lovingscience/chembl-v37-raw-activities huggingface dataset:
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 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 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 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 = 186.21 nM (pChEMBL 6.730000019073486)
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 human CXCR3 expressed in HEK293T cell membranes after 30 mins by [35S]GTPgammaS incorporation assay
Measurement: EC50 = 2238.72 nM (pChEMBL 5.650000095367432)
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 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 = 112.2 nM (pChEMBL 6.949999809265137)
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 human CXCR3 expressed in HEK293T cell membranes after 30 mins by [35S]GTPgammaS incorporation assay
Measurement: EC50 = 9.772 nM (pChEMBL 8.010000228881836)
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 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P19490
Assay: Displacement of [3H]AMPA from recombinant rat GluA1 receptor flop isoform expressed in sf9 insect cells
Measurement: Ki = 434 nM (pChEMBL 6.360000133514404)
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 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P19490
Assay: Displacement of [3H]AMPA from recombinant rat GluA1 receptor flop isoform expressed in sf9 insect cells
Measurement: Ki = 10800 nM (pChEMBL 4.96999979019165)
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 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P19490
Assay: Displacement of [3H]AMPA from recombinant rat GluA1 receptor flop isoform expressed in sf9 insect cells
Measurement: Ki = 5290 nM (pChEMBL 5.28000020980835)
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 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P19490
Assay: Displacement of [3H]AMPA from recombinant rat GluA1 receptor flop isoform expressed in sf9 insect cells
Measurement: Ki = 3200 nM (pChEMBL 5.5)
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: 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 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: 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 = 251 nM (pChEMBL 6.599999904632568)
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: 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 = 750 nM (pChEMBL 6.119999885559082)
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: 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 = 55 nM (pChEMBL 7.260000228881836)
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: 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 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: 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 = 269 nM (pChEMBL 6.570000171661377)
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: 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)c3cn(C)c4ccccc34)[nH]c3ccccc23)cc(C)c1Cl
InChIKey: GUKNVQSEBBJHKI-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 = 432 nM (pChEMBL 6.369999885559082)
Descriptors: MW 621.16, ALogP 5.43, HBA 6, HBD 3, PSA 122.29, QED 0.17
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: 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 = 298 nM (pChEMBL 6.53000020980835)
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)c3cc4ccccc4o3)[nH]c3ccccc23)cc(C)c1Cl
InChIKey: PBCZQMXRKDXOJO-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 = 311 nM (pChEMBL 6.510000228881836)
Descriptors: MW 608.12, ALogP 5.69, HBA 6, HBD 3, PSA 130.5, QED 0.17
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: 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 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: 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 = 46 nM (pChEMBL 7.340000152587891)
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)[C@H]3Cc4ccccc4N3)[nH]c3cc(Cl)ccc23)cc(C)c1Cl
InChIKey: XCGQNVFQNMUDAL-HHHXNRCGSA-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 = 28 nM (pChEMBL 7.550000190734863)
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: 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 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: 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 = 148 nM (pChEMBL 6.829999923706055)
Descriptors: MW 647.2, ALogP 5.79, HBA 6, HBD 3, PSA 122.29, QED 0.14
Compound (SMILES): Cc1cc(OCCCc2c(C(=O)NS(=O)(=O)CCNC(=O)c3ccc[nH]3)[nH]c3cc(Cl)ccc23)cc(C)c1Cl
InChIKey: HFCBKAAPWROWEM-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 = 782 nM (pChEMBL 6.110000133514404)
Descriptors: MW 591.52, ALogP 4.92, HBA 5, HBD 4, PSA 133.15, QED 0.18
Compound (SMILES): Cc1cc(OCCCc2c(C(=O)NS(=O)(=O)CCNC(=O)c3cccn3C)[nH]c3ccccc23)cc(C)c1Cl
InChIKey: UIHPPEAWUFEMKF-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 = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 571.1, ALogP 4.28, HBA 6, HBD 3, PSA 122.29, QED 0.23
Compound (SMILES): Cc1cc(OCCCc2c(C(=O)NS(=O)(=O)CCNC(=O)c3ccco3)[nH]c3cc(Cl)ccc23)cc(C)c1Cl
InChIKey: KLFPHYXJXWJDKF-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 = 53 nM (pChEMBL 7.28000020980835)
Descriptors: MW 592.5, ALogP 5.19, HBA 6, HBD 3, PSA 130.5, QED 0.21
Compound (SMILES): Cc1cc(OCCCc2c(C(=O)NS(=O)(=O)CCNC(=O)c3ccoc3)[nH]c3cc(Cl)ccc23)cc(C)c1Cl
InChIKey: CGDLPVKXRQHGMX-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 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 592.5, ALogP 5.19, HBA 6, HBD 3, PSA 130.5, QED 0.21
Compound (SMILES): Cc1cc(OCCCc2c(C(=O)NS(=O)(=O)CCNC(=O)c3cc(-c4ccccc4O)n[nH]3)[nH]c3cc(Cl)ccc23)cc(C)c1Cl
InChIKey: JDKOAPLWVFCYIU-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 = 308 nM (pChEMBL 6.510000228881836)
Descriptors: MW 684.6, ALogP 5.69, HBA 7, HBD 5, PSA 166.27, QED 0.11
Compound (SMILES): Cc1cc(OCCCc2c(C(=O)NS(=O)(=O)CCNC(=O)c3ccccc3F)[nH]c3ccccc23)cc(C)c1Cl
InChIKey: JZKGOXRJWHSWCJ-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 = 336 nM (pChEMBL 6.46999979019165)
Descriptors: MW 586.09, ALogP 5.08, HBA 5, HBD 3, PSA 117.36, QED 0.21
Compound (SMILES): Cc1cc(OCCCc2c(C(=O)NS(=O)(=O)CCNC(=O)c3cccc(F)c3)[nH]c3ccccc23)cc(C)c1Cl
InChIKey: FTTGSEYXXAOJHN-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 = 100 nM (pChEMBL 7)
Descriptors: MW 586.09, ALogP 5.08, HBA 5, HBD 3, PSA 117.36, QED 0.21
Compound (SMILES): Cc1cc(OCCCc2c(C(=O)NS(=O)(=O)CCNC(=O)c3ccc(F)cc3)[nH]c3ccccc23)cc(C)c1Cl
InChIKey: GKTQSVKGYNEZCV-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 = 117 nM (pChEMBL 6.929999828338623)
Descriptors: MW 586.09, ALogP 5.08, HBA 5, HBD 3, PSA 117.36, QED 0.21
Compound (SMILES): Cc1cc(OCCCc2c(C(=O)NS(=O)(=O)CCNC(=O)c3ccccc3C(F)(F)F)[nH]c3cc(Cl)ccc23)cc(C)c1Cl
InChIKey: HJKPOBRXJDMTHB-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 = 18 nM (pChEMBL 7.75)
Descriptors: MW 670.54, ALogP 6.61, HBA 5, HBD 3, PSA 117.36, QED 0.16
Compound (SMILES): Cc1cc(OCCCc2c(C(=O)NS(=O)(=O)CCNC(=O)c3cccc(C(F)(F)F)c3)[nH]c3cc(Cl)ccc23)cc(C)c1Cl
InChIKey: DXESQVROCCECGJ-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 = 79 nM (pChEMBL 7.099999904632568)
Descriptors: MW 670.54, ALogP 6.61, HBA 5, HBD 3, PSA 117.36, QED 0.16
Compound (SMILES): Cc1cc(OCCCc2c(C(=O)NS(=O)(=O)CCNC(=O)c3ccc(C(F)(F)F)cc3)[nH]c3cc(Cl)ccc23)cc(C)c1Cl
InChIKey: OVKHIDWQHSVTSW-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 = 119 nM (pChEMBL 6.920000076293945)
Descriptors: MW 670.54, ALogP 6.61, HBA 5, HBD 3, PSA 117.36, QED 0.16
Compound (SMILES): CC(=O)NCCS(=O)(=O)NC(=O)c1[nH]c2cc(Cl)ccc2c1CCCOc1cc(C)c(Cl)c(C)c1
InChIKey: GKHXEHAANGIXOE-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 540.47, ALogP 4.3, HBA 5, HBD 3, PSA 117.36, QED 0.33
Compound (SMILES): Cc1cc(OCCCc2c(C(=O)NS(=O)(=O)CCNC(=O)C(F)(F)F)[nH]c3cc(Cl)ccc23)cc(C)c1Cl
InChIKey: UFJRDUXURXDSQI-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 = 116 nM (pChEMBL 6.940000057220459)
Descriptors: MW 594.44, ALogP 4.84, HBA 5, HBD 3, PSA 117.36, QED 0.29
Compound (SMILES): CCC(=O)NCCS(=O)(=O)NC(=O)c1[nH]c2cc(Cl)ccc2c1CCCOc1cc(C)c(Cl)c(C)c1
InChIKey: UGYTUHFXEWCFQO-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 554.5, ALogP 4.69, HBA 5, HBD 3, PSA 117.36, QED 0.3
Compound (SMILES): Cc1cc(OCCCc2c(C(=O)NS(=O)(=O)CCNC(=O)C(C)C)[nH]c3cc(Cl)ccc23)cc(C)c1Cl
InChIKey: YTGNUHNSSYYFLS-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 568.52, ALogP 4.93, HBA 5, HBD 3, PSA 117.36, QED 0.28
Compound (SMILES): CCC(CC)C(=O)NCCS(=O)(=O)NC(=O)c1[nH]c2cc(Cl)ccc2c1CCCOc1cc(C)c(Cl)c(C)c1
InChIKey: UDWGSSPXSAXPBO-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 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 596.58, ALogP 5.72, HBA 5, HBD 3, PSA 117.36, QED 0.22
Compound (SMILES): Cc1cc(OCCCc2c(C(=O)NS(=O)(=O)CCNC(=O)CC(C)C)[nH]c3cc(Cl)ccc23)cc(C)c1Cl
InChIKey: AYLQSMGRRXZGPL-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 = 10 nM (pChEMBL 8)
Descriptors: MW 582.55, ALogP 5.33, HBA 5, HBD 3, PSA 117.36, QED 0.25
Compound (SMILES): Cc1cc(OCCCc2c(C(=O)NS(=O)(=O)c3ccccc3)[nH]c3ccccc23)cc(C)c1Cl
InChIKey: SMGRUAFEHILHHU-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 = 361 nM (pChEMBL 6.440000057220459)
Descriptors: MW 497.02, ALogP 5.57, HBA 4, HBD 2, PSA 88.26, QED 0.31
Compound (SMILES): Cc1cc(OCCCc2c(C(=O)NS(=O)(=O)c3ccccc3)[nH]c3cc(Cl)ccc23)cc(C)c1Cl
InChIKey: UPSTZIYEYCDOAV-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 531.46, ALogP 6.22, HBA 4, HBD 2, PSA 88.26, QED 0.26
Compound (SMILES): Cc1cc(OCCCc2c(C(=O)NS(=O)(=O)c3ccncc3)[nH]c3ccccc23)cc(C)c1Cl
InChIKey: JTLPBIUYANETOW-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 498, ALogP 4.96, HBA 5, HBD 2, PSA 101.15, QED 0.33
Compound (SMILES): Cc1cc(OCCCc2c(C(=O)NS(=O)(=O)c3ccco3)[nH]c3cc(Cl)ccc23)cc(C)c1Cl
InChIKey: OSWGCBZOVLVZFD-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 = 116 nM (pChEMBL 6.940000057220459)
Descriptors: MW 521.42, ALogP 5.81, HBA 5, HBD 2, PSA 101.4, QED 0.28
Compound (SMILES): Cc1cc(OCCCc2c(C(=O)NS(=O)(=O)c3ccccc3)[nH]c3c(-c4cccnc4)cccc23)cc(C)c1Cl
InChIKey: DKBRDQPCALJYNG-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 574.1, ALogP 6.63, HBA 5, HBD 2, PSA 101.15, QED 0.19