lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC#CC(=O)N[C@H]1CC[C@H](CCN2CCC(c3cccc4c3CCO4)CC2)CC1
InChIKey: XBBWJMUBMHLUNQ-XUTJKUGGSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Radioligand Binding Assay: Aliquots of membrane preparations were thawed at RT, resupended in assay buffer (D2, D3: 50 mM Tris-HCl, 120 mM NaCl, 5 mM MgCl2, 1 mM EDTA, 5 mM KCl, 1.5 mM CaCl2, pH=7.4; 5-HT2A: 50 mM Tris-HCl, 10 mM MgCl2, 1 mM EGTA, pH=7.4), homogenized with a Polytron for 20-30 sec at 12.000 rpm and adjusted to a final concentration of approximately 7.5 ug protein/well (D2, D3) and 15 ug protein/well (5-HT2A), respectively.The binding affinity (Ki) of the compounds was determined using radioligand binding. Membranes were incubated in a total volume of 200 ul with a fixed concentration of radioligand (final concentration approximately 0.7 nM [3H]-spiperone for D2, 0.5 nM [3H]-spiperone for D3, and 1.1 nM [3H]-ketanserin for 5-HT2A) and ten concentrations of test compound in ranging between 10 uM-0.1 nM for 1 h at RT. At the end of the incubation, the reaction mixtures were filtered on to unifilter 96-well white microplates with bonded GF/C filters.
Measurement: Ki = 45.9 nM (pChEMBL 7.340000152587891)
Descriptors: MW 394.56, ALogP 3.89, HBA 3, HBD 1, PSA 41.57, QED 0.77
Compound (SMILES): O=CN[C@H]1CC[C@H](CCN2CCC(c3cccc4c3CCO4)CC2)CC1
InChIKey: GZNLRQUVYFCLCG-UAPYVXQJSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Radioligand Binding Assay: Aliquots of membrane preparations were thawed at RT, resupended in assay buffer (D2, D3: 50 mM Tris-HCl, 120 mM NaCl, 5 mM MgCl2, 1 mM EDTA, 5 mM KCl, 1.5 mM CaCl2, pH=7.4; 5-HT2A: 50 mM Tris-HCl, 10 mM MgCl2, 1 mM EGTA, pH=7.4), homogenized with a Polytron for 20-30 sec at 12.000 rpm and adjusted to a final concentration of approximately 7.5 ug protein/well (D2, D3) and 15 ug protein/well (5-HT2A), respectively.The binding affinity (Ki) of the compounds was determined using radioligand binding. Membranes were incubated in a total volume of 200 ul with a fixed concentration of radioligand (final concentration approximately 0.7 nM [3H]-spiperone for D2, 0.5 nM [3H]-spiperone for D3, and 1.1 nM [3H]-ketanserin for 5-HT2A) and ten concentrations of test compound in ranging between 10 uM-0.1 nM for 1 h at RT. At the end of the incubation, the reaction mixtures were filtered on to unifilter 96-well white microplates with bonded GF/C filters.
Measurement: Ki = 11.5 nM (pChEMBL 7.940000057220459)
Descriptors: MW 356.51, ALogP 3.5, HBA 3, HBD 1, PSA 41.57, QED 0.79
Compound (SMILES): CC(C)(C)Oc1ccc(C(=O)N[C@H]2CC[C@H](CCN3CCC(c4cccc5c4CCO5)CC3)CC2)cc1
InChIKey: XKUSJISCOLOOOS-OJBMAJLDSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Radioligand Binding Assay: Aliquots of membrane preparations were thawed at RT, resupended in assay buffer (D2, D3: 50 mM Tris-HCl, 120 mM NaCl, 5 mM MgCl2, 1 mM EDTA, 5 mM KCl, 1.5 mM CaCl2, pH=7.4; 5-HT2A: 50 mM Tris-HCl, 10 mM MgCl2, 1 mM EGTA, pH=7.4), homogenized with a Polytron for 20-30 sec at 12.000 rpm and adjusted to a final concentration of approximately 7.5 ug protein/well (D2, D3) and 15 ug protein/well (5-HT2A), respectively.The binding affinity (Ki) of the compounds was determined using radioligand binding. Membranes were incubated in a total volume of 200 ul with a fixed concentration of radioligand (final concentration approximately 0.7 nM [3H]-spiperone for D2, 0.5 nM [3H]-spiperone for D3, and 1.1 nM [3H]-ketanserin for 5-HT2A) and ten concentrations of test compound in ranging between 10 uM-0.1 nM for 1 h at RT. At the end of the incubation, the reaction mixtures were filtered on to unifilter 96-well white microplates with bonded GF/C filters.
Measurement: Ki = 42.8 nM (pChEMBL 7.369999885559082)
Descriptors: MW 504.72, ALogP 6.36, HBA 4, HBD 1, PSA 50.8, QED 0.48
Compound (SMILES): O=C(N[C@H]1CC[C@H](CCN2CCC(c3cccc4c3CCO4)CC2)CC1)c1ccc(Cl)cc1Cl
InChIKey: VZIIAQQJQFQYID-XYWHTSSQSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Radioligand Binding Assay: Aliquots of membrane preparations were thawed at RT, resupended in assay buffer (D2, D3: 50 mM Tris-HCl, 120 mM NaCl, 5 mM MgCl2, 1 mM EDTA, 5 mM KCl, 1.5 mM CaCl2, pH=7.4; 5-HT2A: 50 mM Tris-HCl, 10 mM MgCl2, 1 mM EGTA, pH=7.4), homogenized with a Polytron for 20-30 sec at 12.000 rpm and adjusted to a final concentration of approximately 7.5 ug protein/well (D2, D3) and 15 ug protein/well (5-HT2A), respectively.The binding affinity (Ki) of the compounds was determined using radioligand binding. Membranes were incubated in a total volume of 200 ul with a fixed concentration of radioligand (final concentration approximately 0.7 nM [3H]-spiperone for D2, 0.5 nM [3H]-spiperone for D3, and 1.1 nM [3H]-ketanserin for 5-HT2A) and ten concentrations of test compound in ranging between 10 uM-0.1 nM for 1 h at RT. At the end of the incubation, the reaction mixtures were filtered on to unifilter 96-well white microplates with bonded GF/C filters.
Measurement: Ki = 31.5 nM (pChEMBL 7.5)
Descriptors: MW 501.5, ALogP 6.49, HBA 3, HBD 1, PSA 41.57, QED 0.49
Compound (SMILES): O=C(N[C@H]1CC[C@H](CCN2CCC(c3cccc4c3CCO4)CC2)CC1)c1ccc(-n2cccc2)cc1
InChIKey: FMLDUWPAAHKNPY-HNKWHGCMSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Radioligand Binding Assay: Aliquots of membrane preparations were thawed at RT, resupended in assay buffer (D2, D3: 50 mM Tris-HCl, 120 mM NaCl, 5 mM MgCl2, 1 mM EDTA, 5 mM KCl, 1.5 mM CaCl2, pH=7.4; 5-HT2A: 50 mM Tris-HCl, 10 mM MgCl2, 1 mM EGTA, pH=7.4), homogenized with a Polytron for 20-30 sec at 12.000 rpm and adjusted to a final concentration of approximately 7.5 ug protein/well (D2, D3) and 15 ug protein/well (5-HT2A), respectively.The binding affinity (Ki) of the compounds was determined using radioligand binding. Membranes were incubated in a total volume of 200 ul with a fixed concentration of radioligand (final concentration approximately 0.7 nM [3H]-spiperone for D2, 0.5 nM [3H]-spiperone for D3, and 1.1 nM [3H]-ketanserin for 5-HT2A) and ten concentrations of test compound in ranging between 10 uM-0.1 nM for 1 h at RT. At the end of the incubation, the reaction mixtures were filtered on to unifilter 96-well white microplates with bonded GF/C filters.
Measurement: Ki = 85.1 nM (pChEMBL 7.070000171661377)
Descriptors: MW 497.68, ALogP 5.97, HBA 4, HBD 1, PSA 46.5, QED 0.44
Compound (SMILES): O=C(N[C@H]1CC[C@H](CCN2CCC(c3cccc4c3CCO4)CC2)CC1)c1ccc(-c2ccccc2)cc1
InChIKey: LYHUWMRZCXPRBP-BEESLVRJSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Radioligand Binding Assay: Aliquots of membrane preparations were thawed at RT, resupended in assay buffer (D2, D3: 50 mM Tris-HCl, 120 mM NaCl, 5 mM MgCl2, 1 mM EDTA, 5 mM KCl, 1.5 mM CaCl2, pH=7.4; 5-HT2A: 50 mM Tris-HCl, 10 mM MgCl2, 1 mM EGTA, pH=7.4), homogenized with a Polytron for 20-30 sec at 12.000 rpm and adjusted to a final concentration of approximately 7.5 ug protein/well (D2, D3) and 15 ug protein/well (5-HT2A), respectively.The binding affinity (Ki) of the compounds was determined using radioligand binding. Membranes were incubated in a total volume of 200 ul with a fixed concentration of radioligand (final concentration approximately 0.7 nM [3H]-spiperone for D2, 0.5 nM [3H]-spiperone for D3, and 1.1 nM [3H]-ketanserin for 5-HT2A) and ten concentrations of test compound in ranging between 10 uM-0.1 nM for 1 h at RT. At the end of the incubation, the reaction mixtures were filtered on to unifilter 96-well white microplates with bonded GF/C filters.
Measurement: Ki = 501.4 nM (pChEMBL 6.300000190734863)
Descriptors: MW 508.71, ALogP 6.85, HBA 3, HBD 1, PSA 41.57, QED 0.38
Compound (SMILES): O=C(N[C@H]1CC[C@H](CCN2CCC(c3cccc4c3CCO4)CC2)CC1)c1ccc(-c2cccnc2)cc1
InChIKey: MOHZYINNROZMOQ-YLIUREIVSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Radioligand Binding Assay: Aliquots of membrane preparations were thawed at RT, resupended in assay buffer (D2, D3: 50 mM Tris-HCl, 120 mM NaCl, 5 mM MgCl2, 1 mM EDTA, 5 mM KCl, 1.5 mM CaCl2, pH=7.4; 5-HT2A: 50 mM Tris-HCl, 10 mM MgCl2, 1 mM EGTA, pH=7.4), homogenized with a Polytron for 20-30 sec at 12.000 rpm and adjusted to a final concentration of approximately 7.5 ug protein/well (D2, D3) and 15 ug protein/well (5-HT2A), respectively.The binding affinity (Ki) of the compounds was determined using radioligand binding. Membranes were incubated in a total volume of 200 ul with a fixed concentration of radioligand (final concentration approximately 0.7 nM [3H]-spiperone for D2, 0.5 nM [3H]-spiperone for D3, and 1.1 nM [3H]-ketanserin for 5-HT2A) and ten concentrations of test compound in ranging between 10 uM-0.1 nM for 1 h at RT. At the end of the incubation, the reaction mixtures were filtered on to unifilter 96-well white microplates with bonded GF/C filters.
Measurement: Ki = 5.35 nM (pChEMBL 8.270000457763672)
Descriptors: MW 509.69, ALogP 6.24, HBA 4, HBD 1, PSA 54.46, QED 0.41
Compound (SMILES): O=C(Cc1noc2ccccc12)N[C@H]1CC[C@H](CCN2CCC(c3cccc4c3CCO4)CC2)CC1
InChIKey: XOPMGCDIMXYMGV-AFARHQOCSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Radioligand Binding Assay: Aliquots of membrane preparations were thawed at RT, resupended in assay buffer (D2, D3: 50 mM Tris-HCl, 120 mM NaCl, 5 mM MgCl2, 1 mM EDTA, 5 mM KCl, 1.5 mM CaCl2, pH=7.4; 5-HT2A: 50 mM Tris-HCl, 10 mM MgCl2, 1 mM EGTA, pH=7.4), homogenized with a Polytron for 20-30 sec at 12.000 rpm and adjusted to a final concentration of approximately 7.5 ug protein/well (D2, D3) and 15 ug protein/well (5-HT2A), respectively.The binding affinity (Ki) of the compounds was determined using radioligand binding. Membranes were incubated in a total volume of 200 ul with a fixed concentration of radioligand (final concentration approximately 0.7 nM [3H]-spiperone for D2, 0.5 nM [3H]-spiperone for D3, and 1.1 nM [3H]-ketanserin for 5-HT2A) and ten concentrations of test compound in ranging between 10 uM-0.1 nM for 1 h at RT. At the end of the incubation, the reaction mixtures were filtered on to unifilter 96-well white microplates with bonded GF/C filters.
Measurement: Ki = 243.6 nM (pChEMBL 6.610000133514404)
Descriptors: MW 487.64, ALogP 5.25, HBA 5, HBD 1, PSA 67.6, QED 0.49
Compound (SMILES): O=C(Cc1ccc2c(c1)OCO2)N[C@H]1CC[C@H](CCN2CCC(c3cccc4c3CCO4)CC2)CC1
InChIKey: ZTIHCPRBAJJIRW-SAIGFBBZSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Radioligand Binding Assay: Aliquots of membrane preparations were thawed at RT, resupended in assay buffer (D2, D3: 50 mM Tris-HCl, 120 mM NaCl, 5 mM MgCl2, 1 mM EDTA, 5 mM KCl, 1.5 mM CaCl2, pH=7.4; 5-HT2A: 50 mM Tris-HCl, 10 mM MgCl2, 1 mM EGTA, pH=7.4), homogenized with a Polytron for 20-30 sec at 12.000 rpm and adjusted to a final concentration of approximately 7.5 ug protein/well (D2, D3) and 15 ug protein/well (5-HT2A), respectively.The binding affinity (Ki) of the compounds was determined using radioligand binding. Membranes were incubated in a total volume of 200 ul with a fixed concentration of radioligand (final concentration approximately 0.7 nM [3H]-spiperone for D2, 0.5 nM [3H]-spiperone for D3, and 1.1 nM [3H]-ketanserin for 5-HT2A) and ten concentrations of test compound in ranging between 10 uM-0.1 nM for 1 h at RT. At the end of the incubation, the reaction mixtures were filtered on to unifilter 96-well white microplates with bonded GF/C filters.
Measurement: Ki = 3.65 nM (pChEMBL 8.4399995803833)
Descriptors: MW 490.64, ALogP 4.84, HBA 5, HBD 1, PSA 60.03, QED 0.6
Compound (SMILES): CS(=O)(=O)c1ccc(C(=O)N[C@H]2CC[C@H](CCN3CCC(c4cccc5c4CCO5)CC3)CC2)cc1
InChIKey: OVSOSNSBPWXIPD-SAIGFBBZSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Radioligand Binding Assay: Aliquots of membrane preparations were thawed at RT, resupended in assay buffer (D2, D3: 50 mM Tris-HCl, 120 mM NaCl, 5 mM MgCl2, 1 mM EDTA, 5 mM KCl, 1.5 mM CaCl2, pH=7.4; 5-HT2A: 50 mM Tris-HCl, 10 mM MgCl2, 1 mM EGTA, pH=7.4), homogenized with a Polytron for 20-30 sec at 12.000 rpm and adjusted to a final concentration of approximately 7.5 ug protein/well (D2, D3) and 15 ug protein/well (5-HT2A), respectively.The binding affinity (Ki) of the compounds was determined using radioligand binding. Membranes were incubated in a total volume of 200 ul with a fixed concentration of radioligand (final concentration approximately 0.7 nM [3H]-spiperone for D2, 0.5 nM [3H]-spiperone for D3, and 1.1 nM [3H]-ketanserin for 5-HT2A) and ten concentrations of test compound in ranging between 10 uM-0.1 nM for 1 h at RT. At the end of the incubation, the reaction mixtures were filtered on to unifilter 96-well white microplates with bonded GF/C filters.
Measurement: Ki = 14.7 nM (pChEMBL 7.829999923706055)
Descriptors: MW 510.7, ALogP 4.58, HBA 5, HBD 1, PSA 75.71, QED 0.59
Compound (SMILES): CCOC(=O)[C@H](C)N[C@@H](Cc1ccc(-c2cccc(Cl)c2)cc1)C(=O)Nc1nnn[nH]1
InChIKey: SAPRXCUXOWRKQA-UGSOOPFHSA-N
Target: Neprilysin (SINGLE PROTEIN), Homo sapiens
UniProt: P08473
Assay: In Vitro Inhibition Assay: The in vitro inhibition of recombinant human neutral endopeptidase (NEP, EC 3.424.11) can be determined as follows:Recombinant human neutral endopeptidase (expressed in insect cells and purified using standard methods, final concentration 7 pM) is pre-incubated with test compounds at various concentrations for 1 hour at room temperature in 10 mM sodium phosphate buffer at pH 7.4, containing 150 mM NaCl and 0.05% (w/v) CHAPS. The enzymatic reaction is started by the addition of a synthetic peptide substrate Cys(PT14)-Arg-Arg-Leu-Trp-OH to a final concentration of 0.7 uM. Substrate hydrolysis leads to an increase fluorescence lifetime (FLT) of PT14 measured by the means of a FLT reader as described by Doering et al. (2009). The effect of the compound on the enzymatic activity was determined after 1 hour (t=60 min) incubation at room temperature.
Measurement: IC50 = 0.09 nM (pChEMBL 10.050000190734863)
Descriptors: MW 442.91, ALogP 2.61, HBA 7, HBD 3, PSA 121.89, QED 0.44
Compound (SMILES): C[C@H](N[C@@H](Cc1ccc(-c2cc(Cl)ccc2Cl)cc1)C(=O)Nc1nnn[nH]1)C(=O)OC(C)(C)C
InChIKey: JBZSEEYKQRWFMS-DJJJIMSYSA-N
Target: Neprilysin (SINGLE PROTEIN), Homo sapiens
UniProt: P08473
Assay: In Vitro Inhibition Assay: The in vitro inhibition of recombinant human neutral endopeptidase (NEP, EC 3.424.11) can be determined as follows:Recombinant human neutral endopeptidase (expressed in insect cells and purified using standard methods, final concentration 7 pM) is pre-incubated with test compounds at various concentrations for 1 hour at room temperature in 10 mM sodium phosphate buffer at pH 7.4, containing 150 mM NaCl and 0.05% (w/v) CHAPS. The enzymatic reaction is started by the addition of a synthetic peptide substrate Cys(PT14)-Arg-Arg-Leu-Trp-OH to a final concentration of 0.7 uM. Substrate hydrolysis leads to an increase fluorescence lifetime (FLT) of PT14 measured by the means of a FLT reader as described by Doering et al. (2009). The effect of the compound on the enzymatic activity was determined after 1 hour (t=60 min) incubation at room temperature.
Measurement: IC50 = 0.3 nM (pChEMBL 9.520000457763672)
Descriptors: MW 505.41, ALogP 4.04, HBA 7, HBD 3, PSA 121.89, QED 0.4
Compound (SMILES): C[C@H](N[C@@H](Cc1ccc(-c2ccccc2)cc1)C(=O)NC1=NNNN1)C(=O)O
InChIKey: FBGDBZRYMVLGTB-LRDDRELGSA-N
Target: Neprilysin (SINGLE PROTEIN), Homo sapiens
UniProt: P08473
Assay: In Vitro Inhibition Assay: The in vitro inhibition of recombinant human neutral endopeptidase (NEP, EC 3.424.11) can be determined as follows:Recombinant human neutral endopeptidase (expressed in insect cells and purified using standard methods, final concentration 7 pM) is pre-incubated with test compounds at various concentrations for 1 hour at room temperature in 10 mM sodium phosphate buffer at pH 7.4, containing 150 mM NaCl and 0.05% (w/v) CHAPS. The enzymatic reaction is started by the addition of a synthetic peptide substrate Cys(PT14)-Arg-Arg-Leu-Trp-OH to a final concentration of 0.7 uM. Substrate hydrolysis leads to an increase fluorescence lifetime (FLT) of PT14 measured by the means of a FLT reader as described by Doering et al. (2009). The effect of the compound on the enzymatic activity was determined after 1 hour (t=60 min) incubation at room temperature.
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 382.42, ALogP 0.33, HBA 7, HBD 6, PSA 126.88, QED 0.41
Compound (SMILES): C[C@H](N[C@@H](Cc1ccc(-c2cccc(Cl)c2)cc1)C(=O)Nc1cc(O)no1)C(=O)O
InChIKey: WTZARVQRNNDSGI-SJCJKPOMSA-N
Target: Neprilysin (SINGLE PROTEIN), Homo sapiens
UniProt: P08473
Assay: In Vitro Inhibition Assay: The in vitro inhibition of recombinant human neutral endopeptidase (NEP, EC 3.424.11) can be determined as follows:Recombinant human neutral endopeptidase (expressed in insect cells and purified using standard methods, final concentration 7 pM) is pre-incubated with test compounds at various concentrations for 1 hour at room temperature in 10 mM sodium phosphate buffer at pH 7.4, containing 150 mM NaCl and 0.05% (w/v) CHAPS. The enzymatic reaction is started by the addition of a synthetic peptide substrate Cys(PT14)-Arg-Arg-Leu-Trp-OH to a final concentration of 0.7 uM. Substrate hydrolysis leads to an increase fluorescence lifetime (FLT) of PT14 measured by the means of a FLT reader as described by Doering et al. (2009). The effect of the compound on the enzymatic activity was determined after 1 hour (t=60 min) incubation at room temperature.
Measurement: IC50 = 2.4 nM (pChEMBL 8.619999885559082)
Descriptors: MW 429.86, ALogP 3.31, HBA 6, HBD 4, PSA 124.69, QED 0.43
Compound (SMILES): C[C@H](N[C@@H](Cc1ccc(-c2cccc(Cl)c2)cc1)C(=O)NC1=NNNN1C)C(=O)O
InChIKey: MTJFYHNYFJERSW-SJCJKPOMSA-N
Target: Neprilysin (SINGLE PROTEIN), Homo sapiens
UniProt: P08473
Assay: In Vitro Inhibition Assay: The in vitro inhibition of recombinant human neutral endopeptidase (NEP, EC 3.424.11) can be determined as follows:Recombinant human neutral endopeptidase (expressed in insect cells and purified using standard methods, final concentration 7 pM) is pre-incubated with test compounds at various concentrations for 1 hour at room temperature in 10 mM sodium phosphate buffer at pH 7.4, containing 150 mM NaCl and 0.05% (w/v) CHAPS. The enzymatic reaction is started by the addition of a synthetic peptide substrate Cys(PT14)-Arg-Arg-Leu-Trp-OH to a final concentration of 0.7 uM. Substrate hydrolysis leads to an increase fluorescence lifetime (FLT) of PT14 measured by the means of a FLT reader as described by Doering et al. (2009). The effect of the compound on the enzymatic activity was determined after 1 hour (t=60 min) incubation at room temperature.
Measurement: IC50 = 91 nM (pChEMBL 7.039999961853027)
Descriptors: MW 430.9, ALogP 1.32, HBA 7, HBD 5, PSA 118.09, QED 0.45
Compound (SMILES): O=C(O)[C@H](CCc1ccccc1)N[C@@H](Cc1ccc(-c2cccc(Cl)c2)cc1)C(=O)NC1=NNNN1
InChIKey: UICHKPYJUXBLSG-GOTSBHOMSA-N
Target: Neprilysin (SINGLE PROTEIN), Homo sapiens
UniProt: P08473
Assay: In Vitro Inhibition Assay: The in vitro inhibition of recombinant human neutral endopeptidase (NEP, EC 3.424.11) can be determined as follows:Recombinant human neutral endopeptidase (expressed in insect cells and purified using standard methods, final concentration 7 pM) is pre-incubated with test compounds at various concentrations for 1 hour at room temperature in 10 mM sodium phosphate buffer at pH 7.4, containing 150 mM NaCl and 0.05% (w/v) CHAPS. The enzymatic reaction is started by the addition of a synthetic peptide substrate Cys(PT14)-Arg-Arg-Leu-Trp-OH to a final concentration of 0.7 uM. Substrate hydrolysis leads to an increase fluorescence lifetime (FLT) of PT14 measured by the means of a FLT reader as described by Doering et al. (2009). The effect of the compound on the enzymatic activity was determined after 1 hour (t=60 min) incubation at room temperature.
Measurement: IC50 = 0.2 nM (pChEMBL 9.699999809265137)
Descriptors: MW 506.99, ALogP 2.59, HBA 7, HBD 6, PSA 126.88, QED 0.25
Compound (SMILES): CC[C@H](N[C@@H](Cc1ccc(-c2cccc(Cl)c2)cc1)C(=O)NC1=NNNN1)C(=O)O
InChIKey: XNHFEUDQDQMOGY-IRXDYDNUSA-N
Target: Neprilysin (SINGLE PROTEIN), Homo sapiens
UniProt: P08473
Assay: In Vitro Inhibition Assay: The in vitro inhibition of recombinant human neutral endopeptidase (NEP, EC 3.424.11) can be determined as follows:Recombinant human neutral endopeptidase (expressed in insect cells and purified using standard methods, final concentration 7 pM) is pre-incubated with test compounds at various concentrations for 1 hour at room temperature in 10 mM sodium phosphate buffer at pH 7.4, containing 150 mM NaCl and 0.05% (w/v) CHAPS. The enzymatic reaction is started by the addition of a synthetic peptide substrate Cys(PT14)-Arg-Arg-Leu-Trp-OH to a final concentration of 0.7 uM. Substrate hydrolysis leads to an increase fluorescence lifetime (FLT) of PT14 measured by the means of a FLT reader as described by Doering et al. (2009). The effect of the compound on the enzymatic activity was determined after 1 hour (t=60 min) incubation at room temperature.
Measurement: IC50 = 0.2 nM (pChEMBL 9.699999809265137)
Descriptors: MW 430.9, ALogP 1.37, HBA 7, HBD 6, PSA 126.88, QED 0.37
Compound (SMILES): CC(=O)CSc1ccc(-n2c(C)ccc2C)cc1
InChIKey: VQOCPXWGLNYGCL-UHFFFAOYSA-N
Target: Pyruvate kinase PKM (SINGLE PROTEIN), Homo sapiens
UniProt: P14618
Assay: Inhibition Assay: Primary screening was performed using PKM2 in the presence of FBP. Compounds were chosen as potential "hits" if the compound demonstrated inhibition of PKM2 activity greater than 50%. Activity was measured by monitoring the concentration of NADH. Pyruvate, produced by the enzymatic activity of pyruvate kinase, is converted into lactate by lactate dehydrogenase, which requires the consumption of NADH (NADH→NAD+). Thus, the activity of PKM2 was indirectly measured by monitoring the consumption of NADH through fluorescence assays. Additionally, the activity of the PKM2 enzyme was directly monitored by measuring the production of ATP, as ATP is produced when phosphoenolpyruvate is converted to pyruvate by PKM2.
Measurement: IC50 = 90000 nM (pChEMBL 4.050000190734863)
Descriptors: MW 259.37, ALogP 3.78, HBA 3, HBD 0, PSA 22, QED 0.78
Compound (SMILES): CCCCCN1/C(=C/C=C/c2n(CCCCC)c3cc(Cl)c(Cl)cc3[n+]2CCCC)N(CCCC)c2cc(Cl)c(Cl)cc21
InChIKey: KWYWEULYVHSAMT-UHFFFAOYSA-N
Target: Pyruvate kinase PKM (SINGLE PROTEIN), Homo sapiens
UniProt: P14618
Assay: Inhibition Assay: Primary screening was performed using PKM2 in the presence of FBP. Compounds were chosen as potential "hits" if the compound demonstrated inhibition of PKM2 activity greater than 50%. Activity was measured by monitoring the concentration of NADH. Pyruvate, produced by the enzymatic activity of pyruvate kinase, is converted into lactate by lactate dehydrogenase, which requires the consumption of NADH (NADH→NAD+). Thus, the activity of PKM2 was indirectly measured by monitoring the consumption of NADH through fluorescence assays. Additionally, the activity of the PKM2 enzyme was directly monitored by measuring the production of ATP, as ATP is produced when phosphoenolpyruvate is converted to pyruvate by PKM2.
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 665.6, ALogP 11.7, HBA 3, HBD 0, PSA 15.29, QED 0.11
Compound (SMILES): O=C(O)CN1C(=O)/C(=C/c2ccc(OC(=O)c3ccccc3I)cc2)SC1=S
InChIKey: RYIHRMGNQOGLPJ-DHDCSXOGSA-N
Target: Pyruvate kinase PKM (SINGLE PROTEIN), Homo sapiens
UniProt: P14618
Assay: Inhibition Assay: Primary screening was performed using PKM2 in the presence of FBP. Compounds were chosen as potential "hits" if the compound demonstrated inhibition of PKM2 activity greater than 50%. Activity was measured by monitoring the concentration of NADH. Pyruvate, produced by the enzymatic activity of pyruvate kinase, is converted into lactate by lactate dehydrogenase, which requires the consumption of NADH (NADH→NAD+). Thus, the activity of PKM2 was indirectly measured by monitoring the consumption of NADH through fluorescence assays. Additionally, the activity of the PKM2 enzyme was directly monitored by measuring the production of ATP, as ATP is produced when phosphoenolpyruvate is converted to pyruvate by PKM2.
Measurement: IC50 = 20000 nM (pChEMBL 4.699999809265137)
Descriptors: MW 525.35, ALogP 3.8, HBA 6, HBD 1, PSA 83.91, QED 0.21
Compound (SMILES): C=C(NC(C)C)c1cc2c(=O)oc3ccc(C)cc3c2s1
InChIKey: JNTPJFIGZNHYRW-UHFFFAOYSA-N
Target: Pyruvate kinase PKM (SINGLE PROTEIN), Homo sapiens
UniProt: P14618
Assay: Inhibition Assay: Primary screening was performed using PKM2 in the presence of FBP. Compounds were chosen as potential "hits" if the compound demonstrated inhibition of PKM2 activity greater than 50%. Activity was measured by monitoring the concentration of NADH. Pyruvate, produced by the enzymatic activity of pyruvate kinase, is converted into lactate by lactate dehydrogenase, which requires the consumption of NADH (NADH→NAD+). Thus, the activity of PKM2 was indirectly measured by monitoring the consumption of NADH through fluorescence assays. Additionally, the activity of the PKM2 enzyme was directly monitored by measuring the production of ATP, as ATP is produced when phosphoenolpyruvate is converted to pyruvate by PKM2.
Measurement: IC50 = 70000 nM (pChEMBL 4.159999847412109)
Descriptors: MW 299.39, ALogP 4.28, HBA 4, HBD 1, PSA 42.24, QED 0.73
Compound (SMILES): COc1ccc(/C=N/n2c(S)nnc2C(F)(F)F)cc1O
InChIKey: ZIYNKKNAQUMLPF-PJQLUOCWSA-N
Target: Transthyretin (SINGLE PROTEIN), Homo sapiens
UniProt: P02766
Assay: FP Assay: The FP assay was then adapted for HTS and used to screen ~120,000 small molecule library for compounds that displaced probe 5 from the T4 binding of TTR. The FP assay was performed in 384-well plate using very low concentration of probe 5 (1.5 nM) and TTR (50 nM) in a 10 μL assay volume. A detergent (0.01% Triton-X100) was added to the assay buffer to avoid any false positive hits from promiscuous, aggregate-based inhibitors. The assay demonstrated robust performance, with a very good dynamic range (−70-230 mP) and a Z′ factor in the range of 0.57-0.78 (FIGS. 4A and 4B). "Hits" were defined as compounds that resulted in at least 50% decrease in fluorescence polarization and demonstrated relative fluorescence between 70 and 130%. Many fluorescence quenchers and enhancers having less than 70% and greater than 130% total fluorescence relative to a control, respectively, were excluded from the hit list. 200 compounds were designated as positive hits (0.167% hit rate).
Measurement: IC50 = 277 nM (pChEMBL 6.559999942779541)
Descriptors: MW 318.28, ALogP 2.18, HBA 7, HBD 2, PSA 72.53, QED 0.67
Compound (SMILES): Cc1n[nH]c(C)c1CCCOc1ccccc1F
InChIKey: SIXWAFDHGGAHMK-UHFFFAOYSA-N
Target: Transthyretin (SINGLE PROTEIN), Homo sapiens
UniProt: P02766
Assay: FP Assay: The FP assay was then adapted for HTS and used to screen ~120,000 small molecule library for compounds that displaced probe 5 from the T4 binding of TTR. The FP assay was performed in 384-well plate using very low concentration of probe 5 (1.5 nM) and TTR (50 nM) in a 10 μL assay volume. A detergent (0.01% Triton-X100) was added to the assay buffer to avoid any false positive hits from promiscuous, aggregate-based inhibitors. The assay demonstrated robust performance, with a very good dynamic range (−70-230 mP) and a Z′ factor in the range of 0.57-0.78 (FIGS. 4A and 4B). "Hits" were defined as compounds that resulted in at least 50% decrease in fluorescence polarization and demonstrated relative fluorescence between 70 and 130%. Many fluorescence quenchers and enhancers having less than 70% and greater than 130% total fluorescence relative to a control, respectively, were excluded from the hit list. 200 compounds were designated as positive hits (0.167% hit rate).
Measurement: IC50 = 296 nM (pChEMBL 6.53000020980835)
Descriptors: MW 248.3, ALogP 3.18, HBA 2, HBD 1, PSA 37.91, QED 0.83
Compound (SMILES): Cc1ccc(O)c(Nc2ccccc2C(=O)O)c1Cl
InChIKey: KIGPXNGSSJLSBH-UHFFFAOYSA-N
Target: Transthyretin (SINGLE PROTEIN), Homo sapiens
UniProt: P02766
Assay: FP Assay: The FP assay was then adapted for HTS and used to screen ~120,000 small molecule library for compounds that displaced probe 5 from the T4 binding of TTR. The FP assay was performed in 384-well plate using very low concentration of probe 5 (1.5 nM) and TTR (50 nM) in a 10 μL assay volume. A detergent (0.01% Triton-X100) was added to the assay buffer to avoid any false positive hits from promiscuous, aggregate-based inhibitors. The assay demonstrated robust performance, with a very good dynamic range (−70-230 mP) and a Z′ factor in the range of 0.57-0.78 (FIGS. 4A and 4B). "Hits" were defined as compounds that resulted in at least 50% decrease in fluorescence polarization and demonstrated relative fluorescence between 70 and 130%. Many fluorescence quenchers and enhancers having less than 70% and greater than 130% total fluorescence relative to a control, respectively, were excluded from the hit list. 200 compounds were designated as positive hits (0.167% hit rate).
Measurement: IC50 = 504 nM (pChEMBL 6.300000190734863)
Descriptors: MW 277.71, ALogP 3.8, HBA 3, HBD 3, PSA 69.56, QED 0.75
Compound (SMILES): N#CC1(C#N)c2c([nH]c3ccccc23)OC2c3ccccc3C(=O)C21
InChIKey: WIXKBVZEUXXNDG-UHFFFAOYSA-N
Target: Transthyretin (SINGLE PROTEIN), Homo sapiens
UniProt: P02766
Assay: FP Assay: The FP assay was then adapted for HTS and used to screen ~120,000 small molecule library for compounds that displaced probe 5 from the T4 binding of TTR. The FP assay was performed in 384-well plate using very low concentration of probe 5 (1.5 nM) and TTR (50 nM) in a 10 μL assay volume. A detergent (0.01% Triton-X100) was added to the assay buffer to avoid any false positive hits from promiscuous, aggregate-based inhibitors. The assay demonstrated robust performance, with a very good dynamic range (−70-230 mP) and a Z′ factor in the range of 0.57-0.78 (FIGS. 4A and 4B). "Hits" were defined as compounds that resulted in at least 50% decrease in fluorescence polarization and demonstrated relative fluorescence between 70 and 130%. Many fluorescence quenchers and enhancers having less than 70% and greater than 130% total fluorescence relative to a control, respectively, were excluded from the hit list. 200 compounds were designated as positive hits (0.167% hit rate).
Measurement: IC50 = 586 nM (pChEMBL 6.230000019073486)
Descriptors: MW 325.33, ALogP 3.4, HBA 4, HBD 1, PSA 89.67, QED 0.69
Compound (SMILES): CN1C(=N)NC(=O)/C1=C/c1cc(Br)c(O)c(Br)c1
InChIKey: XBSUMZSVMPLGBU-YWEYNIOJSA-N
Target: Transthyretin (SINGLE PROTEIN), Homo sapiens
UniProt: P02766
Assay: Determination of Binding Constants of HITS to TTR: Dissociation Constants (Kd) associated with the binding of ligands to TTR are expressed in nM. Thermodynamic Binding Parameters associated with ligand binding to TTR; Binding free energies (ΔG), enthalpies (ΔH), and binding entropies (TΔS) values are reported in units of kcal mol−1.
Measurement: Kd = 245 nM (pChEMBL 6.610000133514404)
Descriptors: MW 375.02, ALogP 2.25, HBA 3, HBD 3, PSA 76.42, QED 0.66
Compound (SMILES): Cc1n[nH]c(C)c1CCc1nc2c3ccccc3[nH]c(=S)n2n1
InChIKey: WZWIDDPFFNKVMF-UHFFFAOYSA-N
Target: Transthyretin (SINGLE PROTEIN), Homo sapiens
UniProt: P02766
Assay: FP Assay: The FP assay was then adapted for HTS and used to screen ~120,000 small molecule library for compounds that displaced probe 5 from the T4 binding of TTR. The FP assay was performed in 384-well plate using very low concentration of probe 5 (1.5 nM) and TTR (50 nM) in a 10 μL assay volume. A detergent (0.01% Triton-X100) was added to the assay buffer to avoid any false positive hits from promiscuous, aggregate-based inhibitors. The assay demonstrated robust performance, with a very good dynamic range (−70-230 mP) and a Z′ factor in the range of 0.57-0.78 (FIGS. 4A and 4B). "Hits" were defined as compounds that resulted in at least 50% decrease in fluorescence polarization and demonstrated relative fluorescence between 70 and 130%. Many fluorescence quenchers and enhancers having less than 70% and greater than 130% total fluorescence relative to a control, respectively, were excluded from the hit list. 200 compounds were designated as positive hits (0.167% hit rate).
Measurement: IC50 = 1306 nM (pChEMBL 5.880000114440918)
Descriptors: MW 324.41, ALogP 3.07, HBA 5, HBD 2, PSA 74.66, QED 0.57
Compound (SMILES): O=C(O)c1cc2nc(-c3ccc(Cl)c(Cl)c3)cc(C(F)(F)F)n2n1
InChIKey: LVEXBYVBMOIMAU-UHFFFAOYSA-N
Target: Transthyretin (SINGLE PROTEIN), Homo sapiens
UniProt: P02766
Assay: FP Assay: The FP assay was then adapted for HTS and used to screen ~120,000 small molecule library for compounds that displaced probe 5 from the T4 binding of TTR. The FP assay was performed in 384-well plate using very low concentration of probe 5 (1.5 nM) and TTR (50 nM) in a 10 μL assay volume. A detergent (0.01% Triton-X100) was added to the assay buffer to avoid any false positive hits from promiscuous, aggregate-based inhibitors. The assay demonstrated robust performance, with a very good dynamic range (−70-230 mP) and a Z′ factor in the range of 0.57-0.78 (FIGS. 4A and 4B). "Hits" were defined as compounds that resulted in at least 50% decrease in fluorescence polarization and demonstrated relative fluorescence between 70 and 130%. Many fluorescence quenchers and enhancers having less than 70% and greater than 130% total fluorescence relative to a control, respectively, were excluded from the hit list. 200 compounds were designated as positive hits (0.167% hit rate).
Measurement: IC50 = 2585 nM (pChEMBL 5.590000152587891)
Descriptors: MW 376.12, ALogP 4.42, HBA 4, HBD 1, PSA 67.49, QED 0.72
Compound (SMILES): COc1ccccc1CC(=O)c1ccc(O)cc1O
InChIKey: MNDXXAUUVUMRBM-UHFFFAOYSA-N
Target: Transthyretin (SINGLE PROTEIN), Homo sapiens
UniProt: P02766
Assay: FP Assay: The FP assay was then adapted for HTS and used to screen ~120,000 small molecule library for compounds that displaced probe 5 from the T4 binding of TTR. The FP assay was performed in 384-well plate using very low concentration of probe 5 (1.5 nM) and TTR (50 nM) in a 10 μL assay volume. A detergent (0.01% Triton-X100) was added to the assay buffer to avoid any false positive hits from promiscuous, aggregate-based inhibitors. The assay demonstrated robust performance, with a very good dynamic range (−70-230 mP) and a Z′ factor in the range of 0.57-0.78 (FIGS. 4A and 4B). "Hits" were defined as compounds that resulted in at least 50% decrease in fluorescence polarization and demonstrated relative fluorescence between 70 and 130%. Many fluorescence quenchers and enhancers having less than 70% and greater than 130% total fluorescence relative to a control, respectively, were excluded from the hit list. 200 compounds were designated as positive hits (0.167% hit rate).
Measurement: IC50 = 2656 nM (pChEMBL 5.579999923706055)
Descriptors: MW 258.27, ALogP 2.53, HBA 4, HBD 2, PSA 66.76, QED 0.83
Compound (SMILES): Cc1ccccc1/C=C1\SC(=O)NC1=O
InChIKey: PWNAVEGPVDNSIM-TWGQIWQCSA-N
Target: Transthyretin (SINGLE PROTEIN), Homo sapiens
UniProt: P02766
Assay: FP Assay: The FP assay was then adapted for HTS and used to screen ~120,000 small molecule library for compounds that displaced probe 5 from the T4 binding of TTR. The FP assay was performed in 384-well plate using very low concentration of probe 5 (1.5 nM) and TTR (50 nM) in a 10 μL assay volume. A detergent (0.01% Triton-X100) was added to the assay buffer to avoid any false positive hits from promiscuous, aggregate-based inhibitors. The assay demonstrated robust performance, with a very good dynamic range (−70-230 mP) and a Z′ factor in the range of 0.57-0.78 (FIGS. 4A and 4B). "Hits" were defined as compounds that resulted in at least 50% decrease in fluorescence polarization and demonstrated relative fluorescence between 70 and 130%. Many fluorescence quenchers and enhancers having less than 70% and greater than 130% total fluorescence relative to a control, respectively, were excluded from the hit list. 200 compounds were designated as positive hits (0.167% hit rate).
Measurement: IC50 = 3349 nM (pChEMBL 5.46999979019165)
Descriptors: MW 219.26, ALogP 2.32, HBA 3, HBD 1, PSA 46.17, QED 0.74
Compound (SMILES): O=C(O)Cc1ccccc1Nc1c(O)cccc1Cl
InChIKey: BKAGDCNIMWLNRF-UHFFFAOYSA-N
Target: Transthyretin (SINGLE PROTEIN), Homo sapiens
UniProt: P02766
Assay: Determination of Binding Constants of HITS to TTR: Dissociation Constants (Kd) associated with the binding of ligands to TTR are expressed in nM. Thermodynamic Binding Parameters associated with ligand binding to TTR; Binding free energies (ΔG), enthalpies (ΔH), and binding entropies (TΔS) values are reported in units of kcal mol−1.
Measurement: Kd = 370 nM (pChEMBL 6.429999828338623)
Descriptors: MW 277.71, ALogP 3.42, HBA 3, HBD 3, PSA 69.56, QED 0.75
Compound (SMILES): O=C1NC(=O)/C(=C/c2ccc(-c3ccc(Cl)c(C(=O)O)c3)o2)S1
InChIKey: FULWCUIFMVEEMF-SDQBBNPISA-N
Target: Transthyretin (SINGLE PROTEIN), Homo sapiens
UniProt: P02766
Assay: FP Assay: The FP assay was then adapted for HTS and used to screen ~120,000 small molecule library for compounds that displaced probe 5 from the T4 binding of TTR. The FP assay was performed in 384-well plate using very low concentration of probe 5 (1.5 nM) and TTR (50 nM) in a 10 μL assay volume. A detergent (0.01% Triton-X100) was added to the assay buffer to avoid any false positive hits from promiscuous, aggregate-based inhibitors. The assay demonstrated robust performance, with a very good dynamic range (−70-230 mP) and a Z′ factor in the range of 0.57-0.78 (FIGS. 4A and 4B). "Hits" were defined as compounds that resulted in at least 50% decrease in fluorescence polarization and demonstrated relative fluorescence between 70 and 130%. Many fluorescence quenchers and enhancers having less than 70% and greater than 130% total fluorescence relative to a control, respectively, were excluded from the hit list. 200 compounds were designated as positive hits (0.167% hit rate).
Measurement: IC50 = 3927 nM (pChEMBL 5.409999847412109)
Descriptors: MW 349.75, ALogP 3.62, HBA 5, HBD 2, PSA 96.61, QED 0.82
Compound (SMILES): O=c1c(Oc2ccccc2Cl)c(C(F)(F)F)oc2cc(O)ccc12
InChIKey: BFBFOFMWNXVUDJ-UHFFFAOYSA-N
Target: Transthyretin (SINGLE PROTEIN), Homo sapiens
UniProt: P02766
Assay: FP Assay: The FP assay was then adapted for HTS and used to screen ~120,000 small molecule library for compounds that displaced probe 5 from the T4 binding of TTR. The FP assay was performed in 384-well plate using very low concentration of probe 5 (1.5 nM) and TTR (50 nM) in a 10 μL assay volume. A detergent (0.01% Triton-X100) was added to the assay buffer to avoid any false positive hits from promiscuous, aggregate-based inhibitors. The assay demonstrated robust performance, with a very good dynamic range (−70-230 mP) and a Z′ factor in the range of 0.57-0.78 (FIGS. 4A and 4B). "Hits" were defined as compounds that resulted in at least 50% decrease in fluorescence polarization and demonstrated relative fluorescence between 70 and 130%. Many fluorescence quenchers and enhancers having less than 70% and greater than 130% total fluorescence relative to a control, respectively, were excluded from the hit list. 200 compounds were designated as positive hits (0.167% hit rate).
Measurement: IC50 = 4217 nM (pChEMBL 5.380000114440918)
Descriptors: MW 356.68, ALogP 4.96, HBA 4, HBD 1, PSA 59.67, QED 0.7
Compound (SMILES): CSC1=NSC2=NC(=O)/C(=C\c3cccc4ccccc34)C(=N)N12
InChIKey: UUYGEGVBCPXEGL-KXXGJRMMSA-N
Target: Transthyretin (SINGLE PROTEIN), Homo sapiens
UniProt: P02766
Assay: FP Assay: The FP assay was then adapted for HTS and used to screen ~120,000 small molecule library for compounds that displaced probe 5 from the T4 binding of TTR. The FP assay was performed in 384-well plate using very low concentration of probe 5 (1.5 nM) and TTR (50 nM) in a 10 μL assay volume. A detergent (0.01% Triton-X100) was added to the assay buffer to avoid any false positive hits from promiscuous, aggregate-based inhibitors. The assay demonstrated robust performance, with a very good dynamic range (−70-230 mP) and a Z′ factor in the range of 0.57-0.78 (FIGS. 4A and 4B). "Hits" were defined as compounds that resulted in at least 50% decrease in fluorescence polarization and demonstrated relative fluorescence between 70 and 130%. Many fluorescence quenchers and enhancers having less than 70% and greater than 130% total fluorescence relative to a control, respectively, were excluded from the hit list. 200 compounds were designated as positive hits (0.167% hit rate).
Measurement: IC50 = 4881 nM (pChEMBL 5.309999942779541)
Descriptors: MW 352.44, ALogP 3.78, HBA 5, HBD 1, PSA 68.88, QED 0.63
Compound (SMILES): CCOc1cc(C2NC(C(=O)O)CS2)cc(Br)c1OCc1ccccc1C
InChIKey: MKHFUVFCQDZCDM-UHFFFAOYSA-N
Target: Transthyretin (SINGLE PROTEIN), Homo sapiens
UniProt: P02766
Assay: FP Assay: The FP assay was then adapted for HTS and used to screen ~120,000 small molecule library for compounds that displaced probe 5 from the T4 binding of TTR. The FP assay was performed in 384-well plate using very low concentration of probe 5 (1.5 nM) and TTR (50 nM) in a 10 μL assay volume. A detergent (0.01% Triton-X100) was added to the assay buffer to avoid any false positive hits from promiscuous, aggregate-based inhibitors. The assay demonstrated robust performance, with a very good dynamic range (−70-230 mP) and a Z′ factor in the range of 0.57-0.78 (FIGS. 4A and 4B). "Hits" were defined as compounds that resulted in at least 50% decrease in fluorescence polarization and demonstrated relative fluorescence between 70 and 130%. Many fluorescence quenchers and enhancers having less than 70% and greater than 130% total fluorescence relative to a control, respectively, were excluded from the hit list. 200 compounds were designated as positive hits (0.167% hit rate).
Measurement: IC50 = 4933 nM (pChEMBL 5.309999942779541)
Descriptors: MW 452.37, ALogP 4.52, HBA 5, HBD 2, PSA 67.79, QED 0.64
Compound (SMILES): O=C1C(Br)=CC(=NS(=O)(=O)c2ccccc2)C=C1Br
InChIKey: DLDKUYJBRIGKML-UHFFFAOYSA-N
Target: Transthyretin (SINGLE PROTEIN), Homo sapiens
UniProt: P02766
Assay: FP Assay: The FP assay was then adapted for HTS and used to screen ~120,000 small molecule library for compounds that displaced probe 5 from the T4 binding of TTR. The FP assay was performed in 384-well plate using very low concentration of probe 5 (1.5 nM) and TTR (50 nM) in a 10 μL assay volume. A detergent (0.01% Triton-X100) was added to the assay buffer to avoid any false positive hits from promiscuous, aggregate-based inhibitors. The assay demonstrated robust performance, with a very good dynamic range (−70-230 mP) and a Z′ factor in the range of 0.57-0.78 (FIGS. 4A and 4B). "Hits" were defined as compounds that resulted in at least 50% decrease in fluorescence polarization and demonstrated relative fluorescence between 70 and 130%. Many fluorescence quenchers and enhancers having less than 70% and greater than 130% total fluorescence relative to a control, respectively, were excluded from the hit list. 200 compounds were designated as positive hits (0.167% hit rate).
Measurement: IC50 = 5414 nM (pChEMBL 5.269999980926514)
Descriptors: MW 405.07, ALogP 2.96, HBA 3, HBD 0, PSA 63.57, QED 0.71
Compound (SMILES): Oc1nc(O)c2sc3nc(C(F)(F)F)cc(Cc4ccccc4)c3c2n1
InChIKey: VCMGBFQVEWTQPX-UHFFFAOYSA-N
Target: Transthyretin (SINGLE PROTEIN), Homo sapiens
UniProt: P02766
Assay: FP Assay: The FP assay was then adapted for HTS and used to screen ~120,000 small molecule library for compounds that displaced probe 5 from the T4 binding of TTR. The FP assay was performed in 384-well plate using very low concentration of probe 5 (1.5 nM) and TTR (50 nM) in a 10 μL assay volume. A detergent (0.01% Triton-X100) was added to the assay buffer to avoid any false positive hits from promiscuous, aggregate-based inhibitors. The assay demonstrated robust performance, with a very good dynamic range (−70-230 mP) and a Z′ factor in the range of 0.57-0.78 (FIGS. 4A and 4B). "Hits" were defined as compounds that resulted in at least 50% decrease in fluorescence polarization and demonstrated relative fluorescence between 70 and 130%. Many fluorescence quenchers and enhancers having less than 70% and greater than 130% total fluorescence relative to a control, respectively, were excluded from the hit list. 200 compounds were designated as positive hits (0.167% hit rate).
Measurement: IC50 = 5604 nM (pChEMBL 5.25)
Descriptors: MW 377.35, ALogP 4.26, HBA 6, HBD 2, PSA 79.13, QED 0.55
Compound (SMILES): CC1=C(CCC(=O)O)C(=O)N2c3ccccc3NC2C1C#N
InChIKey: ADRWNCJPSMZZOJ-UHFFFAOYSA-N
Target: Transthyretin (SINGLE PROTEIN), Homo sapiens
UniProt: P02766
Assay: FP Assay: The FP assay was then adapted for HTS and used to screen ~120,000 small molecule library for compounds that displaced probe 5 from the T4 binding of TTR. The FP assay was performed in 384-well plate using very low concentration of probe 5 (1.5 nM) and TTR (50 nM) in a 10 μL assay volume. A detergent (0.01% Triton-X100) was added to the assay buffer to avoid any false positive hits from promiscuous, aggregate-based inhibitors. The assay demonstrated robust performance, with a very good dynamic range (−70-230 mP) and a Z′ factor in the range of 0.57-0.78 (FIGS. 4A and 4B). "Hits" were defined as compounds that resulted in at least 50% decrease in fluorescence polarization and demonstrated relative fluorescence between 70 and 130%. Many fluorescence quenchers and enhancers having less than 70% and greater than 130% total fluorescence relative to a control, respectively, were excluded from the hit list. 200 compounds were designated as positive hits (0.167% hit rate).
Measurement: IC50 = 8690 nM (pChEMBL 5.059999942779541)
Descriptors: MW 297.31, ALogP 2.11, HBA 4, HBD 2, PSA 93.43, QED 0.89
Compound (SMILES): COc1cc(/C=C2\C(=N)N3N=C(S(C)(=O)=O)SC3=NC2=O)ccc1OCc1ccccc1C
InChIKey: JWFKTYNENPTZCD-ONVPTEKUSA-N
Target: Transthyretin (SINGLE PROTEIN), Homo sapiens
UniProt: P02766
Assay: FP Assay: The FP assay was then adapted for HTS and used to screen ~120,000 small molecule library for compounds that displaced probe 5 from the T4 binding of TTR. The FP assay was performed in 384-well plate using very low concentration of probe 5 (1.5 nM) and TTR (50 nM) in a 10 μL assay volume. A detergent (0.01% Triton-X100) was added to the assay buffer to avoid any false positive hits from promiscuous, aggregate-based inhibitors. The assay demonstrated robust performance, with a very good dynamic range (−70-230 mP) and a Z′ factor in the range of 0.57-0.78 (FIGS. 4A and 4B). "Hits" were defined as compounds that resulted in at least 50% decrease in fluorescence polarization and demonstrated relative fluorescence between 70 and 130%. Many fluorescence quenchers and enhancers having less than 70% and greater than 130% total fluorescence relative to a control, respectively, were excluded from the hit list. 200 compounds were designated as positive hits (0.167% hit rate).
Measurement: IC50 = 9764 nM (pChEMBL 5.010000228881836)
Descriptors: MW 484.56, ALogP 3.2, HBA 8, HBD 1, PSA 121.48, QED 0.65
Compound (SMILES): O=C(NCc1cc(Br)cc(Br)c1O)c1ccccc1
InChIKey: OWQKOVGAVCGSTE-UHFFFAOYSA-N
Target: Transthyretin (SINGLE PROTEIN), Homo sapiens
UniProt: P02766
Assay: FP Assay: The FP assay was then adapted for HTS and used to screen ~120,000 small molecule library for compounds that displaced probe 5 from the T4 binding of TTR. The FP assay was performed in 384-well plate using very low concentration of probe 5 (1.5 nM) and TTR (50 nM) in a 10 μL assay volume. A detergent (0.01% Triton-X100) was added to the assay buffer to avoid any false positive hits from promiscuous, aggregate-based inhibitors. The assay demonstrated robust performance, with a very good dynamic range (−70-230 mP) and a Z′ factor in the range of 0.57-0.78 (FIGS. 4A and 4B). "Hits" were defined as compounds that resulted in at least 50% decrease in fluorescence polarization and demonstrated relative fluorescence between 70 and 130%. Many fluorescence quenchers and enhancers having less than 70% and greater than 130% total fluorescence relative to a control, respectively, were excluded from the hit list. 200 compounds were designated as positive hits (0.167% hit rate).
Measurement: IC50 = 10039 nM (pChEMBL 5)
Descriptors: MW 385.06, ALogP 3.85, HBA 2, HBD 2, PSA 49.33, QED 0.84