lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cn1nccc1CN1CCC(NS(=O)(=O)c2ccc(Cl)cc2C(=O)O)CC1
InChIKey: PUMSMOJYYSIKGI-UHFFFAOYSA-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 > 99500 nM (pChEMBL 4.001999855041504)
Descriptors: MW 412.9, ALogP 1.71, HBA 6, HBD 2, PSA 104.53, QED 0.75
Compound (SMILES): C[C@H](C(=O)O)N(C)C(=O)c1cc(Cl)cc(NC(=O)OCc2ccccc2)c1
InChIKey: BDFMPRXUUQXYAG-GFCCVEGCSA-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 > 99500 nM (pChEMBL 4.001999855041504)
Descriptors: MW 390.82, ALogP 3.63, HBA 4, HBD 2, PSA 95.94, QED 0.78
Compound (SMILES): O=C(Nc1ccc2c(c1)CNC2)c1ccc2ncsc2c1
InChIKey: WOBUXKXPKQOMFV-UHFFFAOYSA-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 = 997 nM (pChEMBL 6)
Descriptors: MW 295.37, ALogP 3.15, HBA 4, HBD 2, PSA 54.02, QED 0.76
Compound (SMILES): O=C(Nc1ccc2c(c1)CN[C@H]2C[C@H](O)CO)c1cc(Cl)cc2[nH]ncc12
InChIKey: JAXXULLETZFXPQ-GUYCJALGSA-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 > 99500 nM (pChEMBL 4.001999855041504)
Descriptors: MW 386.84, ALogP 2.36, HBA 5, HBD 5, PSA 110.27, QED 0.46
Compound (SMILES): O=C1Cc2c(cccc2C(=O)Nc2ccc3c(c2)CNCCC3)N1
InChIKey: DTBNIIIJXPCKLX-UHFFFAOYSA-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 = 569 nM (pChEMBL 6.25)
Descriptors: MW 321.38, ALogP 2.47, HBA 3, HBD 3, PSA 70.23, QED 0.8
Compound (SMILES): CCOc1cccc(-c2ccc(S(=O)(=O)Nc3cc(F)c(Cl)cc3C(=O)O)cc2)c1
InChIKey: ZVFVGHHUGNPVHP-UHFFFAOYSA-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 = 5088 nM (pChEMBL 5.289999961853027)
Descriptors: MW 449.89, ALogP 5.04, HBA 4, HBD 2, PSA 92.7, QED 0.53
Compound (SMILES): CC(C)(C)OC(=O)NCc1cccc(NC(=O)[C@@H](NC(=O)OCc2ccccc2)c2cccc(O)c2)c1
InChIKey: ILEFLSMALAQHJP-DEOSSOPVSA-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 > 99500 nM (pChEMBL 4.001999855041504)
Descriptors: MW 505.57, ALogP 5.02, HBA 6, HBD 4, PSA 125.99, QED 0.34
Compound (SMILES): Cc1cc(NC(=O)c2cc(C3CC3)n(C)c2C)ccc1OC1CCOCC1
InChIKey: UYVPSPACZXQYLS-UHFFFAOYSA-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 Enamine biological services, Bienta Ltd.The protocol is publicly available: dx.doi.org/10.17504/protocols.io.36wgqn273gk5/v1
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 368.48, ALogP 4.33, HBA 4, HBD 1, PSA 52.49, QED 0.85
Compound (SMILES): CN(C)CCNC(=O)[C@H](NC(=O)OCc1ccccc1)c1ccc(OCc2ccccc2)cc1
InChIKey: WAWOOGLUPSLJEX-RUZDIDTESA-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 > 99500 nM (pChEMBL 4.001999855041504)
Descriptors: MW 461.56, ALogP 3.91, HBA 5, HBD 2, PSA 79.9, QED 0.45
Compound (SMILES): NCc1ccc2c(c1)CCC[C@H]2NCc1cc(Cl)cc2c1OCC2
InChIKey: JDWUTUZUPJGYFC-LJQANCHMSA-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 > 99500 nM (pChEMBL 4.001999855041504)
Descriptors: MW 342.87, ALogP 3.9, HBA 3, HBD 2, PSA 47.28, QED 0.89
Compound (SMILES): O=C(Nc1cc2c(cn1)CNC2)c1cc(F)cc2[nH]ncc12
InChIKey: JJFSNAIZYWNQHJ-UHFFFAOYSA-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 > 99500 nM (pChEMBL 4.001999855041504)
Descriptors: MW 297.29, ALogP 1.95, HBA 4, HBD 3, PSA 82.7, QED 0.67
Compound (SMILES): C=CC[C@H]1NCc2cc(NCc3cc(Cl)cc4[nH]ncc34)ccc21
InChIKey: KLPDBLCEXHGTCN-GOSISDBHSA-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 > 99500 nM (pChEMBL 4.001999855041504)
Descriptors: MW 338.84, ALogP 4.55, HBA 3, HBD 3, PSA 52.74, QED 0.6
Compound (SMILES): O=C1Nc2ncccc2C[C@H]1NCc1n[nH]c2ccccc12
InChIKey: FSKOZYMAHWOVOV-CYBMUJFWSA-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 > 99500 nM (pChEMBL 4.001999855041504)
Descriptors: MW 293.33, ALogP 1.61, HBA 4, HBD 3, PSA 82.7, QED 0.68
Compound (SMILES): Cc1ccc(NC(=O)c2cc(Cl)cc(NC(=O)OCc3ccccc3)c2)cc1CN
InChIKey: SJZTVWLKQSUBJS-UHFFFAOYSA-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 > 99500 nM (pChEMBL 4.001999855041504)
Descriptors: MW 423.9, ALogP 5.11, HBA 4, HBD 3, PSA 93.45, QED 0.51
Compound (SMILES): O=C1Cc2c(cccc2C(=O)NC2CC3(CCOCC3)C2)N1
InChIKey: GFMJKYAJOMOKBT-UHFFFAOYSA-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 > 99500 nM (pChEMBL 4.001999855041504)
Descriptors: MW 300.36, ALogP 1.87, HBA 3, HBD 2, PSA 67.43, QED 0.88
Compound (SMILES): CC[C@H](Cc1nnn[nH]1)c1ccc(NC(=O)c2cc(Cl)cc(C3CC3)c2)cc1
InChIKey: IRYWFLURZGVJRL-CYBMUJFWSA-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 = 35070 nM (pChEMBL 4.460000038146973)
Descriptors: MW 395.89, ALogP 4.72, HBA 4, HBD 2, PSA 83.56, QED 0.61
Compound (SMILES): Cc1c(C(=O)Nc2cccc(-c3ccccc3)c2)cc(C2CC2)n1C
InChIKey: OPZNOPVKYFZWBY-UHFFFAOYSA-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 > 24950 nM (pChEMBL 4.603000164031982)
Descriptors: MW 330.43, ALogP 5.13, HBA 2, HBD 1, PSA 34.03, QED 0.71
Compound (SMILES): CCn1nccc1-c1cn(CC)c(=O)c(N2CC[C@@H](CO)C2)n1
InChIKey: MSLMHBOVTNUGLU-GFCCVEGCSA-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 > 99500 nM (pChEMBL 4.001999855041504)
Descriptors: MW 317.39, ALogP 0.97, HBA 7, HBD 1, PSA 76.18, QED 0.89
Compound (SMILES): N[C@@H]1CC[C@H](NC(=O)c2cc(Cl)cc(NC(=O)OCc3ccccc3)c2)C1
InChIKey: FDDZYYUGMXTWBY-SJORKVTESA-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 > 99500 nM (pChEMBL 4.001999855041504)
Descriptors: MW 387.87, ALogP 3.7, HBA 4, HBD 3, PSA 93.45, QED 0.73
Compound (SMILES): NCc1cccc(NC(=O)C[C@H](NC(=O)OCc2ccccc2)C2CCCCC2)c1
InChIKey: UDFJLXVTLYRNIH-QFIPXVFZSA-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 = 83138 nM (pChEMBL 4.079999923706055)
Descriptors: MW 409.53, ALogP 4.35, HBA 4, HBD 3, PSA 93.45, QED 0.6
Compound (SMILES): O=C(Nc1ccc2c(c1)CNC2)c1cc(F)cc2[nH]c(-c3ccccc3)nc12
InChIKey: DWEGWCUYPPIYDT-UHFFFAOYSA-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 = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 372.4, ALogP 4.22, HBA 3, HBD 3, PSA 69.81, QED 0.5
Compound (SMILES): Cc1c(C(=O)Nc2cc(C#N)cn(C)c2=O)cc(C2CC2)n1C
InChIKey: GNJNNUJBZBJHPG-UHFFFAOYSA-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 > 99500 nM (pChEMBL 4.001999855041504)
Descriptors: MW 310.36, ALogP 2.03, HBA 5, HBD 1, PSA 79.82, QED 0.94
Compound (SMILES): CN(c1ccc(Oc2ccccc2Cl)cc1)S(=O)(=O)c1cc(F)c(Cl)cc1C(=O)O
InChIKey: NPFUYAOAIZCKKF-UHFFFAOYSA-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 = 65370 nM (pChEMBL 4.179999828338623)
Descriptors: MW 470.31, ALogP 5.45, HBA 4, HBD 1, PSA 83.91, QED 0.52
Compound (SMILES): NCc1ccccc1NC(=O)c1cc(Cl)cc(NC(=O)OCc2ccccc2)c1
InChIKey: VUNICXDPCANBMY-UHFFFAOYSA-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 > 99500 nM (pChEMBL 4.001999855041504)
Descriptors: MW 409.87, ALogP 4.8, HBA 4, HBD 3, PSA 93.45, QED 0.54
Compound (SMILES): CC(C)(CO)NC(=O)[C@@H](NC(=O)OCc1ccccc1)c1ccc(OCc2ccccc2)cc1
InChIKey: PLXVJANPEAWACM-DEOSSOPVSA-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 > 99500 nM (pChEMBL 4.001999855041504)
Descriptors: MW 462.55, ALogP 4.12, HBA 5, HBD 3, PSA 96.89, QED 0.42
Compound (SMILES): c1cncc(C2CC(NCc3n[nH]c4ccccc34)C2)c1
InChIKey: RDPDGBRXNMSFNX-UHFFFAOYSA-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 > 99500 nM (pChEMBL 4.001999855041504)
Descriptors: MW 278.36, ALogP 2.99, HBA 3, HBD 2, PSA 53.6, QED 0.77
Compound (SMILES): Cc1cc(C=O)c(C)n1-c1cccc(C(=O)N2CCN(C)CC2)c1
InChIKey: POFABYWETIJGLM-UHFFFAOYSA-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 > 99500 nM (pChEMBL 4.001999855041504)
Descriptors: MW 325.41, ALogP 2.29, HBA 4, HBD 0, PSA 45.55, QED 0.81
Compound (SMILES): N[C@H]1CCN(c2ccc(NS(=O)(=O)c3ccc(Oc4ccccc4Cl)cc3)cc2)C1
InChIKey: HNAUEEOENMXDHD-INIZCTEOSA-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 = 37302 nM (pChEMBL 4.429999828338623)
Descriptors: MW 443.96, ALogP 4.47, HBA 5, HBD 2, PSA 84.66, QED 0.59
Compound (SMILES): O=C(Nc1ccc2c(c1)CNC2)c1cc(F)cc2[nH]c(CCc3cccnc3)nc12
InChIKey: UJVXFUWJRHZUBL-UHFFFAOYSA-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 > 99500 nM (pChEMBL 4.001999855041504)
Descriptors: MW 401.45, ALogP 3.74, HBA 4, HBD 3, PSA 82.7, QED 0.48
Compound (SMILES): O=C1Cc2c(cccc2C(=O)N[C@H]2CCc3cnccc32)N1
InChIKey: BIRHOJRSFDRTMZ-HNNXBMFYSA-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 > 99500 nM (pChEMBL 4.001999855041504)
Descriptors: MW 293.33, ALogP 1.99, HBA 3, HBD 2, PSA 71.09, QED 0.89
Compound (SMILES): C[C@](O)(Cc1cc(Cl)cc(NC(=O)OCc2ccccc2)c1)c1cccc(CN)c1
InChIKey: XZOMWXSKVPACEE-DEOSSOPVSA-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 > 99500 nM (pChEMBL 4.001999855041504)
Descriptors: MW 424.93, ALogP 5, HBA 4, HBD 3, PSA 84.58, QED 0.5
Compound (SMILES): NCc1cccc(NC(=O)[C@H](NC(=O)OCc2ccccc2)c2ccc(OCC3CCC3)cc2)c1
InChIKey: OWBHMGMUDMUENH-AREMUKBSSA-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 = 48807 nM (pChEMBL 4.309999942779541)
Descriptors: MW 473.57, ALogP 4.93, HBA 5, HBD 3, PSA 102.68, QED 0.39
Compound (SMILES): C[C@@H](O)[C@H]1C(=O)N2C(C(=O)[O-])=C(S[C@@H]3CN[C@H](C(=O)Nc4cccc(C(=O)O)c4)C3)[C@H](C)[C@H]12.O.[Na+]
InChIKey: KWOXKQSTIUMDIS-SHZCTIMHSA-M
Target: ATP-binding cassette sub-family C member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92887
Assay: Inhibition of human MRP2 overexpressed in Sf9 cell membrane vesicles assessed as uptake of [3H]-estradiol-17beta-D-glucuronide in presence of ATP and GSH measured after 20 mins by membrane vesicle transport assay
Measurement: IC50 = 56200 nM (pChEMBL 4.25)
Descriptors: MW 475.52, ALogP 0.94, HBA 7, HBD 5, PSA 156.27, QED 0.36
Compound (SMILES): CCN1C[C@]2(COC)[C@H](O)C[C@H](OC)[C@@]34[C@@H]5C[C@@]6(O)[C@H](OC(=O)c7ccccc7)[C@@H]5[C@@](OC(C)=O)([C@@H]([C@H](OC)[C@H]23)[C@@H]14)[C@@H](O)[C@@H]6OC
InChIKey: XFSBVAOIAHNAPC-NPVHKAFCSA-N
Target: DNA topoisomerase 2-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P11388
Assay: Inhibition of Topo IIalpha (unknown origin)
Measurement: IC50 = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 645.75, ALogP 0.65, HBA 12, HBD 3, PSA 153.45, QED 0.32
Compound (SMILES): C=C1[C@H](CO)[C@@H](O)C[C@@H]1n1cnc2c(=O)[nH]c(N)nc21.O
InChIKey: YXPVEXCTPGULBZ-WQYNNSOESA-N
Target: Core antigen (SINGLE PROTEIN), Hepatitis B virus
UniProt: Q03732
Assay: Inhibition of hepatitis B virus capsid assembly infected in human HepG2.215 cells assessed as reduction in viral DNA replication measured on day 7 by real time PCR analysis
Measurement: EC50 = 0.24 nM (pChEMBL 9.619999885559082)
Descriptors: MW 277.28, ALogP -0.83, HBA 7, HBD 4, PSA 130.05, QED 0.53
Compound (SMILES): CO[C@H]1O[C@H](COS(=O)(=O)[O-])[C@@H](O[C@@H]2O[C@@H](C(=O)[O-])[C@@H](O[C@H]3O[C@H](COS(=O)(=O)[O-])[C@@H](O[C@@H]4O[C@H](C(=O)[O-])[C@@H](O[C@H]5O[C@H](COS(=O)(=O)[O-])[C@@H](OC)[C@H](OC)[C@H]5OC)[C@H](OC)[C@H]4OC)[C@H](OS(=O)(=O)[O-])[C@H]3OS(=O)(=O)[O-])[C@H](OC)[C@H]2OC)[C@H](OS(=O)(=O)[O-])[C@H]1OS(=O)(=O)[O-].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+]
InChIKey: MVPQUSQUURLQKF-MCPDASDXSA-E
Target: Antithrombin-III (SINGLE PROTEIN), Homo sapiens
UniProt: P01008
Assay: Binding affinity to antithrombin 3
Measurement: Kd = 1 nM (pChEMBL 9)
Descriptors: MW 1529.35
Compound (SMILES): Nc1ccn(C[C@@H](CO)OCP(=O)(O)O)c(=O)n1.O.O
InChIKey: FPKARFMSZDBYQF-ILKKLZGPSA-N
Target: Solute carrier family 22 member 6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q4U2R8
Assay: TP_TRANSPORTER: inhibition of 6-Carboxyfluorescein uptake in OAT1-expressing CHO cells
Measurement: IC50 = 60000 nM (pChEMBL 4.21999979019165)
Descriptors: MW 279.19, ALogP -1.66, HBA 7, HBD 4, PSA 147.9, QED 0.45
Compound (SMILES): CC(=O)O.CC(=O)O.CC/N=C(\NCC)NCCCC[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CCCCN/C(=N/CC)NCC)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CO)NC(=O)[C@@H](Cc1cccnc1)NC(=O)[C@@H](Cc1ccc(Cl)cc1)NC(=O)[C@@H](Cc1ccc2ccccc2c1)NC(C)=O)C(=O)N1CCC[C@H]1C(=O)N[C@H](C)C(N)=O
InChIKey: OVBICQMTCPFEBS-SATRDZAXSA-N
Target: Gonadotropin-releasing hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30968
Assay: Antagonism of human GnHR receptor, determined in a reporter gene assay in HEK293 cells
Measurement: IC50 = 3.6 nM (pChEMBL 8.4399995803833)
Descriptors: MW 1570.35
Compound (SMILES): Cc1ccc(N2c3cccc(C(=O)Nc4ccc(OCC(F)(F)F)nc4)c3OC[C@@H]2CO)nc1
InChIKey: QZUCKCLSVBFSOS-INIZCTEOSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NER1
Assay: Antagonist activity at human recombinant TPRV1
Measurement: IC50 = 236 nM (pChEMBL 6.630000114440918)
Descriptors: MW 474.44, ALogP 3.87, HBA 7, HBD 2, PSA 96.81, QED 0.56
Compound (SMILES): COc1cc(Cl)ccc1CCNC(=O)c1ccc(Oc2cc3c(cc2Cl)[C@@H](C(=O)O)CCO3)cc1
InChIKey: QIDYUNXQPQEJEC-IBGZPJMESA-N
Target: Prostaglandin D2 receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Y4
Assay: Binding Inhibition Assay (4% HSA): The coding sequence of human DP2 was introduced into the human Leukemic cell line K562 by electroporation and stable clones expressing DP2 were obtained by limiting dilution followed by cell surface staining with a rat monoclonal antibody specific for human DP2. Membranes were prepared from one of these DP2 expressing clones and used to determine the ability of compounds of the present invention to inhibit binding of prostaglandin D2 (PGD2) to its receptor DP2 in the presence of one or more of the following serum protein concentrations, 4% HSA, by the following procedure. Membranes (1.25 μg/well for 4% HSA) were mixed with 3H-labeled PGD2 and various concentrations of test compounds in 150 μL of binding buffer (50 mM Tris-HCl, pH 7.4, 40 mM MgCl2, 0.1% bovine serum albumin, 0.1% NaN3) in 96-well U-bottom polypropylene plates. After incubation for 60 minutes at room temperature, the assay was transferred to a filtration plate (#MAFB; Millipore Corporation, Bedford, Mass.), and washed three times with binding buffer. Radioactivity was measured by a scintillation counter (TopCount; PerkinElmer Life Sciences, Boston, Mass.). Nonspecific binding was determined by incubations in the presence of 1 μM unlabeled PGD2 or 5 μM of a known DP2 antagonist. EC50 values for inhibition of binding were determined for each compound tested from the inflexion point of a standard 4-parameter logistical curve fitted to the values obtained. Compounds of the invention had EC50 values less than 5 micromolar in one or more of the binding assays.
Measurement: EC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 516.38, ALogP 5.72, HBA 5, HBD 2, PSA 94.09, QED 0.4
Compound (SMILES): CC[C@H]1[C@@H]2C[C@H]3[C@@H]4N(C)c5ccccc5[C@]45C[C@@H]([C@@H]2[C@H]5O)N3[C@@H]1O
InChIKey: CJDRUOGAGYHKKD-OVXZWHIBSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: DRUGMATRIX: CYP450, 2D6 enzyme inhibition (substrate: 3-Cyano-7-ethoxycoumarin)
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 326.44, ALogP 1.55, HBA 4, HBD 2, PSA 46.94, QED 0.82
Compound (SMILES): CC1(C)COc2ccc(F)cc2CN2c3nc4c(cnn4cc3OC[C@H]2C(F)F)C(=O)N1
InChIKey: ILAMRXVQSGVCJX-AWEZNQCLSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of wild type ALK (unknown origin)
Measurement: IC50 = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 447.42, ALogP 2.8, HBA 7, HBD 1, PSA 80.99, QED 0.62
Compound (SMILES): Cc1ccc2c(-c3nc(Nc4cc(CN5C[C@@H](C)N[C@@H](C)C5)cc(C5CC5)c4)ncc3Cl)c[nH]c2c1
InChIKey: FZLSDZZNPXXBBB-KDURUIRLSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Evaluation of Kinase Inhibitory Activity: The inhibitory activity of some of the compounds described above against FLT3-ITD, FLT3 wild type (WT), VEGFR2 (KDR), and SYK kinase was measured. The inhibitory activity of the compounds against mutant proteins, such as FLT3 VVT and ITD, was evaluated based on the LanthaScreen technology developed by Thermo Fisher Scientific Inc. This assay is based on the binding of Alexa Fluor® 647-labeled, ATP-competitive kinase inhibitor (kinase tracer-236) to kinase, and signals of fluorescence resonance energy transfer (FRET) were measured in the presence of europium-conjugated antibody. This experiment was carried out on a 384-well plate in conditions including 50 mM HEPES pH 7.5, 0.01% BRIJ-35, 10 mM MgCl2, 1 mM EGTA, and 1% DMSO. After measuring the background signal in the absence of proteins such as FLT3 or FLT3-ITD and measuring the non-inhibition signal by adding only the solvent (1% DMSO), an evaluation compound was used at a set concentration (for example, 50 nM to 0.05 nM, 1:10 dilution) to calculate the kinase inhibitory activity of the evaluation compound as IC50.
Measurement: IC50 = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 501.08, ALogP 6.39, HBA 5, HBD 3, PSA 68.87, QED 0.29
Compound (SMILES): CNc1cc(Nc2cccn(-c3ccccn3)c2=O)nc2c(C(=O)N[C@@H]3CC[C@H]3OC)cnn12
InChIKey: BWINBHTTZLVXGT-NVXWUHKLSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Binding affinity to JAK1 JH2 (unknown origin) assessed as dissociation constant
Measurement: Kd = 5000 nM (pChEMBL 5.300000190734863)
Descriptors: MW 460.5, ALogP 1.97, HBA 10, HBD 3, PSA 127.47, QED 0.38
Compound (SMILES): Cc1nc(N2CCC3(CC2)CO[C@@H](C)[C@H]3N)c(CO)nc1Sc1ccnc(N)c1Cl
InChIKey: HISJAYUQVHMWTA-BLLLJJGKSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: Inhibition of wild type SHP2 (unknown origin)
Measurement: IC50 = 1.29 nM (pChEMBL 8.890000343322754)
Descriptors: MW 451, ALogP 2.39, HBA 9, HBD 3, PSA 123.41, QED 0.64
Compound (SMILES): CNC(=O)c1cc2c(Oc3ccc(NC(=O)C4(C(=O)Nc5ccc(F)cc5)CC4)cc3)ccnc2cc1OC
InChIKey: JSPCKALGNNVYOO-UHFFFAOYSA-N
Target: Tyrosine-protein kinase receptor UFO (SINGLE PROTEIN), Homo sapiens
UniProt: P30530
Assay: Inhibition of AXL (unknown origin) by HTRF kinase assay
Measurement: IC50 = 5.8 nM (pChEMBL 8.239999771118164)
Descriptors: MW 528.54, ALogP 4.89, HBA 6, HBD 3, PSA 118.65, QED 0.28
Compound (SMILES): COc1cc2nccc(Oc3ccc(NC(=O)c4cc5c(n(-c6ccccc6)c4=O)CCCC5=O)nc3)c2cc1OC
InChIKey: WHMMKPWGWNYYFE-UHFFFAOYSA-N
Target: Tyrosine-protein kinase receptor UFO (SINGLE PROTEIN), Homo sapiens
UniProt: P30530
Assay: Inhibition of AXL (unknown origin) by HTRF kinase assay
Measurement: IC50 = 0.7 nM (pChEMBL 9.149999618530273)
Descriptors: MW 562.58, ALogP 5.36, HBA 9, HBD 1, PSA 121.64, QED 0.28
Compound (SMILES): CC(C)C[C@@H](C(=O)N1C[C@]2(C[C@H]1C#N)C(=O)Nc1ccccc12)N(C)C(=O)c1cc2c(F)cc(F)c(F)c2[nH]1
InChIKey: ZVSKSJFRHVXDPS-JNFGOLMQSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Biological Activity: SARS-CoV-2 3C-like (3CL) protease fluorescence assay (FRET): Recombinant SARS-CoV-2 3CL-protease was expressed and purified. TAMRA-SITSAVLQSGFRKMK-Dabcyl-OH peptide 3CLpro substrate was synthesized. Black, low volume, round-bottom, 384 well microplates were used. In a typical assay, 0.85 μL of test compound was dissolved in DMSO then incubated with SARS-CoV-2 3CL-protease (10 nM) in 10 μL assay buffer (50 mM HEPES [pH 7.5], 1 mM DTT, 0.01% BSA, 0.01% Triton-X 100) for 30 min at RT. Next, 10 μL of 3CL-protease substrate (40 μM) in assay buffer was added and the assays were monitored continuously for 1 h in an Envision multimode plate reader operating in fluorescence kinetics mode with excitation at 540 nm and emission at 580 nm at RT. No compound (DMSO only) and no enzyme controls were routinely included in each plate. All experiments were run in duplicate. Data Analysis: SARS-CoV-2 3CL-protease enzyme activity was measured as initial velocity of the linear phase (RFU/s) and normalized to controlled samples DMSO (100% activity) and no enzyme (0% activity) to determine percent residual activity at various concentrations of test compounds (0-10 μM). Data were fitted to normalized activity (variable slope) versus concentration fit in GraphPad Prism 7 to determine IC50.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 537.54, ALogP 4.09, HBA 4, HBD 2, PSA 109.3, QED 0.48
Compound (SMILES): NCc1nccc(-c2cc(COc3ccccc3CC(=O)O)cc3ccoc23)c1F
InChIKey: AUARNXJEAZFQCQ-UHFFFAOYSA-N
Target: Complement factor D (SINGLE PROTEIN), Homo sapiens
UniProt: P00746
Assay: Factor D Esterolytic Assay: An established esterolytic assay for the measurement of Factor D activity and inhibition of Factor D activity was used (Kam, C. M.; McRae, B. J.; Harper, J. W.; Niemann, M. A.; Volanakis, J. E.; Powers, J. C. Human complement proteins D, C2, and B Active site mapping with peptide thioester substrates. J Biol. Chem. 1987, 262, 3444-3451). For this assay Z-Lys-SBzl, 1.29 mM (Kim, S.; Narayana, S. V. L; Volanakis, J. E. Mutational analysis of the substrate binding site of human complement Factor D. Biochemistry. 1994, 33, 14393-14399.) was used as the substrate for Factor D (104 mM). Hydrolysis of this compound by Factor D liberated a free sulfhydryl group which is then reacted with 5,5′-dithiobis(2nitrobenzoic acid) producing an intense yellow color (Habeeb, A. F. S. A. Reaction of protein sulfhydryl groups with Ellman's Reagent. Methods in Enzymol. 1976, 25, 457-464). The assays were performed in 96 well microtiter plates and rates of hydrolysis were monitored at 405 nm on a Biotek Synergy H1 plate reader. Hydrolysis rates were reported as change in mOD/min. The assay was conducted in 100 mM HEPES, 500 mM NaCl, pH 7.5 containing 10% DMSO in a final volume of 50 μL per well.
Measurement: IC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 406.41, ALogP 4.3, HBA 5, HBD 2, PSA 98.58, QED 0.47
Compound (SMILES): CC(C)(Cc1cc2c(-c3ccc(C#N)cc3)cncc2s1)C(=O)O
InChIKey: QWCZAFGDQBUAFT-UHFFFAOYSA-N
Target: Solute carrier family 22 member 12 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96S37
Assay: hURAT1 Inhibition Assay: Human embryonic kidney cells (HEK293) was incubated in DMEM tissue culture medium, at 37° C., under 5% CO2 and 95% air atmosphere. TransIT-293 transfection agent (MIRUS BIO, Cat. No. MIR2706) and model URAT1 were used to construct transfected HEK293 cells. Transfected HEK293/hURAT1 cells were used to the test for 14C-uric acid transport activity. HEK293/hURAT1 cells were seeded in a 96-well plate (BD, Cat. No. 356461) fully coating with poly-D-lysine at a density of 6×104 cells per well. Cells were incubated at 37° C. for at least 12 hrs in the calorstat, and then washed with pre-heated washing buffer (125 mM sodium gluconate, 10 mM HEPES pH=7.4) at an amount of 200 μL per well to wash out the culture medium. The uric acid [8-14C] (ARC, Cat. No. ARC0513-250UCI) containing or not containing the compound was added to 50 μL HBSS buffer which was free of chloric ion each well (HBSS buffer: 125 mM sodium gluconate, 4.8 mM potassium gluconate, 1.3 mM calcium gluconate, 1.2 mM potassium dihydrogen phosphate, 1.2 mM magnesium sulfate, 5.6 mM glucose, 25 mM HEPES pH=7.4) to make the specific concentration of the uric acid 1 μCi per well. The incubating solution was removed after 10 mins incubation, followed by adding 100 μL cold washing buffer, after washing with this buffer for 3 times, the buffer was completely removed from the well. 50 μL Lysis buffer (0.1 mM NaOH) was added to each well, and transferred to a 96-well plate (PERKIN ELMER, Cat. No. 6005040) containing scintillation fluid after 5 mins, and counted by MicroBeta Trilux (PerkinElmer) to give IC50 value eventually.
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 336.42, ALogP 4.49, HBA 4, HBD 1, PSA 73.98, QED 0.76
Compound (SMILES): C=C(C)[C@@H]1CC[C@]2(NCCN3CCS(=O)(=O)CC3)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC=C(C6=CC[C@](COc7ncccc7C#N)(C(=O)O)CC6)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
InChIKey: PQBROJOHKLMPKM-WJGXRGGQSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 (unknown origin)
Measurement: IC50 > 4400 nM (pChEMBL 5.35699987411499)
Descriptors: MW 827.19, ALogP 8.78, HBA 8, HBD 2, PSA 132.62, QED 0.22
Compound (SMILES): Cc1c(C(=O)O)ccc2c3n(nc12)[C@@H]1[C@H](C3)N(CC2CC2)[C@@]2(C(=O)Nc3cc(Cl)ccc32)[C@H]1c1cccc(Cl)c1F
InChIKey: AMTXDBGKYPDTTA-SJVQGLCSSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: AlphaScreen Assay: 15 μL of compound in 20% DMSO (serial pre-dilutions of compound are done in 100% DMSO) is pipetted to the wells of a white OptiPlate-96 (Perkin Elmer). A mix consisting of 20 nM GST-MDM2 protein (aa 23-117) and 20 nM biotinylated p53 wt peptide (encompassing aa 16-27 of wt human p53, amino acid sequence QETFSDLWKLLP-Ttds-Lys-Biotin, molecular weight 2132.56 g/mol) is prepared in assay buffer (50 mM Tris/HCl pH 7.2; 120 mM NaCl; 0.1% bovine serum albumin (BSA); 5 mM dithiothreitol (DTT); 1 mM ethylenediaminetetraacetic acid (EDTA); 0.01% Tween 20). 30 μL of the mix is added to the compound dilutions and incubated for 15 min at rt while gently shaking the plate at 300 rounds per minute (rpm). Subsequently, 15 μL of premixed AlphaLISA Glutathione Acceptor Beads and AlphaScreen Streptavidin Donor Beads from PerkinElmer (in assay buffer at a concentration of 10 μg/mL each) are added and the samples are incubated for 30 min at rt in the dark (shaking 300 rpm). Afterwards, the signal is measured in a PerkinElmer Envision HIS Multilabel Reader using the AlphaScreen protocol from Perkin Elmer.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 591.47, ALogP 6.31, HBA 5, HBD 2, PSA 87.46, QED 0.29
Compound (SMILES): NC(=O)c1c(N)nn2ccc(N3C[C@@H](F)C[C@@H]3c3cc(F)ccc3F)nc12
InChIKey: YFTARXQOKASKBW-JOYOIKCWSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: Inhibitory Activity Assay: TrkA, TrkB and TrkC:A testing platform for TrkA, TrkB and TrkC kinase activity was established based on Homogeneous Time-Resolved Fluorescence (HTRF) assay, and the activities of the compounds were tested using the platform. The compounds were subjected to three-fold gradient dilution with 100% DMSO with a starting concentration of 1 mM (11 concentrations in total). 4 μL of diluted sample for each concentration was added to 96 μL of reaction buffer (50 mM HEPES, pH7.4, 5 mM MgCl2, 1 mM NaVO3, 0.001% Tween-20, 0.01% BSA and 1 mM DTT) and mixed homogeneously to be used as a 4* compound. The reaction buffer was used to formulate 2* TrkA, TrkB and TrkC kinases (purchased from Carna Biosciences 08-186, 08-187, 08-197, and the final concentrations thereof were 0.5 nM, 0.1 nM, and 1 nM, respectively) and 4* substrate mixture (ATP+TK peptide) (wherein the final concentrations of ATP were 40 μM, 50 μM, and 20 μM, respectively; TK peptide, HTRF® KinEASE-TK, was purchased from Cisbio, and the final concentration thereof was 100 nM) for use. 2.5 μL of the 4* compound was added to a 384-well plate (OptiPlate-384, purchased from PerkinElmer), and then 5 μL of the 2* TrkA, TrkB and TrkC kinases were added, and mixed homogeneously by centrifugation. Then 2.5 μL of the 4* substrate mixture was added to initiate the reaction (the total reaction volume is 10 μL). The 384-well plate was placed in an incubator and incubated for 60 min at 23° C. Then the reaction was terminated by adding 5 μL of Eu3+ cryptate-labeled anti-phosphotyrosine antibody (HTRF® KinEASE-TK, purchased from Cisbio), and 5 μL of Streptavidin-XL-665 (HTRF® KinEASE-TK, purchased from Cisbio). After incubated for 1 hr in the incubator, the fluorescence values were read on Envision (purchased from PerkinElmer).
Measurement: IC50 < 1 nM (pChEMBL 9)
Descriptors: MW 376.34, ALogP 1.98, HBA 6, HBD 2, PSA 102.54, QED 0.73
Compound (SMILES): O=C(c1nc2n(n1)[C@H](c1ccccc1)C[C@@H]2F)C1CC1
InChIKey: LMXPZWQVDDSYHH-RYUDHWBXSA-N
Target: Receptor-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13546
Assay: Enzyme Assay: The ability of the receptor interacting protein kinase (RIPK1) to catalyze the hydrolysis of adenosine-5′-triphosphate (ATP) is monitored using the Transcreener ADP (adenosine-5′-diphosphate) assay (BellBrook Labs). Purified human RIP1 kinase domain (2-375) (50 nM) derived from a baculovirus-infected insect cell expression system is incubated with test compounds for 2 hours in 50 mM Hepes buffer (pH 7.5) containing 30 mM MgCl2, 1 mM dithiothreitol, 50 μM ATP, 0.002% Brij-35, and 0.5% dimethyl sulfoxide (DMSO). Reactions are quenched by the addition of 1× Bell Brooks Stop buffer B (20 mM Hepes (ph 7.5), 40 mM ethylenediaminetetraacetic acid and 0.02% Brij-35) containing an additional 12 mM EDTA and 55 ug/mL ADP2 antibody and 4 nM ADP-AlexaFluor® 633 tracer. The tracer bound to the antibody is displaced by the ADP generated during the RIP1K reaction, which causes a decrease in fluorescence polarization that is measured by laser excitation at 633 nm with a FP microplate reader M1000.
Measurement: Ki = 3.6 nM (pChEMBL 8.4399995803833)
Descriptors: MW 271.3, ALogP 2.87, HBA 4, HBD 0, PSA 47.78, QED 0.81