lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1cc(O)cc(C)c1C[C@H](N)C(=O)N[C@@H]1CCCCNC(=O)C[C@@H](C(N)=O)NC(=O)[C@@H](Cc2cccc3ccccc23)NC(=O)[C@H](Cc2ccccc2)NC1=O
InChIKey: KZPMZJUWJIEYBH-DUQWPARQSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at human recombinant DOR expressed in CHO cells assessed as calcium mobilization by Fluo-4 AM based fluorescence analysis
Measurement: EC50 = 64.57 nM (pChEMBL 7.190000057220459)
Descriptors: MW 777.92, ALogP 1.63, HBA 8, HBD 8, PSA 234.84, QED 0.12
Compound (SMILES): Cn1ncnc1[C@@H]1c2n[nH]c(=O)c3cc(F)cc(c23)N[C@H]1c1ccc(F)cc1
InChIKey: HWGQMRYQVZSGDQ-HOTGVXAUSA-N
Target: Poly [ADP-ribose] polymerase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGN5
Assay: Inhibition of full length recombinant human His6-tagged PARP2 expressed in Escherichia coli BL21(DE3) preincubated for 15 mins followed by biotinylated NAD+ addition by chemiluminescence assay
Measurement: IC50 = 4.169 nM (pChEMBL 8.380000114440918)
Descriptors: MW 380.36, ALogP 2.63, HBA 6, HBD 2, PSA 88.49, QED 0.56
Compound (SMILES): Nc1nc2cc(-c3ccccc3)ccc2c(=O)n1C[C@@H]1CC[C@H](c2ccccc2)O1
InChIKey: ZFQQCJCOZGMLDR-NZQKXSOJSA-N
Target: Cathepsin D (SINGLE PROTEIN), Homo sapiens
UniProt: P07339
Assay: Inhibition of CatD (unknown origin) preincubated for 30 mins followed by DABCYL-Glu-Arg-Nle-Phe-Leu-Ser-Phe-Pro-EDANS substrate addition by FRET assay
Measurement: IC50 = 22000 nM (pChEMBL 4.659999847412109)
Descriptors: MW 397.48, ALogP 4.57, HBA 5, HBD 1, PSA 70.14, QED 0.55
Compound (SMILES): Cc1ccc(C(C)(C)O)cc1-c1ccc2c(n1)n(C)c(=O)n2CC(C)(C)C
InChIKey: QLTCKDVHRJIRHT-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P31421
Assay: Positive allosteric modulation of recombinant rat mGluR2 preincubated for 5 mins followed by stimulation with EC20 concentration of glutamate for 3 mins by FLIPR assay
Measurement: EC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 367.49, ALogP 3.98, HBA 5, HBD 1, PSA 60.05, QED 0.76
Compound (SMILES): NS(=O)(=O)c1ccc(/N=C2\C(=O)Nc3ccc([N+](=O)[O-])cc32)cc1
InChIKey: MFEYEMJHPUUNEY-UHFFFAOYSA-N
Target: Carbonic anhydrase (SINGLE PROTEIN), Candida albicans (strain SC5314 / ATCC MYA-2876) (Yeast)
UniProt: Q5AJ71
Assay: Inhibition of recombinant Candida albicans beta carbonic anhydrase NCE103 expressed in Escherichia coli preincubated for 15 mins by stopped-flow CO2 hydration assay
Measurement: Ki = 34.1 nM (pChEMBL 7.46999979019165)
Descriptors: MW 346.32, ALogP 1.32, HBA 6, HBD 2, PSA 144.76, QED 0.64
Compound (SMILES): COc1ccccc1N1CCN(CCCCC(=O)n2c3ccccc3c3ccccc32)CC1.Cl
InChIKey: XKAQRWFXAWNZKI-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Binding affinity to recombinant 5-HT1A receptor (unknown origin) after 1.5 hrs by radioligand displacement assay
Measurement: Ki = 122 nM (pChEMBL 6.909999847412109)
Descriptors: MW 441.58, ALogP 5.44, HBA 5, HBD 0, PSA 37.71, QED 0.36
Compound (SMILES): COc1ccccc1N1CCN(CCCCCC(=O)n2c3ccccc3c3ccccc32)CC1.Cl
InChIKey: WMPOYDYTKCFORM-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Binding affinity to recombinant 5-HT1A receptor (unknown origin) after 1.5 hrs by radioligand displacement assay
Measurement: Ki = 549 nM (pChEMBL 6.260000228881836)
Descriptors: MW 455.6, ALogP 5.83, HBA 5, HBD 0, PSA 37.71, QED 0.31
Compound (SMILES): Cl.O=C(CCCCN1CCN(c2ccccc2O)CC1)n1c2ccccc2c2ccccc21
InChIKey: HOTMQGRIKYVWCR-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Binding affinity to recombinant 5-HT2A receptor (unknown origin) after 1.5 hrs by radioligand displacement assay
Measurement: Ki = 257 nM (pChEMBL 6.590000152587891)
Descriptors: MW 427.55, ALogP 5.13, HBA 5, HBD 1, PSA 48.71, QED 0.43
Compound (SMILES): Cl.O=C(CCCCCN1CCN(c2ccccc2O)CC1)n1c2ccccc2c2ccccc21
InChIKey: OGPCEZKIXQTBRH-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1D (SINGLE PROTEIN), Homo sapiens
UniProt: P28221
Assay: Binding affinity to recombinant 5-HT1D receptor (unknown origin) after 1.5 hrs by radioligand displacement assay
Measurement: Ki = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 441.58, ALogP 5.52, HBA 5, HBD 1, PSA 48.71, QED 0.38
Compound (SMILES): CN1CCCN(Cc2ccc(CN)cc2)CC1
InChIKey: AQLZGQUKWNQYPH-UHFFFAOYSA-N
Target: Neutrophil cytosol factor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14598
Assay: Binding affinity to immobilized recombinant human His-tagged p47phox SH3A-B domain (151 to 285 residues) expressed in Escherichia coli BL21 (DE3) cells assessed as dissociation constant by SPR assay
Measurement: Kd = 418000 nM (pChEMBL 3.380000114440918)
Descriptors: MW 233.36, ALogP 1.28, HBA 3, HBD 1, PSA 32.5, QED 0.85
Compound (SMILES): COC(=O)N[C@H](C(=O)N1CCC[C@H]1c1ncc(-c2ccc(-c3cc4cc(-c5cnc([C@@H]6CCCN6C(=O)[C@@H](NC(=O)OC)C(C)C)[nH]5)ccc4o3)cc2)[nH]1)C(C)C
InChIKey: QKFUCROVTLGTAV-VOIOCNMVSA-N
Target: Nonstructural protein 5A (SINGLE PROTEIN), Hepatitis C virus
UniProt: Q5L478
Assay: Inhibition of HCV NS5A in HCV genotype 3a assessed as reduction in viral replication by cell based replicon assay
Measurement: EC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 778.91, ALogP 6.97, HBA 9, HBD 4, PSA 187.78, QED 0.11
Compound (SMILES): CCOC(=O)N1CCN(CC#Cc2ccnc3ccc(-c4cnc(OC)c(NS(=O)(=O)c5ccc(F)cc5F)c4)cc23)CC1
InChIKey: YLOHWEBOWAAUCC-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3K-gamma (unknown origin) after 40 mins by ADP-Glo luminescent kinase assay
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 621.67, ALogP 4.51, HBA 8, HBD 1, PSA 113.96, QED 0.3
Compound (SMILES): COc1ncc(-c2ccc3nccc(C#CCN4CCN(S(C)(=O)=O)CC4)c3c2)cc1NS(=O)(=O)c1ccc(F)cc1F
InChIKey: BBRINJUWZRLWKK-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3K-gamma (unknown origin) after 40 mins by ADP-Glo luminescent kinase assay
Measurement: IC50 = 2.7 nM (pChEMBL 8.569999694824219)
Descriptors: MW 627.69, ALogP 3.31, HBA 8, HBD 1, PSA 121.8, QED 0.31
Compound (SMILES): COc1cccc2c(=O)[nH]c(-c3ccc(C)cc3)cc12
InChIKey: RJVXWJADDFXFIL-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Inhibition of human recombinant PARP1 incubated for 30 mins in the presence of NAD
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 265.31, ALogP 3.51, HBA 2, HBD 1, PSA 42.09, QED 0.77
Compound (SMILES): N=C(N)NC(=N)N/C(=N/O)c1nonc1N
InChIKey: QDFLGWBZRQJVTM-UHFFFAOYSA-N
Target: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P10688
Assay: Antagonist activity at rat PLCdelta1-PH domain assessed as reduction in PI(3,4)P2/PLCdelta1-PH interaction after 30 mins by competitive SPR analysis
Measurement: IC50 = 54000 nM (pChEMBL 4.269999980926514)
Descriptors: MW 227.19, ALogP -2.2, HBA 8, HBD 7, PSA 195.31, QED 0.12
Compound (SMILES): N=C(N/C(=N/O)c1nonc1N)N1CCCN=C1N
InChIKey: XZALCVQZUCMEJE-UHFFFAOYSA-N
Target: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P10688
Assay: Antagonist activity at rat PLCdelta1-PH domain assessed as reduction in PI(3,4)P2/PLCdelta1-PH interaction after 30 mins by competitive SPR analysis
Measurement: IC50 = 28000 nM (pChEMBL 4.550000190734863)
Descriptors: MW 267.25, ALogP -1.67, HBA 9, HBD 5, PSA 175.03, QED 0.17
Compound (SMILES): NC(=O)[C@H]1CC(F)(F)CN1C(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H]1CC(F)(F)CN1C(=O)[C@@H](N)Cc1ccc(O)cc1
InChIKey: OXGIXGFYQQZLSO-KJJMTIBFSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Agonist activity at human recombinant KOR expressed in CHO cells by calcium mobilization assay
Measurement: EC50 = 812.83 nM (pChEMBL 6.090000152587891)
Descriptors: MW 593.58, ALogP 0.95, HBA 6, HBD 4, PSA 159.06, QED 0.32
Compound (SMILES): Nc1nc(C(=O)NCc2cccc3cccnc23)c2ccccc2n1
InChIKey: NAJMQZHVNVHXHN-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Binding affinity to human adenosine A3 receptor
Measurement: Ki = 985 nM (pChEMBL 6.010000228881836)
Descriptors: MW 329.36, ALogP 2.69, HBA 5, HBD 2, PSA 93.79, QED 0.6
Compound (SMILES): CC(C)C(C)n1cc(-c2ccn(C)n2)c2[nH]nc(N)c2c1=O
InChIKey: NIBPOBGOGLVDMA-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of TYK2 in human Jurkat cells assessed as reduction in IL-23-induced luciferase gene expression after 24 hrs
Measurement: IC50 = 310 nM (pChEMBL 6.510000228881836)
Descriptors: MW 300.37, ALogP 1.92, HBA 6, HBD 2, PSA 94.52, QED 0.77
Compound (SMILES): CCC(C)n1cc(-c2ccn(C)n2)c2[nH]nc(N)c2c1=O
InChIKey: QBJJOQKBNNXVHH-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of TYK2 in human Jurkat cells assessed as reduction in IL-23-induced luciferase gene expression after 24 hrs
Measurement: IC50 = 650 nM (pChEMBL 6.190000057220459)
Descriptors: MW 286.34, ALogP 1.68, HBA 6, HBD 2, PSA 94.52, QED 0.77
Compound (SMILES): CC(C)Cn1cc(-c2ccn(C)n2)c2[nH]nc(N)c2c1=O
InChIKey: YODALXHGNBZTIN-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of TYK2 in human Jurkat cells assessed as reduction in IL-23-induced luciferase gene expression after 24 hrs
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 286.34, ALogP 1.36, HBA 6, HBD 2, PSA 94.52, QED 0.76
Compound (SMILES): CCC(C(C)C)n1cc(-c2ccn(C)n2)c2[nH]nc(N)c2c1=O
InChIKey: KJKQUZPNTWUXMZ-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of TYK2 in human Jurkat cells assessed as reduction in IL-23-induced luciferase gene expression after 24 hrs
Measurement: IC50 = 6900 nM (pChEMBL 5.159999847412109)
Descriptors: MW 314.39, ALogP 2.31, HBA 6, HBD 2, PSA 94.52, QED 0.77
Compound (SMILES): CC(C)C(C)n1cc(-c2ccc(N3CCOCC3)cn2)c2[nH]nc(N)c2c1=O
InChIKey: NAGJVNORNVHZDU-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of JAK3 (unknown origin) using Ulight-JAK1 substrate peptide assessed as reduction in ATP-dependent substrate phosphorylation after 45 mins by TR-FRET assay
Measurement: IC50 = 5.3 nM (pChEMBL 8.279999732971191)
Descriptors: MW 382.47, ALogP 2.42, HBA 7, HBD 2, PSA 102.06, QED 0.72
Compound (SMILES): CC(C)[C@H](C)n1cc(-c2ccc(N3CCOCC3)cn2)c2[nH]nc(N)c2c1=O
InChIKey: NAGJVNORNVHZDU-ZDUSSCGKSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of JAK3 (unknown origin) using Ulight-JAK1 substrate peptide assessed as reduction in ATP-dependent substrate phosphorylation after 45 mins by TR-FRET assay
Measurement: IC50 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 382.47, ALogP 2.42, HBA 7, HBD 2, PSA 102.06, QED 0.72
Compound (SMILES): CC(C)[C@@H](C)n1cc(-c2ccc(N3CCOCC3)cn2)c2[nH]nc(N)c2c1=O
InChIKey: NAGJVNORNVHZDU-CYBMUJFWSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of JAK3 (unknown origin) using Ulight-JAK1 substrate peptide assessed as reduction in ATP-dependent substrate phosphorylation after 45 mins by TR-FRET assay
Measurement: IC50 = 85 nM (pChEMBL 7.070000171661377)
Descriptors: MW 382.47, ALogP 2.42, HBA 7, HBD 2, PSA 102.06, QED 0.72
Compound (SMILES): CC(C)[C@H](C)n1cc(-c2ccn(C)n2)c2[nH]nc(N)c2c1=O
InChIKey: NIBPOBGOGLVDMA-VIFPVBQESA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of JAK3 (unknown origin) using Ulight-JAK1 substrate peptide assessed as reduction in ATP-dependent substrate phosphorylation after 45 mins by TR-FRET assay
Measurement: IC50 = 6.4 nM (pChEMBL 8.1899995803833)
Descriptors: MW 300.37, ALogP 1.92, HBA 6, HBD 2, PSA 94.52, QED 0.77
Compound (SMILES): CC(C)[C@H](C)n1cc(-c2cc(N3CCOCC3)n(C)n2)c2[nH]nc(N)c2c1=O
InChIKey: QUFKDMKRCKTXPY-LBPRGKRZSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of JAK3 (unknown origin) using Ulight-JAK1 substrate peptide assessed as reduction in ATP-dependent substrate phosphorylation after 45 mins by TR-FRET assay
Measurement: IC50 = 2.8 nM (pChEMBL 8.550000190734863)
Descriptors: MW 385.47, ALogP 1.76, HBA 8, HBD 2, PSA 106.99, QED 0.71
Compound (SMILES): CC(C)[C@H](C)n1cc(-c2cc(C3CCOCC3)n(C)n2)c2[nH]nc(N)c2c1=O
InChIKey: FIEMEGHBBJADPG-LBPRGKRZSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of JAK3 (unknown origin) using Ulight-JAK1 substrate peptide assessed as reduction in ATP-dependent substrate phosphorylation after 45 mins by TR-FRET assay
Measurement: IC50 = 4.6 nM (pChEMBL 8.34000015258789)
Descriptors: MW 384.48, ALogP 2.82, HBA 7, HBD 2, PSA 103.75, QED 0.72
Compound (SMILES): CC(C)[C@H](C)n1cc(-c2cc(N3CCS(=O)(=O)CC3)n(C)n2)c2[nH]nc(N)c2c1=O
InChIKey: YUYFNYPOTZWGKF-LBPRGKRZSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of JAK3 (unknown origin) using Ulight-JAK1 substrate peptide assessed as reduction in ATP-dependent substrate phosphorylation after 45 mins by TR-FRET assay
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 433.54, ALogP 1.16, HBA 9, HBD 2, PSA 131.9, QED 0.63
Compound (SMILES): CC(C)[C@@H](C)n1cc(-c2cc(C(C)(C)O)n(C)n2)c2[nH]nc(N)c2c1=O
InChIKey: MUDVASGRHKWSTJ-SNVBAGLBSA-N
Target: JAK3/JAK1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P52333
Assay: Inhibition of JAK1/JAK3 in human PBMC assessed as reduction in IL-21-induced STAT3 phosphorylation preincubated for 5 mins followed by IL-21 stimulation for 15 to 60 mins by flow cytometry analysis
Measurement: IC50 = 280 nM (pChEMBL 6.550000190734863)
Descriptors: MW 358.45, ALogP 2.15, HBA 7, HBD 3, PSA 114.75, QED 0.66
Compound (SMILES): O=C(Cn1cnc2ccccc2c1=O)Nc1ccc(C[C@@H]2CC[C@H]([C@H](O)c3ccccc3)N2)cc1
InChIKey: RJTCPQUWULEEAK-GEWUYGHSSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes assessed as dextraomethorphan O-demethylation
Measurement: IC50 = 31000 nM (pChEMBL 4.510000228881836)
Descriptors: MW 468.56, ALogP 3.43, HBA 6, HBD 3, PSA 96.25, QED 0.39
Compound (SMILES): O=C(Cn1ncccc1=O)Nc1ccc(C[C@@H]2CC[C@H]([C@H](O)c3ccccc3)N2)cc1
InChIKey: URLFNGRPGJRFPI-YZUZCNPQSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes assessed as dextraomethorphan O-demethylation
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 418.5, ALogP 2.28, HBA 6, HBD 3, PSA 96.25, QED 0.55
Compound (SMILES): O=C(Cn1cnccc1=O)Nc1ccc(C[C@@H]2CC[C@H]([C@H](O)c3ccccc3)N2)cc1
InChIKey: URTFFBLBZSMIET-YZUZCNPQSA-N
Target: Voltage-dependent L-type calcium channel subunit alpha-1C (SINGLE PROTEIN), Homo sapiens
UniProt: Q13936
Assay: Displacement of [3H]-diltiazem from human Cav1.2 channel
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 418.5, ALogP 2.28, HBA 6, HBD 3, PSA 96.25, QED 0.55
Compound (SMILES): O=C(Cn1cccnc1=O)Nc1ccc(C[C@@H]2CC[C@H]([C@H](O)c3ccccc3)N2)cc1
InChIKey: NLXXAPYWQLPUAG-QZNHQXDQSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes assessed as dextraomethorphan O-demethylation
Measurement: IC50 = 39000 nM (pChEMBL 4.409999847412109)
Descriptors: MW 418.5, ALogP 2.28, HBA 6, HBD 3, PSA 96.25, QED 0.55
Compound (SMILES): C=CCc1cccc(/C=N/NC(=O)Nc2ccc(Oc3ccnc4cc(OCCCN5CCCCC5)c(OC)cc34)c(F)c2)c1O
InChIKey: LJSAOZBYSGZILH-FNTLCPBMSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of Flt-3 (unknown origin) using poly(glu,Tyr)4:1 as substrate incubated for 30 mins by homogeneous time-resolved fluorescence assay
Measurement: IC50 = 366.7 nM (pChEMBL 6.440000057220459)
Descriptors: MW 627.72, ALogP 7.02, HBA 8, HBD 3, PSA 117.54, QED 0.06
Compound (SMILES): O=c1cc(Cl)c2ccc(OCCNC3CCN(Cc4ccccc4)CC3)cc2o1
InChIKey: XATVGNRTOUJFHU-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human recombinant MAO-B using p-tyramine substrate after 15 mins by fluorimetric analysis
Measurement: IC50 = 33900 nM (pChEMBL 4.46999979019165)
Descriptors: MW 412.92, ALogP 4.08, HBA 5, HBD 1, PSA 54.71, QED 0.47
Compound (SMILES): O=C(Cn1ccccc1=O)Nc1ccc(C[C@@H]2CC[C@H]([C@H](O)c3ccccc3)N2)cc1
InChIKey: HSUZTUCBYOJAHK-SGIRGMQISA-N
Target: Voltage-dependent L-type calcium channel subunit alpha-1C (SINGLE PROTEIN), Homo sapiens
UniProt: Q13936
Assay: Displacement of [3H]-diltiazem from human Cav1.2 channel
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 417.51, ALogP 2.88, HBA 5, HBD 3, PSA 83.36, QED 0.55
Compound (SMILES): C[C@@H](C(=O)Nc1ccc(C[C@@H]2CC[C@H]([C@H](O)c3ccccc3)N2)cc1)n1ncccc1=O
InChIKey: PBXGYXYBIGMVQD-KBABAZTHSA-N
Target: Voltage-dependent L-type calcium channel subunit alpha-1C (SINGLE PROTEIN), Homo sapiens
UniProt: Q13936
Assay: Displacement of [3H]-diltiazem from human Cav1.2 channel
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 432.52, ALogP 2.84, HBA 6, HBD 3, PSA 96.25, QED 0.53
Compound (SMILES): C[C@@H](C(=O)Nc1ccc(C[C@@H]2CC[C@H]([C@H](O)c3cccnc3)N2)cc1)n1ncccc1=O
InChIKey: KJQNVVRQSWUQHQ-WWTKIRLPSA-N
Target: Voltage-dependent L-type calcium channel subunit alpha-1C (SINGLE PROTEIN), Homo sapiens
UniProt: Q13936
Assay: Displacement of [3H]-diltiazem from human Cav1.2 channel
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 433.51, ALogP 2.23, HBA 7, HBD 3, PSA 109.14, QED 0.53
Compound (SMILES): O=C(Nc1ccc(C[C@@H]2CC[C@H]([C@H](O)c3ccccc3)N2)cc1)[C@@H]1CCc2cccc(=O)n21
InChIKey: OZXUSBILVIKYQB-GEMTWJNPSA-N
Target: Voltage-dependent L-type calcium channel subunit alpha-1C (SINGLE PROTEIN), Homo sapiens
UniProt: Q13936
Assay: Displacement of [3H]-diltiazem from human Cav1.2 channel
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 443.55, ALogP 3.37, HBA 5, HBD 3, PSA 83.36, QED 0.55
Compound (SMILES): CNC(=O)c1cc2c(Oc3ccc(NC(=S)NC(=O)Cc4ccccc4)cc3F)ccnc2cc1OC
InChIKey: ORRNXRYWGDUDOG-UHFFFAOYSA-N
Target: Tyrosine-protein kinase receptor UFO (SINGLE PROTEIN), Homo sapiens
UniProt: P30530
Assay: Inhibition of AXL (unknown origin) by FRET assay
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 518.57, ALogP 4.59, HBA 6, HBD 3, PSA 101.58, QED 0.31
Compound (SMILES): Cc1cc(C(=O)N2Cc3cnn(C)c3Nc3ccccc32)ccc1CNC(=O)N1CCN(Cc2cc(O)cc(O)c2)CC1
InChIKey: HWPGRFRXZNLZEX-UHFFFAOYSA-N
Target: Oxytocin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30559
Assay: Antagonist activity at human oxytocin receptor expressed in HEK293 cells assessed as inhibition of oxytocin induced IP1 accumulation pretreated for 30 mins measured 1 hr post Ab-Cryptate and IP1-d2 addition by HTRF assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 581.68, ALogP 4.07, HBA 8, HBD 4, PSA 126.2, QED 0.28
Compound (SMILES): COc1cc(CN2CCN(C(=O)NCc3ccc(C(=O)N4Cc5cnn(C)c5Nc5ccccc54)cc3C)CC2)cc(OC)c1
InChIKey: GKUYUWKWQGAJPA-UHFFFAOYSA-N
Target: Vasopressin V1a receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P37288
Assay: Agonist activity at human vasopressin 1a receptor expressed in HEK293 cells assessed as increase in IP1 accumulation preincubated for 1 hr followed by addition of Ab-Cryptate and IP1-d2 by HTRF assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 609.73, ALogP 4.68, HBA 8, HBD 2, PSA 104.2, QED 0.31
Compound (SMILES): Cn1ncc2c1Nc1ccccc1N(C(=O)CCCCN1CCN(Cc3cc(O)cc(O)c3)CC1)C2
InChIKey: XLKQPUKMAZZKTF-UHFFFAOYSA-N
Target: Vasopressin V1a receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P37288
Assay: Agonist activity at human vasopressin 1a receptor expressed in HEK293 cells assessed as increase in IP1 accumulation preincubated for 1 hr followed by addition of Ab-Cryptate and IP1-d2 by HTRF assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 490.61, ALogP 3.41, HBA 8, HBD 3, PSA 97.1, QED 0.44
Compound (SMILES): Cn1ncc2c1Nc1ccccc1N(C(=O)CCCCCN1CCN(Cc3cc(O)cc(O)c3)CC1)C2
InChIKey: HRENYLUIHAWKOD-UHFFFAOYSA-N
Target: Vasopressin V1a receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P37288
Assay: Agonist activity at human vasopressin 1a receptor expressed in HEK293 cells assessed as increase in IP1 accumulation preincubated for 1 hr followed by addition of Ab-Cryptate and IP1-d2 by HTRF assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 504.64, ALogP 3.8, HBA 8, HBD 3, PSA 97.1, QED 0.4
Compound (SMILES): Cn1ncc2c1Nc1ccccc1N(C(=O)CCCCCCN1CCN(Cc3cc(O)cc(O)c3)CC1)C2
InChIKey: UUHHPKDLEFNZAP-UHFFFAOYSA-N
Target: Vasopressin V1a receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P37288
Assay: Agonist activity at human vasopressin 1a receptor expressed in HEK293 cells assessed as increase in IP1 accumulation preincubated for 1 hr followed by addition of Ab-Cryptate and IP1-d2 by HTRF assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 518.66, ALogP 4.19, HBA 8, HBD 3, PSA 97.1, QED 0.37
Compound (SMILES): Cn1ncc2c1Nc1ccccc1N(C(=O)CCCCCCCN1CCN(Cc3cc(O)cc(O)c3)CC1)C2
InChIKey: PBYCSFCOYVZDBM-UHFFFAOYSA-N
Target: Vasopressin V1a receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P37288
Assay: Agonist activity at human vasopressin 1a receptor expressed in HEK293 cells assessed as increase in IP1 accumulation preincubated for 1 hr followed by addition of Ab-Cryptate and IP1-d2 by HTRF assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 532.69, ALogP 4.58, HBA 8, HBD 3, PSA 97.1, QED 0.33
Compound (SMILES): COc1cc(CN2CCN(CCCCC(=O)N3Cc4cnn(C)c4Nc4ccccc43)CC2)cc(OC)c1
InChIKey: IGOVDAPJIXBKMU-UHFFFAOYSA-N
Target: Vasopressin V1a receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P37288
Assay: Agonist activity at human vasopressin 1a receptor expressed in HEK293 cells assessed as increase in IP1 accumulation preincubated for 1 hr followed by addition of Ab-Cryptate and IP1-d2 by HTRF assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 518.66, ALogP 4.02, HBA 8, HBD 1, PSA 75.1, QED 0.43
Compound (SMILES): COc1cc(CN2CCN(CCCCCC(=O)N3Cc4cnn(C)c4Nc4ccccc43)CC2)cc(OC)c1
InChIKey: FWHCOVUYSHAHBM-UHFFFAOYSA-N
Target: Vasopressin V1a receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P37288
Assay: Agonist activity at human vasopressin 1a receptor expressed in HEK293 cells assessed as increase in IP1 accumulation preincubated for 1 hr followed by addition of Ab-Cryptate and IP1-d2 by HTRF assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 532.69, ALogP 4.41, HBA 8, HBD 1, PSA 75.1, QED 0.39
Compound (SMILES): COc1cc(CN2CCN(CCCCCCC(=O)N3Cc4cnn(C)c4Nc4ccccc43)CC2)cc(OC)c1
InChIKey: JMDBRPIWAAFYSL-UHFFFAOYSA-N
Target: Vasopressin V1a receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P37288
Assay: Agonist activity at human vasopressin 1a receptor expressed in HEK293 cells assessed as increase in IP1 accumulation preincubated for 1 hr followed by addition of Ab-Cryptate and IP1-d2 by HTRF assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 546.72, ALogP 4.8, HBA 8, HBD 1, PSA 75.1, QED 0.35
Compound (SMILES): COc1cc(CN2CCN(CCCCCCCC(=O)N3Cc4cnn(C)c4Nc4ccccc43)CC2)cc(OC)c1
InChIKey: DRWATOKSPFWENI-UHFFFAOYSA-N
Target: Vasopressin V1a receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P37288
Assay: Agonist activity at human vasopressin 1a receptor expressed in HEK293 cells assessed as increase in IP1 accumulation preincubated for 1 hr followed by addition of Ab-Cryptate and IP1-d2 by HTRF assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 560.74, ALogP 5.19, HBA 8, HBD 1, PSA 75.1, QED 0.31
Compound (SMILES): Cn1c(SCCCN2CCOC(c3ccc(C(F)(F)F)cc3)C2)nnc1-c1ccc(-c2nnco2)cc1
InChIKey: IMTICVASEJSMDW-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: [3H]-Spiperone Binding Assay at hD3: [3H]-Spiperone Binding Assay at hD3 and hD4 recombinant receptors CHO cells transiently transfected with human dopamine type 3 or 4 receptors (CHO-hD3 or CHO-hD4, respectively), were re-suspended in 20 mM HEPES, 2 mM EDTA (pH 7.4), homogenised and centrifuged at 40,000 g (20 min, 4° C.). After re-suspension, homogenization and centrifugation as above, the final pellet was re-suspended in 20 mM HEPES, 100 mM NaCl, 10 mM MgCl2, 1 mM EDTA (pH 7.4) and aliquots were kept at −80° C. [3H]-Spiperone Binding experiments were performed in 96 deep-well polypropylene plates in 50 mM Tris/HCl, 120 mM NaCl, 5 mM KCl, 5 mM MgCl2 (pH 7.4). Compounds of invention were serially diluted in DMSO at 100 fold final concentrations in the assay (1% DMSO final in the assay). Displacement was performed in the presence of 0.3 nM [3H]-Spiperone. The reaction was initiated by the addition of membrane suspension (4 μg and 12 μg of protein for CHO-hD3- and CHO-hD4 membranes, respectively) and lasted for 90 or 100 min (for hD3 or hD4 membranes, respectively) at 23° C. in a final volume of 500 μl. Non specific binding (NSB) was determined in the presence of 1 μM Spiperone. The binding reaction was stopped by rapid filtration through GF/B filterplates pre-soaked in 0.5% polyetylenimmine (PEI) using a Packard cell harvester. After washing with ice-cold 0.9% NaCl, the plate was left to dry before the addition of Microscint 20 (50 l/well, PerkinElmer). Radioactivity was counted with a TopCount (PerkinElmer). Data were analysed by non-linear regression analysis using GraphPad Prism 5.0 (GraphPad Software). Saturation binding experiments were performed similar to the competition binding experiments using a radioligand concentrations ranging from 0.015 to 4.0 nM. Ref: Mackenzie R. G. et al. (1994). Characterization of the human dopamine D3 receptor expressed in transfected cell lines. Eur. J. Pharmacol., 266:79-8.
Measurement: Ki = 16.2 nM (pChEMBL 7.789999961853027)
Descriptors: MW 530.58, ALogP 5.11, HBA 9, HBD 0, PSA 82.1, QED 0.23
Compound (SMILES): Cn1cccc1-c1nnc(SCCCN2CCOC(c3ccc(C(F)(F)F)cc3)C2)n1C
InChIKey: BLGOAHHKRXNKKY-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Agonist activity at human dopamine D3 receptor expressed in CHO cells after 90 mins by [35S]-GTPgamma S assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 465.55, ALogP 4.4, HBA 7, HBD 0, PSA 48.11, QED 0.38
Compound (SMILES): Cc1nc(-c2ccc(-c3nnc(SCCCN4CCOC(c5ccc(C(F)(F)F)cc5)C4)n3C)cc2)no1
InChIKey: CRCNNTYVVVULMG-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: [3H]-Spiperone Binding Assay at hD3: [3H]-Spiperone Binding Assay at hD3 and hD4 recombinant receptors CHO cells transiently transfected with human dopamine type 3 or 4 receptors (CHO-hD3 or CHO-hD4, respectively), were re-suspended in 20 mM HEPES, 2 mM EDTA (pH 7.4), homogenised and centrifuged at 40,000 g (20 min, 4° C.). After re-suspension, homogenization and centrifugation as above, the final pellet was re-suspended in 20 mM HEPES, 100 mM NaCl, 10 mM MgCl2, 1 mM EDTA (pH 7.4) and aliquots were kept at −80° C. [3H]-Spiperone Binding experiments were performed in 96 deep-well polypropylene plates in 50 mM Tris/HCl, 120 mM NaCl, 5 mM KCl, 5 mM MgCl2 (pH 7.4). Compounds of invention were serially diluted in DMSO at 100 fold final concentrations in the assay (1% DMSO final in the assay). Displacement was performed in the presence of 0.3 nM [3H]-Spiperone. The reaction was initiated by the addition of membrane suspension (4 μg and 12 μg of protein for CHO-hD3- and CHO-hD4 membranes, respectively) and lasted for 90 or 100 min (for hD3 or hD4 membranes, respectively) at 23° C. in a final volume of 500 μl. Non specific binding (NSB) was determined in the presence of 1 μM Spiperone. The binding reaction was stopped by rapid filtration through GF/B filterplates pre-soaked in 0.5% polyetylenimmine (PEI) using a Packard cell harvester. After washing with ice-cold 0.9% NaCl, the plate was left to dry before the addition of Microscint 20 (50 l/well, PerkinElmer). Radioactivity was counted with a TopCount (PerkinElmer). Data were analysed by non-linear regression analysis using GraphPad Prism 5.0 (GraphPad Software). Saturation binding experiments were performed similar to the competition binding experiments using a radioligand concentrations ranging from 0.015 to 4.0 nM. Ref: Mackenzie R. G. et al. (1994). Characterization of the human dopamine D3 receptor expressed in transfected cell lines. Eur. J. Pharmacol., 266:79-8.
Measurement: Ki = 23.4 nM (pChEMBL 7.630000114440918)
Descriptors: MW 544.6, ALogP 5.42, HBA 9, HBD 0, PSA 82.1, QED 0.22
Compound (SMILES): Cc1ccc(C2CN(CCCSc3nnc(-c4ccc(-c5noc(C)n5)cc4)n3C)CCO2)cc1
InChIKey: WQOCUOYKDKZARU-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Agonist activity at human dopamine D3 receptor expressed in CHO cells after 90 mins by [35S]-GTPgamma S assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 490.63, ALogP 4.7, HBA 9, HBD 0, PSA 82.1, QED 0.26
Compound (SMILES): Cn1c(SCCCN2CCOC(c3ccc(C(F)(F)F)cc3)C2)nnc1C1CCCCC1
InChIKey: SNOYXNAOKVYMSM-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: [3H]-Spiperone Binding Assay at hD3: [3H]-Spiperone Binding Assay at hD3 and hD4 recombinant receptors CHO cells transiently transfected with human dopamine type 3 or 4 receptors (CHO-hD3 or CHO-hD4, respectively), were re-suspended in 20 mM HEPES, 2 mM EDTA (pH 7.4), homogenised and centrifuged at 40,000 g (20 min, 4° C.). After re-suspension, homogenization and centrifugation as above, the final pellet was re-suspended in 20 mM HEPES, 100 mM NaCl, 10 mM MgCl2, 1 mM EDTA (pH 7.4) and aliquots were kept at −80° C. [3H]-Spiperone Binding experiments were performed in 96 deep-well polypropylene plates in 50 mM Tris/HCl, 120 mM NaCl, 5 mM KCl, 5 mM MgCl2 (pH 7.4). Compounds of invention were serially diluted in DMSO at 100 fold final concentrations in the assay (1% DMSO final in the assay). Displacement was performed in the presence of 0.3 nM [3H]-Spiperone. The reaction was initiated by the addition of membrane suspension (4 μg and 12 μg of protein for CHO-hD3- and CHO-hD4 membranes, respectively) and lasted for 90 or 100 min (for hD3 or hD4 membranes, respectively) at 23° C. in a final volume of 500 μl. Non specific binding (NSB) was determined in the presence of 1 μM Spiperone. The binding reaction was stopped by rapid filtration through GF/B filterplates pre-soaked in 0.5% polyetylenimmine (PEI) using a Packard cell harvester. After washing with ice-cold 0.9% NaCl, the plate was left to dry before the addition of Microscint 20 (50 l/well, PerkinElmer). Radioactivity was counted with a TopCount (PerkinElmer). Data were analysed by non-linear regression analysis using GraphPad Prism 5.0 (GraphPad Software). Saturation binding experiments were performed similar to the competition binding experiments using a radioligand concentrations ranging from 0.015 to 4.0 nM. Ref: Mackenzie R. G. et al. (1994). Characterization of the human dopamine D3 receptor expressed in transfected cell lines. Eur. J. Pharmacol., 266:79-8.
Measurement: Ki = 43.7 nM (pChEMBL 7.360000133514404)
Descriptors: MW 468.59, ALogP 5.44, HBA 6, HBD 0, PSA 43.18, QED 0.4
Compound (SMILES): Cn1c(SCCCN2CCOC(c3ccc(C(F)(F)F)cc3)C2)nnc1-c1ccncc1
InChIKey: QSGQMVZHKGEIIG-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: [3H]-Spiperone Binding Assay at hD2 Recombinant Receptor: CHO cells stably expressing human dopamine receptor type 2, long variant (hD2L), coupled to Gα16 protein (CHO-Gα16-hD2L) were re-suspended in 20 mM HEPES, 2 mM EDTA (pH 7.4), homogenised and centrifuged at 40,000 g (20 min, 4° C.). After re-suspension, homogenization and centrifugation as above, the final pellet was re-suspended in 20 mM HEPES, 100 mM NaCl, 10 mM MgCl2, 1 mM EDTA (pH 7.4) and aliquots were kept at −80° C. [3H]-Spiperone Binding experiments were performed in 96 deep-well polypropylene plates in 50 mM Tris/HCl, 120 mM NaCl, 5 mM KCl, 5 mM MgCl2 (pH 7.4). Compounds of invention were serially diluted in DMSO at 100 fold final concentrations in the assay (1% DMSO final in the assay). Displacement was performed in the presence of 0.08 nM [3H]-Spiperone. The reaction was initiated by the addition of membrane suspension (2 μg of protein for CHO-hD2 membranes) and lasted for 120 min at 23° C. in a final volume of 1000 μl. Non specific binding (NSB) was determined in the presence of 0.1 μM Spiperone. The binding reaction was stopped by rapid filtration through GF/B filterplates pre-soaked in 0.5% polyetylenimmine (PEI) using a Packard cell harvester. After washing with ice-cold 0.9% NaCl, the plate was left to dry before the addition of Microscint 20 (50 μl/well, PerkinElmer). Radioactivity was counted with a TopCount (PerkinElmer). Data were analysed by non-linear regression analysis using GraphPad Prism 5.0 (GraphPad Software) or XLfit Version 5.2.0.0 (Copyright © 2006-2009 ID Business Solutions Ltd). Saturation binding experiments were performed similar to the competition binding experiments using a radioligand concentrations ranging from 0.011 to 3.0 nM. Ref: Durcan M. J. et al. (1995). Is Clozapine selective for the dopamine D4 receptor? Life Sciences, 57: 275-283. Petrus J. et al. (2001). Real-time analysis of dopamine: antagonist interactions at recombinant human D2long receptor upon modulation of its activation state. Brit. J. Pharmacol. 134, 88±97.
Measurement: Ki = 11749 nM (pChEMBL 4.929999828338623)
Descriptors: MW 463.53, ALogP 4.45, HBA 7, HBD 0, PSA 56.07, QED 0.38
Compound (SMILES): Cn1c(SCCCN2CCOC(c3ccc(C(F)(F)F)cc3)C2)nnc1-c1cccnc1
InChIKey: WHEWCDCGFVTYAK-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: [3H]-Spiperone Binding Assay at hD2 Recombinant Receptor: CHO cells stably expressing human dopamine receptor type 2, long variant (hD2L), coupled to Gα16 protein (CHO-Gα16-hD2L) were re-suspended in 20 mM HEPES, 2 mM EDTA (pH 7.4), homogenised and centrifuged at 40,000 g (20 min, 4° C.). After re-suspension, homogenization and centrifugation as above, the final pellet was re-suspended in 20 mM HEPES, 100 mM NaCl, 10 mM MgCl2, 1 mM EDTA (pH 7.4) and aliquots were kept at −80° C. [3H]-Spiperone Binding experiments were performed in 96 deep-well polypropylene plates in 50 mM Tris/HCl, 120 mM NaCl, 5 mM KCl, 5 mM MgCl2 (pH 7.4). Compounds of invention were serially diluted in DMSO at 100 fold final concentrations in the assay (1% DMSO final in the assay). Displacement was performed in the presence of 0.08 nM [3H]-Spiperone. The reaction was initiated by the addition of membrane suspension (2 μg of protein for CHO-hD2 membranes) and lasted for 120 min at 23° C. in a final volume of 1000 μl. Non specific binding (NSB) was determined in the presence of 0.1 μM Spiperone. The binding reaction was stopped by rapid filtration through GF/B filterplates pre-soaked in 0.5% polyetylenimmine (PEI) using a Packard cell harvester. After washing with ice-cold 0.9% NaCl, the plate was left to dry before the addition of Microscint 20 (50 μl/well, PerkinElmer). Radioactivity was counted with a TopCount (PerkinElmer). Data were analysed by non-linear regression analysis using GraphPad Prism 5.0 (GraphPad Software) or XLfit Version 5.2.0.0 (Copyright © 2006-2009 ID Business Solutions Ltd). Saturation binding experiments were performed similar to the competition binding experiments using a radioligand concentrations ranging from 0.011 to 3.0 nM. Ref: Durcan M. J. et al. (1995). Is Clozapine selective for the dopamine D4 receptor? Life Sciences, 57: 275-283. Petrus J. et al. (2001). Real-time analysis of dopamine: antagonist interactions at recombinant human D2long receptor upon modulation of its activation state. Brit. J. Pharmacol. 134, 88±97.
Measurement: Ki = 14791 nM (pChEMBL 4.829999923706055)
Descriptors: MW 463.53, ALogP 4.45, HBA 7, HBD 0, PSA 56.07, QED 0.38
Compound (SMILES): Cn1c(SCCCN2CCOC(c3ccc(C(F)(F)F)cc3)C2)nnc1-c1ccc(C(N)=O)nc1
InChIKey: GDIAQHPBSQUEQC-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of [3H]-dofetilide from human ERG potassium channel by scintillation proximity assay
Measurement: Ki = 1995.26 nM (pChEMBL 5.699999809265137)
Descriptors: MW 506.55, ALogP 3.55, HBA 8, HBD 1, PSA 99.16, QED 0.37
Compound (SMILES): Cn1c(SCCCN2CCOC(c3ccc(C(F)(F)F)cc3)C2)nnc1-c1ccc(C(N)=O)cc1
InChIKey: UDVBAIMSAZRJGM-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [125I]-7-OH-PIPAT from rat brain dopamine D2 receptor after 45 mins by microplate scintillation counting analysis
Measurement: Ki = 10000 nM (pChEMBL 5)
Descriptors: MW 505.57, ALogP 4.16, HBA 7, HBD 1, PSA 86.27, QED 0.37
Compound (SMILES): Cn1c(SCCCN2CCOC(c3ccc(C(F)(F)F)cc3)C2)nnc1-c1cccc(C(N)=O)c1
InChIKey: ZBGYXTWHZHZMHW-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: [3H]-Spiperone Binding Assay at hD2 Recombinant Receptor: CHO cells stably expressing human dopamine receptor type 2, long variant (hD2L), coupled to Gα16 protein (CHO-Gα16-hD2L) were re-suspended in 20 mM HEPES, 2 mM EDTA (pH 7.4), homogenised and centrifuged at 40,000 g (20 min, 4° C.). After re-suspension, homogenization and centrifugation as above, the final pellet was re-suspended in 20 mM HEPES, 100 mM NaCl, 10 mM MgCl2, 1 mM EDTA (pH 7.4) and aliquots were kept at −80° C. [3H]-Spiperone Binding experiments were performed in 96 deep-well polypropylene plates in 50 mM Tris/HCl, 120 mM NaCl, 5 mM KCl, 5 mM MgCl2 (pH 7.4). Compounds of invention were serially diluted in DMSO at 100 fold final concentrations in the assay (1% DMSO final in the assay). Displacement was performed in the presence of 0.08 nM [3H]-Spiperone. The reaction was initiated by the addition of membrane suspension (2 μg of protein for CHO-hD2 membranes) and lasted for 120 min at 23° C. in a final volume of 1000 μl. Non specific binding (NSB) was determined in the presence of 0.1 μM Spiperone. The binding reaction was stopped by rapid filtration through GF/B filterplates pre-soaked in 0.5% polyetylenimmine (PEI) using a Packard cell harvester. After washing with ice-cold 0.9% NaCl, the plate was left to dry before the addition of Microscint 20 (50 μl/well, PerkinElmer). Radioactivity was counted with a TopCount (PerkinElmer). Data were analysed by non-linear regression analysis using GraphPad Prism 5.0 (GraphPad Software) or XLfit Version 5.2.0.0 (Copyright © 2006-2009 ID Business Solutions Ltd). Saturation binding experiments were performed similar to the competition binding experiments using a radioligand concentrations ranging from 0.011 to 3.0 nM. Ref: Durcan M. J. et al. (1995). Is Clozapine selective for the dopamine D4 receptor? Life Sciences, 57: 275-283. Petrus J. et al. (2001). Real-time analysis of dopamine: antagonist interactions at recombinant human D2long receptor upon modulation of its activation state. Brit. J. Pharmacol. 134, 88±97.
Measurement: Ki = 15136 nM (pChEMBL 4.820000171661377)
Descriptors: MW 505.57, ALogP 4.16, HBA 7, HBD 1, PSA 86.27, QED 0.37
Compound (SMILES): Cc1c(C)c2ccc(OCCNC3CCN(Cc4ccccc4)CC3)cc2oc1=O
InChIKey: IPJZSNUPIXZHAU-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human recombinant MAO-B using p-tyramine substrate after 15 mins by fluorimetric analysis
Measurement: IC50 = 23400 nM (pChEMBL 4.630000114440918)
Descriptors: MW 406.53, ALogP 4.04, HBA 5, HBD 1, PSA 54.71, QED 0.47
Compound (SMILES): Cc1c(Cl)c(=O)oc2cc(OCCNC3CCN(Cc4ccccc4)CC3)ccc12
InChIKey: UUZIPHVUUZOBHC-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human recombinant MAO-B using p-tyramine substrate after 15 mins by fluorimetric analysis
Measurement: IC50 = 14700 nM (pChEMBL 4.829999923706055)
Descriptors: MW 426.94, ALogP 4.39, HBA 5, HBD 1, PSA 54.71, QED 0.45
Compound (SMILES): O=c1oc2cc(OCCNC3CCN(Cc4ccccc4)CC3)ccc2c2c1CCCC2
InChIKey: QZRBOLHGJBENEV-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human recombinant MAO-B using p-tyramine substrate after 15 mins by fluorimetric analysis
Measurement: IC50 = 2620 nM (pChEMBL 5.579999923706055)
Descriptors: MW 432.56, ALogP 4.3, HBA 5, HBD 1, PSA 54.71, QED 0.45
Compound (SMILES): Cc1cc(=O)oc2cc(CNCCC3CCN(Cc4ccccc4)CC3)ccc12
InChIKey: HZEOKPNLIUABIQ-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human recombinant MAO-B using p-tyramine substrate after 15 mins by fluorimetric analysis
Measurement: IC50 = 40500 nM (pChEMBL 4.389999866485596)
Descriptors: MW 390.53, ALogP 4.49, HBA 4, HBD 1, PSA 45.48, QED 0.48
Compound (SMILES): O=C(O)CN(C1(c2ccc(-c3ccccc3OC(F)(F)F)cc2)CCC1)S(=O)(=O)c1ccc(OC(F)F)cc1
InChIKey: YZMDTMVHQAUYGH-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human liver microsomes using (S)-mephenytoin as substrate incubated for 5 mins by LC-MS analysis
Measurement: IC50 = 13000 nM (pChEMBL 4.889999866485596)
Descriptors: MW 571.52, ALogP 6.01, HBA 5, HBD 1, PSA 93.14, QED 0.3
Compound (SMILES): CC(=O)c1ccc(-c2nnc(SCCCN3CCOC(c4ccc(C(F)(F)F)cc4)C3)n2C)cc1
InChIKey: YSOFLAUQLXWHBW-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: [3H]-Spiperone Binding Assay at hD3: [3H]-Spiperone Binding Assay at hD3 and hD4 recombinant receptors CHO cells transiently transfected with human dopamine type 3 or 4 receptors (CHO-hD3 or CHO-hD4, respectively), were re-suspended in 20 mM HEPES, 2 mM EDTA (pH 7.4), homogenised and centrifuged at 40,000 g (20 min, 4° C.). After re-suspension, homogenization and centrifugation as above, the final pellet was re-suspended in 20 mM HEPES, 100 mM NaCl, 10 mM MgCl2, 1 mM EDTA (pH 7.4) and aliquots were kept at −80° C. [3H]-Spiperone Binding experiments were performed in 96 deep-well polypropylene plates in 50 mM Tris/HCl, 120 mM NaCl, 5 mM KCl, 5 mM MgCl2 (pH 7.4). Compounds of invention were serially diluted in DMSO at 100 fold final concentrations in the assay (1% DMSO final in the assay). Displacement was performed in the presence of 0.3 nM [3H]-Spiperone. The reaction was initiated by the addition of membrane suspension (4 μg and 12 μg of protein for CHO-hD3- and CHO-hD4 membranes, respectively) and lasted for 90 or 100 min (for hD3 or hD4 membranes, respectively) at 23° C. in a final volume of 500 μl. Non specific binding (NSB) was determined in the presence of 1 μM Spiperone. The binding reaction was stopped by rapid filtration through GF/B filterplates pre-soaked in 0.5% polyetylenimmine (PEI) using a Packard cell harvester. After washing with ice-cold 0.9% NaCl, the plate was left to dry before the addition of Microscint 20 (50 l/well, PerkinElmer). Radioactivity was counted with a TopCount (PerkinElmer). Data were analysed by non-linear regression analysis using GraphPad Prism 5.0 (GraphPad Software). Saturation binding experiments were performed similar to the competition binding experiments using a radioligand concentrations ranging from 0.015 to 4.0 nM. Ref: Mackenzie R. G. et al. (1994). Characterization of the human dopamine D3 receptor expressed in transfected cell lines. Eur. J. Pharmacol., 266:79-8.
Measurement: Ki = 66.1 nM (pChEMBL 7.179999828338623)
Descriptors: MW 504.58, ALogP 5.26, HBA 7, HBD 0, PSA 60.25, QED 0.24
Compound (SMILES): Cn1c(SCCCN2CCOC(c3ccc(C(F)(F)F)cc3)C2)nnc1-c1ccc(C#N)cc1
InChIKey: RWOJEGLVFGCYFU-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: [3H]-Spiperone Binding Assay at hD2 Recombinant Receptor: CHO cells stably expressing human dopamine receptor type 2, long variant (hD2L), coupled to Gα16 protein (CHO-Gα16-hD2L) were re-suspended in 20 mM HEPES, 2 mM EDTA (pH 7.4), homogenised and centrifuged at 40,000 g (20 min, 4° C.). After re-suspension, homogenization and centrifugation as above, the final pellet was re-suspended in 20 mM HEPES, 100 mM NaCl, 10 mM MgCl2, 1 mM EDTA (pH 7.4) and aliquots were kept at −80° C. [3H]-Spiperone Binding experiments were performed in 96 deep-well polypropylene plates in 50 mM Tris/HCl, 120 mM NaCl, 5 mM KCl, 5 mM MgCl2 (pH 7.4). Compounds of invention were serially diluted in DMSO at 100 fold final concentrations in the assay (1% DMSO final in the assay). Displacement was performed in the presence of 0.08 nM [3H]-Spiperone. The reaction was initiated by the addition of membrane suspension (2 μg of protein for CHO-hD2 membranes) and lasted for 120 min at 23° C. in a final volume of 1000 μl. Non specific binding (NSB) was determined in the presence of 0.1 μM Spiperone. The binding reaction was stopped by rapid filtration through GF/B filterplates pre-soaked in 0.5% polyetylenimmine (PEI) using a Packard cell harvester. After washing with ice-cold 0.9% NaCl, the plate was left to dry before the addition of Microscint 20 (50 μl/well, PerkinElmer). Radioactivity was counted with a TopCount (PerkinElmer). Data were analysed by non-linear regression analysis using GraphPad Prism 5.0 (GraphPad Software) or XLfit Version 5.2.0.0 (Copyright © 2006-2009 ID Business Solutions Ltd). Saturation binding experiments were performed similar to the competition binding experiments using a radioligand concentrations ranging from 0.011 to 3.0 nM. Ref: Durcan M. J. et al. (1995). Is Clozapine selective for the dopamine D4 receptor? Life Sciences, 57: 275-283. Petrus J. et al. (2001). Real-time analysis of dopamine: antagonist interactions at recombinant human D2long receptor upon modulation of its activation state. Brit. J. Pharmacol. 134, 88±97.
Measurement: Ki = 11220 nM (pChEMBL 4.949999809265137)
Descriptors: MW 487.55, ALogP 4.93, HBA 7, HBD 0, PSA 66.97, QED 0.35
Compound (SMILES): Cn1c(SCCCN2CCOC(c3ccc(C(F)(F)F)cc3F)C2)nnc1-c1ccc(C(N)=O)cc1
InChIKey: ODRXDASPVTXFDY-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: [3H]-Spiperone Binding Assay at hD3: [3H]-Spiperone Binding Assay at hD3 and hD4 recombinant receptors CHO cells transiently transfected with human dopamine type 3 or 4 receptors (CHO-hD3 or CHO-hD4, respectively), were re-suspended in 20 mM HEPES, 2 mM EDTA (pH 7.4), homogenised and centrifuged at 40,000 g (20 min, 4° C.). After re-suspension, homogenization and centrifugation as above, the final pellet was re-suspended in 20 mM HEPES, 100 mM NaCl, 10 mM MgCl2, 1 mM EDTA (pH 7.4) and aliquots were kept at −80° C. [3H]-Spiperone Binding experiments were performed in 96 deep-well polypropylene plates in 50 mM Tris/HCl, 120 mM NaCl, 5 mM KCl, 5 mM MgCl2 (pH 7.4). Compounds of invention were serially diluted in DMSO at 100 fold final concentrations in the assay (1% DMSO final in the assay). Displacement was performed in the presence of 0.3 nM [3H]-Spiperone. The reaction was initiated by the addition of membrane suspension (4 μg and 12 μg of protein for CHO-hD3- and CHO-hD4 membranes, respectively) and lasted for 90 or 100 min (for hD3 or hD4 membranes, respectively) at 23° C. in a final volume of 500 μl. Non specific binding (NSB) was determined in the presence of 1 μM Spiperone. The binding reaction was stopped by rapid filtration through GF/B filterplates pre-soaked in 0.5% polyetylenimmine (PEI) using a Packard cell harvester. After washing with ice-cold 0.9% NaCl, the plate was left to dry before the addition of Microscint 20 (50 l/well, PerkinElmer). Radioactivity was counted with a TopCount (PerkinElmer). Data were analysed by non-linear regression analysis using GraphPad Prism 5.0 (GraphPad Software). Saturation binding experiments were performed similar to the competition binding experiments using a radioligand concentrations ranging from 0.015 to 4.0 nM. Ref: Mackenzie R. G. et al. (1994). Characterization of the human dopamine D3 receptor expressed in transfected cell lines. Eur. J. Pharmacol., 266:79-8.
Measurement: Ki = 87.1 nM (pChEMBL 7.059999942779541)
Descriptors: MW 523.56, ALogP 4.29, HBA 7, HBD 1, PSA 86.27, QED 0.27