lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)c1nccs1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(N)=O)c1ccc(OCc2ccc(C(F)(F)F)cc2)cc1
InChIKey: AKRJOEANBCUPHB-CCDWMCETSA-N
Target: Nonstructural protein 3 (SINGLE PROTEIN), Zika virus
UniProt: A0A024AXB9
Assay: Functional biochemical assay to identify treatments for viral infectious disease that targets Zika NS2B-NS3 protease. Utilizing a direct enzyme activity measurement method, reading the fluorescence intensity is used to characterize the relative potency of inhibitors as IC50. Synthetic construct has been made based on Zika virus (strain PRVABC59) by Centre for Medicines Discovery, University of Oxford, and the assay has been performed by Weizmann Institute of Science.The protocol is publicly available: dx.doi.org/10.17504/protocols.io.q26g7yebkgwz/v3
Measurement: IC50 = 2513 nM (pChEMBL 5.599999904632568)
Descriptors: MW 719.79, ALogP 2.06, HBA 9, HBD 8, PSA 240.43, QED 0.05
Compound (SMILES): O=C(O)C1CN(Cc2ccc(OCc3ccc(Cl)c(Cl)c3)cc2)C1
InChIKey: WAAWETUDFSIYSD-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Srms (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3Y6
Assay: Inhibition of SRMS (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 366.24, ALogP 4.09, HBA 3, HBD 1, PSA 49.77, QED 0.84
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)c1nccs1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(N)=O)c1ccc(OCc2ccc(C(F)(F)F)cc2)cc1
InChIKey: AKRJOEANBCUPHB-CCDWMCETSA-N
Target: Genome polyprotein (SINGLE PROTEIN), dengue virus type 2
UniProt: P29990
Assay: Functional biochemical assay to identify treatments for viral infectious disease that targets Dengue virus type 2 NS2B-NS3 protease. Utilizing a direct enzyme activity measurement method, reading the fluorescence intensity is used to characterize the relative potency of inhibitors as IC50. Synthetic construct has been made based on Dengue virus type 2 (strain Thailand/16681/1984) by Centre for Medicines Discovery, University of Oxford, and the assay has been performed by Enamine biological services, Bienta Ltd.The protocol is publicly available: dx.doi.org/10.17504/protocols.io.kqdg32m87v25/v1
Measurement: IC50 = 2836 nM (pChEMBL 5.550000190734863)
Descriptors: MW 719.79, ALogP 2.06, HBA 9, HBD 8, PSA 240.43, QED 0.05
Compound (SMILES): O=C(O)C1CN(Cc2ccc(OCc3ccc(Cl)c(Cl)c3)cc2)C1
InChIKey: WAAWETUDFSIYSD-UHFFFAOYSA-N
Target: SRSF protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96SB4
Assay: Inhibition of SRPK1(unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 366.24, ALogP 4.09, HBA 3, HBD 1, PSA 49.77, QED 0.84
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)c1nccs1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(N)=O)c1ccc(OCc2ccc(C(F)(F)F)cc2)cc1
InChIKey: AKRJOEANBCUPHB-CCDWMCETSA-N
Target: Genome polyprotein (SINGLE PROTEIN), dengue virus type 2
UniProt: P29990
Assay: Functional biochemical assay to identify treatments for viral infectious disease that targets Dengue virus type 2 NS2B-NS3 protease. Utilizing a direct enzyme activity measurement method, reading the fluorescence intensity is used to characterize the relative potency of inhibitors as IC50. Synthetic construct has been made based on Dengue virus type 2 (strain Thailand/16681/1984) by Centre for Medicines Discovery, University of Oxford, and the assay has been performed by Weizmann Institute of Science.The protocol is publicly available: dx.doi.org/10.17504/protocols.io.q26g7yebkgwz/v3
Measurement: IC50 = 1243 nM (pChEMBL 5.909999847412109)
Descriptors: MW 719.79, ALogP 2.06, HBA 9, HBD 8, PSA 240.43, QED 0.05
Compound (SMILES): O=C(O)C1CN(Cc2ccc(OCc3ccc(Cl)c(Cl)c3)cc2)C1
InChIKey: WAAWETUDFSIYSD-UHFFFAOYSA-N
Target: Tyrosine-protein kinase SYK (SINGLE PROTEIN), Homo sapiens
UniProt: P43405
Assay: Inhibition of SYK (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 366.24, ALogP 4.09, HBA 3, HBD 1, PSA 49.77, QED 0.84
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)c1nccs1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(N)=O)c1ccc(OCc2ccc(C(F)(F)F)cc2)cc1
InChIKey: AKRJOEANBCUPHB-CCDWMCETSA-N
Target: Nonstructural protein 3 (SINGLE PROTEIN), Zika virus
UniProt: A0A024AXB9
Assay: Functional biochemical assay to identify treatments for viral infectious disease that targets Zika NS2B-NS3 protease. Utilizing a direct enzyme activity measurement method, reading the fluorescence intensity is used to characterize the relative potency of inhibitors as IC50. Synthetic construct has been made based on Zika virus (strain PRVABC59) by Centre for Medicines Discovery, University of Oxford, and the assay has been performed by Weizmann Institute of Science.The protocol is publicly available: dx.doi.org/10.17504/protocols.io.q26g7yebkgwz/v3
Measurement: IC50 = 1699 nM (pChEMBL 5.769999980926514)
Descriptors: MW 719.79, ALogP 2.06, HBA 9, HBD 8, PSA 240.43, QED 0.05
Compound (SMILES): O=C(O)C1CN(Cc2ccc(OCc3ccc(Cl)c(Cl)c3)cc2)C1
InChIKey: WAAWETUDFSIYSD-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase TAO2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UL54
Assay: Inhibition of TAOK2 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 366.24, ALogP 4.09, HBA 3, HBD 1, PSA 49.77, QED 0.84
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)c1nccs1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(N)=O)c1ccc(OCc2ccc(C(F)(F)F)cc2)cc1
InChIKey: AKRJOEANBCUPHB-CCDWMCETSA-N
Target: Genome polyprotein (SINGLE PROTEIN), dengue virus type 2
UniProt: P29990
Assay: Functional biochemical assay to identify treatments for viral infectious disease that targets Dengue virus type 2 NS2B-NS3 protease. Utilizing a direct enzyme activity measurement method, reading the fluorescence intensity is used to characterize the relative potency of inhibitors as IC50. Synthetic construct has been made based on Dengue virus type 2 (strain Thailand/16681/1984) by Centre for Medicines Discovery, University of Oxford, and the assay has been performed by Enamine biological services, Bienta Ltd.The protocol is publicly available: dx.doi.org/10.17504/protocols.io.kqdg32m87v25/v1
Measurement: IC50 = 2339 nM (pChEMBL 5.630000114440918)
Descriptors: MW 719.79, ALogP 2.06, HBA 9, HBD 8, PSA 240.43, QED 0.05
Compound (SMILES): O=C(O)C1CN(Cc2ccc(OCc3ccc(Cl)c(Cl)c3)cc2)C1
InChIKey: WAAWETUDFSIYSD-UHFFFAOYSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: Inhibition of TRKA (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 366.24, ALogP 4.09, HBA 3, HBD 1, PSA 49.77, QED 0.84
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)c1nccs1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(N)=O)c1ccc(OCc2ccc(C(F)(F)F)cc2)cc1
InChIKey: AKRJOEANBCUPHB-CCDWMCETSA-N
Target: Genome polyprotein (SINGLE PROTEIN), dengue virus type 2
UniProt: P29990
Assay: Functional biochemical assay to identify treatments for viral infectious disease that targets Dengue virus type 2 NS2B-NS3 protease. Utilizing a direct enzyme activity measurement method, reading the fluorescence intensity is used to characterize the relative potency of inhibitors as IC50. Synthetic construct has been made based on Dengue virus type 2 (strain Thailand/16681/1984) by Centre for Medicines Discovery, University of Oxford, and the assay has been performed by Enamine biological services, Bienta Ltd.The protocol is publicly available: dx.doi.org/10.17504/protocols.io.kqdg32m87v25/v1
Measurement: IC50 = 2394 nM (pChEMBL 5.619999885559082)
Descriptors: MW 719.79, ALogP 2.06, HBA 9, HBD 8, PSA 240.43, QED 0.05
Compound (SMILES): O=C(O)C1CN(Cc2ccc(OCc3ccc(Cl)c(Cl)c3)cc2)C1
InChIKey: WAAWETUDFSIYSD-UHFFFAOYSA-N
Target: BDNF/NT-3 growth factors receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16620
Assay: Inhibition of TRKB (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 366.24, ALogP 4.09, HBA 3, HBD 1, PSA 49.77, QED 0.84
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)c1nccs1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(N)=O)c1ccc(OCc2ccc(C(F)(F)F)cc2)cc1
InChIKey: AKRJOEANBCUPHB-CCDWMCETSA-N
Target: Nonstructural protein 3 (SINGLE PROTEIN), Zika virus
UniProt: A0A024AXB9
Assay: Functional biochemical assay to identify treatments for viral infectious disease that targets Zika NS2B-NS3 protease. Utilizing a direct enzyme activity measurement method, reading the fluorescence intensity is used to characterize the relative potency of inhibitors as IC50. Synthetic construct has been made based on Zika virus (strain PRVABC59) by Centre for Medicines Discovery, University of Oxford, and the assay has been performed by Weizmann Institute of Science.The protocol is publicly available: dx.doi.org/10.17504/protocols.io.q26g7yebkgwz/v3
Measurement: IC50 = 2261 nM (pChEMBL 5.650000095367432)
Descriptors: MW 719.79, ALogP 2.06, HBA 9, HBD 8, PSA 240.43, QED 0.05
Compound (SMILES): O=C(O)C1CN(Cc2ccc(OCc3ccc(Cl)c(Cl)c3)cc2)C1
InChIKey: WAAWETUDFSIYSD-UHFFFAOYSA-N
Target: NT-3 growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16288
Assay: Inhibition of TRKC (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 366.24, ALogP 4.09, HBA 3, HBD 1, PSA 49.77, QED 0.84
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)c1nccs1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(N)=O)c1ccc(OCc2ccc(C(F)(F)F)cc2)cc1
InChIKey: AKRJOEANBCUPHB-CCDWMCETSA-N
Target: Genome polyprotein (SINGLE PROTEIN), dengue virus type 2
UniProt: P29990
Assay: Functional biochemical assay to identify treatments for viral infectious disease that targets Dengue virus type 2 NS2B-NS3 protease. Utilizing a direct enzyme activity measurement method, reading the fluorescence intensity is used to characterize the relative potency of inhibitors as IC50. Synthetic construct has been made based on Dengue virus type 2 (strain Thailand/16681/1984) by Centre for Medicines Discovery, University of Oxford, and the assay has been performed by Weizmann Institute of Science.The protocol is publicly available: dx.doi.org/10.17504/protocols.io.q26g7yebkgwz/v3
Measurement: IC50 = 1639 nM (pChEMBL 5.789999961853027)
Descriptors: MW 719.79, ALogP 2.06, HBA 9, HBD 8, PSA 240.43, QED 0.05
Compound (SMILES): O=C(O)C1CN(Cc2ccc(OCc3ccc(Cl)c(Cl)c3)cc2)C1
InChIKey: WAAWETUDFSIYSD-UHFFFAOYSA-N
Target: Testis-specific serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BXA7
Assay: Inhibition of TSSK1 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 366.24, ALogP 4.09, HBA 3, HBD 1, PSA 49.77, QED 0.84
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)c1nccs1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(N)=O)c1ccc(OCc2ccc(C(F)(F)F)cc2)cc1
InChIKey: AKRJOEANBCUPHB-CCDWMCETSA-N
Target: NS3 protease (SINGLE PROTEIN), dengue virus type 1
UniProt: A0A0K0TQ28
Assay: Functional biochemical assay to identify treatments for viral infectious disease that targets Dengue virus type 1 NS2B-NS3 protease. Utilizing a direct enzyme activity measurement method, reading the fluorescence intensity is used to characterize the relative potency of inhibitors as IC50. Synthetic construct has been made based on Dengue virus type 1 (strain Nauru/West Pac/1974) by Centre for Medicines Discovery, University of Oxford, and the assay has been performed by Weizmann Institute of Science.The protocol is publicly available: dx.doi.org/10.17504/protocols.io.q26g7yebkgwz/v3
Measurement: IC50 = 926 nM (pChEMBL 6.03000020980835)
Descriptors: MW 719.79, ALogP 2.06, HBA 9, HBD 8, PSA 240.43, QED 0.05
Compound (SMILES): O=C(O)C1CN(Cc2ccc(OCc3ccc(Cl)c(Cl)c3)cc2)C1
InChIKey: WAAWETUDFSIYSD-UHFFFAOYSA-N
Target: Testis-specific serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96PF2
Assay: Inhibition of TSSK2 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 366.24, ALogP 4.09, HBA 3, HBD 1, PSA 49.77, QED 0.84
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)c1nccs1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(N)=O)c1ccc(OCc2ccc(C(F)(F)F)cc2)cc1
InChIKey: AKRJOEANBCUPHB-CCDWMCETSA-N
Target: NS3 protease (SINGLE PROTEIN), dengue virus type 3
UniProt: A0A0B5JFF1
Assay: Functional biochemical assay to identify treatments for viral infectious disease that targets Dengue virus type 3 NS2B-NS3 protease. Utilizing a direct enzyme activity measurement method, reading the fluorescence intensity is used to characterize the relative potency of inhibitors as IC50. Synthetic construct has been made based on Dengue virus type 3 (strain Philippines/H87/1956) by Centre for Medicines Discovery, University of Oxford, and the assay has been performed by Weizmann Institute of Science.The protocol is publicly available: dx.doi.org/10.17504/protocols.io.q26g7yebkgwz/v3
Measurement: IC50 = 2186 nM (pChEMBL 5.659999847412109)
Descriptors: MW 719.79, ALogP 2.06, HBA 9, HBD 8, PSA 240.43, QED 0.05
Compound (SMILES): O=C(O)C1CN(Cc2ccc(OCc3ccc(Cl)c(Cl)c3)cc2)C1
InChIKey: WAAWETUDFSIYSD-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of TYK2 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 366.24, ALogP 4.09, HBA 3, HBD 1, PSA 49.77, QED 0.84
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)c1nccs1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(N)=O)c1ccc(OCc2ccc(C(F)(F)F)cc2)cc1
InChIKey: AKRJOEANBCUPHB-CCDWMCETSA-N
Target: NS3 protease (SINGLE PROTEIN), dengue virus type 4
UniProt: A0A0K0TQ36
Assay: Functional biochemical assay to identify treatments for viral infectious disease that targets Dengue virus type 4 NS2B-NS3 protease. Utilizing a direct enzyme activity measurement method, reading the fluorescence intensity is used to characterize the relative potency of inhibitors as IC50. Synthetic construct has been made based on Dengue virus type 4 (strain Philippines/H241/1956) by Centre for Medicines Discovery, University of Oxford, and the assay has been performed by Weizmann Institute of Science.The protocol is publicly available: dx.doi.org/10.17504/protocols.io.q26g7yebkgwz/v3
Measurement: IC50 = 1471 nM (pChEMBL 5.829999923706055)
Descriptors: MW 719.79, ALogP 2.06, HBA 9, HBD 8, PSA 240.43, QED 0.05
Compound (SMILES): O=C(O)C1CN(Cc2ccc(OCc3ccc(Cl)c(Cl)c3)cc2)C1
InChIKey: WAAWETUDFSIYSD-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 20 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYL2
Assay: Inhibition of ZAK (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 366.24, ALogP 4.09, HBA 3, HBD 1, PSA 49.77, QED 0.84
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)c1nccs1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(N)=O)c1ccc(OCc2ccc(C(F)(F)F)cc2)cc1
InChIKey: AKRJOEANBCUPHB-CCDWMCETSA-N
Target: NS3 (SINGLE PROTEIN), West Nile virus
UniProt: K4FQI5
Assay: Functional biochemical assay to identify treatments for viral infectious disease that targets West Nile NS2B-NS3 protease. Utilizing a direct enzyme activity measurement method, reading the fluorescence intensity is used to characterize the relative potency of inhibitors as IC50. Synthetic construct has been made based on West Nile virus (strain NY-99) by Centre for Medicines Discovery, University of Oxford, and the assay has been performed by Weizmann Institute of Science.The protocol is publicly available: dx.doi.org/10.17504/protocols.io.q26g7yebkgwz/v3
Measurement: IC50 = 1548 nM (pChEMBL 5.809999942779541)
Descriptors: MW 719.79, ALogP 2.06, HBA 9, HBD 8, PSA 240.43, QED 0.05
Compound (SMILES): O=C(O)C1CN(Cc2ccc(OCc3ccc(Cl)c(Cl)c3)cc2)C1
InChIKey: WAAWETUDFSIYSD-UHFFFAOYSA-N
Target: Death-associated protein kinase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O43293
Assay: Inhibition of ZIPK (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 366.24, ALogP 4.09, HBA 3, HBD 1, PSA 49.77, QED 0.84
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)c1nccs1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(N)=O)c1ccc(OCc2ccc(C(F)(F)F)cc2)cc1
InChIKey: AKRJOEANBCUPHB-CCDWMCETSA-N
Target: Genome polyprotein (SINGLE PROTEIN), dengue virus type 2
UniProt: P29990
Assay: Functional biochemical assay to identify treatments for viral infectious disease that targets Dengue virus type 2 NS2B-NS3 protease. Utilizing a direct enzyme activity measurement method, reading the fluorescence intensity is used to characterize the relative potency of inhibitors as IC50. Synthetic construct has been made based on Dengue virus type 2 (strain Thailand/16681/1984) by Centre for Medicines Discovery, University of Oxford, and the assay has been performed by Weizmann Institute of Science.The protocol is publicly available: dx.doi.org/10.17504/protocols.io.q26g7yebkgwz/v3
Measurement: IC50 = 1171 nM (pChEMBL 5.929999828338623)
Descriptors: MW 719.79, ALogP 2.06, HBA 9, HBD 8, PSA 240.43, QED 0.05
Compound (SMILES): O=C(O)C1CN(Cc2ccc(OCc3ccc(Cl)c(Cl)c3)cc2)C1
InChIKey: WAAWETUDFSIYSD-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21453
Assay: Modulation of S1PR1 (unknown origin)
Measurement: EC50 = 398.11 nM (pChEMBL 6.400000095367432)
Descriptors: MW 366.24, ALogP 4.09, HBA 3, HBD 1, PSA 49.77, QED 0.84
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)c1nccs1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(N)=O)c1ccc(OCc2ccc(C(F)(F)F)cc2)cc1
InChIKey: AKRJOEANBCUPHB-CCDWMCETSA-N
Target: Nonstructural protein 3 (SINGLE PROTEIN), Zika virus
UniProt: A0A024AXB9
Assay: Functional biochemical assay to identify treatments for viral infectious disease that targets Zika NS2B-NS3 protease. Utilizing a direct enzyme activity measurement method, reading the fluorescence intensity is used to characterize the relative potency of inhibitors as IC50. Synthetic construct has been made based on Zika virus (strain PRVABC59) by Centre for Medicines Discovery, University of Oxford, and the assay has been performed by Weizmann Institute of Science.The protocol is publicly available: dx.doi.org/10.17504/protocols.io.q26g7yebkgwz/v3
Measurement: IC50 = 2550 nM (pChEMBL 5.590000152587891)
Descriptors: MW 719.79, ALogP 2.06, HBA 9, HBD 8, PSA 240.43, QED 0.05
Compound (SMILES): O=C(O)C1CN(Cc2ccc(OCc3ccc(Cl)c(Cl)c3)cc2)C1
InChIKey: WAAWETUDFSIYSD-UHFFFAOYSA-N
Target: Histamine H1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35367
Assay: PDSP Secondary Binding target: HRH1 - Compounds are tested at 10 uM concentration, plate are incubated at room temperature in the dark for 90 minutes. Reaction are stopped by vacuum filtration onto 0.3% polyethyleneimine soaked filter mats using Filtermate harvester. Scintillation cocktail is then melted onto microwave-dried filters on a hot plate and the radio activity is counted in Microbia counter. Compounds showing a minimum of 50% inhibition at 10 uM concentration are carried forward in this secondary binding assay to determine equilibrium binding affinity.
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 366.24, ALogP 4.09, HBA 3, HBD 1, PSA 49.77, QED 0.84
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)c1nccs1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(N)=O)c1ccc(OCc2ccc(C(F)(F)F)cc2)cc1
InChIKey: AKRJOEANBCUPHB-CCDWMCETSA-N
Target: Genome polyprotein (SINGLE PROTEIN), dengue virus type 2
UniProt: P29990
Assay: Functional biochemical assay to identify treatments for viral infectious disease that targets Dengue virus type 2 NS2B-NS3 protease. Utilizing a direct enzyme activity measurement method, reading the fluorescence intensity is used to characterize the relative potency of inhibitors as IC50. Synthetic construct has been made based on Dengue virus type 2 (strain Thailand/16681/1984) by Centre for Medicines Discovery, University of Oxford, and the assay has been performed by Enamine biological services, Bienta Ltd.The protocol is publicly available: dx.doi.org/10.17504/protocols.io.kqdg32m87v25/v1
Measurement: IC50 = 2520 nM (pChEMBL 5.599999904632568)
Descriptors: MW 719.79, ALogP 2.06, HBA 9, HBD 8, PSA 240.43, QED 0.05
Compound (SMILES): O=C(O)C1CN(Cc2ccc(OCc3ccc(Cl)c(Cl)c3)cc2)C1
InChIKey: WAAWETUDFSIYSD-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: PDSP Secondary Binding target: HTR2A - Compounds are tested at 10 uM concentration, plate are incubated at room temperature in the dark for 90 minutes. Reaction are stopped by vacuum filtration onto 0.3% polyethyleneimine soaked filter mats using Filtermate harvester. Scintillation cocktail is then melted onto microwave-dried filters on a hot plate and the radio activity is counted in Microbia counter. Compounds showing a minimum of 50% inhibition at 10 uM concentration are carried forward in this secondary binding assay to determine equilibrium binding affinity.
Measurement: Ki = 4606.27 nM (pChEMBL 5.340000152587891)
Descriptors: MW 366.24, ALogP 4.09, HBA 3, HBD 1, PSA 49.77, QED 0.84
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)c1nccs1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(N)=O)c1ccc(OCc2ccc(C(F)(F)F)cc2)cc1
InChIKey: AKRJOEANBCUPHB-CCDWMCETSA-N
Target: Nonstructural protein 3 (SINGLE PROTEIN), Zika virus
UniProt: A0A024AXB9
Assay: Functional biochemical assay to identify treatments for viral infectious disease that targets Zika NS2B-NS3 protease. Utilizing a direct enzyme activity measurement method, reading the fluorescence intensity is used to characterize the relative potency of inhibitors as IC50. Synthetic construct has been made based on Zika virus (strain PRVABC59) by Centre for Medicines Discovery, University of Oxford, and the assay has been performed by Weizmann Institute of Science.The protocol is publicly available: dx.doi.org/10.17504/protocols.io.q26g7yebkgwz/v3
Measurement: IC50 = 2361 nM (pChEMBL 5.630000114440918)
Descriptors: MW 719.79, ALogP 2.06, HBA 9, HBD 8, PSA 240.43, QED 0.05
Compound (SMILES): O=C(O)C1CN(Cc2ccc(OCc3ccc(Cl)c(Cl)c3)cc2)C1
InChIKey: WAAWETUDFSIYSD-UHFFFAOYSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99720
Assay: PDSP Secondary Binding target: SIGMAR1 - Compounds are tested at 10 uM concentration, plate are incubated at room temperature in the dark for 90 minutes. Reaction are stopped by vacuum filtration onto 0.3% polyethyleneimine soaked filter mats using Filtermate harvester. Scintillation cocktail is then melted onto microwave-dried filters on a hot plate and the radio activity is counted in Microbia counter. Compounds showing a minimum of 50% inhibition at 10 uM concentration are carried forward in this secondary binding assay to determine equilibrium binding affinity.
Measurement: Ki = 487.52 nM (pChEMBL 6.309999942779541)
Descriptors: MW 366.24, ALogP 4.09, HBA 3, HBD 1, PSA 49.77, QED 0.84
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)c1nccs1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(N)=O)c1ccc(OCc2ccc(C(F)(F)F)cc2)cc1
InChIKey: AKRJOEANBCUPHB-CCDWMCETSA-N
Target: Genome polyprotein (SINGLE PROTEIN), dengue virus type 2
UniProt: P29990
Assay: Functional biochemical assay to identify treatments for viral infectious disease that targets Dengue virus type 2 NS2B-NS3 protease. Utilizing a direct enzyme activity measurement method, reading the fluorescence intensity is used to characterize the relative potency of inhibitors as IC50. Synthetic construct has been made based on Dengue virus type 2 (strain Thailand/16681/1984) by Centre for Medicines Discovery, University of Oxford, and the assay has been performed by Weizmann Institute of Science.The protocol is publicly available: dx.doi.org/10.17504/protocols.io.q26g7yebkgwz/v3
Measurement: IC50 = 1376 nM (pChEMBL 5.860000133514404)
Descriptors: MW 719.79, ALogP 2.06, HBA 9, HBD 8, PSA 240.43, QED 0.05
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)c1nccs1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(N)=O)c1ccc(OCc2ccc(C(F)(F)F)cc2)cc1
InChIKey: AKRJOEANBCUPHB-CCDWMCETSA-N
Target: Genome polyprotein (SINGLE PROTEIN), dengue virus type 2
UniProt: P29990
Assay: Functional biochemical assay to identify treatments for viral infectious disease that targets Dengue virus type 2 NS2B-NS3 protease. Utilizing a direct enzyme activity measurement method, reading the fluorescence intensity is used to characterize the relative potency of inhibitors as IC50. Synthetic construct has been made based on Dengue virus type 2 (strain Thailand/16681/1984) by Centre for Medicines Discovery, University of Oxford, and the assay has been performed by Enamine biological services, Bienta Ltd.The protocol is publicly available: dx.doi.org/10.17504/protocols.io.kqdg32m87v25/v1
Measurement: IC50 = 2308 nM (pChEMBL 5.639999866485596)
Descriptors: MW 719.79, ALogP 2.06, HBA 9, HBD 8, PSA 240.43, QED 0.05
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)c1nccs1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(N)=O)c1ccc(OCc2ccc(C(F)(F)F)cc2)cc1
InChIKey: AKRJOEANBCUPHB-CCDWMCETSA-N
Target: Nonstructural protein 3 (SINGLE PROTEIN), Zika virus
UniProt: A0A024AXB9
Assay: Functional biochemical assay to identify treatments for viral infectious disease that targets Zika NS2B-NS3 protease. Utilizing a direct enzyme activity measurement method, reading the fluorescence intensity is used to characterize the relative potency of inhibitors as IC50. Synthetic construct has been made based on Zika virus (strain PRVABC59) by Centre for Medicines Discovery, University of Oxford, and the assay has been performed by Weizmann Institute of Science.The protocol is publicly available: dx.doi.org/10.17504/protocols.io.q26g7yebkgwz/v3
Measurement: IC50 = 2736 nM (pChEMBL 5.559999942779541)
Descriptors: MW 719.79, ALogP 2.06, HBA 9, HBD 8, PSA 240.43, QED 0.05
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)c1nccs1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(N)=O)c1ccc(OCc2ccc(C(F)(F)F)cc2)cc1
InChIKey: AKRJOEANBCUPHB-CCDWMCETSA-N
Target: Genome polyprotein (SINGLE PROTEIN), dengue virus type 2
UniProt: P29990
Assay: Functional biochemical assay to identify treatments for viral infectious disease that targets Dengue virus type 2 NS2B-NS3 protease. Utilizing a direct enzyme activity measurement method, reading the fluorescence intensity is used to characterize the relative potency of inhibitors as IC50. Synthetic construct has been made based on Dengue virus type 2 (strain Thailand/16681/1984) by Centre for Medicines Discovery, University of Oxford, and the assay has been performed by Weizmann Institute of Science.The protocol is publicly available: dx.doi.org/10.17504/protocols.io.q26g7yebkgwz/v3
Measurement: IC50 = 1254 nM (pChEMBL 5.900000095367432)
Descriptors: MW 719.79, ALogP 2.06, HBA 9, HBD 8, PSA 240.43, QED 0.05
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)c1nccs1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(N)=O)c1ccc(OCc2ccc(C(F)(F)F)cc2)cc1
InChIKey: AKRJOEANBCUPHB-CCDWMCETSA-N
Target: Nonstructural protein 3 (SINGLE PROTEIN), Zika virus
UniProt: A0A024AXB9
Assay: Functional biochemical assay to identify treatments for viral infectious disease that targets Zika NS2B-NS3 protease. Utilizing a direct enzyme activity measurement method, reading the fluorescence intensity is used to characterize the relative potency of inhibitors as IC50. Synthetic construct has been made based on Zika virus (strain PRVABC59) by Centre for Medicines Discovery, University of Oxford, and the assay has been performed by Weizmann Institute of Science.The protocol is publicly available: dx.doi.org/10.17504/protocols.io.q26g7yebkgwz/v3
Measurement: IC50 = 2399 nM (pChEMBL 5.619999885559082)
Descriptors: MW 719.79, ALogP 2.06, HBA 9, HBD 8, PSA 240.43, QED 0.05
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)c1nccs1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(N)=O)c1ccc(OCc2ccc(C(F)(F)F)cc2)cc1
InChIKey: AKRJOEANBCUPHB-CCDWMCETSA-N
Target: Genome polyprotein (SINGLE PROTEIN), dengue virus type 2
UniProt: P29990
Assay: Functional biochemical assay to identify treatments for viral infectious disease that targets Dengue virus type 2 NS2B-NS3 protease. Utilizing a direct enzyme activity measurement method, reading the fluorescence intensity is used to characterize the relative potency of inhibitors as IC50. Synthetic construct has been made based on Dengue virus type 2 (strain Thailand/16681/1984) by Centre for Medicines Discovery, University of Oxford, and the assay has been performed by Enamine biological services, Bienta Ltd.The protocol is publicly available: dx.doi.org/10.17504/protocols.io.kqdg32m87v25/v1
Measurement: IC50 = 2486 nM (pChEMBL 5.599999904632568)
Descriptors: MW 719.79, ALogP 2.06, HBA 9, HBD 8, PSA 240.43, QED 0.05
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)c1nccs1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(N)=O)c1ccc(OCc2ccc(C(F)(F)F)cc2)cc1
InChIKey: AKRJOEANBCUPHB-CCDWMCETSA-N
Target: Genome polyprotein (SINGLE PROTEIN), dengue virus type 2
UniProt: P29990
Assay: Functional biochemical assay to identify treatments for viral infectious disease that targets Dengue virus type 2 NS2B-NS3 protease. Utilizing a direct enzyme activity measurement method, reading the fluorescence intensity is used to characterize the relative potency of inhibitors as IC50. Synthetic construct has been made based on Dengue virus type 2 (strain Thailand/16681/1984) by Centre for Medicines Discovery, University of Oxford, and the assay has been performed by Weizmann Institute of Science.The protocol is publicly available: dx.doi.org/10.17504/protocols.io.q26g7yebkgwz/v3
Measurement: IC50 = 1519 nM (pChEMBL 5.820000171661377)
Descriptors: MW 719.79, ALogP 2.06, HBA 9, HBD 8, PSA 240.43, QED 0.05
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)c1nccs1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(N)=O)c1ccc(OCc2ccc(C(F)(F)F)cc2)cc1
InChIKey: AKRJOEANBCUPHB-CCDWMCETSA-N
Target: Genome polyprotein (SINGLE PROTEIN), dengue virus type 2
UniProt: P29990
Assay: Functional biochemical assay to identify treatments for viral infectious disease that targets Dengue virus type 2 NS2B-NS3 protease. Utilizing a direct enzyme activity measurement method, reading the fluorescence intensity is used to characterize the relative potency of inhibitors as IC50. Synthetic construct has been made based on Dengue virus type 2 (strain Thailand/16681/1984) by Centre for Medicines Discovery, University of Oxford, and the assay has been performed by Enamine biological services, Bienta Ltd.The protocol is publicly available: dx.doi.org/10.17504/protocols.io.kqdg32m87v25/v1
Measurement: IC50 = 2928 nM (pChEMBL 5.53000020980835)
Descriptors: MW 719.79, ALogP 2.06, HBA 9, HBD 8, PSA 240.43, QED 0.05
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)c1nccs1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(N)=O)c1ccc(OCc2ccc(C(F)(F)F)cc2)cc1
InChIKey: AKRJOEANBCUPHB-CCDWMCETSA-N
Target: Nonstructural protein 3 (SINGLE PROTEIN), Zika virus
UniProt: A0A024AXB9
Assay: Functional biochemical assay to identify treatments for viral infectious disease that targets Zika NS2B-NS3 protease. Utilizing a direct enzyme activity measurement method, reading the fluorescence intensity is used to characterize the relative potency of inhibitors as IC50. Synthetic construct has been made based on Zika virus (strain PRVABC59) by Centre for Medicines Discovery, University of Oxford, and the assay has been performed by Weizmann Institute of Science.The protocol is publicly available: dx.doi.org/10.17504/protocols.io.q26g7yebkgwz/v3
Measurement: IC50 = 2154 nM (pChEMBL 5.670000076293945)
Descriptors: MW 719.79, ALogP 2.06, HBA 9, HBD 8, PSA 240.43, QED 0.05
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)c1nccs1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(N)=O)c1ccc(OCc2ccc(C(F)(F)F)cc2)cc1
InChIKey: AKRJOEANBCUPHB-CCDWMCETSA-N
Target: Genome polyprotein (SINGLE PROTEIN), dengue virus type 2
UniProt: P29990
Assay: Functional biochemical assay to identify treatments for viral infectious disease that targets Dengue virus type 2 NS2B-NS3 protease. Utilizing a direct enzyme activity measurement method, reading the fluorescence intensity is used to characterize the relative potency of inhibitors as IC50. Synthetic construct has been made based on Dengue virus type 2 (strain Thailand/16681/1984) by Centre for Medicines Discovery, University of Oxford, and the assay has been performed by Enamine biological services, Bienta Ltd.The protocol is publicly available: dx.doi.org/10.17504/protocols.io.kqdg32m87v25/v1
Measurement: IC50 = 2951 nM (pChEMBL 5.53000020980835)
Descriptors: MW 719.79, ALogP 2.06, HBA 9, HBD 8, PSA 240.43, QED 0.05
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)c1nccs1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(N)=O)c1ccc(OCc2ccc(C(F)(F)F)cc2)cc1
InChIKey: AKRJOEANBCUPHB-CCDWMCETSA-N
Target: NS3 (SINGLE PROTEIN), West Nile virus
UniProt: K4FQI5
Assay: Functional biochemical assay to identify treatments for viral infectious disease that targets West Nile NS2B-NS3 protease. Utilizing a direct enzyme activity measurement method, reading the fluorescence intensity is used to characterize the relative potency of inhibitors as IC50. Synthetic construct has been made based on West Nile virus (strain NY-99) by Centre for Medicines Discovery, University of Oxford, and the assay has been performed by Weizmann Institute of Science.The protocol is publicly available: dx.doi.org/10.17504/protocols.io.q26g7yebkgwz/v3
Measurement: IC50 = 1456 nM (pChEMBL 5.840000152587891)
Descriptors: MW 719.79, ALogP 2.06, HBA 9, HBD 8, PSA 240.43, QED 0.05
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)c1nccs1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(N)=O)c1ccc(OCc2ccc(C(F)(F)F)cc2)cc1
InChIKey: AKRJOEANBCUPHB-CCDWMCETSA-N
Target: NS3 protease (SINGLE PROTEIN), dengue virus type 1
UniProt: A0A0K0TQ28
Assay: Functional biochemical assay to identify treatments for viral infectious disease that targets Dengue virus type 1 NS2B-NS3 protease. Utilizing a direct enzyme activity measurement method, reading the fluorescence intensity is used to characterize the relative potency of inhibitors as IC50. Synthetic construct has been made based on Dengue virus type 1 (strain Nauru/West Pac/1974) by Centre for Medicines Discovery, University of Oxford, and the assay has been performed by Weizmann Institute of Science.The protocol is publicly available: dx.doi.org/10.17504/protocols.io.q26g7yebkgwz/v3
Measurement: IC50 = 1028 nM (pChEMBL 5.989999771118164)
Descriptors: MW 719.79, ALogP 2.06, HBA 9, HBD 8, PSA 240.43, QED 0.05
Compound (SMILES): COc1cc(OC)cc(N(c2ccc3ncc(-c4cnn(C)c4)nc3c2)C(C)CN)c1
InChIKey: SOYCCBHGJYSWNQ-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of FGFR3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 = 58.88 nM (pChEMBL 7.230000019073486)
Descriptors: MW 418.5, ALogP 3.53, HBA 8, HBD 1, PSA 91.32, QED 0.49
Compound (SMILES): CCN1CC(C)(C)Oc2nc(N3CC4CCC(C3)O4)nc(-c3ccc(NC(=O)OCCO)c(F)c3)c2C1=O
InChIKey: SQNJLBMCDJRSER-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Assay: The test detects the phosphorylation of the substrate GFP-4EBP1 using a terbium-labelled antibody that is specific for the phospho-Thr46 epitope. Binding of the Tb-antibody to the phosphorylated GFP peptide allows the transfer of energy from Tb, excited at 340 nm, to GFP with an increase in the fluorescence emission of the GFP at 520 nm. The test is performed in 96-well format (Corning/Costar 96 black flat-bottomed half-wells plate, ref. 3694) in a total volume of 30 ul. To 1 ul of inhibitor in 100% DMSO are added (final concentrations) 400 nM of GFP-4EBP1 (Invitrogen PV4759), 8 uM of ATP, 200 ng/ml of enzyme (human recombinant aa mTOR 1360-2549, Invitrogen PV4753) in a buffer of HEPES 50 mM pH 7.5, EGTA 1 mM, MnCl2 10 mM, BSA 0.1 mg/ml, glycerol 0.5%, NV-10 0.1 mg/ml, DTT 2 mM. The mixture is incubated for 30 minutes at room temperature. 10 ul of solution are taken up and the reaction is quenched by adding 10 ul of Tb-antibody solution (Invitrogen PV4757)/EDTA.
Measurement: IC50 = 123 nM (pChEMBL 6.909999847412109)
Descriptors: MW 529.57, ALogP 2.82, HBA 9, HBD 2, PSA 126.35, QED 0.58
Compound (SMILES): O=C(NC1CCN(Cc2ccccc2)C1)c1cccc(-c2n[nH]c3ccc(-c4nc[nH]n4)cc23)c1
InChIKey: RQSNBTLCFQVWGQ-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P45984
Assay: Inhibition of His6-tagged JNK2 (unknown origin) assessed as reduction in c-Jun phosphorylation using GST-c-Jun (1 to 79 residues) and [gamma32P]ATP incubated for 1 hr by scintillation counting assay
Measurement: IC50 <= 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 463.55, ALogP 4.02, HBA 5, HBD 3, PSA 102.59, QED 0.35
Compound (SMILES): OC(COc1cccc(OCc2ccccc2)c1)CN1CCc2ccccc2C1
InChIKey: WYHHSWYAZANDKQ-UHFFFAOYSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9BQA1
Assay: Inhibition of recombinant human fetal brain FLAG-tagged PRMT5/full length human testis 6His-tagged MEP50 expressed in baculovirus infected insect Sf9 cells using human histone H4 (1 to 15 residues) as substrate preincubated for 30 mins followed by [3H]-SAM addition
Measurement: IC50 = 1001 nM (pChEMBL 6)
Descriptors: MW 389.5, ALogP 4.06, HBA 4, HBD 1, PSA 41.93, QED 0.63
Compound (SMILES): CCc1cncc(-c2cc3c(cn2)cnn3-c2cccc(N3CCNCC(O)C3)n2)c1
InChIKey: QBMHBUSZNODSPS-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: Kinase Binding Assay: PIM-1, -2, and -3 enzymes were generated as fusion proteins expressed in bacteria and purified by IMAC column chromatography (Sun, X., Chiu, J. F., and He, Q. Y. (2005) Expert Rev. Proteomics, 2:649-657). A fluorescent-labeled Pim-specific peptide substrate, was custom synthesized by American Peptide Company (Sunnyvale, Calif.). Reaction Buffer contained 10 mM HEPES, pH 7.2, 10 mM MgCl2, 0.01% Tween 20, 2 mM DTT. Termination Buffer contained 190 mM HEPES, pH 7.2, 0.015% Brij-35, 0.2% Coating Reagent 3 (Caliper Life Sciences, Hopkinton, Mass.), 20 mM EDTA. Separation Buffer contained 100 mM HEPES, pH 7.2, 0.015% Brij-35, 0.1% Coating Reagent 3, 1:200 Coating Reagent 8 (Caliper Life Sciences, Hopkinton, Mass.), 10 mM EDTA and 5% DMSO.PIM reactions were carried out in a final volume of 10 uL per well in a 384-well plate. A standard enzymatic reaction, initiated by the addition of 5 uL 2Ã¿Â¿ATP and test compound to 5 uL of 2x enzyme and FAM-peptide, contained 20 uM PIM1, 50 uM PIM2, or 55 uM PIM3, 1 uM FAM-peptide, and 10 uM ATP, in Reaction Buffer. After 90 minutes of incubation at room temperature, the phosphorylation reaction was stopped by the addition of 10 uL Termination Buffer. The product and substrate in each independent reaction were separated on a 12-sipper microfluidic chip (Caliper Life Sciences, Hopkinton, Mass.) run on a Caliper LC3000 (Caliper Life Sciences, Hopkinton, Mass.). The separation of product and substrate was optimized by choosing voltages and pressure using Caliper's Optimizer software (Hopkinton, Mass.). The separation conditions used a downstream voltage of -500V, an upstream voltage of -2150V, and a screening pressure of -1.2 psi. The product and substrate fluorophore were excited at 488 nm and detected at 530 nm. Substrate conversion was calculated from the electropherogram using HTS Well Analyzer software (Caliper Life Sciences, Hopkinton, Mass.). Ki values for the test compound were calculated.
Measurement: Ki = 0.104 nM (pChEMBL 9.979999542236328)
Descriptors: MW 415.5, ALogP 2.21, HBA 8, HBD 2, PSA 91.99, QED 0.53
Compound (SMILES): O=C(CC1CCOC1)N1CCCC(Oc2ccc(NC(=O)N3Cc4ccncc4C3)cc2)C1
InChIKey: WCRWZAGXGQAXKF-UHFFFAOYSA-N
Target: Nicotinamide phosphoribosyltransferase (SINGLE PROTEIN), Homo sapiens
UniProt: P43490
Assay: Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) Binding Assay : Probe 2:The assay was carried out in 18 uL low volume plates (Owens Corning) in reaction buffer (50 mM HEPES (NaOH), pH 7.5, 100 mM NaCl, 10 mM MgCl2, 1 mM DTT, 1% Glycerol) using 6.8 nM recombinant, human, C-terminally-His tagged NAMPT, 1 nM Tb-anti-His antibody (Invitrogen, Cat #PV5895), and 200 nM probe (Oregon Green 488-conjugated APO0866; A-1287128.0. Plates were covered, and reactions were carried out for 2-3 hours. Plates were read with Envision (Laser Lantha low volume protocol) after 2 to 3 hours. Excitation was carried out at 337 nm, and the ratio of emission of Oregon Green (520 nm) to terbium (492 nm) was determined and used to calculate IC50 values of test compounds.
Measurement: IC50 = 76.7 nM (pChEMBL 7.119999885559082)
Descriptors: MW 450.54, ALogP 3.43, HBA 5, HBD 1, PSA 84, QED 0.75
Compound (SMILES): C[C@H]1Cc2c(nnn2-c2ncc(F)cn2)CN1C(=O)c1ccnc(C(F)(F)F)c1Cl
InChIKey: LJCBBTIERFXFGK-QMMMGPOBSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: FLIPR Assay: 1321 N1 cells expressing the recombinant human, rat or mouse P2X7 channel was cultured in HyQ DME/(HyClone/Dulbecco's Modified Eagle Medium) high glucose supplemented with 10% Fetal Bovine Serum (FBS) and appropriate selection marker. Cells were seeded at a density of 25000 cells/well (96-well clear bottom black walled plates) in 100 ul volume/well. On the day of the experiment, cell plates were washed with assay buffer, containing (in mM): 130 NaCl, 2 KCl, 1 CaCl2, 1 MgCl2, 10 HEPES, 5 glucose; pH 7.40 and 300 mOs. After the wash, cells were loaded with the Calcium-4 dye (Molecular Device) and incubated in the dark for 60 minutes. Test compounds were prepared at 250Ã¿ the test concentration in neat DMSO. Intermediate 96-well compound plates were prepared by transferring 1.2 uL of the compound into 300 uL of assay buffer. A further 3x dilution occurred when transferring 50 uL/well of the compound plate to 100 uL/well in the cell plate. Cells were incubateÂ  with test compounds and dye for 30 minutes. Calcium dye fluorescence was monitored in FLIPR as the cells were challenged by adding 50 uL/well of BzATP (final concentration is 250 uM BzATP (human and rat) or 600 (mouse)). The fluorescence change was measured 180 seconds after adding the agonist.
Measurement: IC50 = 20.4 nM (pChEMBL 7.690000057220459)
Descriptors: MW 441.78, ALogP 2.85, HBA 7, HBD 0, PSA 89.69, QED 0.57
Compound (SMILES): CCOc1ccc(C[C@@H](NC(=O)c2ccc(Cl)c(Cl)c2)C(=O)N[C@@H](Cc2ccccc2)C(=O)NCc2ccc(CN)cc2)cc1
InChIKey: MOIZOCHEDGLANE-AJQTZOPKSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: In Vitro Inhibition Assay: Plasma kallikrein inhibitory activity in vitro was determined using standard published methods (see e.g. Johansen et al., Int. J. Tiss. Reac. 1986, 8, 185; Shori et al., Biochem. Pharmacol., 1992, 43, 1209; Stiirzebecher et al., Biol. Chem. Hoppe-Seyler, 1992, 373, 1025). Human plasma kallikrein (Protogen) was incubated at 37° C. with the fluorogenic substrate H-DPro-Phe-Arg-AFC and various concentrations of the test compound. Residual enzyme activity (initial rate of reaction) was determined by measuring the change in optical absorbance at 410 nm and the IC50 value for the test compound was determined.
Measurement: IC50 = 175 nM (pChEMBL 6.760000228881836)
Descriptors: MW 647.6, ALogP 5.24, HBA 5, HBD 4, PSA 122.55, QED 0.15
Compound (SMILES): CC1=NOC(CN2CCC(CC#N)(n3cc(C(N)=O)c(Nc4ccnc(F)c4)n3)CC2)C1
InChIKey: GXHDNWXDNQBGRH-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: HTRF 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 uL of 1.11x enzyme and 1.11x substrate in 1x 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 uL of 10xATP in 1x assay buffer was added to initiate the kinase reaction and the plates were shaken and then incubated at room temperature for 120 minutes. At the end of the incubation, 20 uL of 2x stop buffer (streptavidin-Dylight 650 (Thermo #84547B/100 mL), Eu-tagged pY20 antibody (Perkin Elmer #AD0067), EDTA, HEPES, and Triton) was added to quench the reaction.
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 440.48, ALogP 2.13, HBA 9, HBD 2, PSA 134.45, QED 0.63
Compound (SMILES): COCCNC(=O)N1C(=O)N(c2cccc(C(F)F)c2)C2=C(C(=O)CC2)C1c1ccc(C#N)cc1
InChIKey: YLFLZXBUDAJXCY-UHFFFAOYSA-N
Target: Neutrophil elastase (SINGLE PROTEIN), Homo sapiens
UniProt: P08246
Assay: Neutrophil Elastase Assay: Materials: Human neutrophil elastase was purchased from Calbiochem (Cat. No.: 324681) and the elastase substrate MeOSuc-Ala-Ala-Pro-Val-AMC from Bachem (Cat. No.: I-1270). All other materials were of the highest grade commercially available. The following buffers were used: Compound buffer: 100 mM Tris, 500 mM NaCl, adjusted to pH 7.5; Assay buffer: 100 mM Tris, 500 mM NaCl, adjusted to pH 7.5, containing 0.01% BSA. Assay conditions: Test compounds were prediluted in DMSO and subsequently in compound buffer (5% DMSO final). 5 uL of these compound dilutions were mixed with 10 ul Neutrophil elastase (9 ng/ml in assay buffer) in a black 384 well OptiPlate (Perkin Elmer, Cat No.: 6007270) and incubated for 15 min at room temperature. Subsequently 10 uL substrate solution in assay buffer were added (250 uM final concentration) and the plates were incubated for 60 min at room temperature. After inactivation of the enzyme, fluorescence intensities were measured at 380 nm excitation and 460 nm emission wavelengths. Each plate contains wells with a high value control (DMSO+enzyme+substrate) and wells with a low value control (DMSO+inactivated enzyme+substrate). IC50 values were estimated using a sigmoidal concentration response curve with variable slope.
Measurement: IC50 < 1 nM (pChEMBL 9)
Descriptors: MW 480.47, ALogP 4.45, HBA 5, HBD 1, PSA 102.74, QED 0.62
Compound (SMILES): O=C(Nc1nc(-c2ccncc2)cs1)N1CCN(C(=O)c2ccco2)CC1
InChIKey: NJOCNWCGLUKBIZ-UHFFFAOYSA-N
Target: Rho-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13464
Assay: Inhibition Assay: Attention was focused on exploring, in turn, the SAR around the phenyl ring A, branching and substitution at the benzylic position, urea linkage of 1aa, without varying the [4-(4-pyridinyl)-2-thiazolyl] terminus (FIG. 4). The [4-(4-pyridinyl)-2-thiazolyl] group was believed to act as a hinge-binding moiety with the nitrogen of the pyridyl H-bonding to the back bone NH of the hinge Met156, as seen in the crystal complex of ROCK1 with Fasudil (PDB ID 2ESM) (Jacobs, et al., The structure of dimeric ROCK I reveals the mechanism for ligand selectivity, J Biol Chem, 2006, 281:260-8).All compounds were systematically screened against ROCK1 and ROCK2. IC50 values were systematically determined only for compounds that inhibit 40% of ROCK1 kinase activities at 50 μM.
Measurement: IC50 = 35050 nM (pChEMBL 4.460000038146973)
Descriptors: MW 383.43, ALogP 2.79, HBA 6, HBD 1, PSA 91.57, QED 0.75
Compound (SMILES): CSCC[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CCC(N)=O)NC(=O)CCNC(=O)CN1CCN(CC(=O)O)CCN(CC(=O)O)CCN(CC(=O)O)CC1)C(C)C)C(N)=O
InChIKey: OKVBZLIYEWXGDZ-RQEMYVTLSA-N
Target: Gastrin-releasing peptide receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30550
Assay: Displacement of [125I]-BBN from GRPR in human PC3 cells after 1 hr by compuGamma counting or microplate scintillation counting method
Measurement: IC50 = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 1397.63
Compound (SMILES): Cc1ccc2[nH]nc(-c3ccccc3)c2c1
InChIKey: BKFJFOATAKURAK-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P45984
Assay: Inhibition of His6-tagged JNK2 (unknown origin) assessed as reduction in c-Jun phosphorylation using GST-c-Jun (1 to 79 residues) and [gamma32P]ATP incubated for 1 hr by scintillation counting assay
Measurement: IC50 <= 10000 nM (pChEMBL 5)
Descriptors: MW 208.26, ALogP 3.54, HBA 1, HBD 1, PSA 28.68, QED 0.65
Compound (SMILES): CN1CCOc2cc(N(C(=O)c3cc(-c4cc5c(cc4C(=O)N4Cc6ccccc6C[C@H]4CN4CCOCC4)OCCO5)n4c3CCCC4)c3ccc(O)cc3)ccc21
InChIKey: ZDSMEUKVBPFEEU-DHUJRADRSA-N
Target: Apoptosis regulator Bcl-2 (SINGLE PROTEIN), Mus musculus
UniProt: P10417
Assay: Fluorescence Polarisation Assay: The fluorescence polarisation tests were carried out on microplates (384 wells). The Bcl-2 protein, at a final concentration of 2.50×10−8 M, is mixed with a fluorescent peptide (Fluorescein-REIGAQLRRMADDLNAQY), at a final concentration of 1.00×10−8 M in a buffer solution (Hepes 10 mM, NaCl 150 mM, Tween20 0.05%, pH 7.4), in the presence or in the absence of increasing concentrations of test compounds. After incubation for 2 hours, the fluorescence polarisation is measured.
Measurement: IC50 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 795.94, ALogP 6.67, HBA 10, HBD 1, PSA 109.18, QED 0.19