lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): C[n+]1ccc2c(c1)c1ccccc1n2CCCCCCCCn1c2ccccc2c2c[n+](C)ccc21.[I-].[I-]
InChIKey: DQGOQXAHWCYMFP-UHFFFAOYSA-L
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human recombinant MAOB
Measurement: IC50 = 66 nM (pChEMBL 7.179999828338623)
Descriptors: MW 476.67, ALogP 6.59, HBA 2, HBD 0, PSA 17.62, QED 0.17
Compound (SMILES): C[n+]1ccc2c(c1)c1ccccc1n2CCCCCCCCCn1c2ccccc2c2c[n+](C)ccc21.[I-].[I-]
InChIKey: JMXLLZKAAIMOBQ-UHFFFAOYSA-L
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human recombinant MAOB
Measurement: IC50 = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 490.7, ALogP 6.98, HBA 2, HBD 0, PSA 17.62, QED 0.15
Compound (SMILES): COc1ccc2c(c1)c1c[n+](C)ccc1n2CCCCCCCCCn1c2ccc(OC)cc2c2c[n+](C)ccc21.[I-].[I-]
InChIKey: RPVPAKIWTVNRFR-UHFFFAOYSA-L
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human recombinant MAOB
Measurement: IC50 = 5100 nM (pChEMBL 5.289999961853027)
Descriptors: MW 550.75, ALogP 7, HBA 4, HBD 0, PSA 36.08, QED 0.12
Compound (SMILES): CC[n+]1ccc2c(c1)c1ccccc1n2CCCCCCCCCn1c2ccccc2c2c[n+](CC)ccc21.[I-].[I-]
InChIKey: NCGXVXAWEHFENJ-UHFFFAOYSA-L
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human recombinant MAOB
Measurement: IC50 = 2900 nM (pChEMBL 5.539999961853027)
Descriptors: MW 518.75, ALogP 7.95, HBA 2, HBD 0, PSA 17.62, QED 0.12
Compound (SMILES): OCC[n+]1ccc2c(c1)c1ccccc1n2CCCCCCCCCn1c2ccccc2c2c[n+](CCO)ccc21.[I-].[I-]
InChIKey: PMUWDIDEHFRKTL-UHFFFAOYSA-L
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human recombinant MAOB
Measurement: IC50 = 23100 nM (pChEMBL 4.639999866485596)
Descriptors: MW 550.75, ALogP 5.89, HBA 4, HBD 2, PSA 58.08, QED 0.13
Compound (SMILES): CCC[n+]1ccc2c(c1)c1ccccc1n2CCCCCCCCCn1c2ccccc2c2c[n+](CCC)ccc21.[I-].[I-]
InChIKey: NKPZBKMTEFBLRN-UHFFFAOYSA-L
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human recombinant MAOB
Measurement: IC50 = 20800 nM (pChEMBL 4.679999828338623)
Descriptors: MW 546.8, ALogP 8.73, HBA 2, HBD 0, PSA 17.62, QED 0.1
Compound (SMILES): CN1CCc2c(c3ccccc3n2CCCCCCn2c3c(c4ccccc42)CN(C)CC3)C1
InChIKey: BJBIAMDOQDJAHF-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human recombinant MAOB
Measurement: IC50 = 320 nM (pChEMBL 6.5)
Descriptors: MW 454.66, ALogP 5.83, HBA 4, HBD 0, PSA 16.34, QED 0.33
Compound (SMILES): CN1CCc2c(c3ccccc3n2CCCCCCCn2c3c(c4ccccc42)CN(C)CC3)C1
InChIKey: JYADYCRETGCYTE-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human recombinant MAOB
Measurement: IC50 = 650 nM (pChEMBL 6.190000057220459)
Descriptors: MW 468.69, ALogP 6.22, HBA 4, HBD 0, PSA 16.34, QED 0.29
Compound (SMILES): CN1CCc2c(c3ccccc3n2CCCCCCCCn2c3c(c4ccccc42)CN(C)CC3)C1
InChIKey: HCYMADVHXFCXLJ-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human recombinant MAOB
Measurement: IC50 = 690 nM (pChEMBL 6.159999847412109)
Descriptors: MW 482.72, ALogP 6.61, HBA 4, HBD 0, PSA 16.34, QED 0.25
Compound (SMILES): CN1CCc2c(c3ccccc3n2CCCCCCCCCn2c3c(c4ccccc42)CN(C)CC3)C1
InChIKey: UOUFDKZYWIUMHL-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human recombinant MAOB
Measurement: IC50 = 3900 nM (pChEMBL 5.409999847412109)
Descriptors: MW 496.74, ALogP 7, HBA 4, HBD 0, PSA 16.34, QED 0.22
Compound (SMILES): COc1ccc2c(c1)c1c(n2CCCCCCCCCn2c3c(c4cc(OC)ccc42)CN(C)CC3)CCN(C)C1
InChIKey: IFDUUTRILGIIKH-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human recombinant MAOB
Measurement: IC50 = 9800 nM (pChEMBL 5.010000228881836)
Descriptors: MW 556.8, ALogP 7.02, HBA 6, HBD 0, PSA 34.8, QED 0.18
Compound (SMILES): O=C1NC(=S)N/C1=C/c1ccc(=O)[nH]c1
InChIKey: ILQADRCJYUVSEN-ZZXKWVIFSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Binding affinity to recombinant human IDH1 R132H mutant expressed in Escherichia coli by isothermal titration calorimetric analysis in presence of NADPH
Measurement: Kd = 8900 nM (pChEMBL 5.050000190734863)
Descriptors: MW 221.24, ALogP -0.28, HBA 3, HBD 3, PSA 73.99, QED 0.45
Compound (SMILES): Nc1ccccc1NC(=O)c1ccc(CNC2=N[C@@H](c3ccccc3)CN2)cc1
InChIKey: ICQCMPQEFWZGRJ-OAQYLSRUSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of His-flagged recombinant HDAC8 (unknown origin) expressed in Escherichia coli BL21 pre-incubated for 15 mins before substrate addition by homogeneous fluorogenic HDAC assay
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 385.47, ALogP 3.31, HBA 5, HBD 4, PSA 91.54, QED 0.51
Compound (SMILES): Nc1ccccc1NC(=O)c1ccc(CSC2=N[C@@H](c3ccccc3)CN2)cc1
InChIKey: KHAQNNMTWYYNDF-OAQYLSRUSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of His-flagged recombinant HDAC8 (unknown origin) expressed in Escherichia coli BL21 pre-incubated for 15 mins before substrate addition by homogeneous fluorogenic HDAC assay
Measurement: IC50 = 14300 nM (pChEMBL 4.840000152587891)
Descriptors: MW 402.52, ALogP 4.45, HBA 5, HBD 3, PSA 79.51, QED 0.55
Compound (SMILES): Nc1ccccc1NC(=O)c1ccc(CSC2=N[C@@H](c3ccccc3)CO2)cc1
InChIKey: RALPPESOHBXWNC-OAQYLSRUSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of His-flagged recombinant HDAC8 (unknown origin) expressed in Escherichia coli BL21 pre-incubated for 15 mins before substrate addition by homogeneous fluorogenic HDAC assay
Measurement: IC50 = 9500 nM (pChEMBL 5.019999980926514)
Descriptors: MW 403.51, ALogP 4.88, HBA 5, HBD 2, PSA 76.71, QED 0.6
Compound (SMILES): CCS(=O)(=O)N1CCC([C@@H](C)n2c(C)c(C(=O)NCc3c(C)cc(C)[nH]c3=O)c3ccccc32)CC1
InChIKey: IOGHJBSCCRITPR-LJQANCHMSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Inhibition of EZH2 (unknown origin)
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 512.68, ALogP 3.81, HBA 5, HBD 2, PSA 104.27, QED 0.5
Compound (SMILES): COc1cc(C)[nH]c(=O)c1CNC(=O)c1c(C)n([C@H](C)C2CCOCC2)c2ccccc12
InChIKey: PFPSFENQCNMITC-MRXNPFEDSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Inhibition of wild type EZH2 (unknown origin) using histone H3 peptide (17 to 38 residues) by radiometric method
Measurement: IC50 = 0.5 nM (pChEMBL 9.300000190734863)
Descriptors: MW 437.54, ALogP 3.87, HBA 5, HBD 2, PSA 85.35, QED 0.61
Compound (SMILES): CCS(=O)(=O)N1CCC([C@@H](C)n2c(C)c(C(=O)NCc3c(OC)cc(C)[nH]c3=O)c3ccccc32)CC1
InChIKey: LHGUZCKPFXXVPV-GOSISDBHSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Inhibition of wild-type EZH2 in PRC2 complex (unknown origin) using RKQLATKAARK(Me3)SAPATGGVKKP-NH2 peptide substrate preincubated for 30 mins followed by addition of [3H]-SAM measured after 2 hrs by Topcount scintillation proximity assay
Measurement: IC50 < 1 nM (pChEMBL 9)
Descriptors: MW 528.68, ALogP 3.51, HBA 6, HBD 2, PSA 113.5, QED 0.46
Compound (SMILES): Nc1ccccc1NC(=O)c1ccc(CSC2=N[C@@H](Cc3ccccc3)CO2)cc1
InChIKey: NZBHFBGHVBAHOW-FQEVSTJZSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of His-flagged recombinant HDAC8 (unknown origin) expressed in Escherichia coli BL21 pre-incubated for 15 mins before substrate addition by homogeneous fluorogenic HDAC assay
Measurement: IC50 = 88000 nM (pChEMBL 4.059999942779541)
Descriptors: MW 417.53, ALogP 4.75, HBA 5, HBD 2, PSA 76.71, QED 0.57
Compound (SMILES): Nc1ccccc1NC(=O)c1ccc(CNC2=N[C@@H](c3ccccc3)CO2)cc1
InChIKey: FZUOCKMNLCIHTJ-OAQYLSRUSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of His-flagged recombinant HDAC8 (unknown origin) expressed in Escherichia coli BL21 pre-incubated for 15 mins before substrate addition by homogeneous fluorogenic HDAC assay
Measurement: IC50 = 88000 nM (pChEMBL 4.059999942779541)
Descriptors: MW 386.46, ALogP 3.74, HBA 5, HBD 3, PSA 88.74, QED 0.58
Compound (SMILES): Nc1ccccc1NC(=O)c1ccc(CNC2=N[C@H](c3ccccc3)CO2)cc1
InChIKey: FZUOCKMNLCIHTJ-NRFANRHFSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of His-flagged recombinant HDAC8 (unknown origin) expressed in Escherichia coli BL21 pre-incubated for 15 mins before substrate addition by homogeneous fluorogenic HDAC assay
Measurement: IC50 = 80700 nM (pChEMBL 4.090000152587891)
Descriptors: MW 386.46, ALogP 3.74, HBA 5, HBD 3, PSA 88.74, QED 0.58
Compound (SMILES): Nc1ccccc1NC(=O)c1ccc(CNC2=NC(c3ccc(F)cc3)CO2)cc1
InChIKey: PXBKFXDPVCGEAM-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of His-flagged recombinant HDAC8 (unknown origin) expressed in Escherichia coli BL21 pre-incubated for 15 mins before substrate addition by homogeneous fluorogenic HDAC assay
Measurement: IC50 = 33900 nM (pChEMBL 4.46999979019165)
Descriptors: MW 404.45, ALogP 3.88, HBA 5, HBD 3, PSA 88.74, QED 0.56
Compound (SMILES): Nc1ccccc1NC(=O)c1ccc(CNC2=NC(c3cccc(F)c3)CO2)cc1
InChIKey: OXEVGGGODZSGHA-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of His-flagged recombinant HDAC8 (unknown origin) expressed in Escherichia coli BL21 pre-incubated for 15 mins before substrate addition by homogeneous fluorogenic HDAC assay
Measurement: IC50 = 52200 nM (pChEMBL 4.28000020980835)
Descriptors: MW 404.45, ALogP 3.88, HBA 5, HBD 3, PSA 88.74, QED 0.56
Compound (SMILES): Nc1ccccc1NC(=O)c1ccc(CNC2=N[C@@H](c3ccc(O)cc3)CO2)cc1
InChIKey: QOEJRHVNEAVQSB-OAQYLSRUSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of His-flagged recombinant HDAC8 (unknown origin) expressed in Escherichia coli BL21 pre-incubated for 15 mins before substrate addition by homogeneous fluorogenic HDAC assay
Measurement: IC50 = 83300 nM (pChEMBL 4.079999923706055)
Descriptors: MW 402.45, ALogP 3.44, HBA 6, HBD 4, PSA 108.97, QED 0.49
Compound (SMILES): Nc1ccccc1NC(=O)c1ccc(CNC2=N[C@@H](Cc3ccccc3)CO2)cc1
InChIKey: XGUMOIKZVRQIMY-FQEVSTJZSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of His-flagged recombinant HDAC8 (unknown origin) expressed in Escherichia coli BL21 pre-incubated for 15 mins before substrate addition by homogeneous fluorogenic HDAC assay
Measurement: IC50 = 63000 nM (pChEMBL 4.199999809265137)
Descriptors: MW 400.48, ALogP 3.61, HBA 5, HBD 3, PSA 88.74, QED 0.55
Compound (SMILES): Nc1ccccc1NC(=O)c1ccc(CNC2=NC[C@H](c3ccccc3)O2)cc1
InChIKey: HIKRXEASUUGCMM-OAQYLSRUSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of His-flagged recombinant HDAC8 (unknown origin) expressed in Escherichia coli BL21 pre-incubated for 15 mins before substrate addition by homogeneous fluorogenic HDAC assay
Measurement: IC50 = 8100 nM (pChEMBL 5.090000152587891)
Descriptors: MW 386.46, ALogP 3.74, HBA 5, HBD 3, PSA 88.74, QED 0.58
Compound (SMILES): Nc1ccccc1NC(=O)c1ccc(CNC2=N[C@@H](c3ccccc3)[C@H](c3ccccc3)O2)cc1
InChIKey: FYAWEPJUGYZQDE-SVBPBHIXSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of His-flagged recombinant HDAC8 (unknown origin) expressed in Escherichia coli BL21 pre-incubated for 15 mins before substrate addition by homogeneous fluorogenic HDAC assay
Measurement: IC50 = 29200 nM (pChEMBL 4.539999961853027)
Descriptors: MW 462.55, ALogP 5.48, HBA 5, HBD 3, PSA 88.74, QED 0.33
Compound (SMILES): Nc1ccccc1NC(=O)c1ccc(CNC2=N[C@H](c3ccccc3)[C@H](c3ccccc3)O2)cc1
InChIKey: FYAWEPJUGYZQDE-SXOMAYOGSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of His-flagged recombinant HDAC8 (unknown origin) expressed in Escherichia coli BL21 pre-incubated for 15 mins before substrate addition by homogeneous fluorogenic HDAC assay
Measurement: IC50 = 25200 nM (pChEMBL 4.599999904632568)
Descriptors: MW 462.55, ALogP 5.48, HBA 5, HBD 3, PSA 88.74, QED 0.33
Compound (SMILES): CCn1c([C@@H](C)NS(=O)(=O)c2ccc(C#N)nc2)nc2cnc(C(F)(F)F)cc21
InChIKey: GAPKQSFTRWQZTL-SNVBAGLBSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes incubated for 5 mins in presence of NADPH and specific substrates by LC/MS/MS method
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 424.41, ALogP 2.78, HBA 7, HBD 1, PSA 113.56, QED 0.67
Compound (SMILES): CCn1c([C@@H](C)NS(=O)(=O)c2ccc(C#N)nc2)nc2cnc(C3CC3)cc21
InChIKey: BBYGAEPKKAXIBP-GFCCVEGCSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes incubated for 5 mins in presence of NADPH and specific substrates by LC/MS/MS method
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 396.48, ALogP 2.63, HBA 7, HBD 1, PSA 113.56, QED 0.69
Compound (SMILES): CC(=O)OC[C@]12CC[C@H]3[C@@H](CC=C4C=CCC(=O)[C@@]43C)[C@]1(O)CC[C@@]2(O)[C@@](C)(O)[C@H]1CC(C)=C(C)C(=O)O1
InChIKey: BFDSCBNQKZOCJH-GRVQADPTSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of BRD4-BD2 (unknown origin) by fluorescence polarization assay
Measurement: IC50 = 294 nM (pChEMBL 6.53000020980835)
Descriptors: MW 528.64, ALogP 3.09, HBA 8, HBD 3, PSA 130.36, QED 0.47
Compound (SMILES): CC(=O)OC[C@]12CC[C@H]3[C@@H](CC=C4CC=CC(=O)[C@@]43C)[C@]1(O)CC[C@@]2(O)[C@@](C)(O)[C@H]1CC(C)=C(C)C(=O)O1
InChIKey: RGHQRULWHKEQHE-GRVQADPTSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of BRD4-BD2 (unknown origin) by fluorescence polarization assay
Measurement: IC50 = 3917 nM (pChEMBL 5.409999847412109)
Descriptors: MW 528.64, ALogP 3.09, HBA 8, HBD 3, PSA 130.36, QED 0.37
Compound (SMILES): CC(=O)OC[C@]12CC[C@H]3[C@@H](C[C@H]4O[C@]45CC=CC(=O)[C@]35C)[C@]1(O)CC[C@@]2(O)[C@@](C)(O)[C@H]1CC(C)=C(C)C(=O)O1
InChIKey: GKMMNQCWGZRQTN-XVRWHRFDSA-N
Target: Bromodomain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25440
Assay: Binding affinity to human partial length BRD2 BD2 (E348to D455 residues) expressed in bacterial expression system using H4K5acIC8acK12acK16ac-biotinylated peptide as substrate preincubated for 30 mins followed by substrate addition by AlphaScreen assay
Measurement: IC50 = 244 nM (pChEMBL 6.610000133514404)
Descriptors: MW 544.64, ALogP 2.3, HBA 9, HBD 3, PSA 142.89, QED 0.36
Compound (SMILES): CC(=O)OC[C@]12CC[C@H]3[C@@H](C[C@@H]4O[C@@]45CC=CC(=O)[C@]35C)[C@]1(O)CC[C@@]2(O)[C@@](C)(O)[C@H]1CC(C)=C(C)C(=O)O1
InChIKey: GKMMNQCWGZRQTN-HBLJOAJLSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of BRD4-BD2 (unknown origin) by fluorescence polarization assay
Measurement: IC50 = 10770 nM (pChEMBL 4.96999979019165)
Descriptors: MW 544.64, ALogP 2.3, HBA 9, HBD 3, PSA 142.89, QED 0.36
Compound (SMILES): COc1cc(F)ccc1-c1c(CN(C)Cc2ccccc2)[nH]c2c(NS(C)(=O)=O)cc(C(C)C)cc12
InChIKey: MFAGIEMFDDDLMT-UHFFFAOYSA-N
Target: Progesterone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06401
Assay: Displacement of [3H]-progesterone from human progesterone receptor expressed in HEK293 cells by scintillation counting based radioligand competition binding assay
Measurement: Ki = 64.2 nM (pChEMBL 7.190000057220459)
Descriptors: MW 509.65, ALogP 6.11, HBA 4, HBD 2, PSA 74.43, QED 0.29
Compound (SMILES): COc1ccc(F)cc1-c1c[nH]c2c(NC(C)=O)cccc12
InChIKey: CVQKNTTYZMQDMD-UHFFFAOYSA-N
Target: Progesterone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06401
Assay: Displacement of [3H]-progesterone from human progesterone receptor expressed in HEK293 cells by scintillation counting based radioligand competition binding assay
Measurement: Ki = 688 nM (pChEMBL 6.159999847412109)
Descriptors: MW 298.32, ALogP 3.94, HBA 2, HBD 2, PSA 54.12, QED 0.77
Compound (SMILES): COc1cc(NS(C)(=O)=O)c2[nH]c(C)c(-c3ccccc3)c2c1
InChIKey: KBXBYJUQOSJVJK-UHFFFAOYSA-N
Target: Progesterone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06401
Assay: Displacement of [3H]-progesterone from human progesterone receptor expressed in HEK293 cells by scintillation counting based radioligand competition binding assay
Measurement: Ki = 3940 nM (pChEMBL 5.409999847412109)
Descriptors: MW 330.41, ALogP 3.52, HBA 3, HBD 2, PSA 71.19, QED 0.77
Compound (SMILES): COc1cc(NS(C)(=O)=O)c2[nH]c(C)c(-c3cc(F)ccc3OC)c2c1
InChIKey: URYARKSTCIJGME-UHFFFAOYSA-N
Target: Progesterone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06401
Assay: Displacement of [3H]-progesterone from human progesterone receptor expressed in HEK293 cells by scintillation counting based radioligand competition binding assay
Measurement: Ki = 22.3 nM (pChEMBL 7.650000095367432)
Descriptors: MW 378.43, ALogP 3.67, HBA 4, HBD 2, PSA 80.42, QED 0.71
Compound (SMILES): CS(=O)(=O)Nc1cccc2cc[nH]c12
InChIKey: MEWQFKSUHJZGCA-UHFFFAOYSA-N
Target: Progesterone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06401
Assay: Displacement of [3H]-progesterone from human progesterone receptor expressed in HEK293 cells by scintillation counting based radioligand competition binding assay
Measurement: Ki = 104 nM (pChEMBL 6.980000019073486)
Descriptors: MW 210.26, ALogP 1.54, HBA 2, HBD 2, PSA 61.96, QED 0.79
Compound (SMILES): COc1cc(F)ccc1-c1c(CN(C)Cc2ccccc2)[nH]c2c(NS(C)(=O)=O)cc(C(C)(C)C)cc12
InChIKey: KPKCYUMBFMYREG-UHFFFAOYSA-N
Target: Progesterone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06401
Assay: Displacement of [3H]-progesterone from human progesterone receptor expressed in HEK293 cells by scintillation counting based radioligand competition binding assay
Measurement: Ki = 253 nM (pChEMBL 6.599999904632568)
Descriptors: MW 523.67, ALogP 6.28, HBA 4, HBD 2, PSA 74.43, QED 0.28
Compound (SMILES): COc1cc(F)ccc1-c1c(Cc2ccccc2)[nH]c2c(NS(C)(=O)=O)cc(C(C)C)cc12
InChIKey: DLHJAQJQFLHXNZ-UHFFFAOYSA-N
Target: Progesterone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06401
Assay: Displacement of [3H]-progesterone from human progesterone receptor expressed in HEK293 cells by scintillation counting based radioligand competition binding assay
Measurement: Ki = 4000 nM (pChEMBL 5.400000095367432)
Descriptors: MW 466.58, ALogP 6.07, HBA 3, HBD 2, PSA 71.19, QED 0.35
Compound (SMILES): COc1ccc(F)cc1-c1c(-c2ccccc2)[nH]c2c(NS(C)(=O)=O)cccc12
InChIKey: VBGYFNUDIFNZRO-UHFFFAOYSA-N
Target: Progesterone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06401
Assay: Displacement of [3H]-progesterone from human progesterone receptor expressed in HEK293 cells by scintillation counting based radioligand competition binding assay
Measurement: Ki = 44.2 nM (pChEMBL 7.360000133514404)
Descriptors: MW 410.47, ALogP 5.02, HBA 3, HBD 2, PSA 71.19, QED 0.49
Compound (SMILES): COc1cc(F)ccc1-c1c(C)[nH]c2c(NS(C)(=O)=O)cc(F)cc12
InChIKey: SAVAEFOXNWPFKB-UHFFFAOYSA-N
Target: Progesterone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06401
Assay: Displacement of [3H]-progesterone from human progesterone receptor expressed in HEK293 cells by scintillation counting based radioligand competition binding assay
Measurement: Ki = 20.5 nM (pChEMBL 7.690000057220459)
Descriptors: MW 366.39, ALogP 3.8, HBA 3, HBD 2, PSA 71.19, QED 0.74
Compound (SMILES): COc1ccc(Cl)cc1-c1c[nH]c2c(NS(C)(=O)=O)cccc12
InChIKey: XCCRMYVOJIFMED-UHFFFAOYSA-N
Target: Progesterone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06401
Assay: Displacement of [3H]-progesterone from human progesterone receptor expressed in HEK293 cells by scintillation counting based radioligand competition binding assay
Measurement: Ki = 233 nM (pChEMBL 6.630000114440918)
Descriptors: MW 350.83, ALogP 3.87, HBA 3, HBD 2, PSA 71.19, QED 0.75
Compound (SMILES): CS(=O)(=O)Nc1cccc2c(-c3cccc(Cl)c3)c[nH]c12
InChIKey: SXIDZLMPGLSSSR-UHFFFAOYSA-N
Target: Progesterone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06401
Assay: Displacement of [3H]-progesterone from human progesterone receptor expressed in HEK293 cells by scintillation counting based radioligand competition binding assay
Measurement: Ki = 5.51 nM (pChEMBL 8.260000228881836)
Descriptors: MW 320.8, ALogP 3.86, HBA 2, HBD 2, PSA 61.96, QED 0.77
Compound (SMILES): COc1ccccc1-c1c[nH]c2c(NS(C)(=O)=O)cccc12
InChIKey: UTPNUAIWPWLJEC-UHFFFAOYSA-N
Target: Progesterone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06401
Assay: Displacement of [3H]-progesterone from human progesterone receptor expressed in HEK293 cells by scintillation counting based radioligand competition binding assay
Measurement: Ki = 86 nM (pChEMBL 7.070000171661377)
Descriptors: MW 316.38, ALogP 3.22, HBA 3, HBD 2, PSA 71.19, QED 0.78
Compound (SMILES): CS(=O)(=O)Nc1cccc2c(-c3ccc(F)cc3)c[nH]c12
InChIKey: JXRAVTIDZDMHLO-UHFFFAOYSA-N
Target: Progesterone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06401
Assay: Displacement of [3H]-progesterone from human progesterone receptor expressed in HEK293 cells by scintillation counting based radioligand competition binding assay
Measurement: Ki = 29 nM (pChEMBL 7.539999961853027)
Descriptors: MW 304.35, ALogP 3.35, HBA 2, HBD 2, PSA 61.96, QED 0.78
Compound (SMILES): NC(=O)c1cccc2c1C(=O)N(CCCN1CCOCC1)C2
InChIKey: FGRNZZFSZOJDGC-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Biochemical Assay: Preferably, for the screening method above cited, both the PARP protein and the 5H-phenanthridin-6-one-derived probe of formula (IP) are pre-mixed, or the PARP protein and the test compound are pre-mixed. In a further preferred screening method, the PARP proteins are PARP-1, PARP-2 and PARP-3. The term PARP protein encompasses full-length native proteins as well as fragments thereof. More preferably, R11 is hydrogen or methyl, m is 0 or 1; when m is 1, n is 3 or 6, X′″ is trifluoroacetate. The 5H-phenanthridin-6-one-derived probe (IP) was selected for its capability of binding to the PARP proteins, both encompassing full-length native proteins and fragments thereof.The polarization signal can be measured, e.g., by a plate reader such as the Saphire2 (Tecan). Data analysis was performed, e.g., by using the Dynafit software. Displacement data were also fitted, e.g., by using Excel spreadsheet (Microsoft Inc. Seattle, USA) to a four parameter logistic model (4PL), or Hill-Slope model. The assay was used to test compounds of the present invention. The displacement ability of the test compounds of formula (I) is in correlation with the compounds affinity for the NAD pocket of the enzyme. Specific probes of formula (IP) used in the assay are:  P1. 9-Dimethylamino-11,11-dimethyl-1-(3-{methyl-[(6-oxo-5,6-dihydro-phenanthridin-2-ylcarbamoyl)-methyl]-carbamoyl}-propyl-2,3,4,11-tetrahydro-naphtho[2,3-g]quinolinium trifluoroacetate;  P2. 9-Dimethylamino-11,11-dimethyl-1-[3-(3-{[(6-oxo-5,6-dihydro-phenanthridin-2-ylcarbamoyl)-methyl]-amino}-propylcarbamoyl)-propyl])-2,3,4,11-tetrahydro-naphtho[2,3-g]quinolinium trifluoroacetate;  P3. 9-Dimethylamino-11,11-dimethyl-1-[3-(6-{[(6-oxo-5,6-dihydro-phenanthridin-2-ylcarbamoyl)-methyl]-amino}-hexylcarbamoyl)-propyl]-2,3,4,11-tetrahydro-naphtho[2,3-g]quinolinium trifluoroacetate.A compound of formula (IP) as defined above can be prepared as described in WO 2010/133647.The assay is based on the use of a probe of formula (IP) that binds to the NAD binding pocket and takes advantage of the significant change in the polarization signal observed upon binding of the probe to PARP-1, -2 and -3. The ability of the probe of formula (IP) to bind full-length PARP-1, -2 and -3 has been previously reported (WO 2010/133647). The assay has been validated as described in WO 2010/133647.
Measurement: Kd = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 303.36, ALogP 0.46, HBA 4, HBD 1, PSA 75.87, QED 0.86
Compound (SMILES): NC(=O)c1cccc2c1C(=O)N(CCN1CCCc3ccccc31)C2
InChIKey: WGTJWDKKJAQXMI-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Biochemical Assay: Preferably, for the screening method above cited, both the PARP protein and the 5H-phenanthridin-6-one-derived probe of formula (IP) are pre-mixed, or the PARP protein and the test compound are pre-mixed. In a further preferred screening method, the PARP proteins are PARP-1, PARP-2 and PARP-3. The term PARP protein encompasses full-length native proteins as well as fragments thereof. More preferably, R11 is hydrogen or methyl, m is 0 or 1; when m is 1, n is 3 or 6, X′″ is trifluoroacetate. The 5H-phenanthridin-6-one-derived probe (IP) was selected for its capability of binding to the PARP proteins, both encompassing full-length native proteins and fragments thereof.The polarization signal can be measured, e.g., by a plate reader such as the Saphire2 (Tecan). Data analysis was performed, e.g., by using the Dynafit software. Displacement data were also fitted, e.g., by using Excel spreadsheet (Microsoft Inc. Seattle, USA) to a four parameter logistic model (4PL), or Hill-Slope model. The assay was used to test compounds of the present invention. The displacement ability of the test compounds of formula (I) is in correlation with the compounds affinity for the NAD pocket of the enzyme. Specific probes of formula (IP) used in the assay are:  P1. 9-Dimethylamino-11,11-dimethyl-1-(3-{methyl-[(6-oxo-5,6-dihydro-phenanthridin-2-ylcarbamoyl)-methyl]-carbamoyl}-propyl-2,3,4,11-tetrahydro-naphtho[2,3-g]quinolinium trifluoroacetate;  P2. 9-Dimethylamino-11,11-dimethyl-1-[3-(3-{[(6-oxo-5,6-dihydro-phenanthridin-2-ylcarbamoyl)-methyl]-amino}-propylcarbamoyl)-propyl])-2,3,4,11-tetrahydro-naphtho[2,3-g]quinolinium trifluoroacetate;  P3. 9-Dimethylamino-11,11-dimethyl-1-[3-(6-{[(6-oxo-5,6-dihydro-phenanthridin-2-ylcarbamoyl)-methyl]-amino}-hexylcarbamoyl)-propyl]-2,3,4,11-tetrahydro-naphtho[2,3-g]quinolinium trifluoroacetate.A compound of formula (IP) as defined above can be prepared as described in WO 2010/133647.The assay is based on the use of a probe of formula (IP) that binds to the NAD binding pocket and takes advantage of the significant change in the polarization signal observed upon binding of the probe to PARP-1, -2 and -3. The ability of the probe of formula (IP) to bind full-length PARP-1, -2 and -3 has been previously reported (WO 2010/133647). The assay has been validated as described in WO 2010/133647.
Measurement: Kd < 30 nM (pChEMBL 7.5229997634887695)
Descriptors: MW 335.41, ALogP 2.19, HBA 3, HBD 1, PSA 66.64, QED 0.93
Compound (SMILES): Cc1ccc(CN2CCC(CN3Cc4cccc(C(N)=O)c4C3=O)CC2)cc1
InChIKey: BIQGCSULLOYSIK-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P11103
Assay: Biochemical Assay: Affinity evaluation of the tested compounds and their selectivity with respect to the different PARP isoforms of interest was assessed in a displacement assay.The identification of compounds capable of binding several PARP proteins is carried out through a screening method including the steps ofa) providing a reaction mixture containing:the PARP protein isoform under investigation,a compound of formula (IP): wherein R10 is hydrogen or methyl, B is (CH2)nNH group, n is 2 to 6; m is 0 or 1 and X− is a counterion, and serial dilutions of the test compound;b) comparing the polarization signal generated in the absence of the test compound with the one generated in the presence of different concentrations of the test compound, andc) evaluating the ability of the test compound to displace the compound of formula (IP) as defined above indicated from a decreased fluorescence polarization level. The polarization signal can be measured, e.g., by a plate reader such as the Saphire2 (Tecan).
Measurement: IC50 = 80 nM (pChEMBL 7.099999904632568)
Descriptors: MW 377.49, ALogP 2.96, HBA 3, HBD 1, PSA 66.64, QED 0.87
Compound (SMILES): Cc1cccc(CN2CCC(CN3Cc4cccc(C(N)=O)c4C3=O)CC2)c1
InChIKey: CJNLSQVARWMQSJ-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P11103
Assay: Biochemical Assay: Affinity evaluation of the tested compounds and their selectivity with respect to the different PARP isoforms of interest was assessed in a displacement assay.The identification of compounds capable of binding several PARP proteins is carried out through a screening method including the steps ofa) providing a reaction mixture containing:the PARP protein isoform under investigation,a compound of formula (IP): wherein R10 is hydrogen or methyl, B is (CH2)nNH group, n is 2 to 6; m is 0 or 1 and X− is a counterion, and serial dilutions of the test compound;b) comparing the polarization signal generated in the absence of the test compound with the one generated in the presence of different concentrations of the test compound, andc) evaluating the ability of the test compound to displace the compound of formula (IP) as defined above indicated from a decreased fluorescence polarization level. The polarization signal can be measured, e.g., by a plate reader such as the Saphire2 (Tecan).
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 377.49, ALogP 2.96, HBA 3, HBD 1, PSA 66.64, QED 0.87
Compound (SMILES): CC(C)N1CCC(N2Cc3cccc(C(N)=O)c3C2=O)CC1
InChIKey: MSOMGRYOZBJWOT-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGN5
Assay: Binding affinity to recombinant human HisGST-tagged PARP-2 catalytic domain by surface plasmon resonance analysis
Measurement: Kd = 118 nM (pChEMBL 6.929999828338623)
Descriptors: MW 301.39, ALogP 1.61, HBA 3, HBD 1, PSA 66.64, QED 0.92
Compound (SMILES): Cc1ccccc1CN1CCC(N2Cc3cccc(C(N)=O)c3C2=O)CC1
InChIKey: LVFBZVPGEPDXOE-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Inhibition of PARP1 in human HeLa cells assessed as reduction of H2O2-induced PAR formation preincubated for 30 mins followed by H2O2 addition measured after 15 mins by immunocytochemical analysis
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 363.46, ALogP 2.71, HBA 3, HBD 1, PSA 66.64, QED 0.91
Compound (SMILES): Cc1cccc(CN2CCC(N3Cc4cccc(C(N)=O)c4C3=O)CC2)c1
InChIKey: ITESAINVLAOGRP-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P11103
Assay: Biochemical Assay: The assay is based on the use of a probe of formula (IP) that binds to the NAD binding pocket and takes advantage of the significant change in the polarization signal observed upon binding of the probe to PARP-1, -2 and -3.The probe of formula (IP) was tested for its ability to bind FL PARP-1, -2 and -3 in a titration experiment. The assay performances were then evaluated (ZÃ¢ factor) as well as the displacement of the probe by its scaffold and known commercially available PARP inhibitors. In all of the experiments, the polarization signal was measured using a Saphire2 plate reader (Tecan). Data analysis was performed using Dynafit software. In particular, titration data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, while displacement data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, Enzyme+Compound <==> Complex Enzyme-Compound, whereby binding of probe and compound on the enzyme are mutually exclusive.
Measurement: Kd < 30 nM (pChEMBL 7.5229997634887695)
Descriptors: MW 363.46, ALogP 2.71, HBA 3, HBD 1, PSA 66.64, QED 0.91
Compound (SMILES): Cc1ccc(CN2CCC(N3Cc4cccc(C(N)=O)c4C3=O)CC2)cc1
InChIKey: AHFNDPZJODGJTG-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P11103
Assay: Biochemical Assay: Affinity evaluation of the tested compounds and their selectivity with respect to the different PARP isoforms of interest was assessed in a displacement assay.The identification of compounds capable of binding several PARP proteins is carried out through a screening method including the steps ofa) providing a reaction mixture containing:the PARP protein isoform under investigation,a compound of formula (IP): wherein R10 is hydrogen or methyl, B is (CH2)nNH group, n is 2 to 6; m is 0 or 1 and X− is a counterion, and serial dilutions of the test compound;b) comparing the polarization signal generated in the absence of the test compound with the one generated in the presence of different concentrations of the test compound, andc) evaluating the ability of the test compound to displace the compound of formula (IP) as defined above indicated from a decreased fluorescence polarization level. The polarization signal can be measured, e.g., by a plate reader such as the Saphire2 (Tecan).
Measurement: IC50 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 363.46, ALogP 2.71, HBA 3, HBD 1, PSA 66.64, QED 0.91
Compound (SMILES): NC(=O)c1cccc2c1C(=O)N(C1CCN(Cc3cccc(Br)c3)CC1)C2
InChIKey: QPPJBNCZSPEBMT-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P11103
Assay: Biochemical Assay: The assay is based on the use of a probe of formula (IP) that binds to the NAD binding pocket and takes advantage of the significant change in the polarization signal observed upon binding of the probe to PARP-1, -2 and -3.The probe of formula (IP) was tested for its ability to bind FL PARP-1, -2 and -3 in a titration experiment. The assay performances were then evaluated (ZÃ¢ factor) as well as the displacement of the probe by its scaffold and known commercially available PARP inhibitors. In all of the experiments, the polarization signal was measured using a Saphire2 plate reader (Tecan). Data analysis was performed using Dynafit software. In particular, titration data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, while displacement data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, Enzyme+Compound <==> Complex Enzyme-Compound, whereby binding of probe and compound on the enzyme are mutually exclusive.
Measurement: Kd = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 428.33, ALogP 3.17, HBA 3, HBD 1, PSA 66.64, QED 0.81
Compound (SMILES): NC(=O)c1cccc2c1C(=O)N(C1CCN(Cc3ccc(Br)cc3)CC1)C2
InChIKey: UZWHCDLHNJMQBC-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P11103
Assay: Biochemical Assay: The assay is based on the use of a probe of formula (IP) that binds to the NAD binding pocket and takes advantage of the significant change in the polarization signal observed upon binding of the probe to PARP-1, -2 and -3.The probe of formula (IP) was tested for its ability to bind FL PARP-1, -2 and -3 in a titration experiment. The assay performances were then evaluated (ZÃ¢ factor) as well as the displacement of the probe by its scaffold and known commercially available PARP inhibitors. In all of the experiments, the polarization signal was measured using a Saphire2 plate reader (Tecan). Data analysis was performed using Dynafit software. In particular, titration data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, while displacement data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, Enzyme+Compound <==> Complex Enzyme-Compound, whereby binding of probe and compound on the enzyme are mutually exclusive.
Measurement: Kd < 30 nM (pChEMBL 7.5229997634887695)
Descriptors: MW 428.33, ALogP 3.17, HBA 3, HBD 1, PSA 66.64, QED 0.81
Compound (SMILES): NC(=O)c1cccc2c1C(=O)N(C1CCN(Cc3cccc(C(F)(F)F)c3)CC1)C2
InChIKey: HRVLKKDUPMXUNN-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P11103
Assay: Biochemical Assay: The assay is based on the use of a probe of formula (IP) that binds to the NAD binding pocket and takes advantage of the significant change in the polarization signal observed upon binding of the probe to PARP-1, -2 and -3.The probe of formula (IP) was tested for its ability to bind FL PARP-1, -2 and -3 in a titration experiment. The assay performances were then evaluated (ZÃ¢ factor) as well as the displacement of the probe by its scaffold and known commercially available PARP inhibitors. In all of the experiments, the polarization signal was measured using a Saphire2 plate reader (Tecan). Data analysis was performed using Dynafit software. In particular, titration data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, while displacement data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, Enzyme+Compound <==> Complex Enzyme-Compound, whereby binding of probe and compound on the enzyme are mutually exclusive.
Measurement: Kd = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 417.43, ALogP 3.42, HBA 3, HBD 1, PSA 66.64, QED 0.83
Compound (SMILES): CN(C)c1ccc(CN2CCC(N3Cc4cccc(C(N)=O)c4C3=O)CC2)cc1
InChIKey: SIZUTXILIWZSBX-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P11103
Assay: Biochemical Assay: The assay is based on the use of a probe of formula (IP) that binds to the NAD binding pocket and takes advantage of the significant change in the polarization signal observed upon binding of the probe to PARP-1, -2 and -3.The probe of formula (IP) was tested for its ability to bind FL PARP-1, -2 and -3 in a titration experiment. The assay performances were then evaluated (ZÃ¢ factor) as well as the displacement of the probe by its scaffold and known commercially available PARP inhibitors. In all of the experiments, the polarization signal was measured using a Saphire2 plate reader (Tecan). Data analysis was performed using Dynafit software. In particular, titration data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, while displacement data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, Enzyme+Compound <==> Complex Enzyme-Compound, whereby binding of probe and compound on the enzyme are mutually exclusive.
Measurement: Kd = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 392.5, ALogP 2.47, HBA 4, HBD 1, PSA 69.88, QED 0.85
Compound (SMILES): NC(=O)c1cccc2c1C(=O)N(C1CCN(Cc3cccnc3)CC1)C2
InChIKey: OVLKNUOJLKTKMD-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Inhibition of PARP1 in human HeLa cells assessed as reduction of H2O2-induced PAR formation preincubated for 30 mins followed by H2O2 addition measured after 15 mins by immunocytochemical analysis
Measurement: IC50 = 13400 nM (pChEMBL 4.869999885559082)
Descriptors: MW 350.42, ALogP 1.8, HBA 4, HBD 1, PSA 79.53, QED 0.91
Compound (SMILES): NC(=O)c1cccc2c1C(=O)N(C1CCN(Cc3ccccn3)CC1)C2
InChIKey: CCGJVGSERDTSKY-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Biochemical Assay: The assay is based on the use of a probe of formula (IP) that binds to the NAD binding pocket and takes advantage of the significant change in the polarization signal observed upon binding of the probe to PARP-1, -2 and -3. The ability of the probe of formula (IP) to bind full-length PARP-1, -2 and -3 has been previously reported (WO 2010/133647). The assay has been validated as described in WO 2010/133647.Affinity binding constants (Kd) and DC50s (the compound concentration at which the polarization signal is diminished by 50% compared to untreated controls) of the test compounds can be determined as explained in WO 2010133647.
Measurement: Kd = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 350.42, ALogP 1.8, HBA 4, HBD 1, PSA 79.53, QED 0.91
Compound (SMILES): Cn1cccc1CN1CCC(N2Cc3cccc(C(N)=O)c3C2=O)CC1
InChIKey: RQJRYJMBMVWZEY-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P11103
Assay: Biochemical Assay: The assay is based on the use of a probe of formula (IP) that binds to the NAD binding pocket and takes advantage of the significant change in the polarization signal observed upon binding of the probe to PARP-1, -2 and -3.The probe of formula (IP) was tested for its ability to bind FL PARP-1, -2 and -3 in a titration experiment. The assay performances were then evaluated (ZÃ¢ factor) as well as the displacement of the probe by its scaffold and known commercially available PARP inhibitors. In all of the experiments, the polarization signal was measured using a Saphire2 plate reader (Tecan). Data analysis was performed using Dynafit software. In particular, titration data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, while displacement data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, Enzyme+Compound <==> Complex Enzyme-Compound, whereby binding of probe and compound on the enzyme are mutually exclusive.
Measurement: Kd = 66 nM (pChEMBL 7.179999828338623)
Descriptors: MW 352.44, ALogP 1.74, HBA 4, HBD 1, PSA 71.57, QED 0.91
Compound (SMILES): NC(=O)c1cccc2c1C(=O)N(C1CCN(Cc3cccc4[nH]ccc34)CC1)C2
InChIKey: ZAILEKMOQXHRQJ-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P11103
Assay: Biochemical Assay: The assay is based on the use of a probe of formula (IP) that binds to the NAD binding pocket and takes advantage of the significant change in the polarization signal observed upon binding of the probe to PARP-1, -2 and -3.The probe of formula (IP) was tested for its ability to bind FL PARP-1, -2 and -3 in a titration experiment. The assay performances were then evaluated (ZÃ¢ factor) as well as the displacement of the probe by its scaffold and known commercially available PARP inhibitors. In all of the experiments, the polarization signal was measured using a Saphire2 plate reader (Tecan). Data analysis was performed using Dynafit software. In particular, titration data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, while displacement data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, Enzyme+Compound <==> Complex Enzyme-Compound, whereby binding of probe and compound on the enzyme are mutually exclusive.
Measurement: Kd = 34 nM (pChEMBL 7.46999979019165)
Descriptors: MW 388.47, ALogP 2.89, HBA 3, HBD 2, PSA 82.43, QED 0.72
Compound (SMILES): NC(=O)c1cccc2c1C(=O)N(C1CCN(Cc3ccc4[nH]ccc4c3)CC1)C2
InChIKey: WFMWDGUOCLWPNZ-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Inhibition of PARP1 in human HeLa cells assessed as reduction of H2O2-induced PAR formation preincubated for 30 mins followed by H2O2 addition measured after 15 mins by immunocytochemical analysis
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 388.47, ALogP 2.89, HBA 3, HBD 2, PSA 82.43, QED 0.72
Compound (SMILES): NC(=O)c1cccc2c1C(=O)N(C1CCN(C3CCC(F)(F)CC3)CC1)C2
InChIKey: UYRWBJIRLVJAMX-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Binding affinity to recombinant human HisGST-tagged PARP-1 catalytic domain by surface plasmon resonance analysis
Measurement: Kd = 15.7 nM (pChEMBL 7.800000190734863)
Descriptors: MW 377.44, ALogP 2.78, HBA 3, HBD 1, PSA 66.64, QED 0.88
Compound (SMILES): NC(=O)c1cc(F)cc2c1C(=O)N(C1CCN(C3CCC(F)(F)CC3)CC1)C2
InChIKey: ARYVAQSYRLZVQD-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase tankyrase-1 (SINGLE PROTEIN), Homo sapiens
UniProt: O95271
Assay: Inhibition of human recombinant PARP5a (E1023 to T1327 amino acids) incubated for 4 hrs by fluorescence anisotropy binding assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 395.43, ALogP 2.92, HBA 3, HBD 1, PSA 66.64, QED 0.86
Compound (SMILES): NC(=O)c1ccc(F)c2c1C(=O)N(C1CCN(C3CCC(F)(F)CC3)CC1)C2
InChIKey: MSLJBNUZYHPJBH-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P11103
Assay: Biochemical Assay: The assay is based on the use of a probe of formula (IP) that binds to the NAD binding pocket and takes advantage of the significant change in the polarization signal observed upon binding of the probe to PARP-1, -2 and -3.The probe of formula (IP) was tested for its ability to bind FL PARP-1, -2 and -3 in a titration experiment. The assay performances were then evaluated (ZÃ¢ factor) as well as the displacement of the probe by its scaffold and known commercially available PARP inhibitors. In all of the experiments, the polarization signal was measured using a Saphire2 plate reader (Tecan). Data analysis was performed using Dynafit software. In particular, titration data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, while displacement data were fitted to the following equilibria: Enzyme+probe <==> Complex Enzyme-probe, Enzyme+Compound <==> Complex Enzyme-Compound, whereby binding of probe and compound on the enzyme are mutually exclusive.
Measurement: Kd = 80 nM (pChEMBL 7.099999904632568)
Descriptors: MW 395.43, ALogP 2.92, HBA 3, HBD 1, PSA 66.64, QED 0.86
Compound (SMILES): NC(=O)c1cc(Cl)cc2c1C(=O)N(C1CCN(C3CCC(F)(F)CC3)CC1)C2
InChIKey: MDAVOHPUDVLWCS-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P11103
Assay: Biochemical Assay: Affinity evaluation of the tested compounds and their selectivity with respect to the different PARP isoforms of interest was assessed in a displacement assay.The identification of compounds capable of binding several PARP proteins is carried out through a screening method including the steps ofa) providing a reaction mixture containing:the PARP protein isoform under investigation,a compound of formula (IP): wherein R10 is hydrogen or methyl, B is (CH2)nNH group, n is 2 to 6; m is 0 or 1 and X− is a counterion, and serial dilutions of the test compound;b) comparing the polarization signal generated in the absence of the test compound with the one generated in the presence of different concentrations of the test compound, andc) evaluating the ability of the test compound to displace the compound of formula (IP) as defined above indicated from a decreased fluorescence polarization level. The polarization signal can be measured, e.g., by a plate reader such as the Saphire2 (Tecan).
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 411.88, ALogP 3.44, HBA 3, HBD 1, PSA 66.64, QED 0.83
Compound (SMILES): NC(=O)c1cc(F)cc2c1C(=O)N(C1CCN(C3CCC(Cl)(Cl)CC3)CC1)C2
InChIKey: CXTSPYBVOJLLFL-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P11103
Assay: Biochemical Assay: Affinity evaluation of the tested compounds and their selectivity with respect to the different PARP isoforms of interest was assessed in a displacement assay.The identification of compounds capable of binding several PARP proteins is carried out through a screening method including the steps ofa) providing a reaction mixture containing:the PARP protein isoform under investigation,a compound of formula (IP): wherein R10 is hydrogen or methyl, B is (CH2)nNH group, n is 2 to 6; m is 0 or 1 and X− is a counterion, and serial dilutions of the test compound;b) comparing the polarization signal generated in the absence of the test compound with the one generated in the presence of different concentrations of the test compound, andc) evaluating the ability of the test compound to displace the compound of formula (IP) as defined above indicated from a decreased fluorescence polarization level. The polarization signal can be measured, e.g., by a plate reader such as the Saphire2 (Tecan).
Measurement: IC50 = 80 nM (pChEMBL 7.099999904632568)
Descriptors: MW 428.34, ALogP 3.46, HBA 3, HBD 1, PSA 66.64, QED 0.75
Compound (SMILES): O=c1[nH]c(=O)n([C@@H]2O[C@H](COP(=O)(O)CP(=O)(O)O)[C@@H](O)[C@H]2O)cc1F
InChIKey: UTTXPVADCDYRBS-JXOAFFINSA-N
Target: 5'-nucleotidase (SINGLE PROTEIN), Homo sapiens
UniProt: P21589
Assay: Inhibition of CD73 in human MDA-MB-231 cell membranes using [2,8-3H]AMP as substrate measured after 25 mins by scintillation counting method
Measurement: Ki = 4.51 nM (pChEMBL 8.350000381469727)
Descriptors: MW 420.18, ALogP -2.37, HBA 9, HBD 6, PSA 208.61, QED 0.27