lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CCOC(=O)c1c[nH]c2ncnc(-c3cccc(OCC(F)(F)F)c3)c12
InChIKey: CELFNLGAHYGWTE-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: HTRF Assay: The ability of compounds to inhibit the activity of JAKl, JAK2, JAK3, and Tyk2 was measured using a recombinant purified GST-tagged catalytic domain for each enzyme (Invitrogen JAKl #M4290, JAK2 #M4290, JAK3 #M4290, Tyk2 #M4290) in an HTRF format biochemical assay. The reactions employed a common peptide substrate, LCB-EQEDEPEGDYFEWLW-NH2 (in-house). The basic assay protocol is as follows: First, 250 nL of diluted compounds in DMSO were dispensed into the wells of a dry 384- well Black plate (Greiner #781076) using a Labcyte Echo 555 acoustic dispenser.Subsequent reagent additions employed an Agilent Bravo. Next, 18 of 1.1 IX enzyme and 1.1 IX substrate in IX assay buffer (Invitrogen kinase buffer # PV3189, 2 mM DTT, 0.05% BSA) were added to the wells and shaken and then preincubated for 30 minutes at room temperature to allow compound binding to equilibrate. After equilibration, 2 \xL of 10X ATP in IX assay buffer was added to initiate the kinase reaction and the plates were shaken.
Measurement: IC50 = 73 nM (pChEMBL 7.139999866485596)
Descriptors: MW 365.31, ALogP 3.74, HBA 5, HBD 1, PSA 77.1, QED 0.7
Compound (SMILES): CCOC(=O)c1c[nH]c2ncnc(-c3ccc(C)c(N)c3)c12
InChIKey: KGAFXLBEPZNOQZ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: HTRF Assay: The ability of compounds to inhibit the activity of JAKl, JAK2, JAK3, and Tyk2 was measured using a recombinant purified GST-tagged catalytic domain for each enzyme (Invitrogen JAKl #M4290, JAK2 #M4290, JAK3 #M4290, Tyk2 #M4290) in an HTRF format biochemical assay. The reactions employed a common peptide substrate, LCB-EQEDEPEGDYFEWLW-NH2 (in-house). The basic assay protocol is as follows: First, 250 nL of diluted compounds in DMSO were dispensed into the wells of a dry 384- well Black plate (Greiner #781076) using a Labcyte Echo 555 acoustic dispenser.Subsequent reagent additions employed an Agilent Bravo. Next, 18 of 1.1 IX enzyme and 1.1 IX substrate in IX assay buffer (Invitrogen kinase buffer # PV3189, 2 mM DTT, 0.05% BSA) were added to the wells and shaken and then preincubated for 30 minutes at room temperature to allow compound binding to equilibrate. After equilibration, 2 \xL of 10X ATP in IX assay buffer was added to initiate the kinase reaction and the plates were shaken.
Measurement: IC50 = 78 nM (pChEMBL 7.110000133514404)
Descriptors: MW 296.33, ALogP 2.69, HBA 5, HBD 2, PSA 93.89, QED 0.57
Compound (SMILES): CCOC(=O)c1c[nH]c2ncnc(C3=CCCCC3)c12
InChIKey: KQURPHNEBAHFIV-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: HTRF Assay: The ability of compounds to inhibit the activity of JAKl, JAK2, JAK3, and Tyk2 was measured using a recombinant purified GST-tagged catalytic domain for each enzyme (Invitrogen JAKl #M4290, JAK2 #M4290, JAK3 #M4290, Tyk2 #M4290) in an HTRF format biochemical assay. The reactions employed a common peptide substrate, LCB-EQEDEPEGDYFEWLW-NH2 (in-house). The basic assay protocol is as follows: First, 250 nL of diluted compounds in DMSO were dispensed into the wells of a dry 384- well Black plate (Greiner #781076) using a Labcyte Echo 555 acoustic dispenser.Subsequent reagent additions employed an Agilent Bravo. Next, 18 of 1.1 IX enzyme and 1.1 IX substrate in IX assay buffer (Invitrogen kinase buffer # PV3189, 2 mM DTT, 0.05% BSA) were added to the wells and shaken and then preincubated for 30 minutes at room temperature to allow compound binding to equilibrate. After equilibration, 2 \xL of 10X ATP in IX assay buffer was added to initiate the kinase reaction and the plates were shaken.
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 271.32, ALogP 3.09, HBA 4, HBD 1, PSA 67.87, QED 0.87
Compound (SMILES): CCOC(=O)c1c[nH]c2ncnc(-c3ccc(Cl)c(N)c3)c12
InChIKey: DQULGJXYBCCGQV-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: HTRF Assay: The ability of compounds to inhibit the activity of JAKl, JAK2, JAK3, and Tyk2 was measured using a recombinant purified GST-tagged catalytic domain for each enzyme (Invitrogen JAKl #M4290, JAK2 #M4290, JAK3 #M4290, Tyk2 #M4290) in an HTRF format biochemical assay. The reactions employed a common peptide substrate, LCB-EQEDEPEGDYFEWLW-NH2 (in-house). The basic assay protocol is as follows: First, 250 nL of diluted compounds in DMSO were dispensed into the wells of a dry 384- well Black plate (Greiner #781076) using a Labcyte Echo 555 acoustic dispenser.Subsequent reagent additions employed an Agilent Bravo. Next, 18 of 1.1 IX enzyme and 1.1 IX substrate in IX assay buffer (Invitrogen kinase buffer # PV3189, 2 mM DTT, 0.05% BSA) were added to the wells and shaken and then preincubated for 30 minutes at room temperature to allow compound binding to equilibrate. After equilibration, 2 \xL of 10X ATP in IX assay buffer was added to initiate the kinase reaction and the plates were shaken.
Measurement: IC50 = 125 nM (pChEMBL 6.900000095367432)
Descriptors: MW 316.75, ALogP 3.04, HBA 5, HBD 2, PSA 93.89, QED 0.57
Compound (SMILES): CCOC(=O)c1c[nH]c2ncnc(-c3ccc4c(F)n(C)nc4c3)c12
InChIKey: BBIURQGUTVKUJP-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: HTRF Assay: The ability of compounds to inhibit the activity of JAKl, JAK2, JAK3, and Tyk2 was measured using a recombinant purified GST-tagged catalytic domain for each enzyme (Invitrogen JAKl #M4290, JAK2 #M4290, JAK3 #M4290, Tyk2 #M4290) in an HTRF format biochemical assay. The reactions employed a common peptide substrate, LCB-EQEDEPEGDYFEWLW-NH2 (in-house). The basic assay protocol is as follows: First, 250 nL of diluted compounds in DMSO were dispensed into the wells of a dry 384- well Black plate (Greiner #781076) using a Labcyte Echo 555 acoustic dispenser.Subsequent reagent additions employed an Agilent Bravo. Next, 18 of 1.1 IX enzyme and 1.1 IX substrate in IX assay buffer (Invitrogen kinase buffer # PV3189, 2 mM DTT, 0.05% BSA) were added to the wells and shaken and then preincubated for 30 minutes at room temperature to allow compound binding to equilibrate. After equilibration, 2 \xL of 10X ATP in IX assay buffer was added to initiate the kinase reaction and the plates were shaken.
Measurement: IC50 = 8.1 nM (pChEMBL 8.09000015258789)
Descriptors: MW 339.33, ALogP 2.83, HBA 6, HBD 1, PSA 85.69, QED 0.58
Compound (SMILES): CCOC(=O)c1c[nH]c2ncnc(-c3ccc4c(c3)NCC4)c12
InChIKey: DRDZLMIYYXXXBJ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: HTRF Assay: The ability of compounds to inhibit the activity of JAKl, JAK2, JAK3, and Tyk2 was measured using a recombinant purified GST-tagged catalytic domain for each enzyme (Invitrogen JAKl #M4290, JAK2 #M4290, JAK3 #M4290, Tyk2 #M4290) in an HTRF format biochemical assay. The reactions employed a common peptide substrate, LCB-EQEDEPEGDYFEWLW-NH2 (in-house). The basic assay protocol is as follows: First, 250 nL of diluted compounds in DMSO were dispensed into the wells of a dry 384- well Black plate (Greiner #781076) using a Labcyte Echo 555 acoustic dispenser.Subsequent reagent additions employed an Agilent Bravo. Next, 18 of 1.1 IX enzyme and 1.1 IX substrate in IX assay buffer (Invitrogen kinase buffer # PV3189, 2 mM DTT, 0.05% BSA) were added to the wells and shaken and then preincubated for 30 minutes at room temperature to allow compound binding to equilibrate. After equilibration, 2 \xL of 10X ATP in IX assay buffer was added to initiate the kinase reaction and the plates were shaken.
Measurement: IC50 = 4.6 nM (pChEMBL 8.34000015258789)
Descriptors: MW 308.34, ALogP 2.77, HBA 5, HBD 2, PSA 79.9, QED 0.73
Compound (SMILES): CCOC(=O)c1c[nH]c2ncnc(-c3ccc(CO)c(N)c3)c12
InChIKey: AROYAHIHIHHAQG-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: HTRF Assay: The ability of compounds to inhibit the activity of JAKl, JAK2, JAK3, and Tyk2 was measured using a recombinant purified GST-tagged catalytic domain for each enzyme (Invitrogen JAKl #M4290, JAK2 #M4290, JAK3 #M4290, Tyk2 #M4290) in an HTRF format biochemical assay. The reactions employed a common peptide substrate, LCB-EQEDEPEGDYFEWLW-NH2 (in-house). The basic assay protocol is as follows: First, 250 nL of diluted compounds in DMSO were dispensed into the wells of a dry 384- well Black plate (Greiner #781076) using a Labcyte Echo 555 acoustic dispenser.Subsequent reagent additions employed an Agilent Bravo. Next, 18 of 1.1 IX enzyme and 1.1 IX substrate in IX assay buffer (Invitrogen kinase buffer # PV3189, 2 mM DTT, 0.05% BSA) were added to the wells and shaken and then preincubated for 30 minutes at room temperature to allow compound binding to equilibrate. After equilibration, 2 \xL of 10X ATP in IX assay buffer was added to initiate the kinase reaction and the plates were shaken.
Measurement: IC50 = 215 nM (pChEMBL 6.670000076293945)
Descriptors: MW 312.33, ALogP 1.88, HBA 6, HBD 3, PSA 114.12, QED 0.5
Compound (SMILES): CCOC(=O)c1c[nH]c2ncnc(-c3ccc(O)cc3)c12
InChIKey: WFZVLXFDJPXDGD-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: HTRF Assay: The ability of compounds to inhibit the activity of JAKl, JAK2, JAK3, and Tyk2 was measured using a recombinant purified GST-tagged catalytic domain for each enzyme (Invitrogen JAKl #M4290, JAK2 #M4290, JAK3 #M4290, Tyk2 #M4290) in an HTRF format biochemical assay. The reactions employed a common peptide substrate, LCB-EQEDEPEGDYFEWLW-NH2 (in-house). The basic assay protocol is as follows: First, 250 nL of diluted compounds in DMSO were dispensed into the wells of a dry 384- well Black plate (Greiner #781076) using a Labcyte Echo 555 acoustic dispenser.Subsequent reagent additions employed an Agilent Bravo. Next, 18 of 1.1 IX enzyme and 1.1 IX substrate in IX assay buffer (Invitrogen kinase buffer # PV3189, 2 mM DTT, 0.05% BSA) were added to the wells and shaken and then preincubated for 30 minutes at room temperature to allow compound binding to equilibrate. After equilibration, 2 \xL of 10X ATP in IX assay buffer was added to initiate the kinase reaction and the plates were shaken.
Measurement: IC50 = 134 nM (pChEMBL 6.869999885559082)
Descriptors: MW 283.29, ALogP 2.51, HBA 5, HBD 2, PSA 88.1, QED 0.72
Compound (SMILES): CCOC(=O)c1c[nH]c2ncnc(-c3cccc(Cl)c3)c12
InChIKey: UXAHINXBJCETJY-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: HTRF Assay: The ability of compounds to inhibit the activity of JAKl, JAK2, JAK3, and Tyk2 was measured using a recombinant purified GST-tagged catalytic domain for each enzyme (Invitrogen JAKl #M4290, JAK2 #M4290, JAK3 #M4290, Tyk2 #M4290) in an HTRF format biochemical assay. The reactions employed a common peptide substrate, LCB-EQEDEPEGDYFEWLW-NH2 (in-house). The basic assay protocol is as follows: First, 250 nL of diluted compounds in DMSO were dispensed into the wells of a dry 384- well Black plate (Greiner #781076) using a Labcyte Echo 555 acoustic dispenser.Subsequent reagent additions employed an Agilent Bravo. Next, 18 of 1.1 IX enzyme and 1.1 IX substrate in IX assay buffer (Invitrogen kinase buffer # PV3189, 2 mM DTT, 0.05% BSA) were added to the wells and shaken and then preincubated for 30 minutes at room temperature to allow compound binding to equilibrate. After equilibration, 2 \xL of 10X ATP in IX assay buffer was added to initiate the kinase reaction and the plates were shaken.
Measurement: IC50 = 8.4 nM (pChEMBL 8.079999923706055)
Descriptors: MW 301.73, ALogP 3.46, HBA 4, HBD 1, PSA 67.87, QED 0.75
Compound (SMILES): CCOC(=O)c1c[nH]c2ncnc(-c3ccc4ccccc4c3)c12
InChIKey: OEXWALMSGRIUHV-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: HTRF Assay: The ability of compounds to inhibit the activity of JAKl, JAK2, JAK3, and Tyk2 was measured using a recombinant purified GST-tagged catalytic domain for each enzyme (Invitrogen JAKl #M4290, JAK2 #M4290, JAK3 #M4290, Tyk2 #M4290) in an HTRF format biochemical assay. The reactions employed a common peptide substrate, LCB-EQEDEPEGDYFEWLW-NH2 (in-house). The basic assay protocol is as follows: First, 250 nL of diluted compounds in DMSO were dispensed into the wells of a dry 384- well Black plate (Greiner #781076) using a Labcyte Echo 555 acoustic dispenser.Subsequent reagent additions employed an Agilent Bravo. Next, 18 of 1.1 IX enzyme and 1.1 IX substrate in IX assay buffer (Invitrogen kinase buffer # PV3189, 2 mM DTT, 0.05% BSA) were added to the wells and shaken and then preincubated for 30 minutes at room temperature to allow compound binding to equilibrate. After equilibration, 2 \xL of 10X ATP in IX assay buffer was added to initiate the kinase reaction and the plates were shaken.
Measurement: IC50 = 186 nM (pChEMBL 6.730000019073486)
Descriptors: MW 317.35, ALogP 3.95, HBA 4, HBD 1, PSA 67.87, QED 0.58
Compound (SMILES): CCOC(=O)c1c[nH]c2ncnc(-c3ccccc3F)c12
InChIKey: ICKDMNWCSKPSHN-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: HTRF Assay: The ability of compounds to inhibit the activity of JAKl, JAK2, JAK3, and Tyk2 was measured using a recombinant purified GST-tagged catalytic domain for each enzyme (Invitrogen JAKl #M4290, JAK2 #M4290, JAK3 #M4290, Tyk2 #M4290) in an HTRF format biochemical assay. The reactions employed a common peptide substrate, LCB-EQEDEPEGDYFEWLW-NH2 (in-house). The basic assay protocol is as follows: First, 250 nL of diluted compounds in DMSO were dispensed into the wells of a dry 384- well Black plate (Greiner #781076) using a Labcyte Echo 555 acoustic dispenser.Subsequent reagent additions employed an Agilent Bravo. Next, 18 of 1.1 IX enzyme and 1.1 IX substrate in IX assay buffer (Invitrogen kinase buffer # PV3189, 2 mM DTT, 0.05% BSA) were added to the wells and shaken and then preincubated for 30 minutes at room temperature to allow compound binding to equilibrate. After equilibration, 2 \xL of 10X ATP in IX assay buffer was added to initiate the kinase reaction and the plates were shaken.
Measurement: IC50 = 7.5 nM (pChEMBL 8.119999885559082)
Descriptors: MW 285.28, ALogP 2.94, HBA 4, HBD 1, PSA 67.87, QED 0.75
Compound (SMILES): CCOC(=O)c1c[nH]c2ncnc(-c3cccc(F)c3)c12
InChIKey: ZODOBCONXXFIFU-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: HTRF Assay: The ability of compounds to inhibit the activity of JAKl, JAK2, JAK3, and Tyk2 was measured using a recombinant purified GST-tagged catalytic domain for each enzyme (Invitrogen JAKl #M4290, JAK2 #M4290, JAK3 #M4290, Tyk2 #M4290) in an HTRF format biochemical assay. The reactions employed a common peptide substrate, LCB-EQEDEPEGDYFEWLW-NH2 (in-house). The basic assay protocol is as follows: First, 250 nL of diluted compounds in DMSO were dispensed into the wells of a dry 384- well Black plate (Greiner #781076) using a Labcyte Echo 555 acoustic dispenser.Subsequent reagent additions employed an Agilent Bravo. Next, 18 of 1.1 IX enzyme and 1.1 IX substrate in IX assay buffer (Invitrogen kinase buffer # PV3189, 2 mM DTT, 0.05% BSA) were added to the wells and shaken and then preincubated for 30 minutes at room temperature to allow compound binding to equilibrate. After equilibration, 2 \xL of 10X ATP in IX assay buffer was added to initiate the kinase reaction and the plates were shaken.
Measurement: IC50 = 121 nM (pChEMBL 6.920000076293945)
Descriptors: MW 285.28, ALogP 2.94, HBA 4, HBD 1, PSA 67.87, QED 0.75
Compound (SMILES): CCOC(=O)c1c[nH]c2ncnc(-c3ccc(-c4ccccc4)cc3)c12
InChIKey: JKDFAIDFNLNJDT-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: HTRF Assay: The ability of compounds to inhibit the activity of JAKl, JAK2, JAK3, and Tyk2 was measured using a recombinant purified GST-tagged catalytic domain for each enzyme (Invitrogen JAKl #M4290, JAK2 #M4290, JAK3 #M4290, Tyk2 #M4290) in an HTRF format biochemical assay. The reactions employed a common peptide substrate, LCB-EQEDEPEGDYFEWLW-NH2 (in-house). The basic assay protocol is as follows: First, 250 nL of diluted compounds in DMSO were dispensed into the wells of a dry 384- well Black plate (Greiner #781076) using a Labcyte Echo 555 acoustic dispenser.Subsequent reagent additions employed an Agilent Bravo. Next, 18 of 1.1 IX enzyme and 1.1 IX substrate in IX assay buffer (Invitrogen kinase buffer # PV3189, 2 mM DTT, 0.05% BSA) were added to the wells and shaken and then preincubated for 30 minutes at room temperature to allow compound binding to equilibrate. After equilibration, 2 \xL of 10X ATP in IX assay buffer was added to initiate the kinase reaction and the plates were shaken.
Measurement: IC50 = 47 nM (pChEMBL 7.329999923706055)
Descriptors: MW 343.39, ALogP 4.47, HBA 4, HBD 1, PSA 67.87, QED 0.56
Compound (SMILES): CCOC(=O)c1c[nH]c2ncnc(-c3cccc(O)c3)c12
InChIKey: AIQGIEYNEKMKSN-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: HTRF Assay: The ability of compounds to inhibit the activity of JAKl, JAK2, JAK3, and Tyk2 was measured using a recombinant purified GST-tagged catalytic domain for each enzyme (Invitrogen JAKl #M4290, JAK2 #M4290, JAK3 #M4290, Tyk2 #M4290) in an HTRF format biochemical assay. The reactions employed a common peptide substrate, LCB-EQEDEPEGDYFEWLW-NH2 (in-house). The basic assay protocol is as follows: First, 250 nL of diluted compounds in DMSO were dispensed into the wells of a dry 384- well Black plate (Greiner #781076) using a Labcyte Echo 555 acoustic dispenser.Subsequent reagent additions employed an Agilent Bravo. Next, 18 of 1.1 IX enzyme and 1.1 IX substrate in IX assay buffer (Invitrogen kinase buffer # PV3189, 2 mM DTT, 0.05% BSA) were added to the wells and shaken and then preincubated for 30 minutes at room temperature to allow compound binding to equilibrate. After equilibration, 2 \xL of 10X ATP in IX assay buffer was added to initiate the kinase reaction and the plates were shaken.
Measurement: IC50 = 5.6 nM (pChEMBL 8.25)
Descriptors: MW 283.29, ALogP 2.51, HBA 5, HBD 2, PSA 88.1, QED 0.72
Compound (SMILES): CCOC(=O)c1c[nH]c2ncnc(-c3cccc(C)c3)c12
InChIKey: RYFVZDPCOBOOJI-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: HTRF Assay: The ability of compounds to inhibit the activity of JAKl, JAK2, JAK3, and Tyk2 was measured using a recombinant purified GST-tagged catalytic domain for each enzyme (Invitrogen JAKl #M4290, JAK2 #M4290, JAK3 #M4290, Tyk2 #M4290) in an HTRF format biochemical assay. The reactions employed a common peptide substrate, LCB-EQEDEPEGDYFEWLW-NH2 (in-house). The basic assay protocol is as follows: First, 250 nL of diluted compounds in DMSO were dispensed into the wells of a dry 384- well Black plate (Greiner #781076) using a Labcyte Echo 555 acoustic dispenser.Subsequent reagent additions employed an Agilent Bravo. Next, 18 of 1.1 IX enzyme and 1.1 IX substrate in IX assay buffer (Invitrogen kinase buffer # PV3189, 2 mM DTT, 0.05% BSA) were added to the wells and shaken and then preincubated for 30 minutes at room temperature to allow compound binding to equilibrate. After equilibration, 2 \xL of 10X ATP in IX assay buffer was added to initiate the kinase reaction and the plates were shaken.
Measurement: IC50 = 143 nM (pChEMBL 6.840000152587891)
Descriptors: MW 281.31, ALogP 3.11, HBA 4, HBD 1, PSA 67.87, QED 0.75
Compound (SMILES): CCOC(=O)c1c[nH]c2ncnc(-c3ccc(N(C)C)cc3)c12
InChIKey: BEHBSLVENAZCTB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: HTRF Assay: The ability of compounds to inhibit the activity of JAKl, JAK2, JAK3, and Tyk2 was measured using a recombinant purified GST-tagged catalytic domain for each enzyme (Invitrogen JAKl #M4290, JAK2 #M4290, JAK3 #M4290, Tyk2 #M4290) in an HTRF format biochemical assay. The reactions employed a common peptide substrate, LCB-EQEDEPEGDYFEWLW-NH2 (in-house). The basic assay protocol is as follows: First, 250 nL of diluted compounds in DMSO were dispensed into the wells of a dry 384- well Black plate (Greiner #781076) using a Labcyte Echo 555 acoustic dispenser.Subsequent reagent additions employed an Agilent Bravo. Next, 18 of 1.1 IX enzyme and 1.1 IX substrate in IX assay buffer (Invitrogen kinase buffer # PV3189, 2 mM DTT, 0.05% BSA) were added to the wells and shaken and then preincubated for 30 minutes at room temperature to allow compound binding to equilibrate. After equilibration, 2 \xL of 10X ATP in IX assay buffer was added to initiate the kinase reaction and the plates were shaken.
Measurement: IC50 = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 310.36, ALogP 2.87, HBA 5, HBD 1, PSA 71.11, QED 0.75
Compound (SMILES): CCOC(=O)c1c[nH]c2ncnc(-c3ccc4c(c3)OCO4)c12
InChIKey: MIVFGKXUCKNNID-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: HTRF Assay: The ability of compounds to inhibit the activity of JAKl, JAK2, JAK3, and Tyk2 was measured using a recombinant purified GST-tagged catalytic domain for each enzyme (Invitrogen JAKl #M4290, JAK2 #M4290, JAK3 #M4290, Tyk2 #M4290) in an HTRF format biochemical assay. The reactions employed a common peptide substrate, LCB-EQEDEPEGDYFEWLW-NH2 (in-house). The basic assay protocol is as follows: First, 250 nL of diluted compounds in DMSO were dispensed into the wells of a dry 384- well Black plate (Greiner #781076) using a Labcyte Echo 555 acoustic dispenser.Subsequent reagent additions employed an Agilent Bravo. Next, 18 of 1.1 IX enzyme and 1.1 IX substrate in IX assay buffer (Invitrogen kinase buffer # PV3189, 2 mM DTT, 0.05% BSA) were added to the wells and shaken and then preincubated for 30 minutes at room temperature to allow compound binding to equilibrate. After equilibration, 2 \xL of 10X ATP in IX assay buffer was added to initiate the kinase reaction and the plates were shaken.
Measurement: IC50 = 66 nM (pChEMBL 7.179999828338623)
Descriptors: MW 311.3, ALogP 2.53, HBA 6, HBD 1, PSA 86.33, QED 0.75
Compound (SMILES): CCOC(=O)c1c[nH]c2ncnc(-c3cc4ccccc4s3)c12
InChIKey: IIDNLAYDSJPTEU-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: HTRF Assay: The ability of compounds to inhibit the activity of JAKl, JAK2, JAK3, and Tyk2 was measured using a recombinant purified GST-tagged catalytic domain for each enzyme (Invitrogen JAKl #M4290, JAK2 #M4290, JAK3 #M4290, Tyk2 #M4290) in an HTRF format biochemical assay. The reactions employed a common peptide substrate, LCB-EQEDEPEGDYFEWLW-NH2 (in-house). The basic assay protocol is as follows: First, 250 nL of diluted compounds in DMSO were dispensed into the wells of a dry 384- well Black plate (Greiner #781076) using a Labcyte Echo 555 acoustic dispenser.Subsequent reagent additions employed an Agilent Bravo. Next, 18 of 1.1 IX enzyme and 1.1 IX substrate in IX assay buffer (Invitrogen kinase buffer # PV3189, 2 mM DTT, 0.05% BSA) were added to the wells and shaken and then preincubated for 30 minutes at room temperature to allow compound binding to equilibrate. After equilibration, 2 \xL of 10X ATP in IX assay buffer was added to initiate the kinase reaction and the plates were shaken.
Measurement: IC50 = 4.8 nM (pChEMBL 8.319999694824219)
Descriptors: MW 323.38, ALogP 4.02, HBA 5, HBD 1, PSA 67.87, QED 0.58
Compound (SMILES): CCOC(=O)c1c[nH]c2ncnc(-c3cccc(OCc4ccccc4)c3)c12
InChIKey: VGRAPZNCKREIAJ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: HTRF Assay: The ability of compounds to inhibit the activity of JAKl, JAK2, JAK3, and Tyk2 was measured using a recombinant purified GST-tagged catalytic domain for each enzyme (Invitrogen JAKl #M4290, JAK2 #M4290, JAK3 #M4290, Tyk2 #M4290) in an HTRF format biochemical assay. The reactions employed a common peptide substrate, LCB-EQEDEPEGDYFEWLW-NH2 (in-house). The basic assay protocol is as follows: First, 250 nL of diluted compounds in DMSO were dispensed into the wells of a dry 384- well Black plate (Greiner #781076) using a Labcyte Echo 555 acoustic dispenser.Subsequent reagent additions employed an Agilent Bravo. Next, 18 of 1.1 IX enzyme and 1.1 IX substrate in IX assay buffer (Invitrogen kinase buffer # PV3189, 2 mM DTT, 0.05% BSA) were added to the wells and shaken and then preincubated for 30 minutes at room temperature to allow compound binding to equilibrate. After equilibration, 2 \xL of 10X ATP in IX assay buffer was added to initiate the kinase reaction and the plates were shaken.
Measurement: IC50 = 3.3 nM (pChEMBL 8.479999542236328)
Descriptors: MW 373.41, ALogP 4.38, HBA 5, HBD 1, PSA 77.1, QED 0.51
Compound (SMILES): Cc1cc(C)n2nc(CCc3nc(-c4ccccc4)cn3C)nc2n1
InChIKey: CHOZGBJYIPUZGG-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Inhibition Assay: A PDE10A assay may for example, be performed as follows: The assay is performed in 60 uL samples containing a fixed amount of the relevant PDE enzyme (sufficient to convert 20-25% of the cyclic nucleotide substrate), a buffer (50 mM HEPES7.6; 10 mM MgCl2; 0.02% Tween20), 0.1 mg/ml BSA, 225 pCi of 3H-labelled cyclic nucleotide substrate, tritium labeled cAMP to a final concentration of 5 nM and varying amounts of inhibitors. Reactions are initiated by addition of the cyclic nucleotide substrate, and reactions are allowed to proceed for one hr at room temperature before being terminated through mixing with 15 uL 8 mg/mL yttrium silicate SPA beads (Amersham). The beads are allowed to settle for one hr in the dark before the plates are counted in a Wallac 1450 Microbeta counter. The measured signal can be converted to activity relative to an uninhibited control (100%) and IC50 values can be calculated using the Xlfit extension to EXCEL.
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 332.41, ALogP 2.93, HBA 6, HBD 0, PSA 60.9, QED 0.58
Compound (SMILES): [C-]#[N+]C1=C(c2ccc(F)cc2)NC(C(F)F)=C(C#N)C1c1ccc2[nH]nc(C)c2c1
InChIKey: CYACZDGKXWSRQL-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Receptor Tyrosine Kinase Activity Assay: Recombinant human c-Met protein (Invitrogen, Carlsbad, Calif., USA) is used. As substrate for the kinase reaction the peptide KKKSPGEYVNIEFG (JPT, Germany) is used. For the assay, 1 uL of a 51-fold concentrated solution of the test compound in DMSO is pipetted into a white 384-well microtiter plate (Greiner Bio-One, Frickenhausen, Germany). 25 uL of a solution of c-Met (final concentration 30 nM) and pyruvate kinase/lactate dehydrogenase (Roche Diagnostics, Mannheim, Germany; final concentration 8 mg/L) in assay buffer [3-(N-morpholino)propanesulfonic acid (MOPS), 50 mM, pH 7; MgCl2, 10 mM; bovine serum albumin (BSA), 0.01%; Triton X 100, 0.01%; DTT, 2 mM] are added, and the mixture is incubated for 5 min at room temperature. Then, the kinase reaction is started by the addition of 25 uL of a solution of adenosine triphosphate (ATP, final concentration 30 uM), substrate (final concentration 100 uM), nicotinamide adenine dinucleotide.
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 405.38, ALogP 5.03, HBA 3, HBD 2, PSA 68.86, QED 0.6
Compound (SMILES): OC1CS[C@@H](n2cnc3c(NCc4cccc(I)c4)nc(Cl)nc32)[C@H]1O
InChIKey: QMJFSSNSVVHFPD-PMPKIWSKSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Binding Assay: CHO cells (ATCC No. CCL-61), in which A1 and A3 adenosine receptors were expressed, were cultured in F-12 media (Gibco, U.S.A.) supplemented with 10% fetal bovine serum (FBS) and penicillin/streptomycin (100 units/ml and 100 Î¼g/ml), at 37Â°C in a 5% CO2 atmosphere. A predetermined amount of suitable hAR-expressed CHO cells was mixed with labeled ligands (1 nM [3H]CCPA and 0.5 nM [125I]AB-MECA) specifically binding to A1 and A3 adenosine receptors in a 50/10/1 buffer in test tubes . The derivatives of the present invention were dissolved at various concentrations in dimethylsulfoxide (DMSO) and diluted in the buffer, taking care that the final concentration of DMSO did not exceed 1%. Incubation for 1 hr in a 370C incubator was followed by rapid filtration in a vacuum using a cell collector (TOMTEC, U.S.A.). Subsequently, the test tubes were washed three times with 3 ml of the buffer before radioactivity was measured using a Î³-counter.
Measurement: Ki = 4.16 nM (pChEMBL 8.380000114440918)
Descriptors: MW 503.75, ALogP 2.66, HBA 8, HBD 3, PSA 96.09, QED 0.37
Compound (SMILES): OC1CS[C@@H](n2cnc3c(NCc4ccccc4Cl)nc(Cl)nc32)[C@H]1O
InChIKey: XUIYCLQDMOOVSQ-PMPKIWSKSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Binding Assay: CHO cells (ATCC No. CCL-61), in which A1 and A3 adenosine receptors were expressed, were cultured in F-12 media (Gibco, U.S.A.) supplemented with 10% fetal bovine serum (FBS) and penicillin/streptomycin (100 units/ml and 100 Î¼g/ml), at 37Â°C in a 5% CO2 atmosphere. A predetermined amount of suitable hAR-expressed CHO cells was mixed with labeled ligands (1 nM [3H]CCPA and 0.5 nM [125I]AB-MECA) specifically binding to A1 and A3 adenosine receptors in a 50/10/1 buffer in test tubes . The derivatives of the present invention were dissolved at various concentrations in dimethylsulfoxide (DMSO) and diluted in the buffer, taking care that the final concentration of DMSO did not exceed 1%. Incubation for 1 hr in a 370C incubator was followed by rapid filtration in a vacuum using a cell collector (TOMTEC, U.S.A.). Subsequently, the test tubes were washed three times with 3 ml of the buffer before radioactivity was measured using a Î³-counter.
Measurement: Ki = 25.8 nM (pChEMBL 7.590000152587891)
Descriptors: MW 412.3, ALogP 2.71, HBA 8, HBD 3, PSA 96.09, QED 0.57
Compound (SMILES): COc1ccc(Cl)cc1CNc1nc(Cl)nc2c1ncn2[C@@H]1SCC(O)[C@@H]1O
InChIKey: LJLMHEFJMXWPHX-ALWGXXCGSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Binding Assay: CHO cells (ATCC No. CCL-61), in which A1 and A3 adenosine receptors were expressed, were cultured in F-12 media (Gibco, U.S.A.) supplemented with 10% fetal bovine serum (FBS) and penicillin/streptomycin (100 units/ml and 100 Î¼g/ml), at 37Â°C in a 5% CO2 atmosphere. A predetermined amount of suitable hAR-expressed CHO cells was mixed with labeled ligands (1 nM [3H]CCPA and 0.5 nM [125I]AB-MECA) specifically binding to A1 and A3 adenosine receptors in a 50/10/1 buffer in test tubes . The derivatives of the present invention were dissolved at various concentrations in dimethylsulfoxide (DMSO) and diluted in the buffer, taking care that the final concentration of DMSO did not exceed 1%. Incubation for 1 hr in a 370C incubator was followed by rapid filtration in a vacuum using a cell collector (TOMTEC, U.S.A.). Subsequently, the test tubes were washed three times with 3 ml of the buffer before radioactivity was measured using a Î³-counter.
Measurement: Ki = 12.7 nM (pChEMBL 7.900000095367432)
Descriptors: MW 442.33, ALogP 2.72, HBA 9, HBD 3, PSA 105.32, QED 0.52
Compound (SMILES): OC1CS[C@@H](n2cnc3c(NCc4cccc(F)c4)ncnc32)[C@H]1O
InChIKey: YDNYUMZDXCVVRT-GRLMSTMOSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Binding Assay: CHO cells (ATCC No. CCL-61), in which A1 and A3 adenosine receptors were expressed, were cultured in F-12 media (Gibco, U.S.A.) supplemented with 10% fetal bovine serum (FBS) and penicillin/streptomycin (100 units/ml and 100 Î¼g/ml), at 37Â°C in a 5% CO2 atmosphere. A predetermined amount of suitable hAR-expressed CHO cells was mixed with labeled ligands (1 nM [3H]CCPA and 0.5 nM [125I]AB-MECA) specifically binding to A1 and A3 adenosine receptors in a 50/10/1 buffer in test tubes . The derivatives of the present invention were dissolved at various concentrations in dimethylsulfoxide (DMSO) and diluted in the buffer, taking care that the final concentration of DMSO did not exceed 1%. Incubation for 1 hr in a 370C incubator was followed by rapid filtration in a vacuum using a cell collector (TOMTEC, U.S.A.). Subsequently, the test tubes were washed three times with 3 ml of the buffer before radioactivity was measured using a Î³-counter.
Measurement: Ki = 1260 nM (pChEMBL 5.900000095367432)
Descriptors: MW 361.4, ALogP 1.54, HBA 8, HBD 3, PSA 96.09, QED 0.65
Compound (SMILES): OC1CS[C@@H](n2cnc3c(NCc4cccc(Cl)c4)ncnc32)[C@H]1O
InChIKey: CKXSTCOOOXXOLA-GRLMSTMOSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Binding Assay: CHO cells (ATCC No. CCL-61), in which A1 and A3 adenosine receptors were expressed, were cultured in F-12 media (Gibco, U.S.A.) supplemented with 10% fetal bovine serum (FBS) and penicillin/streptomycin (100 units/ml and 100 Î¼g/ml), at 37Â°C in a 5% CO2 atmosphere. A predetermined amount of suitable hAR-expressed CHO cells was mixed with labeled ligands (1 nM [3H]CCPA and 0.5 nM [125I]AB-MECA) specifically binding to A1 and A3 adenosine receptors in a 50/10/1 buffer in test tubes . The derivatives of the present invention were dissolved at various concentrations in dimethylsulfoxide (DMSO) and diluted in the buffer, taking care that the final concentration of DMSO did not exceed 1%. Incubation for 1 hr in a 370C incubator was followed by rapid filtration in a vacuum using a cell collector (TOMTEC, U.S.A.). Subsequently, the test tubes were washed three times with 3 ml of the buffer before radioactivity was measured using a Î³-counter.
Measurement: Ki = 440 nM (pChEMBL 6.360000133514404)
Descriptors: MW 377.86, ALogP 2.06, HBA 8, HBD 3, PSA 96.09, QED 0.64
Compound (SMILES): OC1CS[C@@H](n2cnc3c(NCc4cccc(Br)c4)ncnc32)[C@H]1O
InChIKey: YPCLFHBYRDLMJY-GRLMSTMOSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Binding Assay: CHO cells (ATCC No. CCL-61), in which A1 and A3 adenosine receptors were expressed, were cultured in F-12 media (Gibco, U.S.A.) supplemented with 10% fetal bovine serum (FBS) and penicillin/streptomycin (100 units/ml and 100 Î¼g/ml), at 37Â°C in a 5% CO2 atmosphere. A predetermined amount of suitable hAR-expressed CHO cells was mixed with labeled ligands (1 nM [3H]CCPA and 0.5 nM [125I]AB-MECA) specifically binding to A1 and A3 adenosine receptors in a 50/10/1 buffer in test tubes . The derivatives of the present invention were dissolved at various concentrations in dimethylsulfoxide (DMSO) and diluted in the buffer, taking care that the final concentration of DMSO did not exceed 1%. Incubation for 1 hr in a 370C incubator was followed by rapid filtration in a vacuum using a cell collector (TOMTEC, U.S.A.). Subsequently, the test tubes were washed three times with 3 ml of the buffer before radioactivity was measured using a Î³-counter.
Measurement: Ki = 420 nM (pChEMBL 6.380000114440918)
Descriptors: MW 422.31, ALogP 2.17, HBA 8, HBD 3, PSA 96.09, QED 0.59
Compound (SMILES): OC1CS[C@@H](n2cnc3c(NCc4cccc(I)c4)ncnc32)[C@H]1O
InChIKey: IDVXTFYPPUNLDO-GRLMSTMOSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Binding Assay: CHO cells (ATCC No. CCL-61), in which A1 and A3 adenosine receptors were expressed, were cultured in F-12 media (Gibco, U.S.A.) supplemented with 10% fetal bovine serum (FBS) and penicillin/streptomycin (100 units/ml and 100 Î¼g/ml), at 37Â°C in a 5% CO2 atmosphere. A predetermined amount of suitable hAR-expressed CHO cells was mixed with labeled ligands (1 nM [3H]CCPA and 0.5 nM [125I]AB-MECA) specifically binding to A1 and A3 adenosine receptors in a 50/10/1 buffer in test tubes . The derivatives of the present invention were dissolved at various concentrations in dimethylsulfoxide (DMSO) and diluted in the buffer, taking care that the final concentration of DMSO did not exceed 1%. Incubation for 1 hr in a 370C incubator was followed by rapid filtration in a vacuum using a cell collector (TOMTEC, U.S.A.). Subsequently, the test tubes were washed three times with 3 ml of the buffer before radioactivity was measured using a Î³-counter.
Measurement: Ki = 2.5 nM (pChEMBL 8.600000381469727)
Descriptors: MW 469.31, ALogP 2.01, HBA 8, HBD 3, PSA 96.09, QED 0.5
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: 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 = 0.3 nM (pChEMBL 9.520000457763672)
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: 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 < 0.3 nM (pChEMBL 9.52299976348877)
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: 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 = 0.5 nM (pChEMBL 9.300000190734863)
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: 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 = 0.8 nM (pChEMBL 9.100000381469727)
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: 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 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: 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 = 2 nM (pChEMBL 8.699999809265137)
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: 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 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: 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 1025.53