lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CCN/C(=N\S(=O)(=O)c1ccc(O)cc1)N1CC2(C=N1)CCCC2
InChIKey: WRBDQDVGFONMDA-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H]-N-Methyl-Lysergic acid diethylamide from human 5-HT6 receptor expressed in CHO cells after 30 mins by liquid scintillation counting analysis
Measurement: Ki = 5.8 nM (pChEMBL 8.239999771118164)
Descriptors: MW 350.44, ALogP 1.91, HBA 4, HBD 2, PSA 94.36, QED 0.64
Compound (SMILES): CCN/C(=N\S(=O)(=O)c1ccc(OC)cc1)N1CC2(C=N1)CCCC2
InChIKey: AKSCLMQRDRHQNG-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H]-N-Methyl-Lysergic acid diethylamide from human 5-HT6 receptor expressed in CHO cells after 30 mins by liquid scintillation counting analysis
Measurement: Ki = 210.2 nM (pChEMBL 6.679999828338623)
Descriptors: MW 364.47, ALogP 2.21, HBA 4, HBD 1, PSA 83.36, QED 0.65
Compound (SMILES): CCN/C(=N\S(=O)(=O)c1ccc(O)c(Cl)c1)N1CC2(C=N1)CCCC2
InChIKey: HUJIOLMFBKMOIZ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H]-N-Methyl-Lysergic acid diethylamide from human 5-HT6 receptor expressed in CHO cells after 30 mins by liquid scintillation counting analysis
Measurement: Ki = 14.6 nM (pChEMBL 7.840000152587891)
Descriptors: MW 384.89, ALogP 2.56, HBA 4, HBD 2, PSA 94.36, QED 0.62
Compound (SMILES): CCN/C(=N\S(=O)(=O)c1ccc(OC)c(Cl)c1)N1CC2(C=N1)CCCC2
InChIKey: LDDMSCHPVKCVDL-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H]-N-Methyl-Lysergic acid diethylamide from human 5-HT6 receptor expressed in CHO cells after 30 mins by liquid scintillation counting analysis
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 398.92, ALogP 2.86, HBA 4, HBD 1, PSA 83.36, QED 0.62
Compound (SMILES): CCN/C(=N\S(=O)(=O)c1ccc2c(c1)CCN2)N1CC2(C=N1)CCCC2
InChIKey: QXNAGNYRKNJLHW-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H]-N-Methyl-Lysergic acid diethylamide from human 5-HT6 receptor expressed in CHO cells after 30 mins by liquid scintillation counting analysis
Measurement: Ki = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 375.5, ALogP 2.17, HBA 4, HBD 2, PSA 86.16, QED 0.62
Compound (SMILES): CCN/C(=N\S(=O)(=O)c1ccc2[nH]ccc2c1)N1CC2(C=N1)CCCC2
InChIKey: PSBLPQHOIHNPBG-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H]-N-Methyl-Lysergic acid diethylamide from human 5-HT6 receptor expressed in CHO cells after 30 mins by liquid scintillation counting analysis
Measurement: Ki = 4.8 nM (pChEMBL 8.319999694824219)
Descriptors: MW 373.48, ALogP 2.68, HBA 3, HBD 2, PSA 89.92, QED 0.64
Compound (SMILES): CCN/C(=N\S(=O)(=O)c1ccc2[nH]ncc2c1)N1CC2(C=N1)CCCC2
InChIKey: RGYUHWISLHLCCL-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H]-N-Methyl-Lysergic acid diethylamide from human 5-HT6 receptor expressed in CHO cells after 30 mins by liquid scintillation counting analysis
Measurement: Ki = 28.6 nM (pChEMBL 7.539999961853027)
Descriptors: MW 374.47, ALogP 2.08, HBA 4, HBD 2, PSA 102.81, QED 0.63
Compound (SMILES): CCN/C(=N\S(=O)(=O)c1ccc2[nH]c(C(F)(F)F)cc2c1)N1CC(C)(C)C=N1
InChIKey: DJJDUYJZKRGQQO-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H]-N-Methyl-Lysergic acid diethylamide from human 5-HT6 receptor expressed in CHO cells after 30 mins by liquid scintillation counting analysis
Measurement: Ki = 160.2 nM (pChEMBL 6.789999961853027)
Descriptors: MW 415.44, ALogP 3.17, HBA 3, HBD 2, PSA 89.92, QED 0.6
Compound (SMILES): CCN/C(=N\S(=O)(=O)c1ccc2[nH]ccc2c1)N1CC2(C=N1)CCNCC2
InChIKey: IXNHIGPTXXHTOM-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H]-N-Methyl-Lysergic acid diethylamide from human 5-HT6 receptor expressed in CHO cells after 30 mins by liquid scintillation counting analysis
Measurement: Ki = 11.6 nM (pChEMBL 7.940000057220459)
Descriptors: MW 388.5, ALogP 1.49, HBA 4, HBD 3, PSA 101.95, QED 0.55
Compound (SMILES): CCN/C(=N\S(=O)(=O)c1cccc(N)c1)N1CC2(C=N1)CCCC2
InChIKey: TZECKIWOLLTNSY-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H]-N-Methyl-Lysergic acid diethylamide from human 5-HT6 receptor expressed in CHO cells after 30 mins by liquid scintillation counting analysis
Measurement: Ki = 97.2 nM (pChEMBL 7.010000228881836)
Descriptors: MW 349.46, ALogP 1.78, HBA 4, HBD 2, PSA 100.15, QED 0.49
Compound (SMILES): CCN/C(=N\S(=O)(=O)c1ccc2c(c1)NCC2)N1CC(CC)C=N1
InChIKey: NNRSFWTVDGRFEI-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H]-N-Methyl-Lysergic acid diethylamide from human 5-HT6 receptor expressed in CHO cells after 30 mins by liquid scintillation counting analysis
Measurement: Ki = 399.1 nM (pChEMBL 6.400000095367432)
Descriptors: MW 349.46, ALogP 1.64, HBA 4, HBD 2, PSA 86.16, QED 0.64
Compound (SMILES): CCN/C(=N\S(=O)(=O)c1ccc2cc[nH]c2c1)N1CC(CC)C=N1
InChIKey: DFPUPZMYPJSLGL-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H]-N-Methyl-Lysergic acid diethylamide from human 5-HT6 receptor expressed in CHO cells after 30 mins by liquid scintillation counting analysis
Measurement: Ki = 31.6 nM (pChEMBL 7.5)
Descriptors: MW 347.44, ALogP 2.15, HBA 3, HBD 2, PSA 89.92, QED 0.65
Compound (SMILES): CCN/C(=N\S(=O)(=O)c1cccc(O)c1)N1CC2(C=N1)CCCC2
InChIKey: APUZUMIUOBMCPE-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H]-N-Methyl-Lysergic acid diethylamide from human 5-HT6 receptor expressed in CHO cells after 30 mins by liquid scintillation counting analysis
Measurement: Ki = 18.5 nM (pChEMBL 7.730000019073486)
Descriptors: MW 350.44, ALogP 1.91, HBA 4, HBD 2, PSA 94.36, QED 0.64
Compound (SMILES): CCN/C(=N\S(=O)(=O)c1cccc(OC)c1)N1CC2(C=N1)CCCC2
InChIKey: MTWIVDFPOVDEGP-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H]-N-Methyl-Lysergic acid diethylamide from human 5-HT6 receptor expressed in CHO cells after 30 mins by liquid scintillation counting analysis
Measurement: Ki = 97.1 nM (pChEMBL 7.010000228881836)
Descriptors: MW 364.47, ALogP 2.21, HBA 4, HBD 1, PSA 83.36, QED 0.65
Compound (SMILES): CCN/C(=N\S(=O)(=O)c1cc(O)cc(Cl)c1)N1CC2(C=N1)CCCC2
InChIKey: WCSSZEWVWBHIEJ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H]-N-Methyl-Lysergic acid diethylamide from human 5-HT6 receptor expressed in CHO cells after 30 mins by liquid scintillation counting analysis
Measurement: Ki = 6.1 nM (pChEMBL 8.210000038146973)
Descriptors: MW 384.89, ALogP 2.56, HBA 4, HBD 2, PSA 94.36, QED 0.62
Compound (SMILES): CCN/C(=N\S(=O)(=O)c1cc(Cl)cc(OC)c1)N1CC2(C=N1)CCCC2
InChIKey: ZVXFIKHFADRTGS-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H]-N-Methyl-Lysergic acid diethylamide from human 5-HT6 receptor expressed in CHO cells after 30 mins by liquid scintillation counting analysis
Measurement: Ki = 47.5 nM (pChEMBL 7.320000171661377)
Descriptors: MW 398.92, ALogP 2.86, HBA 4, HBD 1, PSA 83.36, QED 0.62
Compound (SMILES): Cc1cc(OCCCc2c(C(=O)NS(C)(=O)=O)[nH]c3cc(Cl)ccc23)cc(C)c1Cl
InChIKey: BNYCCIRSMLMXSF-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Displacement of FITC-Bak-BH3 peptide probe from N-terminal His-tagged human Mcl-1 (172 to 327 residues) expressed in Escherichia coli BL21(DE3) after 1.5 hrs by FPA based competition assay
Measurement: Ki = 209 nM (pChEMBL 6.679999828338623)
Descriptors: MW 469.39, ALogP 4.79, HBA 4, HBD 2, PSA 88.26, QED 0.49
Compound (SMILES): CS(=O)(=O)NC(=O)c1[nH]c2cc(Cl)ccc2c1CCCOc1cccc2ccccc12
InChIKey: UTSWEVNFLYKBLS-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Displacement of FITC-Bak-BH3 peptide probe from N-terminal His-tagged human Mcl-1 (172 to 327 residues) expressed in Escherichia coli BL21(DE3) after 1.5 hrs by FPA based competition assay
Measurement: Ki = 231 nM (pChEMBL 6.639999866485596)
Descriptors: MW 456.95, ALogP 4.68, HBA 4, HBD 2, PSA 88.26, QED 0.4
Compound (SMILES): Cc1cc(OCCCc2c(C(=O)NS(C)(=O)=O)[nH]c3ccccc23)cc(C)c1Cl
InChIKey: ZIXKOLODGXYOPU-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Displacement of FITC-Bak-BH3 peptide probe from N-terminal His-tagged human Mcl-1 (172 to 327 residues) expressed in Escherichia coli BL21(DE3) after 1.5 hrs by FPA based competition assay
Measurement: Ki = 655 nM (pChEMBL 6.179999828338623)
Descriptors: MW 434.95, ALogP 4.14, HBA 4, HBD 2, PSA 88.26, QED 0.55
Compound (SMILES): Cc1cc(OCCCc2c(C(=O)NS(=O)(=O)CCOc3ccccc3)[nH]c3ccccc23)cc(C)c1Cl
InChIKey: RJSZFIHODLTGBK-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Bak Peptide Binding Assay: Compound affinity was measured using a fluorescence polarization anisotropy competition assay. Anisotropy measurements were carried out in 384-well, black, flat-bottom plates (Greiner Bio-one, Monroe, N.C., USA). The assay was run using a fluorescein isothiocyanate-labeled BH3 peptide derived from Bak (FITC-AHx-GQVGRQLAIIGDDINR-NH2) that was purchased from GenScript (Piscataway, N.J.) at >95% purity and used without further purification. 10 nM FITC-Bak peptide and 14 nM recombinant Mcl-1 (residues 172-327) were added to assay buffer (3 mM dithiothreitol, 50 mM NaCl, 20 mM Tris, pH 7.5). For selectivity assays, 40 nM Bcl-2 (residues 1-207A96T,G110R, Δ35-91, replaced with Bcl-xL35-50) or 4 nM Bcl-xL (residues 1-209, loop 45-86 deleted) were incubated with 10 nM FITC-Bak in assay buffer. Compounds are diluted in DMSO in a 10-point, 3-fold serial dilution scheme. 2.5 uL compound is added to 47.5 uL of assay buffer containing FITC-Bak and protein, for a final DMSO concentration of 5% and a top concentration of 20 uM. A FITC-Bak peptide alone (100% inhibition) and peptide plus protein (0% inhibition) control is included on each assay plate. The plate was mixed and incubated for 90 minutes at room temperature. Anisotropy is measured at excitation wavelength 480 nm and emission wavelength 535 nm using an EnVision Multi-label plate reader (PerkinElmer, Wellesley, Mass., USA). Fluorescence anisotropy is plotted against compound concentration to generate an IC50 (inhibitor concentration at which 50% of bound peptide is displaced) by fitting the data to a 4-parameter logistic model using XLFit software (Guildford, Surrey, UK). IC50 is converted to a binding dissociation constant (Ki value) according to the formula of Wang Z. FEBS Lett (1996) 3, 245:K i =[I] 50/([L] 50 /K d +[P] 0 /K d+1)where [I]50 is the concentration of the free inhibitor at 50% inhibition, [L]50 is the concentration of the free labeled ligand at 50% inhibition, [P]0 is the concentration of the free protein at 0% inhibition, Kd represents the dissociation constant of the FITC peptide probe.
Measurement: IC50 = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 541.07, ALogP 5.59, HBA 5, HBD 2, PSA 97.49, QED 0.24
Compound (SMILES): Cc1cc(OCCCc2c(C(=O)NS(=O)(=O)CCNC(=O)c3ccccc3)[nH]c3ccccc23)cc(C)c1Cl
InChIKey: OXGRLOVVIBXCRO-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Bak Peptide Binding Assay: Compound affinity was measured using a fluorescence polarization anisotropy competition assay. Anisotropy measurements were carried out in 384-well, black, flat-bottom plates (Greiner Bio-one, Monroe, N.C., USA). The assay was run using a fluorescein isothiocyanate-labeled BH3 peptide derived from Bak (FITC-AHx-GQVGRQLAIIGDDINR-NH2) that was purchased from GenScript (Piscataway, N.J.) at >95% purity and used without further purification. 10 nM FITC-Bak peptide and 14 nM recombinant Mcl-1 (residues 172-327) were added to assay buffer (3 mM dithiothreitol, 50 mM NaCl, 20 mM Tris, pH 7.5). For selectivity assays, 40 nM Bcl-2 (residues 1-207A96T,G110R, Δ35-91, replaced with Bcl-xL35-50) or 4 nM Bcl-xL (residues 1-209, loop 45-86 deleted) were incubated with 10 nM FITC-Bak in assay buffer. Compounds are diluted in DMSO in a 10-point, 3-fold serial dilution scheme. 2.5 uL compound is added to 47.5 uL of assay buffer containing FITC-Bak and protein, for a final DMSO concentration of 5% and a top concentration of 20 uM. A FITC-Bak peptide alone (100% inhibition) and peptide plus protein (0% inhibition) control is included on each assay plate. The plate was mixed and incubated for 90 minutes at room temperature. Anisotropy is measured at excitation wavelength 480 nm and emission wavelength 535 nm using an EnVision Multi-label plate reader (PerkinElmer, Wellesley, Mass., USA). Fluorescence anisotropy is plotted against compound concentration to generate an IC50 (inhibitor concentration at which 50% of bound peptide is displaced) by fitting the data to a 4-parameter logistic model using XLFit software (Guildford, Surrey, UK). IC50 is converted to a binding dissociation constant (Ki value) according to the formula of Wang Z. FEBS Lett (1996) 3, 245:K i =[I] 50/([L] 50 /K d +[P] 0 /K d+1)where [I]50 is the concentration of the free inhibitor at 50% inhibition, [L]50 is the concentration of the free labeled ligand at 50% inhibition, [P]0 is the concentration of the free protein at 0% inhibition, Kd represents the dissociation constant of the FITC peptide probe.
Measurement: IC50 = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 568.1, ALogP 4.94, HBA 5, HBD 3, PSA 117.36, QED 0.22
Compound (SMILES): Cc1cc(OCCCc2c(C(=O)NS(=O)(=O)CCNC(=O)C3CCCCC3)[nH]c3ccccc23)cc(C)c1Cl
InChIKey: CCINIGNSFDEVOS-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Displacement of FITC-Bak-BH3 peptide probe from N-terminal His-tagged human Mcl-1 (172 to 327 residues) expressed in Escherichia coli BL21(DE3) after 1.5 hrs by FPA based competition assay
Measurement: Ki = 118 nM (pChEMBL 6.929999828338623)
Descriptors: MW 574.14, ALogP 5.21, HBA 5, HBD 3, PSA 117.36, QED 0.27
Compound (SMILES): Cc1cc(OCCCc2c(C(=O)NS(=O)(=O)CCNC(=O)CC3CCCCC3)[nH]c3ccccc23)cc(C)c1Cl
InChIKey: HOKCDCDULXEZBD-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Bak Peptide Binding Assay: Compound affinity was measured using a fluorescence polarization anisotropy competition assay. Anisotropy measurements were carried out in 384-well, black, flat-bottom plates (Greiner Bio-one, Monroe, N.C., USA). The assay was run using a fluorescein isothiocyanate-labeled BH3 peptide derived from Bak (FITC-AHx-GQVGRQLAIIGDDINR-NH2) that was purchased from GenScript (Piscataway, N.J.) at >95% purity and used without further purification. 10 nM FITC-Bak peptide and 14 nM recombinant Mcl-1 (residues 172-327) were added to assay buffer (3 mM dithiothreitol, 50 mM NaCl, 20 mM Tris, pH 7.5). For selectivity assays, 40 nM Bcl-2 (residues 1-207A96T,G110R, Δ35-91, replaced with Bcl-xL35-50) or 4 nM Bcl-xL (residues 1-209, loop 45-86 deleted) were incubated with 10 nM FITC-Bak in assay buffer. Compounds are diluted in DMSO in a 10-point, 3-fold serial dilution scheme. 2.5 uL compound is added to 47.5 uL of assay buffer containing FITC-Bak and protein, for a final DMSO concentration of 5% and a top concentration of 20 uM. A FITC-Bak peptide alone (100% inhibition) and peptide plus protein (0% inhibition) control is included on each assay plate. The plate was mixed and incubated for 90 minutes at room temperature. Anisotropy is measured at excitation wavelength 480 nm and emission wavelength 535 nm using an EnVision Multi-label plate reader (PerkinElmer, Wellesley, Mass., USA). Fluorescence anisotropy is plotted against compound concentration to generate an IC50 (inhibitor concentration at which 50% of bound peptide is displaced) by fitting the data to a 4-parameter logistic model using XLFit software (Guildford, Surrey, UK). IC50 is converted to a binding dissociation constant (Ki value) according to the formula of Wang Z. FEBS Lett (1996) 3, 245:K i =[I] 50/([L] 50 /K d +[P] 0 /K d+1)where [I]50 is the concentration of the free inhibitor at 50% inhibition, [L]50 is the concentration of the free labeled ligand at 50% inhibition, [P]0 is the concentration of the free protein at 0% inhibition, Kd represents the dissociation constant of the FITC peptide probe.
Measurement: IC50 = 5495 nM (pChEMBL 5.260000228881836)
Descriptors: MW 588.17, ALogP 5.6, HBA 5, HBD 3, PSA 117.36, QED 0.24
Compound (SMILES): Cc1cc(-c2cc(F)c3nnc([C@@H](C)n4ccc5ncccc5c4=O)n3c2)on1
InChIKey: MUXVJMKIENAXGE-GFCCVEGCSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of HGF-mediated MET autophosphorylation in human PC3 cells preincubated for 1 hr followed by stimulation with human HGF measured after 10 mins by electrochemiluminescence immunoassay
Measurement: IC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 390.38, ALogP 3.15, HBA 8, HBD 0, PSA 91.11, QED 0.47
Compound (SMILES): COc1cnc2ccn([C@H](C)c3nnc4c(F)cc(-c5cc(C)no5)cn34)c(=O)c2c1
InChIKey: GFVGQIFEENPJSC-GFCCVEGCSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of HGF-mediated MET autophosphorylation in human PC3 cells preincubated for 1 hr followed by stimulation with human HGF measured after 10 mins by electrochemiluminescence immunoassay
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 420.4, ALogP 3.16, HBA 9, HBD 0, PSA 100.34, QED 0.44
Compound (SMILES): COCCOc1cnc2ccn([C@H](C)c3nnc4c(F)cc(-c5cc(C)no5)cn34)c(=O)c2c1
InChIKey: IASNQBJQLURUKC-CQSZACIVSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of HGF-mediated MET autophosphorylation in human PC3 cells preincubated for 1 hr followed by stimulation with human HGF measured after 10 mins by electrochemiluminescence immunoassay
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 464.46, ALogP 3.18, HBA 10, HBD 0, PSA 109.57, QED 0.34
Compound (SMILES): COCCOc1cnc2ccn([C@H](C)c3nnc4ccc(-c5cc(C)no5)cn34)c(=O)c2c1
InChIKey: LWFDHDVAJJXJRU-OAHLLOKOSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of HGF-mediated MET autophosphorylation in human PC3 cells preincubated for 1 hr followed by stimulation with human HGF measured after 10 mins by electrochemiluminescence immunoassay
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 446.47, ALogP 3.04, HBA 10, HBD 0, PSA 109.57, QED 0.35
Compound (SMILES): C[C@H](c1nnc2c(F)cc(-c3cnn(C)c3)cn12)n1ccc2ncccc2c1=O
InChIKey: SFSZKIHBSGGKAC-GFCCVEGCSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of HGF-mediated MET autophosphorylation in human PC3 cells preincubated for 1 hr followed by stimulation with human HGF measured after 10 mins by electrochemiluminescence immunoassay
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 389.39, ALogP 2.59, HBA 8, HBD 0, PSA 82.9, QED 0.47
Compound (SMILES): COc1cnc2ccn([C@H](C)c3nnc4c(F)cc(-c5cnn(C)c5)cn34)c(=O)c2c1
InChIKey: NDQAUVKBUXNYED-GFCCVEGCSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of HGF-mediated MET autophosphorylation in human PC3 cells preincubated for 1 hr followed by stimulation with human HGF measured after 10 mins by electrochemiluminescence immunoassay
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 419.42, ALogP 2.6, HBA 9, HBD 0, PSA 92.13, QED 0.44
Compound (SMILES): COCCOc1cnc2ccn([C@H](C)c3nnc4c(F)cc(-c5cnn(C)c5)cn34)c(=O)c2c1
InChIKey: DWHXUGDWKAIASB-CQSZACIVSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of HGF-mediated MET autophosphorylation in human PC3 cells preincubated for 1 hr followed by stimulation with human HGF measured after 10 mins by electrochemiluminescence immunoassay
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 463.47, ALogP 2.61, HBA 10, HBD 0, PSA 101.36, QED 0.34
Compound (SMILES): COc1cnc2ccn([C@H](C)c3nnc4ccc(-c5cnn(C)c5)cn34)c(=O)c2c1
InChIKey: OBCCECQELHQOEU-CYBMUJFWSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of HGF-mediated MET autophosphorylation in human PC3 cells preincubated for 1 hr followed by stimulation with human HGF measured after 10 mins by electrochemiluminescence immunoassay
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 401.43, ALogP 2.46, HBA 9, HBD 0, PSA 92.13, QED 0.46
Compound (SMILES): COCCOc1cnc2ccn([C@H](C)c3nnc4ccc(-c5cnn(C)c5)cn34)c(=O)c2c1
InChIKey: MVLDGYLKKKETQP-OAHLLOKOSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of HGF-mediated MET autophosphorylation in human PC3 cells preincubated for 1 hr followed by stimulation with human HGF measured after 10 mins by electrochemiluminescence immunoassay
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 445.48, ALogP 2.47, HBA 10, HBD 0, PSA 101.36, QED 0.35
Compound (SMILES): N[C@@H](C[C@@]1(C(=O)O)C[C@@H]1C(=O)O)C(=O)O
InChIKey: BHSHZTNHTMTQFY-ZPLJKJSBSA-N
Target: Metabotropic glutamate receptor 6 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35349
Assay: Agonist activity at rat mGlu6 receptor expressed in HEK293 cells assessed as IP1 accumulation by IP-One functional assay
Measurement: EC50 = 17820 nM (pChEMBL 4.75)
Descriptors: MW 217.18, ALogP -1.04, HBA 4, HBD 4, PSA 137.92, QED 0.46
Compound (SMILES): N[C@@H](C[C@]1(C(=O)O)C[C@H]1C(=O)O)C(=O)O
InChIKey: BHSHZTNHTMTQFY-MSIVUJLLSA-N
Target: Metabotropic glutamate receptor 6 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35349
Assay: Agonist activity at rat mGlu6 receptor expressed in HEK293 cells assessed as IP1 accumulation by IP-One functional assay
Measurement: EC50 = 490 nM (pChEMBL 6.309999942779541)
Descriptors: MW 217.18, ALogP -1.04, HBA 4, HBD 4, PSA 137.92, QED 0.46
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](CO)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](N)CCC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccccc1)C(N)=O
InChIKey: JGHPDOKJMQTPSY-NNVBHMPUSA-N
Target: Neuropeptide FF receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X5
Assay: Binding affinity to human NPFF2 receptor expressed in CHO cell membranes after 1 hr by liquid scintillation spectrophotometric counting
Measurement: Kd = 0.54 nM (pChEMBL 9.270000457763672)
Descriptors: MW 1366.55
Compound (SMILES): CC(C)(C)OC(=O)N[C@@H](CCCCNC(=O)[C@@H]1Cc2ccccc2CN1C(=O)CCc1ccccc1)C(=O)NCC(c1ccccc1)c1ccccc1
InChIKey: LWYKXCKHNLEQOC-YDAXCOIMSA-N
Target: C-X-C chemokine receptor type 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49682
Assay: Positive allosteric modulation of ProLink1-tagged wild type CXCR3 (unknown origin) expressed in HEK293T cells assessed as beta-arrestin-2 recruitment incubated for 4 hrs by chemiluminescence-based microplate reader method
Measurement: EC50 = 61.66 nM (pChEMBL 7.210000038146973)
Descriptors: MW 716.92, ALogP 6.7, HBA 5, HBD 3, PSA 116.84, QED 0.12
Compound (SMILES): CC(C)(C)OC(=O)N[C@@H](CCCCNC(=O)[C@@H]1Cc2ccccc2CN1C(=O)CCCC(=O)c1ccccc1)C(=O)NCC(c1ccccc1)c1ccccc1
InChIKey: PHHXQMUBXKXSHA-ZAQUEYBZSA-N
Target: C-X-C chemokine receptor type 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49682
Assay: Positive allosteric modulation of ProLink2-tagged wild type CXCR3 (unknown origin) expressed in HEK293T cells assessed as beta-arrestin-2 recruitment incubated for 4 hrs by chemiluminescence-based microplate reader method
Measurement: EC50 = 165.96 nM (pChEMBL 6.78000020980835)
Descriptors: MW 758.96, ALogP 7.12, HBA 6, HBD 3, PSA 133.91, QED 0.08
Compound (SMILES): N[C@@H](CCCCNC(=O)[C@@H]1Cc2ccccc2CN1C(=O)CCC(=O)c1ccccc1)C(=O)NCC(c1ccccc1)c1ccccc1.O=C(O)C(F)(F)F
InChIKey: FIZFCOARKPHJMU-AIHXPYQNSA-N
Target: C-X-C chemokine receptor type 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49682
Assay: Positive allosteric modulation of ProLink2-tagged wild type CXCR3 (unknown origin) expressed in HEK293T cells assessed as beta-arrestin-2 recruitment incubated for 4 hrs by chemiluminescence-based microplate reader method
Measurement: EC50 = 309.03 nM (pChEMBL 6.510000228881836)
Descriptors: MW 644.82, ALogP 5.17, HBA 5, HBD 3, PSA 121.6, QED 0.12
Compound (SMILES): N[C@@H](CCCCNC(=O)[C@@H]1Cc2ccccc2CN1C(=O)CCCC(=O)c1ccccc1)C(=O)NCC(c1ccccc1)c1ccccc1.O=C(O)C(F)(F)F
InChIKey: BQJJOTPBYNMDQV-GVGVJZOBSA-N
Target: C-X-C chemokine receptor type 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49682
Assay: Positive allosteric modulation of ProLink2-tagged wild type CXCR3 (unknown origin) expressed in HEK293T cells assessed as beta-arrestin-2 recruitment incubated for 4 hrs by chemiluminescence-based microplate reader method
Measurement: EC50 = 125.89 nM (pChEMBL 6.900000095367432)
Descriptors: MW 658.84, ALogP 5.56, HBA 5, HBD 3, PSA 121.6, QED 0.11
Compound (SMILES): N[C@@H](CCCCNC(=O)[C@@H]1Cc2ccccc2CN1)C(=O)NCC(c1ccccc1)c1ccccc1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: VPUWEBBFXUARFV-QLBXQKMFSA-N
Target: C-X-C chemokine receptor type 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49682
Assay: Positive allosteric modulation of ProLink1-tagged wild type CXCR3 (unknown origin) expressed in HEK293T cells assessed as beta-arrestin-2 recruitment incubated for 4 hrs by chemiluminescence-based microplate reader method
Measurement: EC50 = 158.49 nM (pChEMBL 6.800000190734863)
Descriptors: MW 484.64, ALogP 3.26, HBA 4, HBD 4, PSA 96.25, QED 0.31
Compound (SMILES): CC(C)(C)OC(=O)N[C@H](CCCCNC(=O)[C@@H]1Cc2ccccc2CN1C(=O)CCC(=O)c1ccccc1)C(=O)NCC(c1ccccc1)c1ccccc1
InChIKey: NCZATLHAZWNQJH-RGULYWFUSA-N
Target: C-X-C chemokine receptor type 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49682
Assay: Positive allosteric modulation of ProLink2-tagged wild type CXCR3 (unknown origin) expressed in HEK293T cells assessed as beta-arrestin-2 recruitment incubated for 4 hrs by chemiluminescence-based microplate reader method
Measurement: EC50 = 138.04 nM (pChEMBL 6.860000133514404)
Descriptors: MW 744.93, ALogP 6.73, HBA 6, HBD 3, PSA 133.91, QED 0.09
Compound (SMILES): N[C@H](CCCCNC(=O)[C@@H]1Cc2ccccc2CN1C(=O)CCC(=O)c1ccccc1)C(=O)NCC(c1ccccc1)c1ccccc1.O=C(O)C(F)(F)F
InChIKey: FIZFCOARKPHJMU-SZBXYEBXSA-N
Target: C-X-C chemokine receptor type 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49682
Assay: Positive allosteric modulation of ProLink1-tagged wild type CXCR3 (unknown origin) expressed in HEK293T cells assessed as beta-arrestin-2 recruitment incubated for 4 hrs by chemiluminescence-based microplate reader method
Measurement: EC50 = 69.18 nM (pChEMBL 7.159999847412109)
Descriptors: MW 644.82, ALogP 5.17, HBA 5, HBD 3, PSA 121.6, QED 0.12
Compound (SMILES): NCc1cccc(Cn2nnc(-c3onc(O)c3C[C@H](N)C(=O)O)n2)c1
InChIKey: RVAKWTBISFVYTO-NSHDSACASA-N
Target: Glutamate receptor 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P19491
Assay: Displacement of [3H]AMPA from recombinant rat GluA2 receptor flop isoform expressed in sf9 insect cells
Measurement: Ki = 8150 nM (pChEMBL 5.090000152587891)
Descriptors: MW 359.35, ALogP -0.5, HBA 10, HBD 4, PSA 179.2, QED 0.43
Compound (SMILES): CNCc1cccc(Cn2nnc(-c3onc(O)c3C[C@H](N)C(=O)O)n2)c1
InChIKey: YWCWJJAEVUVZKZ-LBPRGKRZSA-N
Target: Glutamate receptor 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P19491
Assay: Displacement of [3H]AMPA from recombinant rat GluA2 receptor flop isoform expressed in sf9 insect cells
Measurement: Ki = 84400 nM (pChEMBL 4.070000171661377)
Descriptors: MW 373.37, ALogP -0.24, HBA 10, HBD 4, PSA 165.21, QED 0.41
Compound (SMILES): CCNCc1cccc(Cn2nnc(-c3onc(O)c3C[C@H](N)C(=O)O)n2)c1
InChIKey: QRYQXJHGHVRNDY-ZDUSSCGKSA-N
Target: Glutamate receptor 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P19491
Assay: Displacement of [3H]AMPA from recombinant rat GluA2 receptor flop isoform expressed in sf9 insect cells
Measurement: Ki = 84500 nM (pChEMBL 4.070000171661377)
Descriptors: MW 387.4, ALogP 0.15, HBA 10, HBD 4, PSA 165.21, QED 0.4
Compound (SMILES): CC(C)NCc1cccc(Cn2nnc(-c3onc(O)c3C[C@H](N)C(=O)O)n2)c1
InChIKey: KTPPVZLNOSGWIY-AWEZNQCLSA-N
Target: Glutamate receptor 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P19491
Assay: Displacement of [3H]AMPA from recombinant rat GluA2 receptor flop isoform expressed in sf9 insect cells
Measurement: Ki = 55000 nM (pChEMBL 4.260000228881836)
Descriptors: MW 401.43, ALogP 0.53, HBA 10, HBD 4, PSA 165.21, QED 0.4
Compound (SMILES): Cc1cc(OCCCc2c(C(=O)NS(=O)(=O)CCCNC3CCCCC3)[nH]c3ccccc23)cc(C)c1Cl
InChIKey: WMIOYNQNQYGUDR-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Displacement of FITC-Bak-BH3 peptide probe from N-terminal His-tagged human Mcl-1 (172 to 327 residues) expressed in Escherichia coli BL21(DE3) after 1.5 hrs by FPA based competition assay
Measurement: Ki = 1015 nM (pChEMBL 5.989999771118164)
Descriptors: MW 560.16, ALogP 5.82, HBA 5, HBD 3, PSA 100.29, QED 0.24
Compound (SMILES): Cc1cc(OCCCc2c(C(=O)NS(=O)(=O)CCNS(=O)(=O)C3CCCCC3)[nH]c3ccccc23)cc(C)c1Cl
InChIKey: YQRMKSWXESHNSY-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Bak Peptide Binding Assay: Compound affinity was measured using a fluorescence polarization anisotropy competition assay. Anisotropy measurements were carried out in 384-well, black, flat-bottom plates (Greiner Bio-one, Monroe, N.C., USA). The assay was run using a fluorescein isothiocyanate-labeled BH3 peptide derived from Bak (FITC-AHx-GQVGRQLAIIGDDINR-NH2) that was purchased from GenScript (Piscataway, N.J.) at >95% purity and used without further purification. 10 nM FITC-Bak peptide and 14 nM recombinant Mcl-1 (residues 172-327) were added to assay buffer (3 mM dithiothreitol, 50 mM NaCl, 20 mM Tris, pH 7.5). For selectivity assays, 40 nM Bcl-2 (residues 1-207A96T,G110R, Δ35-91, replaced with Bcl-xL35-50) or 4 nM Bcl-xL (residues 1-209, loop 45-86 deleted) were incubated with 10 nM FITC-Bak in assay buffer. Compounds are diluted in DMSO in a 10-point, 3-fold serial dilution scheme. 2.5 uL compound is added to 47.5 uL of assay buffer containing FITC-Bak and protein, for a final DMSO concentration of 5% and a top concentration of 20 uM. A FITC-Bak peptide alone (100% inhibition) and peptide plus protein (0% inhibition) control is included on each assay plate. The plate was mixed and incubated for 90 minutes at room temperature. Anisotropy is measured at excitation wavelength 480 nm and emission wavelength 535 nm using an EnVision Multi-label plate reader (PerkinElmer, Wellesley, Mass., USA). Fluorescence anisotropy is plotted against compound concentration to generate an IC50 (inhibitor concentration at which 50% of bound peptide is displaced) by fitting the data to a 4-parameter logistic model using XLFit software (Guildford, Surrey, UK). IC50 is converted to a binding dissociation constant (Ki value) according to the formula of Wang Z. FEBS Lett (1996) 3, 245:K i =[I] 50/([L] 50 /K d +[P] 0 /K d+1)where [I]50 is the concentration of the free inhibitor at 50% inhibition, [L]50 is the concentration of the free labeled ligand at 50% inhibition, [P]0 is the concentration of the free protein at 0% inhibition, Kd represents the dissociation constant of the FITC peptide probe.
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 610.2, ALogP 4.76, HBA 6, HBD 3, PSA 134.43, QED 0.25
Compound (SMILES): CC(=O)NCCS(=O)(=O)NC(=O)c1[nH]c2ccccc2c1CCCOc1cc(C)c(Cl)c(C)c1
InChIKey: JZXOPFNWUSAZOE-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Displacement of FITC-Bak-BH3 peptide probe from N-terminal His-tagged human Mcl-1 (172 to 327 residues) expressed in Escherichia coli BL21(DE3) after 1.5 hrs by FPA based competition assay
Measurement: Ki = 656 nM (pChEMBL 6.179999828338623)
Descriptors: MW 506.02, ALogP 3.65, HBA 5, HBD 3, PSA 117.36, QED 0.36
Compound (SMILES): Cc1cc(OCCCc2c(C(=O)NS(=O)(=O)CCNC(=O)C3CCCCC3)[nH]c3cc(Cl)ccc23)cc(C)c1Cl
InChIKey: NEPGYBYFRTXHOG-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Bak Peptide Binding Assay: Compound affinity was measured using a fluorescence polarization anisotropy competition assay. Anisotropy measurements were carried out in 384-well, black, flat-bottom plates (Greiner Bio-one, Monroe, N.C., USA). The assay was run using a fluorescein isothiocyanate-labeled BH3 peptide derived from Bak (FITC-AHx-GQVGRQLAIIGDDINR-NH2) that was purchased from GenScript (Piscataway, N.J.) at >95% purity and used without further purification. 10 nM FITC-Bak peptide and 14 nM recombinant Mcl-1 (residues 172-327) were added to assay buffer (3 mM dithiothreitol, 50 mM NaCl, 20 mM Tris, pH 7.5). For selectivity assays, 40 nM Bcl-2 (residues 1-207A96T,G110R, Δ35-91, replaced with Bcl-xL35-50) or 4 nM Bcl-xL (residues 1-209, loop 45-86 deleted) were incubated with 10 nM FITC-Bak in assay buffer. Compounds are diluted in DMSO in a 10-point, 3-fold serial dilution scheme. 2.5 uL compound is added to 47.5 uL of assay buffer containing FITC-Bak and protein, for a final DMSO concentration of 5% and a top concentration of 20 uM. A FITC-Bak peptide alone (100% inhibition) and peptide plus protein (0% inhibition) control is included on each assay plate. The plate was mixed and incubated for 90 minutes at room temperature. Anisotropy is measured at excitation wavelength 480 nm and emission wavelength 535 nm using an EnVision Multi-label plate reader (PerkinElmer, Wellesley, Mass., USA). Fluorescence anisotropy is plotted against compound concentration to generate an IC50 (inhibitor concentration at which 50% of bound peptide is displaced) by fitting the data to a 4-parameter logistic model using XLFit software (Guildford, Surrey, UK). IC50 is converted to a binding dissociation constant (Ki value) according to the formula of Wang Z. FEBS Lett (1996) 3, 245:K i =[I] 50/([L] 50 /K d +[P] 0 /K d+1)where [I]50 is the concentration of the free inhibitor at 50% inhibition, [L]50 is the concentration of the free labeled ligand at 50% inhibition, [P]0 is the concentration of the free protein at 0% inhibition, Kd represents the dissociation constant of the FITC peptide probe.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 608.59, ALogP 5.86, HBA 5, HBD 3, PSA 117.36, QED 0.24
Compound (SMILES): O=C(NS(=O)(=O)CCNC(=O)C1CCCCC1)c1[nH]c2cc(Cl)ccc2c1CCCOc1cccc2ccccc12
InChIKey: YIWAWTPDIFYCTH-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Displacement of FITC-Bak-BH3 peptide probe from N-terminal His-tagged human Mcl-1 (172 to 327 residues) expressed in Escherichia coli BL21(DE3) after 1.5 hrs by FPA based competition assay
Measurement: Ki = 374 nM (pChEMBL 6.429999828338623)
Descriptors: MW 596.15, ALogP 5.74, HBA 5, HBD 3, PSA 117.36, QED 0.19
Compound (SMILES): Cc1cc(OCCCc2c(C(=O)NS(=O)(=O)CCNC(=O)c3ccc4[nH]ccc4c3)[nH]c3ccccc23)cc(C)c1Cl
InChIKey: OUJVVYRGZFLQRK-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Bak Peptide Binding Assay: Compound affinity was measured using a fluorescence polarization anisotropy competition assay. Anisotropy measurements were carried out in 384-well, black, flat-bottom plates (Greiner Bio-one, Monroe, N.C., USA). The assay was run using a fluorescein isothiocyanate-labeled BH3 peptide derived from Bak (FITC-AHx-GQVGRQLAIIGDDINR-NH2) that was purchased from GenScript (Piscataway, N.J.) at >95% purity and used without further purification. 10 nM FITC-Bak peptide and 14 nM recombinant Mcl-1 (residues 172-327) were added to assay buffer (3 mM dithiothreitol, 50 mM NaCl, 20 mM Tris, pH 7.5). For selectivity assays, 40 nM Bcl-2 (residues 1-207A96T,G110R, Δ35-91, replaced with Bcl-xL35-50) or 4 nM Bcl-xL (residues 1-209, loop 45-86 deleted) were incubated with 10 nM FITC-Bak in assay buffer. Compounds are diluted in DMSO in a 10-point, 3-fold serial dilution scheme. 2.5 uL compound is added to 47.5 uL of assay buffer containing FITC-Bak and protein, for a final DMSO concentration of 5% and a top concentration of 20 uM. A FITC-Bak peptide alone (100% inhibition) and peptide plus protein (0% inhibition) control is included on each assay plate. The plate was mixed and incubated for 90 minutes at room temperature. Anisotropy is measured at excitation wavelength 480 nm and emission wavelength 535 nm using an EnVision Multi-label plate reader (PerkinElmer, Wellesley, Mass., USA). Fluorescence anisotropy is plotted against compound concentration to generate an IC50 (inhibitor concentration at which 50% of bound peptide is displaced) by fitting the data to a 4-parameter logistic model using XLFit software (Guildford, Surrey, UK). IC50 is converted to a binding dissociation constant (Ki value) according to the formula of Wang Z. FEBS Lett (1996) 3, 245:K i =[I] 50/([L] 50 /K d +[P] 0 /K d+1)where [I]50 is the concentration of the free inhibitor at 50% inhibition, [L]50 is the concentration of the free labeled ligand at 50% inhibition, [P]0 is the concentration of the free protein at 0% inhibition, Kd represents the dissociation constant of the FITC peptide probe.
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 607.13, ALogP 5.42, HBA 5, HBD 4, PSA 133.15, QED 0.15
Compound (SMILES): Cc1cc(OCCCc2c(C(=O)NS(=O)(=O)CCNC(=O)c3ccc4cc[nH]c4c3)[nH]c3ccccc23)cc(C)c1Cl
InChIKey: FAXIGLMQMJMECB-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Displacement of FITC-Bak-BH3 peptide probe from N-terminal His-tagged human Mcl-1 (172 to 327 residues) expressed in Escherichia coli BL21(DE3) after 1.5 hrs by FPA based competition assay
Measurement: Ki = 278 nM (pChEMBL 6.559999942779541)
Descriptors: MW 607.13, ALogP 5.42, HBA 5, HBD 4, PSA 133.15, QED 0.15
Compound (SMILES): Cc1cc(OCCCc2c(C(=O)NS(=O)(=O)CCNC(=O)Cc3cn(C)c4ccccc34)[nH]c3ccccc23)cc(C)c1Cl
InChIKey: YTZZBFCCNZESCZ-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Bak Peptide Binding Assay: Compound affinity was measured using a fluorescence polarization anisotropy competition assay. Anisotropy measurements were carried out in 384-well, black, flat-bottom plates (Greiner Bio-one, Monroe, N.C., USA). The assay was run using a fluorescein isothiocyanate-labeled BH3 peptide derived from Bak (FITC-AHx-GQVGRQLAIIGDDINR-NH2) that was purchased from GenScript (Piscataway, N.J.) at >95% purity and used without further purification. 10 nM FITC-Bak peptide and 14 nM recombinant Mcl-1 (residues 172-327) were added to assay buffer (3 mM dithiothreitol, 50 mM NaCl, 20 mM Tris, pH 7.5). For selectivity assays, 40 nM Bcl-2 (residues 1-207A96T,G110R, Δ35-91, replaced with Bcl-xL35-50) or 4 nM Bcl-xL (residues 1-209, loop 45-86 deleted) were incubated with 10 nM FITC-Bak in assay buffer. Compounds are diluted in DMSO in a 10-point, 3-fold serial dilution scheme. 2.5 uL compound is added to 47.5 uL of assay buffer containing FITC-Bak and protein, for a final DMSO concentration of 5% and a top concentration of 20 uM. A FITC-Bak peptide alone (100% inhibition) and peptide plus protein (0% inhibition) control is included on each assay plate. The plate was mixed and incubated for 90 minutes at room temperature. Anisotropy is measured at excitation wavelength 480 nm and emission wavelength 535 nm using an EnVision Multi-label plate reader (PerkinElmer, Wellesley, Mass., USA). Fluorescence anisotropy is plotted against compound concentration to generate an IC50 (inhibitor concentration at which 50% of bound peptide is displaced) by fitting the data to a 4-parameter logistic model using XLFit software (Guildford, Surrey, UK). IC50 is converted to a binding dissociation constant (Ki value) according to the formula of Wang Z. FEBS Lett (1996) 3, 245:K i =[I] 50/([L] 50 /K d +[P] 0 /K d+1)where [I]50 is the concentration of the free inhibitor at 50% inhibition, [L]50 is the concentration of the free labeled ligand at 50% inhibition, [P]0 is the concentration of the free protein at 0% inhibition, Kd represents the dissociation constant of the FITC peptide probe.
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 635.19, ALogP 5.36, HBA 6, HBD 3, PSA 122.29, QED 0.16
Compound (SMILES): Cc1cc(OCCCc2c(C(=O)NS(=O)(=O)CCNC(=O)[C@@H]3Cc4ccccc4N3)[nH]c3ccccc23)cc(C)c1Cl
InChIKey: MXEDGZADKSLEIL-MHZLTWQESA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Displacement of FITC-Bak-BH3 peptide probe from N-terminal His-tagged human Mcl-1 (172 to 327 residues) expressed in Escherichia coli BL21(DE3) after 1.5 hrs by FPA based competition assay
Measurement: Ki = 193 nM (pChEMBL 6.710000038146973)
Descriptors: MW 609.15, ALogP 4.66, HBA 6, HBD 4, PSA 129.39, QED 0.18
Compound (SMILES): Cc1cc(OCCCc2c(C(=O)NS(=O)(=O)CCNC(=O)[C@@H]3Cc4ccccc4N3)[nH]c3cc(Cl)ccc23)cc(C)c1Cl
InChIKey: XCGQNVFQNMUDAL-MHZLTWQESA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Bak Peptide Binding Assay: Compound affinity was measured using a fluorescence polarization anisotropy competition assay. Anisotropy measurements were carried out in 384-well, black, flat-bottom plates (Greiner Bio-one, Monroe, N.C., USA). The assay was run using a fluorescein isothiocyanate-labeled BH3 peptide derived from Bak (FITC-AHx-GQVGRQLAIIGDDINR-NH2) that was purchased from GenScript (Piscataway, N.J.) at >95% purity and used without further purification. 10 nM FITC-Bak peptide and 14 nM recombinant Mcl-1 (residues 172-327) were added to assay buffer (3 mM dithiothreitol, 50 mM NaCl, 20 mM Tris, pH 7.5). For selectivity assays, 40 nM Bcl-2 (residues 1-207A96T,G110R, Δ35-91, replaced with Bcl-xL35-50) or 4 nM Bcl-xL (residues 1-209, loop 45-86 deleted) were incubated with 10 nM FITC-Bak in assay buffer. Compounds are diluted in DMSO in a 10-point, 3-fold serial dilution scheme. 2.5 uL compound is added to 47.5 uL of assay buffer containing FITC-Bak and protein, for a final DMSO concentration of 5% and a top concentration of 20 uM. A FITC-Bak peptide alone (100% inhibition) and peptide plus protein (0% inhibition) control is included on each assay plate. The plate was mixed and incubated for 90 minutes at room temperature. Anisotropy is measured at excitation wavelength 480 nm and emission wavelength 535 nm using an EnVision Multi-label plate reader (PerkinElmer, Wellesley, Mass., USA). Fluorescence anisotropy is plotted against compound concentration to generate an IC50 (inhibitor concentration at which 50% of bound peptide is displaced) by fitting the data to a 4-parameter logistic model using XLFit software (Guildford, Surrey, UK). IC50 is converted to a binding dissociation constant (Ki value) according to the formula of Wang Z. FEBS Lett (1996) 3, 245:K i =[I] 50/([L] 50 /K d +[P] 0 /K d+1)where [I]50 is the concentration of the free inhibitor at 50% inhibition, [L]50 is the concentration of the free labeled ligand at 50% inhibition, [P]0 is the concentration of the free protein at 0% inhibition, Kd represents the dissociation constant of the FITC peptide probe.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 643.59, ALogP 5.32, HBA 6, HBD 4, PSA 129.39, QED 0.16
Compound (SMILES): Cc1cc(OCCCc2c(C(=O)NS(=O)(=O)CCNC(=O)c3cccn3-c3ccccc3)[nH]c3ccccc23)cc(C)c1Cl
InChIKey: PTEYBPSGJZVDCD-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Displacement of FITC-Bak-BH3 peptide probe from N-terminal His-tagged human Mcl-1 (172 to 327 residues) expressed in Escherichia coli BL21(DE3) after 1.5 hrs by FPA based competition assay
Measurement: Ki = 139 nM (pChEMBL 6.860000133514404)
Descriptors: MW 633.17, ALogP 5.73, HBA 6, HBD 3, PSA 122.29, QED 0.15
Compound (SMILES): Cc1cc(OCCCc2c(C(=O)NS(=O)(=O)CCNC(=O)c3cccn3Cc3ccccc3)[nH]c3ccccc23)cc(C)c1Cl
InChIKey: XYARBKYHURJQAV-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Bak Peptide Binding Assay: Compound affinity was measured using a fluorescence polarization anisotropy competition assay. Anisotropy measurements were carried out in 384-well, black, flat-bottom plates (Greiner Bio-one, Monroe, N.C., USA). The assay was run using a fluorescein isothiocyanate-labeled BH3 peptide derived from Bak (FITC-AHx-GQVGRQLAIIGDDINR-NH2) that was purchased from GenScript (Piscataway, N.J.) at >95% purity and used without further purification. 10 nM FITC-Bak peptide and 14 nM recombinant Mcl-1 (residues 172-327) were added to assay buffer (3 mM dithiothreitol, 50 mM NaCl, 20 mM Tris, pH 7.5). For selectivity assays, 40 nM Bcl-2 (residues 1-207A96T,G110R, Δ35-91, replaced with Bcl-xL35-50) or 4 nM Bcl-xL (residues 1-209, loop 45-86 deleted) were incubated with 10 nM FITC-Bak in assay buffer. Compounds are diluted in DMSO in a 10-point, 3-fold serial dilution scheme. 2.5 uL compound is added to 47.5 uL of assay buffer containing FITC-Bak and protein, for a final DMSO concentration of 5% and a top concentration of 20 uM. A FITC-Bak peptide alone (100% inhibition) and peptide plus protein (0% inhibition) control is included on each assay plate. The plate was mixed and incubated for 90 minutes at room temperature. Anisotropy is measured at excitation wavelength 480 nm and emission wavelength 535 nm using an EnVision Multi-label plate reader (PerkinElmer, Wellesley, Mass., USA). Fluorescence anisotropy is plotted against compound concentration to generate an IC50 (inhibitor concentration at which 50% of bound peptide is displaced) by fitting the data to a 4-parameter logistic model using XLFit software (Guildford, Surrey, UK). IC50 is converted to a binding dissociation constant (Ki value) according to the formula of Wang Z. FEBS Lett (1996) 3, 245:K i =[I] 50/([L] 50 /K d +[P] 0 /K d+1)where [I]50 is the concentration of the free inhibitor at 50% inhibition, [L]50 is the concentration of the free labeled ligand at 50% inhibition, [P]0 is the concentration of the free protein at 0% inhibition, Kd represents the dissociation constant of the FITC peptide probe.
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 647.2, ALogP 5.79, HBA 6, HBD 3, PSA 122.29, QED 0.14