lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COC(=O)[C@H](C)[C@@H]1N=C(c2ccc(Cl)cc2)c2cc(OC)ccc2-n2c(C)nnc21
InChIKey: FENXDXHDXYVGRJ-BLVKFPJESA-N
Target: Bromodomain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25440
Assay: Binding affinity to BRD2 bromodomain 2 L383I mutant (unknown origin) expressed in competent Escherichia coli DH5-alpha cells by isothermal titration calorimetry
Measurement: Kd = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 424.89, ALogP 3.94, HBA 7, HBD 0, PSA 78.6, QED 0.59
Compound (SMILES): CN1C(=O)c2c(nn(Cc3ccc(-c4ccccn4)cc3)c2Nc2ccccc2)N2C1=N[C@@H]1CCC[C@@H]12
InChIKey: RJKWLGFYXTZMOU-RPWUZVMVSA-N
Target: cGMP-specific 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O76074
Assay: Inhibition of recombinant full lenght human PDE5A using fluorescent labeled cGMP as substrate after 15 mins by IMAP assay
Measurement: Ki = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 489.58, ALogP 4.92, HBA 7, HBD 1, PSA 78.65, QED 0.43
Compound (SMILES): CN1C(=O)c2c(nn(Cc3ccc(-c4cccc(F)n4)cc3)c2Nc2ccccc2)N2C1=N[C@@H]1CCC[C@@H]12.O=P(O)(O)O
InChIKey: ZPIAAFIYOPWWJL-RFPXDPOKSA-N
Target: cGMP-specific 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O76074
Assay: Inhibition of recombinant full lenght human PDE5A using fluorescent labeled cGMP as substrate after 15 mins by IMAP assay
Measurement: Ki = 630 nM (pChEMBL 6.199999809265137)
Descriptors: MW 507.57, ALogP 5.06, HBA 7, HBD 1, PSA 78.65, QED 0.38
Compound (SMILES): COC(=O)CC1N=C(c2cccc3[nH]ccc23)c2cc(OC)ccc2-n2c(C)nnc21
InChIKey: RARZHTSXOQRRPR-UHFFFAOYSA-N
Target: Bromodomain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25440
Assay: Binding affinity to N-terminal His6-tagged BRD2 bromodomain 1 (unknown origin) expressed in competent Escherichia coli BL21(DE3) cells by isothermal titration calorimetry
Measurement: Kd = 780 nM (pChEMBL 6.110000133514404)
Descriptors: MW 415.45, ALogP 3.52, HBA 7, HBD 1, PSA 94.39, QED 0.51
Compound (SMILES): CC(=O)NCCCCn1c2c(c3ccccc31)C(=O)NCC2
InChIKey: RYVLOOXFFIFQEN-UHFFFAOYSA-N
Target: Bromodomain-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15059
Assay: Binding affinity to BRD3 BD1 (unknown origin) by isothermal titration calorimetric method
Measurement: Kd = 3300 nM (pChEMBL 5.480000019073486)
Descriptors: MW 299.37, ALogP 1.84, HBA 3, HBD 2, PSA 63.13, QED 0.83
Compound (SMILES): O=C(NO)c1noc(-c2ccc(Br)cc2)n1
InChIKey: LONJOCSUEOBGAW-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of human HDAC8 using Z-L-Lys(eta-trifluoroacetyl)-AMC as substrate after 90 mins by fluorescence analysis
Measurement: IC50 = 20040 nM (pChEMBL 4.699999809265137)
Descriptors: MW 284.07, ALogP 1.62, HBA 5, HBD 2, PSA 88.25, QED 0.65
Compound (SMILES): CC(C)[C@@H]1NC(=O)[C@@H]2CCCN2C(=O)[C@H]2CCCN2C(=O)C[C@@H](C(=O)NCCCC(=O)NO)NC1=O
InChIKey: KEGNHRHLBGEVRZ-GGXPGOJBSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of recombinant human KDAC1 using FAM-labelled substrate A incubated for 60 mins by microfluidic chip-based assay
Measurement: IC50 = 25100 nM (pChEMBL 4.599999904632568)
Descriptors: MW 508.58, ALogP -1.6, HBA 7, HBD 5, PSA 177.25, QED 0.16
Compound (SMILES): CC(=O)SCC/C=C/[C@@H]1CC(=O)NCc2ccc(cc2)C2=N[C@@](C)(CS2)C(=O)N[C@@H](C(C)C)C(=O)O1
InChIKey: RNHTWMJDLDLLGM-TWZYLPHCSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of human KDAC1
Measurement: IC50 = 3480 nM (pChEMBL 5.460000038146973)
Descriptors: MW 531.7, ALogP 3.24, HBA 8, HBD 2, PSA 113.93, QED 0.34
Compound (SMILES): CC(C)[C@@H]1NC(=O)[C@H]2CCCN2C(=O)[C@@H]2CCCN2C(=O)C[C@H](C(=O)NCCCC(=O)NO)NC1=O
InChIKey: KEGNHRHLBGEVRZ-JEWRLFTDSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of recombinant human KDAC1 using FAM-labelled substrate A incubated for 60 mins by microfluidic chip-based assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 508.58, ALogP -1.6, HBA 7, HBD 5, PSA 177.25, QED 0.16
Compound (SMILES): CCOC(=O)c1ccc(Nc2nc(-c3ccncc3)nc3ccccc23)cc1
InChIKey: CWQVIUBBTRVXSZ-UHFFFAOYSA-N
Target: Structural capsid protein (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q76129
Assay: Binding affinity to full length HIV1 NL4-3 capsid (1 to 231 residues) by isothermal titration calorimetry
Measurement: Kd = 140 nM (pChEMBL 6.849999904632568)
Descriptors: MW 370.41, ALogP 4.61, HBA 6, HBD 1, PSA 77, QED 0.52
Compound (SMILES): CCCc1cc(O)cc(O)c1C(=O)O
InChIKey: RIVVNGIVVYEIRS-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P17706
Assay: Inhibition of TCPTP (unknown origin) using p-nitrophenyl phosphate substrate incubated for 30 mins
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 196.2, ALogP 1.75, HBA 3, HBD 3, PSA 77.76, QED 0.69
Compound (SMILES): CCOc1ccc2cc(-c3nn(C(C)C)c(N)c3C(N)=O)cnc2c1
InChIKey: IYNLAGHSNARNHP-UHFFFAOYSA-N
Target: Calmodulin-domain protein kinase 1 (SINGLE PROTEIN), Toxoplasma gondii
UniProt: Q9BJF5
Assay: Inhibition of Toxoplasma gondii CDPK1 assessed as ATP consumption using (Biotin-C6-PLARTLSVAGLPGKK) as substrate after 90 mins by luciferase reporter assay
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 339.4, ALogP 2.76, HBA 6, HBD 2, PSA 109.05, QED 0.74
Compound (SMILES): CCOc1ccc2cc(-c3nn(CC4CC4)c(N)c3C(N)=O)cnc2c1
InChIKey: SOBPJJCTFHUZHH-UHFFFAOYSA-N
Target: Calmodulin-domain protein kinase 1 (SINGLE PROTEIN), Toxoplasma gondii
UniProt: Q9BJF5
Assay: Inhibition Assay: Inhibition of TgCDPK1 and CpCDPK1 was determined using a luminescent kinase assay which measures ATP depletion in the presence of the Syntide 2 peptide substrate (KinaseGlo). For description of the methods and assays, see WO 2011/094628, incorporated by reference herein. Similar to TgCDPK1, exogenous calcium was necessary for CpCDPK1 to possess maximum catalytic activity (data not shown). Notably, both kinases were tested at the same ATP concentration which allows direct comparison of inhibitor potencies due to these enzymes possessing similar Kms for this cofactor.
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 351.41, ALogP 2.59, HBA 6, HBD 2, PSA 109.05, QED 0.71
Compound (SMILES): CCOc1ccc2cc(-c3nn(C4CCCCC4)c(N)c3C(N)=O)cnc2c1
InChIKey: YXEUOWLDWIHNLO-UHFFFAOYSA-N
Target: Calmodulin-domain protein kinase 1 (SINGLE PROTEIN), Toxoplasma gondii
UniProt: Q9BJF5
Assay: Luminescent Kinase Assay: Inhibition of TgCDPK1 and CpCDPK1 was determined using a luminescent kinase assay which measures ATP depletion in the presence of the Syntide 2 peptide substrate (KinaseGlo). For description of the methods and assays, see WO 2011/094628, incorporated by reference herein. Similar to TgCDPK1, exogenous calcium was necessary for CpCDPK1 to possess maximum catalytic activity (data not shown). Notably, both kinases were tested at the same ATP concentration which allows direct comparison of inhibitor potencies due to these enzymes possessing similar Kms for this cofactor.
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 379.46, ALogP 3.68, HBA 6, HBD 2, PSA 109.05, QED 0.7
Compound (SMILES): CCOc1ccc2cc(-c3nn(C(C)CCO)c(N)c3C(N)=O)cnc2c1
InChIKey: CKYKSFPZSGEXCP-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase Src (SINGLE PROTEIN), Homo sapiens
UniProt: P12931
Assay: Inhibition of SRC (unknown origin)
Measurement: IC50 = 3500 nM (pChEMBL 5.460000038146973)
Descriptors: MW 369.43, ALogP 2.12, HBA 7, HBD 3, PSA 129.28, QED 0.58
Compound (SMILES): CCOc1ccc2cc(-c3nn(CC(C)(C)CO)c(N)c3C(N)=O)cnc2c1
InChIKey: JNCYMMFOKVMRMU-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by thallium flux assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 383.45, ALogP 2.2, HBA 7, HBD 3, PSA 129.28, QED 0.57
Compound (SMILES): CCOc1ccc2cc(-c3nn(C(C)C)c(N)c3C(N)=O)ccc2n1
InChIKey: ZJJBVMKTKNKOMY-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase Src (SINGLE PROTEIN), Homo sapiens
UniProt: P12931
Assay: Inhibition of human SRC using Ac-EIYGEFKKK as substrate after 90 mins by luciferase reporter assay
Measurement: IC50 = 3300 nM (pChEMBL 5.480000019073486)
Descriptors: MW 339.4, ALogP 2.76, HBA 6, HBD 2, PSA 109.05, QED 0.74
Compound (SMILES): CCOc1ccc2cc(-c3nn(C4CCCCC4)c(N)c3C(N)=O)ccc2n1
InChIKey: ONQFGFIAOHMNST-UHFFFAOYSA-N
Target: Calmodulin-domain protein kinase 1 (SINGLE PROTEIN), Toxoplasma gondii
UniProt: Q9BJF5
Assay: Inhibition of Toxoplasma gondii CDPK1 assessed as ATP consumption using (Biotin-C6-PLARTLSVAGLPGKK) as substrate after 90 mins by luciferase reporter assay
Measurement: IC50 = 5.5 nM (pChEMBL 8.260000228881836)
Descriptors: MW 379.46, ALogP 3.68, HBA 6, HBD 2, PSA 109.05, QED 0.7
Compound (SMILES): COc1ccc2cc(-c3nn(C(C)(C)C)c(N)c3C(N)=O)cnc2c1
InChIKey: OICIQHXOTTYPMV-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase Src (SINGLE PROTEIN), Homo sapiens
UniProt: P12931
Assay: Inhibition of human SRC using Ac-EIYGEFKKK as substrate after 90 mins by luciferase reporter assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 339.4, ALogP 2.54, HBA 6, HBD 2, PSA 109.05, QED 0.76
Compound (SMILES): CC(C)(C)n1nc(-c2cnc3cc(OC4CC4)ccc3c2)c(C(N)=O)c1N
InChIKey: NPQIPWMDLIWSMO-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase Src (SINGLE PROTEIN), Homo sapiens
UniProt: P12931
Assay: Inhibition of human SRC using Ac-EIYGEFKKK as substrate after 90 mins by luciferase reporter assay
Measurement: IC50 = 4750 nM (pChEMBL 5.320000171661377)
Descriptors: MW 365.44, ALogP 3.08, HBA 6, HBD 2, PSA 109.05, QED 0.74
Compound (SMILES): CC(C)(C)n1nc(-c2ccc3nc(OC4CC4)ccc3c2)c(C(N)=O)c1N
InChIKey: WFGZCBMYRMUNLE-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase Src (SINGLE PROTEIN), Homo sapiens
UniProt: P12931
Assay: Inhibition of human SRC using Ac-EIYGEFKKK as substrate after 90 mins by luciferase reporter assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 365.44, ALogP 3.08, HBA 6, HBD 2, PSA 109.05, QED 0.74
Compound (SMILES): CC(C)(C)n1nc(-c2cnc3cc(OC4CCC4)ccc3c2)c(C(N)=O)c1N
InChIKey: ILMARQUWIMHOSG-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase Src (SINGLE PROTEIN), Homo sapiens
UniProt: P12931
Assay: Inhibition of human SRC using Ac-EIYGEFKKK as substrate after 90 mins by luciferase reporter assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 379.46, ALogP 3.47, HBA 6, HBD 2, PSA 109.05, QED 0.72
Compound (SMILES): CC(C)(C)n1nc(-c2ccc3nc(OC4CCC4)ccc3c2)c(C(N)=O)c1N
InChIKey: BTTULLMSRICKGC-UHFFFAOYSA-N
Target: Calmodulin-domain protein kinase 1 (SINGLE PROTEIN), Toxoplasma gondii
UniProt: Q9BJF5
Assay: Inhibition Assay: Inhibition of TgCDPK1 and CpCDPK1 was determined using a luminescent kinase assay which measures ATP depletion in the presence of the Syntide 2 peptide substrate (KinaseGlo). For description of the methods and assays, see WO 2011/094628, incorporated by reference herein. Similar to TgCDPK1, exogenous calcium was necessary for CpCDPK1 to possess maximum catalytic activity (data not shown). Notably, both kinases were tested at the same ATP concentration which allows direct comparison of inhibitor potencies due to these enzymes possessing similar Kms for this cofactor.
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 379.46, ALogP 3.47, HBA 6, HBD 2, PSA 109.05, QED 0.72
Compound (SMILES): Cc1cc(C)nc(SCC(=O)Nc2ncc(Cc3ccccc3)s2)n1
InChIKey: LHMBJRUBDQYYSV-UHFFFAOYSA-N
Target: NAD-dependent protein deacetylase sirtuin-3, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NTG7
Assay: Inhibition of recombinant human His10-tagged Sirt3 (118 to 395 residues) expressed in Escherichia coli BL21(DE3) using Z-(Ac)Lys-AMC as substrate measured after 4 hrs by high-throughput fluorescence based assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 370.5, ALogP 3.87, HBA 6, HBD 1, PSA 67.77, QED 0.53
Compound (SMILES): Cc1cc(C)nc(SCC(=O)Nc2ncc(Cc3cccc4ccccc34)s2)n1
InChIKey: MENNDDDTIIZDDN-UHFFFAOYSA-N
Target: NAD-dependent protein deacetylase sirtuin-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96EB6
Assay: Inhibition of human SIRT1 (133 to 747 residues) using (Z-Lys(Acetyl)-AMC) as substrate after 4 hrs in presence of NAD+ by fluorescence assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 420.56, ALogP 5.02, HBA 6, HBD 1, PSA 67.77, QED 0.35
Compound (SMILES): Cc1cc(C)nc(SCC(=O)Nc2ncc(Cc3ccc4ccccc4c3)s2)n1
InChIKey: SCGVCPDSOKXNGR-UHFFFAOYSA-N
Target: NAD-dependent protein deacetylase sirtuin-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96EB6
Assay: Inhibition of SIRT1 (unknown origin)
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 420.56, ALogP 5.02, HBA 6, HBD 1, PSA 67.77, QED 0.35
Compound (SMILES): CC1(c2nc(-c3ccccc3)c[nH]2)Cc2c([nH]c3ccccc23)C(C2CCOCC2)N1
InChIKey: VMVCWWJIBFEZGN-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Binding affinity to human ERG
Measurement: IC50 = 2175 nM (pChEMBL 5.659999847412109)
Descriptors: MW 412.54, ALogP 5.09, HBA 3, HBD 3, PSA 65.73, QED 0.44
Compound (SMILES): CCCOc1cccc(Oc2cc3c(cc2NS(=O)(=O)c2ccc(OC)c(OC)c2)n(C)c(=O)n3C)c1
InChIKey: DYNNLYLIKZTWRT-UHFFFAOYSA-N
Target: Transcription intermediary factor 1-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: O15164
Assay: Inhibition of His-tagged TRIM24 (unknown origin) expressed in Escherichia coli BL21(DE3)pLysS competent cells using biotinylated-H3K23ac peptide as substrate incubated for 30 mins by Alphascreen assay
Measurement: IC50 = 217.8 nM (pChEMBL 6.659999847412109)
Descriptors: MW 527.6, ALogP 4.28, HBA 9, HBD 1, PSA 110.02, QED 0.33
Compound (SMILES): CCCCCn1cc(C(=O)NC23CC4CC(CC(C4)C2)C3)c(=O)n2nc(C)nc12
InChIKey: VNPHKYHYGSWGCX-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Antagonist activity at human CB2 receptor transfected in CHO cells assessed as inhibition of WIN 55,212-2 mediated suppression of forksolin induced cAMP production by scintillation counting analysis
Measurement: IC50 = 865 nM (pChEMBL 6.059999942779541)
Descriptors: MW 397.52, ALogP 3.09, HBA 6, HBD 1, PSA 81.29, QED 0.76
Compound (SMILES): CCCCCn1cc(C(=O)NC2CCCCC2)c(=O)n2nc(-c3ccccc3)nc12
InChIKey: XHDDGEHNYUZKBB-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Antagonist activity at human CB2 receptor transfected in CHO cells assessed as inhibition of WIN 55,212-2 mediated suppression of forksolin induced cAMP production by scintillation counting analysis
Measurement: IC50 = 111 nM (pChEMBL 6.960000038146973)
Descriptors: MW 407.52, ALogP 3.81, HBA 6, HBD 1, PSA 81.29, QED 0.6
Compound (SMILES): CCCCCn1cc(C(=O)NC2CCCCCC2)c(=O)n2nc(-c3ccccc3)nc12
InChIKey: RIIBZAQEPLXYLW-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Antagonist activity at human CB2 receptor transfected in CHO cells assessed as inhibition of WIN 55,212-2 mediated suppression of forksolin induced cAMP production by scintillation counting analysis
Measurement: IC50 = 142 nM (pChEMBL 6.849999904632568)
Descriptors: MW 421.55, ALogP 4.2, HBA 6, HBD 1, PSA 81.29, QED 0.46
Compound (SMILES): CCCCCn1cc(C(=O)NC23CC4CC(C)(CC(C)(C4)C2)C3)c(=O)n2nc(-c3ccccc3)nc12
InChIKey: MWXSRLLXUSHOED-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Antagonist activity at human CB2 receptor transfected in CHO cells assessed as inhibition of WIN 55,212-2 mediated suppression of forksolin induced cAMP production by scintillation counting analysis
Measurement: IC50 = 18.4 nM (pChEMBL 7.739999771118164)
Descriptors: MW 487.65, ALogP 5.23, HBA 6, HBD 1, PSA 81.29, QED 0.46
Compound (SMILES): CCCCCn1cc(C(=O)NC23CC4CC(CC(C4)C2)C3)c(=O)n2nc(-c3ccc(Cl)cc3)nc12
InChIKey: RFYZJUMADTXPSQ-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Antagonist activity at human CB2 receptor transfected in CHO cells assessed as inhibition of WIN 55,212-2 mediated suppression of forksolin induced cAMP production by scintillation counting analysis
Measurement: IC50 = 24.6 nM (pChEMBL 7.610000133514404)
Descriptors: MW 494.04, ALogP 5.1, HBA 6, HBD 1, PSA 81.29, QED 0.46
Compound (SMILES): CCCCCn1cc(C(=O)NC23CC4CC(CC(C4)C2)C3)c(=O)n2nc(-c3ccc(OC)cc3)nc12
InChIKey: UDBZOJOCSPLOHN-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Inverse agonist activity at human CB2 receptor transfected in CHO cells assessed as increase in forksolin stimulated cAMP production by scintillation counting analysis
Measurement: EC50 = 858 nM (pChEMBL 6.070000171661377)
Descriptors: MW 489.62, ALogP 4.46, HBA 7, HBD 1, PSA 90.52, QED 0.47
Compound (SMILES): CCCCCn1cc(C(=O)NC2CCCCC2)c(=O)n2nc(-c3ccc(C)cc3)nc12
InChIKey: FCKSNYURLYLZSG-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Inverse agonist activity at human CB2 receptor transfected in CHO cells assessed as increase in forksolin stimulated cAMP production by scintillation counting analysis
Measurement: EC50 = 464 nM (pChEMBL 6.329999923706055)
Descriptors: MW 421.55, ALogP 4.12, HBA 6, HBD 1, PSA 81.29, QED 0.58
Compound (SMILES): CCCCCn1cc(C(=O)NC2CCCCCC2)c(=O)n2nc(-c3ccc(C)cc3)nc12
InChIKey: RWIDNXYLVQGSRW-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Inverse agonist activity at human CB2 receptor transfected in CHO cells assessed as increase in forksolin stimulated cAMP production by scintillation counting analysis
Measurement: EC50 = 393 nM (pChEMBL 6.409999847412109)
Descriptors: MW 435.57, ALogP 4.51, HBA 6, HBD 1, PSA 81.29, QED 0.44
Compound (SMILES): CCCCCn1cc(C(=O)NC23CC4CC(CC(C4)C2)C3)c(=O)n2nc(-c3ccc(C)cc3)nc12
InChIKey: WREPPILXFJFKRQ-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Inverse agonist activity at human CB2 receptor transfected in CHO cells assessed as increase in forksolin stimulated cAMP production by scintillation counting analysis
Measurement: EC50 = 652 nM (pChEMBL 6.190000057220459)
Descriptors: MW 473.62, ALogP 4.76, HBA 6, HBD 1, PSA 81.29, QED 0.5
Compound (SMILES): CCCCCn1cc(C(=O)NC23CC4CC(CC(C4)C2)C3)c(=O)n2nc(-c3ccco3)nc12
InChIKey: CHHUFFBCNAMVKC-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Inverse agonist activity at human CB2 receptor transfected in CHO cells assessed as increase in forksolin stimulated cAMP production by scintillation counting analysis
Measurement: EC50 = 771 nM (pChEMBL 6.110000133514404)
Descriptors: MW 449.56, ALogP 4.04, HBA 7, HBD 1, PSA 94.43, QED 0.55
Compound (SMILES): CCCCCn1cc(C(=O)NC23CC4CC(CC(C4)C2)C3)c(=O)n2nc(SC)nc12
InChIKey: NMBFEWCMSLJPST-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Inverse agonist activity at human CB2 receptor transfected in CHO cells assessed as increase in forksolin stimulated cAMP production by scintillation counting analysis
Measurement: EC50 = 494 nM (pChEMBL 6.309999942779541)
Descriptors: MW 429.59, ALogP 3.5, HBA 7, HBD 1, PSA 81.29, QED 0.54
Compound (SMILES): CCCOc1cc(OCCCCN(C)C)cc(Oc2cc3c(cc2NS(=O)(=O)c2ccc(OC)c(OC)c2)n(C)c(=O)n3C)c1
InChIKey: HYQBRUSSCIAOOD-UHFFFAOYSA-N
Target: Peregrin (SINGLE PROTEIN), Homo sapiens
UniProt: P55201
Assay: Binding affinity to recombinant human BRPF1 expressed in bacterial system by bromoscan assay
Measurement: Kd = 2.1 nM (pChEMBL 8.680000305175781)
Descriptors: MW 642.78, ALogP 5, HBA 11, HBD 1, PSA 122.49, QED 0.17
Compound (SMILES): Cc1nc(N(C)c2ccc(OCC(=O)NO)cc2)c2ccccc2n1
InChIKey: MPMPKDWQOVDGGV-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 in human HeLa cells assessed as induction of tubulin acetylation incubated for 6 hrs by cytoblot assay
Measurement: EC50 = 26.2 nM (pChEMBL 7.579999923706055)
Descriptors: MW 338.37, ALogP 2.59, HBA 6, HBD 2, PSA 87.58, QED 0.55
Compound (SMILES): CN(c1ccc(OCC(=O)NO)cc1)c1ncnc2ccccc12
InChIKey: WKPDRDKNRMYFAG-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 in human HeLa cells assessed as induction of tubulin acetylation incubated for 6 hrs by cytoblot assay
Measurement: EC50 = 49.4 nM (pChEMBL 7.309999942779541)
Descriptors: MW 324.34, ALogP 2.28, HBA 6, HBD 2, PSA 87.58, QED 0.55
Compound (SMILES): Cc1nc2c(c(N(C)c3ccc(OCC(=O)NO)cc3)n1)CCC2
InChIKey: ZDRSRLVZCRYVJO-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 in human HeLa cells assessed as induction of tubulin acetylation incubated for 6 hrs by cytoblot assay
Measurement: EC50 = 50.8 nM (pChEMBL 7.289999961853027)
Descriptors: MW 328.37, ALogP 1.93, HBA 6, HBD 2, PSA 87.58, QED 0.64
Compound (SMILES): COc1ccc(N(C)c2nc(C)nc3ccccc23)cc1OCCCC(=O)NO
InChIKey: FWXZZFONXWYSEF-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 in human HeLa cells assessed as induction of tubulin acetylation incubated for 6 hrs by cytoblot assay
Measurement: EC50 = 58.9 nM (pChEMBL 7.230000019073486)
Descriptors: MW 396.45, ALogP 3.38, HBA 7, HBD 2, PSA 96.81, QED 0.34
Compound (SMILES): CCCCCn1cc(C(=O)NC23CC4CC(CC(C4)C2)C3)c(=O)n2nc(N3CCOCC3)nc12
InChIKey: LICOFLCBNMBWFT-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Inverse agonist activity at human CB2 receptor transfected in CHO cells assessed as increase in forksolin stimulated cAMP production by scintillation counting analysis
Measurement: EC50 = 670 nM (pChEMBL 6.170000076293945)
Descriptors: MW 468.6, ALogP 2.62, HBA 8, HBD 1, PSA 93.76, QED 0.63
Compound (SMILES): CCCCCn1cc(C(=O)NC23CC4CC(CC(C4)C2)C3)c(=O)n2nc(N(C)Cc3ccccc3)nc12
InChIKey: RPLCVHMJHODUMY-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Inverse agonist activity at human CB2 receptor transfected in CHO cells assessed as increase in forksolin stimulated cAMP production by scintillation counting analysis
Measurement: EC50 = 453 nM (pChEMBL 6.340000152587891)
Descriptors: MW 502.66, ALogP 4.42, HBA 7, HBD 1, PSA 84.53, QED 0.44
Compound (SMILES): O=C(Nc1ccc(Oc2ccnc3[nH]ccc23)c(F)c1)c1nnn(-c2ccc(F)cc2)c1C(F)(F)F
InChIKey: ULHLSSWDQFLSBL-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of KDR (unknown origin) using poly (Glu, Tyr) 4:1 as substrate after 30 mins by HTRF assay
Measurement: IC50 = 86.25 nM (pChEMBL 7.059999942779541)
Descriptors: MW 500.39, ALogP 5.49, HBA 6, HBD 2, PSA 97.72, QED 0.31
Compound (SMILES): O=C(O)c1ccnc(-c2cc(NC(=O)c3ccc(O)cc3)ccc2O)c1
InChIKey: MXKVATSZRALAIN-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Competitive inhibition of N-terminal His6-tagged KDM4C (1 to 352 residues) (unknown origin) expressed in Escherichia coli Rosetta 2(DE3)pLysS using 250 uM ARK(Me3)STGGK peptide/50 uM alpha-ketoglutarate as substrate/cofactor by FDH coupling-based Lineweaver-Burk plot analysis
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 350.33, ALogP 3.11, HBA 5, HBD 4, PSA 119.75, QED 0.54
Compound (SMILES): Cc1cc(C(=O)Nc2ccc(O)c(-c3cc(C(=O)O)ccn3)c2)no1
InChIKey: SXVDKQLIPBWXCB-UHFFFAOYSA-N
Target: Hypoxia-inducible factor 1-alpha inhibitor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWT6
Assay: Inhibition of N-terminal His6-tagged full-length FIH (unknown origin) expressed in Escherichia coli Rosetta 2(DE3)pLysS using SMDESGLPQLTSYDCEVNAPIQGSRNLLQGEELLRALDQVN peptide/100 uM alpha-ketoglutarate as substrate/cofactor incubated for 45 mins by MALDI assay
Measurement: IC50 = 473000 nM (pChEMBL 3.3299999237060547)
Descriptors: MW 339.31, ALogP 2.7, HBA 6, HBD 3, PSA 125.55, QED 0.62
Compound (SMILES): COc1cccc(CC(=O)Nc2ccc(O)c(-c3cc(C(=O)O)ccn3)c2)c1
InChIKey: QSWJSOQQNWMPME-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P29375
Assay: Inhibition of KDM5A (1 to 797 residues) (unknown origin) expressed in insect sf21 cells using ARTK(Me3)QTARKSTGGKAPRK peptide/ 100 uM alpha-ketoglutarate as substrate/cofactor incubated for 45 mins by MALDI assay
Measurement: IC50 = 52000 nM (pChEMBL 4.28000020980835)
Descriptors: MW 378.38, ALogP 3.34, HBA 5, HBD 3, PSA 108.75, QED 0.57
Compound (SMILES): COCC(=O)Nc1ccc(O)c(-c2cc(C(=O)O)ccn2)c1
InChIKey: HHHINYOXTBYXCI-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Competitive inhibition of N-terminal His6-tagged KDM4C (1 to 352 residues) (unknown origin) expressed in Escherichia coli Rosetta 2(DE3)pLysS using 250 uM ARK(Me3)STGGK peptide/50 uM alpha-ketoglutarate as substrate/cofactor by FDH coupling-based Lineweaver-Burk plot analysis
Measurement: IC50 = 14900 nM (pChEMBL 4.829999923706055)
Descriptors: MW 302.29, ALogP 1.74, HBA 5, HBD 3, PSA 108.75, QED 0.73
Compound (SMILES): CC(=O)Nc1ccc(O)c(-c2cc(C(=O)O)ccn2)c1
InChIKey: KWHVUGFDWSYWJF-UHFFFAOYSA-N
Target: Hypoxia-inducible factor 1-alpha inhibitor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWT6
Assay: Inhibition of N-terminal His6-tagged full-length FIH (unknown origin) expressed in Escherichia coli Rosetta 2(DE3)pLysS using SMDESGLPQLTSYDCEVNAPIQGSRNLLQGEELLRALDQVN peptide/100 uM alpha-ketoglutarate as substrate/cofactor incubated for 45 mins by MALDI assay
Measurement: IC50 > 500000 nM (pChEMBL 3.3010001182556152)
Descriptors: MW 272.26, ALogP 2.11, HBA 4, HBD 3, PSA 99.52, QED 0.74
Compound (SMILES): COc1ccc(S(=O)(=O)ON=C2C=C(C)C(=O)C(C)=C2)cc1
InChIKey: VEWFTYOFWIXCIO-UHFFFAOYSA-N
Target: Histone acetyltransferase p300 (SINGLE PROTEIN), Homo sapiens
UniProt: Q09472
Assay: Inhibition of P300 (unknown origin)
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 321.35, ALogP 2.23, HBA 6, HBD 0, PSA 82.03, QED 0.63
Compound (SMILES): Cc1ncoc1-c1nnc(SCCCN2CC3CCN(c4ccccc4)C3C2)n1C
InChIKey: SBCYNHCFJBYRJY-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Antagonist activity at human dopamine D2L receptor expressed in CHO cells assessed as inhibition of dopamine-mediated Ca+2 stimulation pretreated for 10 mins followed by addition of dopamine by fluo-4 AM dye-based FLIPR assay
Measurement: Ki = 158.49 nM (pChEMBL 6.800000190734863)
Descriptors: MW 424.57, ALogP 3.47, HBA 8, HBD 0, PSA 63.22, QED 0.43
Compound (SMILES): Cc1ncoc1-c1nnc(SCCCN2CC3CCN(c4ccc(C(F)(F)F)cc4F)C3C2)n1C
InChIKey: YTXILLIRPDSLHZ-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Antagonist activity at human dopamine D3 receptor expressed in CHO-K1 cell membranes after 90 mins by [35S]GTP-gamma-S binding assay in presence of 3 nM quinelorane
Measurement: Ki = 1.585 nM (pChEMBL 8.800000190734863)
Descriptors: MW 510.56, ALogP 4.63, HBA 8, HBD 0, PSA 63.22, QED 0.26
Compound (SMILES): Cc1ncoc1-c1nnc(SCCCN2CC3CCN(c4ccc(F)cc4)C3C2)n1C
InChIKey: FZEUFNLUEJZENL-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of recombinant human CYP2C19 expressed in baculosomes preincubated for 10 mins followed by cofactor addition measured every minute for 10 mins using 3-butyryl-7-methoxycoumarin as substrate by CYPEX assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 442.56, ALogP 3.61, HBA 8, HBD 0, PSA 63.22, QED 0.41
Compound (SMILES): Cc1ncoc1-c1nnc(SCCCN2CC3CCN(c4ccc(OC(F)(F)F)cc4)C3C2)n1C
InChIKey: SOTGCULHLGVSKQ-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Inhibition Assay: 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 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). 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: 79-85.
Measurement: Ki = 13.8 nM (pChEMBL 7.860000133514404)
Descriptors: MW 508.57, ALogP 4.37, HBA 9, HBD 0, PSA 72.45, QED 0.33
Compound (SMILES): Cc1ncoc1-c1nnc(SCCCN2CC3CCN(c4cccc(F)c4)C3C2)n1C
InChIKey: MYIVBWHBNPYKLU-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Inhibition Assay: 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 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). 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: 79-85.
Measurement: Ki = 2.95 nM (pChEMBL 8.529999732971191)
Descriptors: MW 442.56, ALogP 3.61, HBA 8, HBD 0, PSA 63.22, QED 0.41
Compound (SMILES): Cc1ncoc1-c1nnc(SCCCN2CC3CCN(c4cccc(C#N)c4)C3C2)n1C
InChIKey: QCALWRVXYCHRSG-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-spiperone from human dopamine D2 receptor expressed in CHO-K1 cell membranes after 120 mins by liquid scintillation counter method
Measurement: Ki = 31.62 nM (pChEMBL 7.5)
Descriptors: MW 449.58, ALogP 3.34, HBA 9, HBD 0, PSA 87.01, QED 0.4
Compound (SMILES): Cc1ncoc1-c1nnc(SCCCN2CC3CCN(c4cc(Cl)cc(Cl)c4)C3C2)n1C
InChIKey: JYMJYHGKDBZGLV-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Inhibition Assay: 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 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). 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: 79-85.
Measurement: Ki = 0.417 nM (pChEMBL 9.380000114440918)
Descriptors: MW 493.46, ALogP 4.78, HBA 8, HBD 0, PSA 63.22, QED 0.35
Compound (SMILES): Cc1ncoc1-c1nnc(SCCCN2CC3CCN(c4ccc(Cl)cc4Cl)C3C2)n1C
InChIKey: LJXBPSXSJHVHOV-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Inhibition Assay: 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 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). 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: 79-85.
Measurement: Ki = 5.25 nM (pChEMBL 8.279999732971191)
Descriptors: MW 493.46, ALogP 4.78, HBA 8, HBD 0, PSA 63.22, QED 0.35
Compound (SMILES): Cc1ncoc1-c1nnc(SCCCN2CC3CCN(c4c(F)cccc4F)C3C2)n1C
InChIKey: YZMAJSYJKLQFNB-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Inhibition Assay: 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 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). 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: 79-85.
Measurement: Ki = 2.63 nM (pChEMBL 8.579999923706055)
Descriptors: MW 460.55, ALogP 3.75, HBA 8, HBD 0, PSA 63.22, QED 0.39
Compound (SMILES): Cc1ncoc1-c1nnc(SCCCN2CC3CCN(c4ccccc4OC(F)(F)F)C3C2)n1C
InChIKey: ZFACTJHKUXTZMC-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Inhibition Assay: 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 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). 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: 79-85.
Measurement: Ki = 1.07 nM (pChEMBL 8.970000267028809)
Descriptors: MW 508.57, ALogP 4.37, HBA 9, HBD 0, PSA 72.45, QED 0.33
Compound (SMILES): Cn1c(SCCCN2CC3CCN(c4ccc(C(F)(F)F)cc4)C3C2)nnc1-c1cnccn1
InChIKey: IYZBRQAAJGEDNI-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of recombinant human CYP2C19 expressed in baculosomes preincubated for 10 mins followed by cofactor addition measured every minute for 10 mins using 3-butyryl-7-methoxycoumarin as substrate by CYPEX assay
Measurement: IC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 489.57, ALogP 3.98, HBA 8, HBD 0, PSA 62.97, QED 0.37
Compound (SMILES): Cn1c(SCCCN2CC3CCN(c4cccc(C(F)(F)F)c4)C3C2)nnc1-c1cnccn1
InChIKey: AENHFZZMNBETCL-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-spiperone from human dopamine D2 receptor expressed in CHO-K1 cell membranes after 120 mins by liquid scintillation counter method
Measurement: Ki = 31.62 nM (pChEMBL 7.5)
Descriptors: MW 489.57, ALogP 3.98, HBA 8, HBD 0, PSA 62.97, QED 0.37
Compound (SMILES): Cn1c(SCCCN2CC3CCN(c4ccccc4C(F)(F)F)C3C2)nnc1-c1cnccn1
InChIKey: MGPBHFVVGJDFMY-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-spiperone from human dopamine D2 receptor expressed in CHO-K1 cell membranes after 120 mins by liquid scintillation counter method
Measurement: Ki = 251.19 nM (pChEMBL 6.599999904632568)
Descriptors: MW 489.57, ALogP 3.98, HBA 8, HBD 0, PSA 62.97, QED 0.37
Compound (SMILES): Cn1c(SCCCN2CC3CCN(c4ccc(F)cc4)C3C2)nnc1-c1cnccn1
InChIKey: OACVKINMDRORAI-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG tail current expressed in HEK293 cells after 5 mins by patch clamp assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 439.56, ALogP 3.1, HBA 8, HBD 0, PSA 62.97, QED 0.41
Compound (SMILES): Cn1c(SCCCN2CC3CCN(c4cccc(F)c4)C3C2)nnc1-c1cnccn1
InChIKey: UDUUCGMSUBUXNS-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Inhibition Assay: 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 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). 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: 79-85.
Measurement: Ki = 4.57 nM (pChEMBL 8.34000015258789)
Descriptors: MW 439.56, ALogP 3.1, HBA 8, HBD 0, PSA 62.97, QED 0.41
Compound (SMILES): Cn1c(SCCCN2CC3CCN(c4ccccc4F)C3C2)nnc1-c1cnccn1
InChIKey: JRIJSUZYSFOPFI-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Functional Calcium Assay: Functional Calcium 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 seeded into black walled clear-base 384-well plates at a density of 8,000 cells per well and grown overnight at 37° C. After washing with the assay buffer (20 mM HEPES, 145 mM NaCl, 5 mM KCl, 5.5 mM glucose, 1 mM MgCl2 and 2 mM CaCl2, pH 7.4) containing 2.5 mM Probenecid, cells were incubated with the cytoplasmic Ca2+ probe Fluo-4 AM at 1 μM (final concentration), 37° C. for 60 min. Plates were washed three times as above and placed into a Fluorometric Imaging Plate Reader (FLIPR Tetra, Molecular Devices) to monitor cell fluorescence (ex=470-495 nm, em=515-575 nm) before and after the addition of different concentrations of test compounds. Compounds of invention were dissolved in DMSO and 200-fold diluted with assay buffer plus 0.01% Pluronic F-127. Cells were exposed first to test compounds for 10 min, then to a submaximal concentration of the hD2 receptor agonist dopamine (EC80, 50-140 nM). The fluorescence before compound addition (baseline) and before and after addition of agonist challenge was monitored. The peak of Ca2+ stimulation (baseline subtracted) was plotted versus the concentration of test compound and the curve fitted using a four-parameter logistic equation (XLfit) to assess the agonist/antagonist potency and maximal response.
Measurement: Ki = 240 nM (pChEMBL 6.619999885559082)
Descriptors: MW 439.56, ALogP 3.1, HBA 8, HBD 0, PSA 62.97, QED 0.41