCI2, and tween 0.05%) for 1 h at room temperature with about 1 nM of the radioligand [3H]-SB649868, 66 Ci/mmole, 50 μΙ), and with various concentrations of compounds of the invention (50 μΙ) in triplicates.
Measurement: Kd = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 433.49, ALogP 4.04, HBA 6, HBD 1, PSA 81.93, QED 0.5
Compound (SMILES): Cc1ccc2c(n1)CC[C@@H]2NC(=O)COc1cc(C(F)F)c2c(C3CC3)nn(C)c2n1
InChIKey: BEZZNQFBPGIIIH-INIZCTEOSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Radioligand Binding Assay II : For crude cell membrane preparations, cells (CHO, Chinese hamster ovary or HEK, human embryonic kidney) expressing human orexin 1 or human orexin 2 receptors, were washed with HEPES (10 mM, pH 7.5), scraped off the culture plates with the same buffer, and centrifuged at 4 C for 5 min at 2500 x g. The cell pellet was either stored at -80 C or used directly. Before the experiments, cell membranes were re-suspended in binding assay buffer (10 mM HEPES, 0.5% (w/v) bovine serum albumin, pH 7.5) by homogenisation with a Polytron homogeniser at 50 Hz for 20 s. In competition experiments, cell homogenates (150μΙ) were incubated in assay buffer (10 mM HEPES, pH 7.5, 0.5 % (w/v) bovine serum albumin, 5 mM MgCI2, 1 mMCaCI2, and tween 0.05%) for 1 h at room temperature with about 1 nM of the radioligand [3H]-SB649868, 66 Ci/mmole, 50 μΙ), and with various concentrations of compounds of the invention (50 μΙ) in triplicates.
Measurement: Kd = 75 nM (pChEMBL 7.119999885559082)
Descriptors: MW 427.46, ALogP 3.67, HBA 6, HBD 1, PSA 81.93, QED 0.65
Compound (SMILES): COc1ccc2c(c1)CCC2NC(=O)COc1cc(C)c2c(C3CC3)nn(C)c2n1
InChIKey: NHKDZRLVFDFWKF-UHFFFAOYSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Radioligand Binding Assay II : For crude cell membrane preparations, cells (CHO, Chinese hamster ovary or HEK, human embryonic kidney) expressing human orexin 1 or human orexin 2 receptors, were washed with HEPES (10 mM, pH 7.5), scraped off the culture plates with the same buffer, and centrifuged at 4 C for 5 min at 2500 x g. The cell pellet was either stored at -80 C or used directly. Before the experiments, cell membranes were re-suspended in binding assay buffer (10 mM HEPES, 0.5% (w/v) bovine serum albumin, pH 7.5) by homogenisation with a Polytron homogeniser at 50 Hz for 20 s. In competition experiments, cell homogenates (150μΙ) were incubated in assay buffer (10 mM HEPES, pH 7.5, 0.5 % (w/v) bovine serum albumin, 5 mM MgCI2, 1 mMCaCI2, and tween 0.05%) for 1 h at room temperature with about 1 nM of the radioligand [3H]-SB649868, 66 Ci/mmole, 50 μΙ), and with various concentrations of compounds of the invention (50 μΙ) in triplicates.
Measurement: Kd = 39 nM (pChEMBL 7.409999847412109)
Descriptors: MW 406.49, ALogP 3.35, HBA 6, HBD 1, PSA 78.27, QED 0.68
Compound (SMILES): Cc1ccc([C@H](C)NC(=O)COc2cc(C(F)F)c3c(C4CC4)nn(C)c3n2)cc1
InChIKey: MJVATLQDOLXSMC-ZDUSSCGKSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Radioligand Binding Assay II : For crude cell membrane preparations, cells (CHO, Chinese hamster ovary or HEK, human embryonic kidney) expressing human orexin 1 or human orexin 2 receptors, were washed with HEPES (10 mM, pH 7.5), scraped off the culture plates with the same buffer, and centrifuged at 4 C for 5 min at 2500 x g. The cell pellet was either stored at -80 C or used directly. Before the experiments, cell membranes were re-suspended in binding assay buffer (10 mM HEPES, 0.5% (w/v) bovine serum albumin, pH 7.5) by homogenisation with a Polytron homogeniser at 50 Hz for 20 s. In competition experiments, cell homogenates (150μΙ) were incubated in assay buffer (10 mM HEPES, pH 7.5, 0.5 % (w/v) bovine serum albumin, 5 mM MgCI2, 1 mMCaCI2, and tween 0.05%) for 1 h at room temperature with about 1 nM of the radioligand [3H]-SB649868, 66 Ci/mmole, 50 μΙ), and with various concentrations of compounds of the invention (50 μΙ) in triplicates.
Measurement: Kd = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 414.46, ALogP 4.35, HBA 5, HBD 1, PSA 69.04, QED 0.62
Compound (SMILES): CCOc1cc(CN2CCC3(CC2)CN(c2ccc(C(=O)O)cc2)C(=O)O3)cc(OCC)c1-c1ccc(F)cc1
InChIKey: KKHVNUWBIYHFEO-UHFFFAOYSA-N
Target: Somatostatin receptor type 5 (SINGLE PROTEIN), Mus musculus
UniProt: O08858
Assay: Antagonist activity at mouse SSR5 expressed in CHOK1 cells assessed as inhibition of forskolin-induced cAMP accumulation preincubated for 15 mins followed by forskolin addition measured after 1 hr by LANCE assay
Measurement: IC50 = 0.3 nM (pChEMBL 9.520000457763672)
Descriptors: MW 548.61, ALogP 5.98, HBA 6, HBD 1, PSA 88.54, QED 0.35
Compound (SMILES): COc1cc(-c2ccc3ncnc(Nc4cc(O)c(C)cc4F)c3c2)ccc1O
InChIKey: MZDUBFXCVNFNTD-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Kinase Assay: Inhibition of kinase activity by test compound disclosed herein was estimated by quantifying the amount of [33P] incorporation of substrate in the presence of test compound. Standard assay conditions were 2 ng of recombinant C-Raf or 5 ng of recombinant B-Raf or 5 ng of recombinant B-Raf (V600E) kinase (Upstate Biotechnology) with 500 ng MEK1(K97R) in assay buffer {8 μM ATP, 0.5 μCi [33P]ATP (specific activity 3000 Ci/mmol, PerkinElmer), 50 mM Tris/HCl (pH7.5), and 1 mM EGTA, 1 mM Na3VO4, 1% 2-mercaptoethanol, 0.1% Brij 35, and 0.2 mg/ml BSA} at a final volume of 25 μL. Reactions were incubated at 30° C. for 30 min and stopped by adding 3% phosphoric acid, harvested onto a 96-well GF/B UniFilter (PerkinElmer) using a unifilter harvester (PerkinElmer), and counted with a TopCount microplate scintillation counter (PerkinElmer). The IC50 values of inhibitors were determined after carrying out assays at 3-fold serially diluted concentrations of each compound in duplication.
Measurement: IC50 = 81.7 nM (pChEMBL 7.090000152587891)
Descriptors: MW 391.4, ALogP 4.91, HBA 6, HBD 3, PSA 87.5, QED 0.46
Compound (SMILES): COc1cc(-c2ccc3ncnc(Nc4ccc(Cl)c(O)c4)c3c2)ccc1O
InChIKey: ACVWWDRVNBIHJC-UHFFFAOYSA-N
Target: RAF proto-oncogene serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P04049
Assay: Kinase Assay: Inhibition of kinase activity by test compound disclosed herein was estimated by quantifying the amount of [33P] incorporation of substrate in the presence of test compound. Standard assay conditions were 2 ng of recombinant C-Raf or 5 ng of recombinant B-Raf or 5 ng of recombinant B-Raf (V600E) kinase (Upstate Biotechnology) with 500 ng MEK1(K97R) in assay buffer {8 μM ATP, 0.5 μCi [33P]ATP (specific activity 3000 Ci/mmol, PerkinElmer), 50 mM Tris/HCl (pH7.5), and 1 mM EGTA, 1 mM Na3VO4, 1% 2-mercaptoethanol, 0.1% Brij 35, and 0.2 mg/ml BSA} at a final volume of 25 μL. Reactions were incubated at 30° C. for 30 min and stopped by adding 3% phosphoric acid, harvested onto a 96-well GF/B UniFilter (PerkinElmer) using a unifilter harvester (PerkinElmer), and counted with a TopCount microplate scintillation counter (PerkinElmer). The IC50 values of inhibitors were determined after carrying out assays at 3-fold serially diluted concentrations of each compound in duplication.
Measurement: IC50 = 160.6 nM (pChEMBL 6.789999961853027)
Descriptors: MW 393.83, ALogP 5.11, HBA 6, HBD 3, PSA 87.5, QED 0.45
Compound (SMILES): COc1cc(-c2ccc3ncnc(Nc4cc(O)c(F)cc4F)c3c2)ccc1O
InChIKey: UQWLFAYGQCXZLD-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Kinase Assay: Inhibition of kinase activity by test compound disclosed herein was estimated by quantifying the amount of [33P] incorporation of substrate in the presence of test compound. Standard assay conditions were 2 ng of recombinant C-Raf or 5 ng of recombinant B-Raf or 5 ng of recombinant B-Raf (V600E) kinase (Upstate Biotechnology) with 500 ng MEK1(K97R) in assay buffer {8 μM ATP, 0.5 μCi [33P]ATP (specific activity 3000 Ci/mmol, PerkinElmer), 50 mM Tris/HCl (pH7.5), and 1 mM EGTA, 1 mM Na3VO4, 1% 2-mercaptoethanol, 0.1% Brij 35, and 0.2 mg/ml BSA} at a final volume of 25 μL. Reactions were incubated at 30° C. for 30 min and stopped by adding 3% phosphoric acid, harvested onto a 96-well GF/B UniFilter (PerkinElmer) using a unifilter harvester (PerkinElmer), and counted with a TopCount microplate scintillation counter (PerkinElmer). The IC50 values of inhibitors were determined after carrying out assays at 3-fold serially diluted concentrations of each compound in duplication.
Measurement: IC50 = 7.1 nM (pChEMBL 8.149999618530273)
Descriptors: MW 395.37, ALogP 4.74, HBA 6, HBD 3, PSA 87.5, QED 0.46
Compound (SMILES): COc1cc(-c2ccc3ncnc(Nc4cc(O)c(Cl)cc4F)c3c2)ccc1O
InChIKey: DYRMWMUNPOELJX-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Kinase Assay: Inhibition of kinase activity by test compound disclosed herein was estimated by quantifying the amount of [33P] incorporation of substrate in the presence of test compound. Standard assay conditions were 2 ng of recombinant C-Raf or 5 ng of recombinant B-Raf or 5 ng of recombinant B-Raf (V600E) kinase (Upstate Biotechnology) with 500 ng MEK1(K97R) in assay buffer {8 μM ATP, 0.5 μCi [33P]ATP (specific activity 3000 Ci/mmol, PerkinElmer), 50 mM Tris/HCl (pH7.5), and 1 mM EGTA, 1 mM Na3VO4, 1% 2-mercaptoethanol, 0.1% Brij 35, and 0.2 mg/ml BSA} at a final volume of 25 μL. Reactions were incubated at 30° C. for 30 min and stopped by adding 3% phosphoric acid, harvested onto a 96-well GF/B UniFilter (PerkinElmer) using a unifilter harvester (PerkinElmer), and counted with a TopCount microplate scintillation counter (PerkinElmer). The IC50 values of inhibitors were determined after carrying out assays at 3-fold serially diluted concentrations of each compound in duplication.
Measurement: IC50 = 19.7 nM (pChEMBL 7.710000038146973)
Descriptors: MW 411.82, ALogP 5.25, HBA 6, HBD 3, PSA 87.5, QED 0.42
Compound (SMILES): Oc1cc(Nc2ncnc3ccc(-c4ccc(Cl)cc4)cc23)c(F)cc1F
InChIKey: LSFNHAFZZXYIDB-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Kinase Assay: Inhibition of kinase activity by test compound disclosed herein was estimated by quantifying the amount of [33P] incorporation of substrate in the presence of test compound. Standard assay conditions were 2 ng of recombinant C-Raf or 5 ng of recombinant B-Raf or 5 ng of recombinant B-Raf (V600E) kinase (Upstate Biotechnology) with 500 ng MEK1(K97R) in assay buffer {8 μM ATP, 0.5 μCi [33P]ATP (specific activity 3000 Ci/mmol, PerkinElmer), 50 mM Tris/HCl (pH7.5), and 1 mM EGTA, 1 mM Na3VO4, 1% 2-mercaptoethanol, 0.1% Brij 35, and 0.2 mg/ml BSA} at a final volume of 25 μL. Reactions were incubated at 30° C. for 30 min and stopped by adding 3% phosphoric acid, harvested onto a 96-well GF/B UniFilter (PerkinElmer) using a unifilter harvester (PerkinElmer), and counted with a TopCount microplate scintillation counter (PerkinElmer). The IC50 values of inhibitors were determined after carrying out assays at 3-fold serially diluted concentrations of each compound in duplication.
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 383.79, ALogP 5.68, HBA 4, HBD 2, PSA 58.04, QED 0.48
Compound (SMILES): COc1cc(-c2ccc3ncnc(Nc4ccc(F)c(O)c4)c3c2)ccc1O
InChIKey: WNVLKTDQXHZUGV-UHFFFAOYSA-N
Target: RAF proto-oncogene serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P04049
Assay: Kinase Assay: Inhibition of kinase activity by test compound disclosed herein was estimated by quantifying the amount of [33P] incorporation of substrate in the presence of test compound. Standard assay conditions were 2 ng of recombinant C-Raf or 5 ng of recombinant B-Raf or 5 ng of recombinant B-Raf (V600E) kinase (Upstate Biotechnology) with 500 ng MEK1(K97R) in assay buffer {8 μM ATP, 0.5 μCi [33P]ATP (specific activity 3000 Ci/mmol, PerkinElmer), 50 mM Tris/HCl (pH7.5), and 1 mM EGTA, 1 mM Na3VO4, 1% 2-mercaptoethanol, 0.1% Brij 35, and 0.2 mg/ml BSA} at a final volume of 25 μL. Reactions were incubated at 30° C. for 30 min and stopped by adding 3% phosphoric acid, harvested onto a 96-well GF/B UniFilter (PerkinElmer) using a unifilter harvester (PerkinElmer), and counted with a TopCount microplate scintillation counter (PerkinElmer). The IC50 values of inhibitors were determined after carrying out assays at 3-fold serially diluted concentrations of each compound in duplication.
Measurement: IC50 = 132.8 nM (pChEMBL 6.880000114440918)
Descriptors: MW 377.38, ALogP 4.6, HBA 6, HBD 3, PSA 87.5, QED 0.48