lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CCOC(=O)c1c[nH]c2ncnc(-c3cccc(Nc4nc(Cl)ns4)c3)c12
InChIKey: BBIQFSOCGAJPGP-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 = 9.2 nM (pChEMBL 8.039999961853027)
Descriptors: MW 400.85, ALogP 4.05, HBA 8, HBD 2, PSA 105.68, QED 0.49
Compound (SMILES): C=CS(=O)(=O)Nc1cccc(-c2ncnc3[nH]cc(C(=O)OCC)c23)c1
InChIKey: WWGASLJTUAXCRF-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 > 1496 nM (pChEMBL 5.824999809265137)
Descriptors: MW 372.41, ALogP 2.69, HBA 6, HBD 2, PSA 114.04, QED 0.64
Compound (SMILES): C/C=C/S(=O)(=O)Nc1cccc(-c2ncnc3[nH]cc(C(=O)OCC)c23)c1
InChIKey: KYENMINJJCKMNI-FPYGCLRLSA-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 = 8.2 nM (pChEMBL 8.09000015258789)
Descriptors: MW 386.43, ALogP 3.08, HBA 6, HBD 2, PSA 114.04, QED 0.63
Compound (SMILES): C=C(C)C(=O)Nc1cc(-c2ncnc3[nH]cc(C(=O)OC)c23)ccc1F
InChIKey: WWKYFKYUXOUHFG-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 > 1496 nM (pChEMBL 5.824999809265137)
Descriptors: MW 354.34, ALogP 3.07, HBA 5, HBD 2, PSA 96.97, QED 0.55
Compound (SMILES): C=C(C)C(=O)Nc1cccc(-c2ncnc3[nH]cc(C(=O)OC)c23)c1
InChIKey: XKQWRUYPFFVOQA-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 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 336.35, ALogP 2.93, HBA 5, HBD 2, PSA 96.97, QED 0.56
Compound (SMILES): C=CC(=O)N(C)c1cccc(-c2ncnc3[nH]cc(C(=O)OCC)c23)c1
InChIKey: UQOBGKQNECGMLF-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 > 1496 nM (pChEMBL 5.824999809265137)
Descriptors: MW 350.38, ALogP 2.95, HBA 5, HBD 1, PSA 88.18, QED 0.56
Compound (SMILES): C=C(CNS(C)(=O)=O)C(=O)Nc1cccc(-c2ncnc3[nH]cc(C(=O)OCC)c23)c1
InChIKey: XSQCOVLPFPTCLO-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 = 0.052 nM (pChEMBL 10.279999732971191)
Descriptors: MW 443.49, ALogP 1.85, HBA 7, HBD 3, PSA 143.14, QED 0.36
Compound (SMILES): C=C(CF)C(=O)Nc1cccc(-c2ncnc3[nH]cc(C(=O)OCC)c23)c1
InChIKey: LBGKSTCCHAQOEK-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 = 0.024 nM (pChEMBL 10.619999885559082)
Descriptors: MW 368.37, ALogP 3.27, HBA 5, HBD 2, PSA 96.97, QED 0.51
Compound (SMILES): C=C(CO)C(=O)Nc1cccc(-c2ncnc3[nH]cc(C(=O)OCC)c23)c1
InChIKey: OOKHLJVVFRLORH-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 > 1496 nM (pChEMBL 5.824999809265137)
Descriptors: MW 366.38, ALogP 2.29, HBA 6, HBD 3, PSA 117.2, QED 0.46
Compound (SMILES): CCOC(=O)c1c[nH]c2ncnc(-c3cccc(NC(=O)C4(C)CO4)c3)c12
InChIKey: UDEGYXCRYLCDOO-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 = 0.056 nM (pChEMBL 10.25)
Descriptors: MW 366.38, ALogP 2.53, HBA 6, HBD 2, PSA 109.5, QED 0.53
Compound (SMILES): C=C(C)C(=O)Nc1cccc(-c2ncnc3[nH]cc(-c4cccc(C)c4)c23)c1
InChIKey: XCHSXEOQITWOFN-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 > 1496 nM (pChEMBL 5.824999809265137)
Descriptors: MW 368.44, ALogP 5.11, HBA 3, HBD 2, PSA 70.67, QED 0.49
Compound (SMILES): C=C(C)C(=O)Nc1cccc(-c2ncnc3[nH]cc(-c4cccc(F)c4)c23)c1
InChIKey: PPGXNCSWBPUOOT-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 > 1496 nM (pChEMBL 5.824999809265137)
Descriptors: MW 372.4, ALogP 4.95, HBA 3, HBD 2, PSA 70.67, QED 0.5
Compound (SMILES): C=C(C)C(=O)Nc1cccc(-c2ncnc3[nH]cc(-c4ccccc4F)c23)c1
InChIKey: DJQYUNLSKBBFMO-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 > 1496 nM (pChEMBL 5.824999809265137)
Descriptors: MW 372.4, ALogP 4.95, HBA 3, HBD 2, PSA 70.67, QED 0.5
Compound (SMILES): C=C(C)C(=O)Nc1cccc(-c2ncnc3[nH]cc(-c4ccc(F)cc4)c23)c1
InChIKey: SVTKVVAFLMAKBU-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 > 1496 nM (pChEMBL 5.824999809265137)
Descriptors: MW 372.4, ALogP 4.95, HBA 3, HBD 2, PSA 70.67, QED 0.5
Compound (SMILES): C=C(C)C(=O)Nc1cccc(-c2ncnc3[nH]cc(-c4cccc(F)c4Cl)c23)c1
InChIKey: ANPFPYRJWBYGSI-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 > 1496 nM (pChEMBL 5.824999809265137)
Descriptors: MW 406.85, ALogP 5.6, HBA 3, HBD 2, PSA 70.67, QED 0.43
Compound (SMILES): C=C(C)C(=O)Nc1cccc(-c2ncnc3[nH]cc(-c4ccccc4C)c23)c1
InChIKey: HNEUAEMHMXKTMX-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 = 5.2 nM (pChEMBL 8.279999732971191)
Descriptors: MW 368.44, ALogP 5.11, HBA 3, HBD 2, PSA 70.67, QED 0.49
Compound (SMILES): C=C(C)C(=O)Nc1cccc(-c2ncnc3[nH]cc(-c4ccc(C)cc4)c23)c1
InChIKey: FVWPCNHBSIAOBB-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 = 5.4 nM (pChEMBL 8.270000457763672)
Descriptors: MW 368.44, ALogP 5.11, HBA 3, HBD 2, PSA 70.67, QED 0.49
Compound (SMILES): C=CC(=O)Nc1cccc(-c2ncnc3[nH]cc(-c4ccccc4)c23)c1
InChIKey: ZZQAUPMZTTVWNS-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Kinase-Inhibiting Activity Assay: JAK 2: Among materials for the measurement of this inhibiting activity, a substrate peptide and a kinase protein were acquired as follows. As such a substrate peptide, FL-Peptide 22 (Perkin Elmer Corp.) was purchased. As such a kinase protein, a purified recombinant human JAK2 protein (Carna Biosciences, Inc.) was purchased.The method for measuring the inhibiting activity is as follows. First, a serial dilution of the compound of the present invention was prepared by the same method as that described in the above section regarding JAK1. This serial dilution solution (the final concentration of DMSO upon a kinase reaction: 5.0%) or DMSO (final concentration: 5.0%) was mixed with a solution comprising the substrate peptide (final concentration: 1 μM), magnesium chloride (final concentration: 10 mM) and ATP (final concentration: 10 μM) in a buffer for kinase reaction (15 mM Tris (pH 7.5), 2 mM dithiothreitol and 0.01% Tween 20). Thereafter, a JAK2 protein was further added to the mixed solution, and the obtained mixture was then incubated at 25° C. for 80 minutes to carry out a kinase reaction. To the reaction solution, EDTA was added to a final concentration of 30 mM, so as to terminate the reaction.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 340.39, ALogP 4.42, HBA 3, HBD 2, PSA 70.67, QED 0.54
Compound (SMILES): C=C(C)C(=O)Nc1cccc(-c2ncnc3[nH]cc(-c4cnc[nH]4)c23)c1
InChIKey: BRPJTSQFVJHLFW-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 > 1496 nM (pChEMBL 5.824999809265137)
Descriptors: MW 344.38, ALogP 3.53, HBA 4, HBD 3, PSA 99.35, QED 0.49
Compound (SMILES): C=C(C)C(=O)Nc1cccc(-c2ncnc3[nH]cc(-c4cccnc4)c23)c1
InChIKey: KIQSBYGVSHMWEP-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 > 1496 nM (pChEMBL 5.824999809265137)
Descriptors: MW 355.4, ALogP 4.2, HBA 4, HBD 2, PSA 83.56, QED 0.54
Compound (SMILES): C=C(C)C(=O)Nc1cccc(-c2ncnc3[nH]cc(C4=CCOCC4)c23)c1
InChIKey: BLERMYUAOLEVKX-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 > 1496 nM (pChEMBL 5.824999809265137)
Descriptors: MW 360.42, ALogP 3.94, HBA 4, HBD 2, PSA 79.9, QED 0.69
Compound (SMILES): C=C(C)C(=O)Nc1cccc(-c2ncnc3[nH]cc(-c4cnc(C)s4)c23)c1
InChIKey: QORLSVZRDWHSLZ-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 > 1496 nM (pChEMBL 5.824999809265137)
Descriptors: MW 375.46, ALogP 4.57, HBA 5, HBD 2, PSA 83.56, QED 0.51
Compound (SMILES): C=C(C)C(=O)Nc1cccc(-c2ncnc3[nH]cc(-c4cncs4)c23)c1
InChIKey: NHPRXSXXOAKKKT-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 > 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 361.43, ALogP 4.26, HBA 5, HBD 2, PSA 83.56, QED 0.53
Compound (SMILES): COC(=O)Cc1ccc(OC)c(-c2c[nH]c3ncnc(-c4ccccc4)c23)c1
InChIKey: OQBZZSDJTOAVJM-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 = 3.1 nM (pChEMBL 8.510000228881836)
Descriptors: MW 373.41, ALogP 4.02, HBA 5, HBD 1, PSA 77.1, QED 0.53
Compound (SMILES): COc1ccccc1-c1c[nH]c2ncnc(-c3ccccc3)c12
InChIKey: XTJMNLKLSRUBKX-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 = 3.4 nM (pChEMBL 8.470000267028809)
Descriptors: MW 301.35, ALogP 4.3, HBA 3, HBD 1, PSA 50.8, QED 0.61
Compound (SMILES): COc1ccccc1-c1c[nH]c2ncnc(-c3ccc4cn(C)nc4c3)c12
InChIKey: UXUZYJDYRPTVAC-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 = 6.9 nM (pChEMBL 8.15999984741211)
Descriptors: MW 355.4, ALogP 4.19, HBA 5, HBD 1, PSA 68.62, QED 0.53
Compound (SMILES): COc1ccc(F)cc1-c1c[nH]c2ncnc(-c3ccccc3)c12
InChIKey: BCNPPSRRHIVGRC-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 = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 319.34, ALogP 4.44, HBA 3, HBD 1, PSA 50.8, QED 0.61
Compound (SMILES): CCOC(=O)c1c[nH]c2ncnc(-c3cccc(NC(=O)/C=C/CN(C)C)c3)c12
InChIKey: FFEKIHZPWVHWSQ-RMKNXTFCSA-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 = 0.02 nM (pChEMBL 10.699999809265137)
Descriptors: MW 393.45, ALogP 2.86, HBA 6, HBD 2, PSA 100.21, QED 0.47
Compound (SMILES): CCOC(=O)c1c[nH]c2ncnc(-c3cccc(NC(=O)/C(C)=C/CN(C)C)c3)c12
InChIKey: WCJFTAJHZRRUBX-NTEUORMPSA-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 > 1496 nM (pChEMBL 5.824999809265137)
Descriptors: MW 407.47, ALogP 3.25, HBA 6, HBD 2, PSA 100.21, QED 0.46
Compound (SMILES): C=C(C)C(=O)Nc1cccc(-c2ncnc3[nH]cc(-c4ncco4)c23)c1
InChIKey: XRGGGFFXOCIEOE-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 > 1496 nM (pChEMBL 5.824999809265137)
Descriptors: MW 345.36, ALogP 3.79, HBA 5, HBD 2, PSA 96.7, QED 0.55
Compound (SMILES): C=C(C)C(=O)Nc1cccc(-c2ncnc3[nH]cc(C4CCOCC4)c23)c1
InChIKey: VQHJDOQOJLSROF-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 = 8.3 nM (pChEMBL 8.079999923706055)
Descriptors: MW 362.43, ALogP 4.03, HBA 4, HBD 2, PSA 79.9, QED 0.69
Compound (SMILES): C=C(C)C(=O)Nc1cccc(-c2ncnc3[nH]cc(-c4cnco4)c23)c1
InChIKey: ZUQAMLOMWHLOHN-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 nM (pChEMBL 8.300000190734863)
Descriptors: MW 345.36, ALogP 3.79, HBA 5, HBD 2, PSA 96.7, QED 0.55
Compound (SMILES): CC1Cc2c(c3ccc(-n4ccc(OCc5ccccc5)cc4=O)nc3n2C)CN1
InChIKey: PEBIQXSORDHCAI-UHFFFAOYSA-N
Target: Melanin-concentrating hormone receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99705
Assay: Binding Assay: Evaluation of the affinity of compounds for the human MCH-1 receptor was accomplished using 4-(3,4,5-tritritiumbenzyloxy)-1-(1-(2-(pyrrolidin-1-yl)ethyl)-1H-indazol-5-yl)pyridin-2(1H)-one and membranes prepared from stable CHO-K1 cells expressing the human MCH-1 receptor obtained from Euroscreen (Batch 1138). Cell membrane homogenates (8.92 μg protein) were incubated for 60 min at 25° C. with 1.4 μM of the [3H]-labeled compound in the absence or presence of the test compound in 50 mM Tris-HCl buffer, pH 7.4. Nonspecific binding was determined in the presence of 50 μM 1-(5-(4-cyanophenyl)bicyclo[3.1.0]hexan-2-yl)-3-(4-fluoro-3-(trifluoromethyl)phenyl)-1-(3-(4-methylpiperazin-1-yl)propyl)urea. Following incubation, the samples were filtered rapidly under vacuum through Skatron 11731 filters, pre-soaked in 0.5% polyethylenimine, and washed with ice-cold 50 mM Tris-HCl buffer, pH 7.4, (wash setting 9,9,0) using a Skatron cell harvester.
Measurement: Ki = 9.1 nM (pChEMBL 8.039999961853027)
Descriptors: MW 400.48, ALogP 3.34, HBA 6, HBD 1, PSA 61.08, QED 0.57
Compound (SMILES): Fc1ccc(CN[C@H]2CC2c2ccccc2)cc1
InChIKey: LUVOTYXXGWODOF-LYKKTTPLSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Amplex Red Peroxide/Peroxidase-Coupled Assay: The compounds of the invention can be tested for their ability to inhibit LSD1. The ability of the compounds of the invention to inhibit LSD1 can be tested as follows. Human recombinant LSD1 protein was purchased from BPS Bioscience Inc. In order to monitor LSD1 enzymatic activity and/or its inhibition rate by our inhibitor(s) of interest, di-methylated H3-K4 peptide (Millipore) was chosen as a substrate. The demethylase activity was estimated, under aerobic conditions, by measuring the release of H2O2 produced during the catalytic process, using the Amplex Red peroxide/peroxidase-coupled assay kit (Invitrogen).Briefly, a fixed amount of LSD1 was incubated on ice for 15 minutes, in the absence and/or in the presence of various concentrations of inhibitor (from 0 to 75 uM, depending on the inhibitor strength). Tranylcypromine (Biomol International) was used as a control for inhibition. Within the experiment, each concentration of inhibitor was tested in triplicate.
Measurement: IC50 = 800 nM (pChEMBL 6.099999904632568)
Descriptors: MW 241.31, ALogP 3.47, HBA 1, HBD 1, PSA 12.03, QED 0.86
Compound (SMILES): N#Cc1ccc(CN[C@H]2CC2c2ccccc2)cc1
InChIKey: GSSKGGXAODPANR-DJNXLDHESA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Fluorescent-Based (Inhibitor) Screening Assay: Human recombinant monoamine oxidase proteins MAO-A and MAO-B were purchased from Sigma Aldrich. MAOs catalyze the oxidative deamination of 1, 2 and 3 amines. In order to monitor MAO enzymatic activities and/or their inhibition rate by inhibitor(s) of interest, a fluorescent-based (inhibitor)-screening assay was set up. 3-(2-Aminophenyl)-3-oxopropamamine (kynuramine dihydrobromide, Sigma Aldrich), a non fluorescent compound was chosen as a substrate. Kynuramine is a non-specific substrate for both MAOs activities. While undergoing oxidative deamination by MAO activities, kynuramine is converted into 4-hydroxyquinoline (4-HQ), a resulting fluorescent product.The monoamine oxidase activity was estimated by measuring the conversion of kynuramine into 4-hydroxyquinoline. Assays were conducted in 96-well black plates with clear bottom (Corning) in a final volume of 100 uL. The assay buffer was 100 mM HEPES, pH 7.5. Each experiment was performed in triplicate within the same experiment.
Measurement: IC50 = 7000 nM (pChEMBL 5.159999847412109)
Descriptors: MW 248.33, ALogP 3.2, HBA 2, HBD 1, PSA 35.82, QED 0.9
Compound (SMILES): FC(F)(F)c1ccc(CN[C@H]2CC2c2ccccc2)cc1
InChIKey: JENCIJJNTCBGHX-LYKKTTPLSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Fluorescent-Based (Inhibitor) Screening Assay: Human recombinant monoamine oxidase proteins MAO-A and MAO-B were purchased from Sigma Aldrich. MAOs catalyze the oxidative deamination of 1, 2 and 3 amines. In order to monitor MAO enzymatic activities and/or their inhibition rate by inhibitor(s) of interest, a fluorescent-based (inhibitor)-screening assay was set up. 3-(2-Aminophenyl)-3-oxopropamamine (kynuramine dihydrobromide, Sigma Aldrich), a non fluorescent compound was chosen as a substrate. Kynuramine is a non-specific substrate for both MAOs activities. While undergoing oxidative deamination by MAO activities, kynuramine is converted into 4-hydroxyquinoline (4-HQ), a resulting fluorescent product.The monoamine oxidase activity was estimated by measuring the conversion of kynuramine into 4-hydroxyquinoline. Assays were conducted in 96-well black plates with clear bottom (Corning) in a final volume of 100 uL. The assay buffer was 100 mM HEPES, pH 7.5. Each experiment was performed in triplicate within the same experiment.
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 291.32, ALogP 4.35, HBA 1, HBD 1, PSA 12.03, QED 0.88