lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=C(NS(=O)(=O)c1ccc(N[C@H](CCN2CCN(CCO)CC2)CSc2ccccc2)c(S(=O)(=O)C(F)(F)F)c1)c1ccc(N2CCC([C@@H](O)c3ccccc3-c3ccc(Cl)cc3)CC2)cc1
InChIKey: DCHCBRYRKFZMDP-OIZGGULRSA-N
Target: Apoptosis regulator Bcl-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P10415
Assay: Fluorescence Polarization: Bcl-xL and Bcl-2 FP binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) may be determined using a variety of known methods. One such assay is a sensitive and quantitative in vitro binding assay using fluorescence polarization ("FP") described by Wang, J.-L.; Zhang, Z-J.; Choksi, S.; Sjam. S.; Lu, Z.; Croce, C. M.; Alnemri, E. S.; Komgold, R.; Huang, Z. Cell permeable Bcl-2 binding peptides: a chemical approach to apoptosis induction in tumor cells. Cancer Res. 2000, 60, 1498-1502).Additionally, the binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) to Bcl-2 protein in vitro was determined by a competitive binding assay based on fluorescence polarization. For example, fluorescence polarization ("FP") assays may be developed using a c-terminal 6.times.HIS tagged Bcl-2 (aa 1-204) and a C-terminal 6.times.HIS tagged Bcl-X.sub.L (aa 1-209). The tracer may be a synthetic peptide BH-3 peptide Bim conjugated to Fluores.
Measurement: IC50 < 1 nM (pChEMBL 9)
Descriptors: MW 1000.63
Compound (SMILES): CN(C)CC[C@H](CSc1ccccc1)Nc1ccc(S(=O)(=O)NC(=O)c2ccc(N3CCC([C@@H](O)c4ccccc4-c4ccc(Cl)cc4)CC3)cc2)cc1[N+](=O)[O-]
InChIKey: CWJNKHAZRAKLJR-VJKWZVKUSA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07817
Assay: Fluorescence Polarization: Bcl-xL and Bcl-2 FP binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) may be determined using a variety of known methods. One such assay is a sensitive and quantitative in vitro binding assay using fluorescence polarization ("FP") described by Wang, J.-L.; Zhang, Z-J.; Choksi, S.; Sjam. S.; Lu, Z.; Croce, C. M.; Alnemri, E. S.; Komgold, R.; Huang, Z. Cell permeable Bcl-2 binding peptides: a chemical approach to apoptosis induction in tumor cells. Cancer Res. 2000, 60, 1498-1502).Additionally, the binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) to Bcl-2 protein in vitro was determined by a competitive binding assay based on fluorescence polarization. For example, fluorescence polarization ("FP") assays may be developed using a c-terminal 6.times.HIS tagged Bcl-2 (aa 1-204) and a C-terminal 6.times.HIS tagged Bcl-X.sub.L (aa 1-209). The tracer may be a synthetic peptide BH-3 peptide Bim conjugated to Fluores.
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 828.46, ALogP 8.51, HBA 10, HBD 3, PSA 145.12, QED 0.05
Compound (SMILES): CN(CCO)CC[C@H](CSc1ccccc1)Nc1ccc(S(=O)(=O)NC(=O)c2ccc(N3CCC([C@@H](O)c4ccccc4-c4ccc(Cl)cc4)CC3)cc2)cc1S(=O)(=O)C(F)(F)F
InChIKey: UNEJSHNDABUZNY-UJNHCCGESA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07817
Assay: Fluorescence Polarization: Bcl-xL and Bcl-2 FP binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) may be determined using a variety of known methods. One such assay is a sensitive and quantitative in vitro binding assay using fluorescence polarization ("FP") described by Wang, J.-L.; Zhang, Z-J.; Choksi, S.; Sjam. S.; Lu, Z.; Croce, C. M.; Alnemri, E. S.; Komgold, R.; Huang, Z. Cell permeable Bcl-2 binding peptides: a chemical approach to apoptosis induction in tumor cells. Cancer Res. 2000, 60, 1498-1502).Additionally, the binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) to Bcl-2 protein in vitro was determined by a competitive binding assay based on fluorescence polarization. For example, fluorescence polarization ("FP") assays may be developed using a c-terminal 6.times.HIS tagged Bcl-2 (aa 1-204) and a C-terminal 6.times.HIS tagged Bcl-X.sub.L (aa 1-209). The tracer may be a synthetic peptide BH-3 peptide Bim conjugated to Fluores.
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 945.55, ALogP 8.26, HBA 11, HBD 4, PSA 156.35, QED 0.06
Compound (SMILES): CCN(CCO)CC[C@H](CSc1ccccc1)Nc1ccc(S(=O)(=O)NC(=O)c2ccc(N3CCC([C@@H](O)c4ccccc4-c4ccc(Cl)cc4)CC3)cc2)cc1S(=O)(=O)C(F)(F)F
InChIKey: CZQCNVJPENOBDV-CAZXVXRPSA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07817
Assay: Fluorescence Polarization: Bcl-xL and Bcl-2 FP binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) may be determined using a variety of known methods. One such assay is a sensitive and quantitative in vitro binding assay using fluorescence polarization ("FP") described by Wang, J.-L.; Zhang, Z-J.; Choksi, S.; Sjam. S.; Lu, Z.; Croce, C. M.; Alnemri, E. S.; Komgold, R.; Huang, Z. Cell permeable Bcl-2 binding peptides: a chemical approach to apoptosis induction in tumor cells. Cancer Res. 2000, 60, 1498-1502).Additionally, the binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) to Bcl-2 protein in vitro was determined by a competitive binding assay based on fluorescence polarization. For example, fluorescence polarization ("FP") assays may be developed using a c-terminal 6.times.HIS tagged Bcl-2 (aa 1-204) and a C-terminal 6.times.HIS tagged Bcl-X.sub.L (aa 1-209). The tracer may be a synthetic peptide BH-3 peptide Bim conjugated to Fluores.
Measurement: IC50 = 0.8 nM (pChEMBL 9.100000381469727)
Descriptors: MW 959.57, ALogP 8.65, HBA 11, HBD 4, PSA 156.35, QED 0.06
Compound (SMILES): O=C(NS(=O)(=O)c1ccc(N[C@H](CCN(CCO)CCO)CSc2ccccc2)c(S(=O)(=O)C(F)(F)F)c1)c1ccc(N2CCC([C@@H](O)c3ccccc3-c3ccc(Cl)cc3)CC2)cc1
InChIKey: DSMKXMINSCXYGH-CAZXVXRPSA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07817
Assay: Fluorescence Polarization: Bcl-xL and Bcl-2 FP binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) may be determined using a variety of known methods. One such assay is a sensitive and quantitative in vitro binding assay using fluorescence polarization ("FP") described by Wang, J.-L.; Zhang, Z-J.; Choksi, S.; Sjam. S.; Lu, Z.; Croce, C. M.; Alnemri, E. S.; Komgold, R.; Huang, Z. Cell permeable Bcl-2 binding peptides: a chemical approach to apoptosis induction in tumor cells. Cancer Res. 2000, 60, 1498-1502).Additionally, the binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) to Bcl-2 protein in vitro was determined by a competitive binding assay based on fluorescence polarization. For example, fluorescence polarization ("FP") assays may be developed using a c-terminal 6.times.HIS tagged Bcl-2 (aa 1-204) and a C-terminal 6.times.HIS tagged Bcl-X.sub.L (aa 1-209). The tracer may be a synthetic peptide BH-3 peptide Bim conjugated to Fluores.
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 975.57, ALogP 7.62, HBA 12, HBD 5, PSA 176.58, QED 0.05
Compound (SMILES): O=C(NS(=O)(=O)c1ccc(N[C@H](CCN2CCN(C[C@H](O)CF)CC2)CSc2ccccc2)c(S(=O)(=O)C(F)(F)F)c1)c1ccc(N2CCC([C@@H](O)c3ccccc3-c3ccc(Cl)cc3)CC2)cc1
InChIKey: RIMLWEFZWHQOEH-KWYPLSMNSA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07817
Assay: Fluorescence Polarization: Bcl-xL and Bcl-2 FP binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) may be determined using a variety of known methods. One such assay is a sensitive and quantitative in vitro binding assay using fluorescence polarization ("FP") described by Wang, J.-L.; Zhang, Z-J.; Choksi, S.; Sjam. S.; Lu, Z.; Croce, C. M.; Alnemri, E. S.; Komgold, R.; Huang, Z. Cell permeable Bcl-2 binding peptides: a chemical approach to apoptosis induction in tumor cells. Cancer Res. 2000, 60, 1498-1502).Additionally, the binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) to Bcl-2 protein in vitro was determined by a competitive binding assay based on fluorescence polarization. For example, fluorescence polarization ("FP") assays may be developed using a c-terminal 6.times.HIS tagged Bcl-2 (aa 1-204) and a C-terminal 6.times.HIS tagged Bcl-X.sub.L (aa 1-209). The tracer may be a synthetic peptide BH-3 peptide Bim conjugated to Fluores.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 1032.64
Compound (SMILES): O=C(NS(=O)(=O)c1ccc(N[C@H](CCN(CCOP(=O)(O)O)CCOP(=O)(O)O)CSc2ccccc2)c(S(=O)(=O)C(F)(F)F)c1)c1ccc(N2CCC([C@@H](O)c3ccccc3-c3ccc(Cl)cc3)CC2)cc1
InChIKey: PXOPKZMWBPBVHT-CAZXVXRPSA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07817
Assay: Fluorescence Polarization: Bcl-xL and Bcl-2 FP binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) may be determined using a variety of known methods. One such assay is a sensitive and quantitative in vitro binding assay using fluorescence polarization ("FP") described by Wang, J.-L.; Zhang, Z-J.; Choksi, S.; Sjam. S.; Lu, Z.; Croce, C. M.; Alnemri, E. S.; Komgold, R.; Huang, Z. Cell permeable Bcl-2 binding peptides: a chemical approach to apoptosis induction in tumor cells. Cancer Res. 2000, 60, 1498-1502).Additionally, the binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) to Bcl-2 protein in vitro was determined by a competitive binding assay based on fluorescence polarization. For example, fluorescence polarization ("FP") assays may be developed using a c-terminal 6.times.HIS tagged Bcl-2 (aa 1-204) and a C-terminal 6.times.HIS tagged Bcl-X.sub.L (aa 1-209). The tracer may be a synthetic peptide BH-3 peptide Bim conjugated to Fluores.
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 1135.53
Compound (SMILES): CCN(CCOP(=O)(O)O)CC[C@H](CSc1ccccc1)Nc1ccc(S(=O)(=O)NC(=O)c2ccc(N3CCC([C@@H](O)c4ccccc4-c4ccc(Cl)cc4)CC3)cc2)cc1S(=O)(=O)C(F)(F)F
InChIKey: NRMPZUJXWZRKTG-CAZXVXRPSA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07817
Assay: Fluorescence Polarization: Bcl-xL and Bcl-2 FP binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) may be determined using a variety of known methods. One such assay is a sensitive and quantitative in vitro binding assay using fluorescence polarization ("FP") described by Wang, J.-L.; Zhang, Z-J.; Choksi, S.; Sjam. S.; Lu, Z.; Croce, C. M.; Alnemri, E. S.; Komgold, R.; Huang, Z. Cell permeable Bcl-2 binding peptides: a chemical approach to apoptosis induction in tumor cells. Cancer Res. 2000, 60, 1498-1502).Additionally, the binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) to Bcl-2 protein in vitro was determined by a competitive binding assay based on fluorescence polarization. For example, fluorescence polarization ("FP") assays may be developed using a c-terminal 6.times.HIS tagged Bcl-2 (aa 1-204) and a C-terminal 6.times.HIS tagged Bcl-X.sub.L (aa 1-209). The tracer may be a synthetic peptide BH-3 peptide Bim conjugated to Fluores.
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 1039.55
Compound (SMILES): CN(CCOP(=O)(O)O)CC[C@H](CSc1ccccc1)Nc1ccc(S(=O)(=O)NC(=O)c2ccc(N3CCC([C@@H](O)c4ccccc4-c4ccc(Cl)cc4)CC3)cc2)cc1S(=O)(=O)C(F)(F)F
InChIKey: MOTYTGFXZSXHOD-UJNHCCGESA-N
Target: Apoptosis regulator Bcl-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P10415
Assay: Fluorescence Polarization: Bcl-xL and Bcl-2 FP binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) may be determined using a variety of known methods. One such assay is a sensitive and quantitative in vitro binding assay using fluorescence polarization ("FP") described by Wang, J.-L.; Zhang, Z-J.; Choksi, S.; Sjam. S.; Lu, Z.; Croce, C. M.; Alnemri, E. S.; Komgold, R.; Huang, Z. Cell permeable Bcl-2 binding peptides: a chemical approach to apoptosis induction in tumor cells. Cancer Res. 2000, 60, 1498-1502).Additionally, the binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) to Bcl-2 protein in vitro was determined by a competitive binding assay based on fluorescence polarization. For example, fluorescence polarization ("FP") assays may be developed using a c-terminal 6.times.HIS tagged Bcl-2 (aa 1-204) and a C-terminal 6.times.HIS tagged Bcl-X.sub.L (aa 1-209). The tracer may be a synthetic peptide BH-3 peptide Bim conjugated to Fluores.
Measurement: IC50 = 0.9 nM (pChEMBL 9.050000190734863)
Descriptors: MW 1025.53
Compound (SMILES): O=C(NS(=O)(=O)c1ccc(N[C@H](CCN2CCN(CCOP(=O)(O)O)CC2)CSc2ccccc2)c(S(=O)(=O)C(F)(F)F)c1)c1ccc(N2CCC([C@@H](O)c3ccccc3-c3ccc(Cl)cc3)CC2)cc1
InChIKey: MRCBJYPJINGJHR-OIZGGULRSA-N
Target: Apoptosis regulator Bcl-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P10415
Assay: Fluorescence Polarization: Bcl-xL and Bcl-2 FP binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) may be determined using a variety of known methods. One such assay is a sensitive and quantitative in vitro binding assay using fluorescence polarization ("FP") described by Wang, J.-L.; Zhang, Z-J.; Choksi, S.; Sjam. S.; Lu, Z.; Croce, C. M.; Alnemri, E. S.; Komgold, R.; Huang, Z. Cell permeable Bcl-2 binding peptides: a chemical approach to apoptosis induction in tumor cells. Cancer Res. 2000, 60, 1498-1502).Additionally, the binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) to Bcl-2 protein in vitro was determined by a competitive binding assay based on fluorescence polarization. For example, fluorescence polarization ("FP") assays may be developed using a c-terminal 6.times.HIS tagged Bcl-2 (aa 1-204) and a C-terminal 6.times.HIS tagged Bcl-X.sub.L (aa 1-209). The tracer may be a synthetic peptide BH-3 peptide Bim conjugated to Fluores.
Measurement: IC50 = 0.7 nM (pChEMBL 9.149999618530273)
Descriptors: MW 1080.61
Compound (SMILES): CN(CCO)CC[C@H](CSc1ccccc1)Nc1ccc(S(=O)(=O)NC(=O)c2ccc(N3CCC([C@@H](N)c4ccccc4-c4ccc(Cl)cc4)CC3)cc2)cc1S(=O)(=O)C(F)(F)F
InChIKey: NMQFUMLYFHPROZ-UJNHCCGESA-N
Target: Apoptosis regulator Bcl-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P10415
Assay: Fluorescence Polarization: Bcl-xL and Bcl-2 FP binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) may be determined using a variety of known methods. One such assay is a sensitive and quantitative in vitro binding assay using fluorescence polarization ("FP") described by Wang, J.-L.; Zhang, Z-J.; Choksi, S.; Sjam. S.; Lu, Z.; Croce, C. M.; Alnemri, E. S.; Komgold, R.; Huang, Z. Cell permeable Bcl-2 binding peptides: a chemical approach to apoptosis induction in tumor cells. Cancer Res. 2000, 60, 1498-1502).Additionally, the binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) to Bcl-2 protein in vitro was determined by a competitive binding assay based on fluorescence polarization. For example, fluorescence polarization ("FP") assays may be developed using a c-terminal 6.times.HIS tagged Bcl-2 (aa 1-204) and a C-terminal 6.times.HIS tagged Bcl-X.sub.L (aa 1-209). The tracer may be a synthetic peptide BH-3 peptide Bim conjugated to Fluores.
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 944.56, ALogP 8.22, HBA 11, HBD 4, PSA 162.14, QED 0.06
Compound (SMILES): CCN(CCO)CC[C@H](CSc1ccccc1)Nc1ccc(S(=O)(=O)NC(=O)c2ccc(N3CCC([C@@H](N)c4ccccc4-c4ccc(Cl)cc4)CC3)cc2)cc1S(=O)(=O)C(F)(F)F
InChIKey: BUTLNWRLMGMMFQ-CAZXVXRPSA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07817
Assay: Fluorescence Polarization: Bcl-xL and Bcl-2 FP binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) may be determined using a variety of known methods. One such assay is a sensitive and quantitative in vitro binding assay using fluorescence polarization ("FP") described by Wang, J.-L.; Zhang, Z-J.; Choksi, S.; Sjam. S.; Lu, Z.; Croce, C. M.; Alnemri, E. S.; Komgold, R.; Huang, Z. Cell permeable Bcl-2 binding peptides: a chemical approach to apoptosis induction in tumor cells. Cancer Res. 2000, 60, 1498-1502).Additionally, the binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) to Bcl-2 protein in vitro was determined by a competitive binding assay based on fluorescence polarization. For example, fluorescence polarization ("FP") assays may be developed using a c-terminal 6.times.HIS tagged Bcl-2 (aa 1-204) and a C-terminal 6.times.HIS tagged Bcl-X.sub.L (aa 1-209). The tracer may be a synthetic peptide BH-3 peptide Bim conjugated to Fluores.
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 958.59, ALogP 8.61, HBA 11, HBD 4, PSA 162.14, QED 0.06
Compound (SMILES): N[C@@H](c1ccccc1-c1ccc(Cl)cc1)C1CCN(c2ccc(C(=O)NS(=O)(=O)c3ccc(N[C@H](CCN4CCN(CCO)CC4)CSc4ccccc4)c(S(=O)(=O)C(F)(F)F)c3)cc2)CC1
InChIKey: WBLFPQKNGJAZLP-OIZGGULRSA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07817
Assay: Fluorescence Polarization: Bcl-xL and Bcl-2 FP binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) may be determined using a variety of known methods. One such assay is a sensitive and quantitative in vitro binding assay using fluorescence polarization ("FP") described by Wang, J.-L.; Zhang, Z-J.; Choksi, S.; Sjam. S.; Lu, Z.; Croce, C. M.; Alnemri, E. S.; Komgold, R.; Huang, Z. Cell permeable Bcl-2 binding peptides: a chemical approach to apoptosis induction in tumor cells. Cancer Res. 2000, 60, 1498-1502).Additionally, the binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) to Bcl-2 protein in vitro was determined by a competitive binding assay based on fluorescence polarization. For example, fluorescence polarization ("FP") assays may be developed using a c-terminal 6.times.HIS tagged Bcl-2 (aa 1-204) and a C-terminal 6.times.HIS tagged Bcl-X.sub.L (aa 1-209). The tracer may be a synthetic peptide BH-3 peptide Bim conjugated to Fluores.
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 999.64, ALogP 7.91, HBA 12, HBD 4, PSA 165.38, QED 0.06
Compound (SMILES): O=C(NS(=O)(=O)c1ccc(N[C@H](CCN2CCOCC2)CSc2ccccc2)c(S(=O)(=O)C(F)(F)F)c1)c1ccc(N2CCC([C@H](O)c3ccccc3-c3ccc(Cl)cc3)CC2)cc1
InChIKey: OFDAVDOQYGEDHJ-KBPOQJSISA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07817
Assay: Fluorescence Polarization: Bcl-xL and Bcl-2 FP binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) may be determined using a variety of known methods. One such assay is a sensitive and quantitative in vitro binding assay using fluorescence polarization ("FP") described by Wang, J.-L.; Zhang, Z-J.; Choksi, S.; Sjam. S.; Lu, Z.; Croce, C. M.; Alnemri, E. S.; Komgold, R.; Huang, Z. Cell permeable Bcl-2 binding peptides: a chemical approach to apoptosis induction in tumor cells. Cancer Res. 2000, 60, 1498-1502).Additionally, the binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) to Bcl-2 protein in vitro was determined by a competitive binding assay based on fluorescence polarization. For example, fluorescence polarization ("FP") assays may be developed using a c-terminal 6.times.HIS tagged Bcl-2 (aa 1-204) and a C-terminal 6.times.HIS tagged Bcl-X.sub.L (aa 1-209). The tracer may be a synthetic peptide BH-3 peptide Bim conjugated to Fluores.
Measurement: IC50 = 78 nM (pChEMBL 7.110000133514404)
Descriptors: MW 957.56, ALogP 8.66, HBA 11, HBD 3, PSA 145.35, QED 0.08
Compound (SMILES): O=C(NS(=O)(=O)c1ccc(N[C@H](CCN2CCOCC2)CSc2ccccc2)c(S(=O)(=O)C(F)(F)F)c1)c1ccc(N2CCC([C@@H](O)c3ccccc3-c3ccc(Cl)cc3)CC2)cc1
InChIKey: OFDAVDOQYGEDHJ-CAZXVXRPSA-N
Target: Apoptosis regulator Bcl-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P10415
Assay: Fluorescence Polarization: Bcl-xL and Bcl-2 FP binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) may be determined using a variety of known methods. One such assay is a sensitive and quantitative in vitro binding assay using fluorescence polarization ("FP") described by Wang, J.-L.; Zhang, Z-J.; Choksi, S.; Sjam. S.; Lu, Z.; Croce, C. M.; Alnemri, E. S.; Komgold, R.; Huang, Z. Cell permeable Bcl-2 binding peptides: a chemical approach to apoptosis induction in tumor cells. Cancer Res. 2000, 60, 1498-1502).Additionally, the binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) to Bcl-2 protein in vitro was determined by a competitive binding assay based on fluorescence polarization. For example, fluorescence polarization ("FP") assays may be developed using a c-terminal 6.times.HIS tagged Bcl-2 (aa 1-204) and a C-terminal 6.times.HIS tagged Bcl-X.sub.L (aa 1-209). The tracer may be a synthetic peptide BH-3 peptide Bim conjugated to Fluores.
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 957.56, ALogP 8.66, HBA 11, HBD 3, PSA 145.35, QED 0.08
Compound (SMILES): O=C(NS(=O)(=O)c1ccc(N[C@H](CCN2CCOCC2)CSc2ccccc2)c([N+](=O)[O-])c1)c1ccc(N2CCC([C@@H](O)c3ccccc3-c3ccc(Cl)cc3)CC2)cc1
InChIKey: STNWTWVPOINSDM-CAZXVXRPSA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07817
Assay: Fluorescence Polarization: Bcl-xL and Bcl-2 FP binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) may be determined using a variety of known methods. One such assay is a sensitive and quantitative in vitro binding assay using fluorescence polarization ("FP") described by Wang, J.-L.; Zhang, Z-J.; Choksi, S.; Sjam. S.; Lu, Z.; Croce, C. M.; Alnemri, E. S.; Komgold, R.; Huang, Z. Cell permeable Bcl-2 binding peptides: a chemical approach to apoptosis induction in tumor cells. Cancer Res. 2000, 60, 1498-1502).Additionally, the binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) to Bcl-2 protein in vitro was determined by a competitive binding assay based on fluorescence polarization. For example, fluorescence polarization ("FP") assays may be developed using a c-terminal 6.times.HIS tagged Bcl-2 (aa 1-204) and a C-terminal 6.times.HIS tagged Bcl-X.sub.L (aa 1-209). The tracer may be a synthetic peptide BH-3 peptide Bim conjugated to Fluores.
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 870.49, ALogP 8.28, HBA 11, HBD 3, PSA 154.35, QED 0.05
Compound (SMILES): N#C[C@@H](c1ccccc1-c1ccc(Cl)cc1)C1CCN(c2ccc(C(=O)NS(=O)(=O)c3ccc(N[C@H](CCN4CCOCC4)CSc4ccccc4)c(S(=O)(=O)C(F)(F)F)c3)cc2)CC1
InChIKey: VSTRECJFPCMULL-GJSZZFLHSA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07817
Assay: Fluorescence Polarization: Bcl-xL and Bcl-2 FP binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) may be determined using a variety of known methods. One such assay is a sensitive and quantitative in vitro binding assay using fluorescence polarization ("FP") described by Wang, J.-L.; Zhang, Z-J.; Choksi, S.; Sjam. S.; Lu, Z.; Croce, C. M.; Alnemri, E. S.; Komgold, R.; Huang, Z. Cell permeable Bcl-2 binding peptides: a chemical approach to apoptosis induction in tumor cells. Cancer Res. 2000, 60, 1498-1502).Additionally, the binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) to Bcl-2 protein in vitro was determined by a competitive binding assay based on fluorescence polarization. For example, fluorescence polarization ("FP") assays may be developed using a c-terminal 6.times.HIS tagged Bcl-2 (aa 1-204) and a C-terminal 6.times.HIS tagged Bcl-X.sub.L (aa 1-209). The tracer may be a synthetic peptide BH-3 peptide Bim conjugated to Fluores.
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 966.57, ALogP 9.24, HBA 11, HBD 2, PSA 148.91, QED 0.09
Compound (SMILES): N#C[C@H](c1ccccc1-c1ccc(Cl)cc1)C1CCN(c2ccc(C(=O)NS(=O)(=O)c3ccc(N[C@H](CCN4CCOCC4)CSc4ccccc4)c(S(=O)(=O)C(F)(F)F)c3)cc2)CC1
InChIKey: VSTRECJFPCMULL-RQSCIUFGSA-N
Target: Apoptosis regulator Bcl-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P10415
Assay: Fluorescence Polarization: Bcl-xL and Bcl-2 FP binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) may be determined using a variety of known methods. One such assay is a sensitive and quantitative in vitro binding assay using fluorescence polarization ("FP") described by Wang, J.-L.; Zhang, Z-J.; Choksi, S.; Sjam. S.; Lu, Z.; Croce, C. M.; Alnemri, E. S.; Komgold, R.; Huang, Z. Cell permeable Bcl-2 binding peptides: a chemical approach to apoptosis induction in tumor cells. Cancer Res. 2000, 60, 1498-1502).Additionally, the binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) to Bcl-2 protein in vitro was determined by a competitive binding assay based on fluorescence polarization. For example, fluorescence polarization ("FP") assays may be developed using a c-terminal 6.times.HIS tagged Bcl-2 (aa 1-204) and a C-terminal 6.times.HIS tagged Bcl-X.sub.L (aa 1-209). The tracer may be a synthetic peptide BH-3 peptide Bim conjugated to Fluores.
Measurement: IC50 = 1195 nM (pChEMBL 5.920000076293945)
Descriptors: MW 966.57, ALogP 9.24, HBA 11, HBD 2, PSA 148.91, QED 0.09
Compound (SMILES): CCN(CC)C[C@H]1COCCN1CC[C@H](CSc1ccccc1)Nc1ccc(S(=O)(=O)NC(=O)c2ccc(N3CCC([C@@H](O)c4ccccc4-c4ccc(Cl)cc4)CC3)cc2)cc1S(=O)(=O)C(F)(F)F
InChIKey: XCVUZMZRKUHGPU-AVHSULOUSA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07817
Assay: Fluorescence Polarization: Bcl-xL and Bcl-2 FP binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) may be determined using a variety of known methods. One such assay is a sensitive and quantitative in vitro binding assay using fluorescence polarization ("FP") described by Wang, J.-L.; Zhang, Z-J.; Choksi, S.; Sjam. S.; Lu, Z.; Croce, C. M.; Alnemri, E. S.; Komgold, R.; Huang, Z. Cell permeable Bcl-2 binding peptides: a chemical approach to apoptosis induction in tumor cells. Cancer Res. 2000, 60, 1498-1502).Additionally, the binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) to Bcl-2 protein in vitro was determined by a competitive binding assay based on fluorescence polarization. For example, fluorescence polarization ("FP") assays may be developed using a c-terminal 6.times.HIS tagged Bcl-2 (aa 1-204) and a C-terminal 6.times.HIS tagged Bcl-X.sub.L (aa 1-209). The tracer may be a synthetic peptide BH-3 peptide Bim conjugated to Fluores.
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 1042.71
Compound (SMILES): CCN(CC)C[C@@H]1COCCN1CC[C@H](CSc1ccccc1)Nc1ccc(S(=O)(=O)NC(=O)c2ccc(N3CCC([C@@H](O)c4ccccc4-c4ccc(Cl)cc4)CC3)cc2)cc1S(=O)(=O)C(F)(F)F
InChIKey: XCVUZMZRKUHGPU-HUANSRBPSA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07817
Assay: Fluorescence Polarization: Bcl-xL and Bcl-2 FP binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) may be determined using a variety of known methods. One such assay is a sensitive and quantitative in vitro binding assay using fluorescence polarization ("FP") described by Wang, J.-L.; Zhang, Z-J.; Choksi, S.; Sjam. S.; Lu, Z.; Croce, C. M.; Alnemri, E. S.; Komgold, R.; Huang, Z. Cell permeable Bcl-2 binding peptides: a chemical approach to apoptosis induction in tumor cells. Cancer Res. 2000, 60, 1498-1502).Additionally, the binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) to Bcl-2 protein in vitro was determined by a competitive binding assay based on fluorescence polarization. For example, fluorescence polarization ("FP") assays may be developed using a c-terminal 6.times.HIS tagged Bcl-2 (aa 1-204) and a C-terminal 6.times.HIS tagged Bcl-X.sub.L (aa 1-209). The tracer may be a synthetic peptide BH-3 peptide Bim conjugated to Fluores.
Measurement: IC50 = 0.5 nM (pChEMBL 9.300000190734863)
Descriptors: MW 1042.71
Compound (SMILES): O=C(NS(=O)(=O)c1ccc(N[C@H](CCN2CCO[C@@H](CO)C2)CSc2ccccc2)c(S(=O)(=O)C(F)(F)F)c1)c1ccc(N2CCC([C@@H](O)c3ccccc3-c3ccc(Cl)cc3)CC2)cc1
InChIKey: UNIDPFJTIWEYGM-UQHKMDGSSA-N
Target: Apoptosis regulator Bcl-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P10415
Assay: Fluorescence Polarization: Bcl-xL and Bcl-2 FP binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) may be determined using a variety of known methods. One such assay is a sensitive and quantitative in vitro binding assay using fluorescence polarization ("FP") described by Wang, J.-L.; Zhang, Z-J.; Choksi, S.; Sjam. S.; Lu, Z.; Croce, C. M.; Alnemri, E. S.; Komgold, R.; Huang, Z. Cell permeable Bcl-2 binding peptides: a chemical approach to apoptosis induction in tumor cells. Cancer Res. 2000, 60, 1498-1502).Additionally, the binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) to Bcl-2 protein in vitro was determined by a competitive binding assay based on fluorescence polarization. For example, fluorescence polarization ("FP") assays may be developed using a c-terminal 6.times.HIS tagged Bcl-2 (aa 1-204) and a C-terminal 6.times.HIS tagged Bcl-X.sub.L (aa 1-209). The tracer may be a synthetic peptide BH-3 peptide Bim conjugated to Fluores.
Measurement: IC50 = 0.6 nM (pChEMBL 9.220000267028809)
Descriptors: MW 987.58, ALogP 8.03, HBA 12, HBD 4, PSA 165.58, QED 0.07
Compound (SMILES): O=C(NS(=O)(=O)c1ccc(N[C@H](CCN2CCO[C@H](CO)C2)CSc2ccccc2)c(S(=O)(=O)C(F)(F)F)c1)c1ccc(N2CCC([C@@H](O)c3ccccc3-c3ccc(Cl)cc3)CC2)cc1
InChIKey: UNIDPFJTIWEYGM-SQKNJAOPSA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07817
Assay: Fluorescence Polarization: Bcl-xL and Bcl-2 FP binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) may be determined using a variety of known methods. One such assay is a sensitive and quantitative in vitro binding assay using fluorescence polarization ("FP") described by Wang, J.-L.; Zhang, Z-J.; Choksi, S.; Sjam. S.; Lu, Z.; Croce, C. M.; Alnemri, E. S.; Komgold, R.; Huang, Z. Cell permeable Bcl-2 binding peptides: a chemical approach to apoptosis induction in tumor cells. Cancer Res. 2000, 60, 1498-1502).Additionally, the binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) to Bcl-2 protein in vitro was determined by a competitive binding assay based on fluorescence polarization. For example, fluorescence polarization ("FP") assays may be developed using a c-terminal 6.times.HIS tagged Bcl-2 (aa 1-204) and a C-terminal 6.times.HIS tagged Bcl-X.sub.L (aa 1-209). The tracer may be a synthetic peptide BH-3 peptide Bim conjugated to Fluores.
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 987.58, ALogP 8.03, HBA 12, HBD 4, PSA 165.58, QED 0.07
Compound (SMILES): O=C(NS(=O)(=O)c1ccc(N[C@H](CCN2CCOC[C@H]2CO)CSc2ccccc2)c(S(=O)(=O)C(F)(F)F)c1)c1ccc(N2CCC([C@@H](O)c3ccccc3-c3ccc(Cl)cc3)CC2)cc1
InChIKey: PULZXBWWMHLNGW-UQHKMDGSSA-N
Target: Apoptosis regulator Bcl-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P10415
Assay: Fluorescence Polarization: Bcl-xL and Bcl-2 FP binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) may be determined using a variety of known methods. One such assay is a sensitive and quantitative in vitro binding assay using fluorescence polarization ("FP") described by Wang, J.-L.; Zhang, Z-J.; Choksi, S.; Sjam. S.; Lu, Z.; Croce, C. M.; Alnemri, E. S.; Komgold, R.; Huang, Z. Cell permeable Bcl-2 binding peptides: a chemical approach to apoptosis induction in tumor cells. Cancer Res. 2000, 60, 1498-1502).Additionally, the binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) to Bcl-2 protein in vitro was determined by a competitive binding assay based on fluorescence polarization. For example, fluorescence polarization ("FP") assays may be developed using a c-terminal 6.times.HIS tagged Bcl-2 (aa 1-204) and a C-terminal 6.times.HIS tagged Bcl-X.sub.L (aa 1-209). The tracer may be a synthetic peptide BH-3 peptide Bim conjugated to Fluores.
Measurement: IC50 = 0.4 nM (pChEMBL 9.399999618530273)
Descriptors: MW 987.58, ALogP 8.03, HBA 12, HBD 4, PSA 165.58, QED 0.07
Compound (SMILES): O=C(NS(=O)(=O)c1ccc(N[C@H](CCN2CCOC[C@@H]2CO)CSc2ccccc2)c(S(=O)(=O)C(F)(F)F)c1)c1ccc(N2CCC([C@@H](O)c3ccccc3-c3ccc(Cl)cc3)CC2)cc1
InChIKey: PULZXBWWMHLNGW-SQKNJAOPSA-N
Target: Apoptosis regulator Bcl-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P10415
Assay: Fluorescence Polarization: Bcl-xL and Bcl-2 FP binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) may be determined using a variety of known methods. One such assay is a sensitive and quantitative in vitro binding assay using fluorescence polarization ("FP") described by Wang, J.-L.; Zhang, Z-J.; Choksi, S.; Sjam. S.; Lu, Z.; Croce, C. M.; Alnemri, E. S.; Komgold, R.; Huang, Z. Cell permeable Bcl-2 binding peptides: a chemical approach to apoptosis induction in tumor cells. Cancer Res. 2000, 60, 1498-1502).Additionally, the binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) to Bcl-2 protein in vitro was determined by a competitive binding assay based on fluorescence polarization. For example, fluorescence polarization ("FP") assays may be developed using a c-terminal 6.times.HIS tagged Bcl-2 (aa 1-204) and a C-terminal 6.times.HIS tagged Bcl-X.sub.L (aa 1-209). The tracer may be a synthetic peptide BH-3 peptide Bim conjugated to Fluores.
Measurement: IC50 = 0.4 nM (pChEMBL 9.399999618530273)
Descriptors: MW 987.58, ALogP 8.03, HBA 12, HBD 4, PSA 165.58, QED 0.07
Compound (SMILES): CCN(CC)CC1CN(CC[C@H](CSc2ccccc2)Nc2ccc(S(=O)(=O)NC(=O)c3ccc(N4CCC([C@@H](O)c5ccccc5-c5ccc(Cl)cc5)CC4)cc3)cc2S(=O)(=O)C(F)(F)F)CCO1
InChIKey: OUKAHIJIQWSMIH-BMEJSGBISA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07817
Assay: Fluorescence Polarization: Bcl-xL and Bcl-2 FP binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) may be determined using a variety of known methods. One such assay is a sensitive and quantitative in vitro binding assay using fluorescence polarization ("FP") described by Wang, J.-L.; Zhang, Z-J.; Choksi, S.; Sjam. S.; Lu, Z.; Croce, C. M.; Alnemri, E. S.; Komgold, R.; Huang, Z. Cell permeable Bcl-2 binding peptides: a chemical approach to apoptosis induction in tumor cells. Cancer Res. 2000, 60, 1498-1502).Additionally, the binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) to Bcl-2 protein in vitro was determined by a competitive binding assay based on fluorescence polarization. For example, fluorescence polarization ("FP") assays may be developed using a c-terminal 6.times.HIS tagged Bcl-2 (aa 1-204) and a C-terminal 6.times.HIS tagged Bcl-X.sub.L (aa 1-209). The tracer may be a synthetic peptide BH-3 peptide Bim conjugated to Fluores.
Measurement: IC50 = 0.5 nM (pChEMBL 9.300000190734863)
Descriptors: MW 1042.71
Compound (SMILES): CC(C)(C)OP(=O)(O)OCO[C@@H](c1ccccc1-c1ccc(Cl)cc1)C1CCN(c2ccc(C(=O)NS(=O)(=O)c3ccc(N[C@H](CCN4CCOCC4)CSc4ccccc4)c(S(=O)(=O)C(F)(F)F)c3)cc2)CC1
InChIKey: XCSXTKCHWCZCSP-GWCDHHBQSA-N
Target: Apoptosis regulator Bcl-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P10415
Assay: Fluorescence Polarization: Bcl-xL and Bcl-2 FP binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) may be determined using a variety of known methods. One such assay is a sensitive and quantitative in vitro binding assay using fluorescence polarization ("FP") described by Wang, J.-L.; Zhang, Z-J.; Choksi, S.; Sjam. S.; Lu, Z.; Croce, C. M.; Alnemri, E. S.; Komgold, R.; Huang, Z. Cell permeable Bcl-2 binding peptides: a chemical approach to apoptosis induction in tumor cells. Cancer Res. 2000, 60, 1498-1502).Additionally, the binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) to Bcl-2 protein in vitro was determined by a competitive binding assay based on fluorescence polarization. For example, fluorescence polarization ("FP") assays may be developed using a c-terminal 6.times.HIS tagged Bcl-2 (aa 1-204) and a C-terminal 6.times.HIS tagged Bcl-X.sub.L (aa 1-209). The tracer may be a synthetic peptide BH-3 peptide Bim conjugated to Fluores.
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 1123.67
Compound (SMILES): CCOP(=O)(OCC)O[C@@H](c1ccccc1-c1ccc(Cl)cc1)C1CCN(c2ccc(C(=O)NS(=O)(=O)c3ccc(N[C@H](CCN4CCOCC4)CSc4ccccc4)c(S(=O)(=O)C(F)(F)F)c3)cc2)CC1
InChIKey: KJKHZPXTVKCPIW-GWCDHHBQSA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07817
Assay: Fluorescence Polarization: Bcl-xL and Bcl-2 FP binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) may be determined using a variety of known methods. One such assay is a sensitive and quantitative in vitro binding assay using fluorescence polarization ("FP") described by Wang, J.-L.; Zhang, Z-J.; Choksi, S.; Sjam. S.; Lu, Z.; Croce, C. M.; Alnemri, E. S.; Komgold, R.; Huang, Z. Cell permeable Bcl-2 binding peptides: a chemical approach to apoptosis induction in tumor cells. Cancer Res. 2000, 60, 1498-1502).Additionally, the binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) to Bcl-2 protein in vitro was determined by a competitive binding assay based on fluorescence polarization. For example, fluorescence polarization ("FP") assays may be developed using a c-terminal 6.times.HIS tagged Bcl-2 (aa 1-204) and a C-terminal 6.times.HIS tagged Bcl-X.sub.L (aa 1-209). The tracer may be a synthetic peptide BH-3 peptide Bim conjugated to Fluores.
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 1093.65
Compound (SMILES): COP(=O)(O)O[C@@H](c1ccccc1-c1ccc(Cl)cc1)C1CCN(c2ccc(C(=O)NS(=O)(=O)c3ccc(N[C@H](CCN4CCOCC4)CSc4ccccc4)c(S(=O)(=O)C(F)(F)F)c3)cc2)CC1
InChIKey: QERZHFJAQRXRIZ-BCQDFQTISA-N
Target: Apoptosis regulator Bcl-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P10415
Assay: Fluorescence Polarization: Bcl-xL and Bcl-2 FP binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) may be determined using a variety of known methods. One such assay is a sensitive and quantitative in vitro binding assay using fluorescence polarization ("FP") described by Wang, J.-L.; Zhang, Z-J.; Choksi, S.; Sjam. S.; Lu, Z.; Croce, C. M.; Alnemri, E. S.; Komgold, R.; Huang, Z. Cell permeable Bcl-2 binding peptides: a chemical approach to apoptosis induction in tumor cells. Cancer Res. 2000, 60, 1498-1502).Additionally, the binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) to Bcl-2 protein in vitro was determined by a competitive binding assay based on fluorescence polarization. For example, fluorescence polarization ("FP") assays may be developed using a c-terminal 6.times.HIS tagged Bcl-2 (aa 1-204) and a C-terminal 6.times.HIS tagged Bcl-X.sub.L (aa 1-209). The tracer may be a synthetic peptide BH-3 peptide Bim conjugated to Fluores.
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 1051.57
Compound (SMILES): N[C@@H](c1ccccc1-c1ccc(Cl)cc1)C1CCN(c2ccc(C(=O)NS(=O)(=O)c3ccc(N[C@H](CCN4CCOCC4)CSc4ccccc4)c(S(=O)(=O)C(F)(F)F)c3)cc2)CC1
InChIKey: RYUDVTAKLQHGHO-CAZXVXRPSA-N
Target: Apoptosis regulator Bcl-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P10415
Assay: Fluorescence Polarization: Bcl-xL and Bcl-2 FP binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) may be determined using a variety of known methods. One such assay is a sensitive and quantitative in vitro binding assay using fluorescence polarization ("FP") described by Wang, J.-L.; Zhang, Z-J.; Choksi, S.; Sjam. S.; Lu, Z.; Croce, C. M.; Alnemri, E. S.; Komgold, R.; Huang, Z. Cell permeable Bcl-2 binding peptides: a chemical approach to apoptosis induction in tumor cells. Cancer Res. 2000, 60, 1498-1502).Additionally, the binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) to Bcl-2 protein in vitro was determined by a competitive binding assay based on fluorescence polarization. For example, fluorescence polarization ("FP") assays may be developed using a c-terminal 6.times.HIS tagged Bcl-2 (aa 1-204) and a C-terminal 6.times.HIS tagged Bcl-X.sub.L (aa 1-209). The tracer may be a synthetic peptide BH-3 peptide Bim conjugated to Fluores.
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 956.58, ALogP 8.63, HBA 11, HBD 3, PSA 151.14, QED 0.08
Compound (SMILES): CNCC(=O)N[C@@H](c1ccccc1-c1ccc(Cl)cc1)C1CCN(c2ccc(C(=O)NS(=O)(=O)c3ccc(N[C@H](CCN4CCOCC4)CSc4ccccc4)c(S(=O)(=O)C(F)(F)F)c3)cc2)CC1
InChIKey: PVPORGAWYHFQGZ-OUDQIDCQSA-N
Target: Apoptosis regulator Bcl-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P10415
Assay: Fluorescence Polarization: Bcl-xL and Bcl-2 FP binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) may be determined using a variety of known methods. One such assay is a sensitive and quantitative in vitro binding assay using fluorescence polarization ("FP") described by Wang, J.-L.; Zhang, Z-J.; Choksi, S.; Sjam. S.; Lu, Z.; Croce, C. M.; Alnemri, E. S.; Komgold, R.; Huang, Z. Cell permeable Bcl-2 binding peptides: a chemical approach to apoptosis induction in tumor cells. Cancer Res. 2000, 60, 1498-1502).Additionally, the binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) to Bcl-2 protein in vitro was determined by a competitive binding assay based on fluorescence polarization. For example, fluorescence polarization ("FP") assays may be developed using a c-terminal 6.times.HIS tagged Bcl-2 (aa 1-204) and a C-terminal 6.times.HIS tagged Bcl-X.sub.L (aa 1-209). The tracer may be a synthetic peptide BH-3 peptide Bim conjugated to Fluores.
Measurement: IC50 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 1027.65
Compound (SMILES): NCC(=O)N[C@@H](c1ccccc1-c1ccc(Cl)cc1)C1CCN(c2ccc(C(=O)NS(=O)(=O)c3ccc(N[C@H](CCN4CCOCC4)CSc4ccccc4)c(S(=O)(=O)C(F)(F)F)c3)cc2)CC1
InChIKey: ZTNPTZAHNNILDS-JMILSRJQSA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07817
Assay: Fluorescence Polarization: Bcl-xL and Bcl-2 FP binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) may be determined using a variety of known methods. One such assay is a sensitive and quantitative in vitro binding assay using fluorescence polarization ("FP") described by Wang, J.-L.; Zhang, Z-J.; Choksi, S.; Sjam. S.; Lu, Z.; Croce, C. M.; Alnemri, E. S.; Komgold, R.; Huang, Z. Cell permeable Bcl-2 binding peptides: a chemical approach to apoptosis induction in tumor cells. Cancer Res. 2000, 60, 1498-1502).Additionally, the binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) to Bcl-2 protein in vitro was determined by a competitive binding assay based on fluorescence polarization. For example, fluorescence polarization ("FP") assays may be developed using a c-terminal 6.times.HIS tagged Bcl-2 (aa 1-204) and a C-terminal 6.times.HIS tagged Bcl-X.sub.L (aa 1-209). The tracer may be a synthetic peptide BH-3 peptide Bim conjugated to Fluores.
Measurement: IC50 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 1013.63
Compound (SMILES): CN(C)[C@@H](c1ccccc1-c1ccc(Cl)cc1)C1CCN(c2ccc(C(=O)NS(=O)(=O)c3ccc(N[C@H](CCN4CCOCC4)CSc4ccccc4)c(S(=O)(=O)C(F)(F)F)c3)cc2)CC1
InChIKey: NKVDBMBUMXFDLS-OIZGGULRSA-N
Target: Apoptosis regulator Bcl-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P10415
Assay: Fluorescence Polarization: Bcl-xL and Bcl-2 FP binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) may be determined using a variety of known methods. One such assay is a sensitive and quantitative in vitro binding assay using fluorescence polarization ("FP") described by Wang, J.-L.; Zhang, Z-J.; Choksi, S.; Sjam. S.; Lu, Z.; Croce, C. M.; Alnemri, E. S.; Komgold, R.; Huang, Z. Cell permeable Bcl-2 binding peptides: a chemical approach to apoptosis induction in tumor cells. Cancer Res. 2000, 60, 1498-1502).Additionally, the binding affinity of compound(s) of Formulae (I), (I-a), (I-b), (I-c), (I-d) and/or (I-e) to Bcl-2 protein in vitro was determined by a competitive binding assay based on fluorescence polarization. For example, fluorescence polarization ("FP") assays may be developed using a c-terminal 6.times.HIS tagged Bcl-2 (aa 1-204) and a C-terminal 6.times.HIS tagged Bcl-X.sub.L (aa 1-209). The tracer may be a synthetic peptide BH-3 peptide Bim conjugated to Fluores.
Measurement: IC50 = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 984.63, ALogP 9.23, HBA 11, HBD 2, PSA 128.36, QED 0.09
Compound (SMILES): COc1ccc(C(Nc2cc(C)ccn2)c2ccc3cccnc3c2O)cc1O
InChIKey: FCTHDIWMHUZDNV-UHFFFAOYSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: AlphaScreen Assay: The following example describes an assay that measured the ability of compounds to inhibit the binding of p53 to MDM2 using the AlphaScreen assay technology (PerkinElmer). The following protocol is an adaptation of the method described by H. R. Lawrence et al. (Bioorg. Med. Chem. Lett. 19 (2009) 3756-3759). Recombinant, truncated, human, N-terminal GST-MDM2 (aa 1-150) was obtained from GeneScript. Wild-type, full length human N-terminal 6-his p53 was purchased from SignalChem.Resulting in a final reaction volume of 24 μl PBS, 0.1% Tween-20, and 10% glycerol, 30 ng of MDM2 was added, followed by the addition of 10 of compound diluted in 100% DMSO that provided a final DMSO concentration of 4%. 30 ng of p53 was then added, mixed, and incubated at room temperature for 1 hour. Glutathione donor beads and Nickel acceptor beads (0.5 μg each; PerkinElmer) were added under subdued lighting conditions to a final reaction volume of 30 μl/well in a 96 well, ½ volume Proxima plate.
Measurement: IC50 = 4200 nM (pChEMBL 5.380000114440918)
Descriptors: MW 387.44, ALogP 4.56, HBA 6, HBD 3, PSA 87.5, QED 0.47
Compound (SMILES): Cc1cccc(NC(c2ccc(OC(F)(F)F)cc2)c2ccc3cccnc3c2O)n1
InChIKey: OGZDISPFPXWYMT-UHFFFAOYSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: AlphaScreen Assay: The following example describes an assay that measured the ability of compounds to inhibit the binding of p53 to MDM2 using the AlphaScreen assay technology (PerkinElmer). The following protocol is an adaptation of the method described by H. R. Lawrence et al. (Bioorg. Med. Chem. Lett. 19 (2009) 3756-3759). Recombinant, truncated, human, N-terminal GST-MDM2 (aa 1-150) was obtained from GeneScript. Wild-type, full length human N-terminal 6-his p53 was purchased from SignalChem.Resulting in a final reaction volume of 24 μl PBS, 0.1% Tween-20, and 10% glycerol, 30 ng of MDM2 was added, followed by the addition of 10 of compound diluted in 100% DMSO that provided a final DMSO concentration of 4%. 30 ng of p53 was then added, mixed, and incubated at room temperature for 1 hour. Glutathione donor beads and Nickel acceptor beads (0.5 μg each; PerkinElmer) were added under subdued lighting conditions to a final reaction volume of 30 μl/well in a 96 well, ½ volume Proxima plate.
Measurement: IC50 = 9400 nM (pChEMBL 5.03000020980835)
Descriptors: MW 425.41, ALogP 5.74, HBA 5, HBD 2, PSA 67.27, QED 0.43
Compound (SMILES): Cc1cccc(NC(c2cccc(C(F)(F)F)c2)c2ccc3cccnc3c2O)n1
InChIKey: FYPUIPYMWVYSSE-UHFFFAOYSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: AlphaScreen Assay: The following example describes an assay that measured the ability of compounds to inhibit the binding of p53 to MDM2 using the AlphaScreen assay technology (PerkinElmer). The following protocol is an adaptation of the method described by H. R. Lawrence et al. (Bioorg. Med. Chem. Lett. 19 (2009) 3756-3759). Recombinant, truncated, human, N-terminal GST-MDM2 (aa 1-150) was obtained from GeneScript. Wild-type, full length human N-terminal 6-his p53 was purchased from SignalChem.Resulting in a final reaction volume of 24 μl PBS, 0.1% Tween-20, and 10% glycerol, 30 ng of MDM2 was added, followed by the addition of 10 of compound diluted in 100% DMSO that provided a final DMSO concentration of 4%. 30 ng of p53 was then added, mixed, and incubated at room temperature for 1 hour. Glutathione donor beads and Nickel acceptor beads (0.5 μg each; PerkinElmer) were added under subdued lighting conditions to a final reaction volume of 30 μl/well in a 96 well, ½ volume Proxima plate.
Measurement: IC50 = 18000 nM (pChEMBL 4.75)
Descriptors: MW 409.41, ALogP 5.86, HBA 4, HBD 2, PSA 58.04, QED 0.44