lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CCc1cc2c(cc1-c1cnn(CC(=O)N(C)C)c1)C(C)(C)c1[nH]c3cc(C#N)ccc3c1C2=O
InChIKey: IDGNCVHQDDOPND-UHFFFAOYSA-N
Target: EML4-ALK (CHIMERIC PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of EML4-ALK S1206Y mutant (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 465.56, ALogP 4.42, HBA 5, HBD 1, PSA 94.78, QED 0.48
Compound (SMILES): COCCN1CCC(CNC(=O)c2n[nH]c3ccc(-c4cccc(F)c4F)cc23)CC1
InChIKey: QCLXNOBXQUWUEW-UHFFFAOYSA-N
Target: Beta-adrenergic receptor kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P25098
Assay: Inhibition of human recombinant GRK2 by LANCE assay
Measurement: IC50 = 530 nM (pChEMBL 6.28000020980835)
Descriptors: MW 428.48, ALogP 3.6, HBA 4, HBD 2, PSA 70.25, QED 0.6
Compound (SMILES): CN(C)Cc1cccc(OCc2ccc3ccc(N)nc3c2)c1
InChIKey: NTASSNARMLLQTN-UHFFFAOYSA-N
Target: Nitric oxide synthase, inducible (SINGLE PROTEIN), Homo sapiens
UniProt: P35228
Assay: Enzyme Assay: Rat and human nNOS, murine macrophage iNOS, and human eNOS were recombinant enzymes (expressed in E. coli and purified as reported previously in the literature). To test for NOS inhibition, the hemoglobin capture assay was used to measure nitric oxide production. The assay was performed at 37° C. in HEPES buffer (100 mM with 10% glycerol, pH 7.4) in the presence of 10 μM L-arginine. Also included were 100 μM NADPH, 0.83 mM CaCl2, approximately 320 units/mL of calmodulin, 10 μM H4B, and human oxyhemoglobin (3 μM). For iNOS, the CaCl2 and calmodulin were omitted and replaced with HEPES buffer (neither are required for activation of iNOS). The assay was performed in 96-well plates using a Synergy 4 BioTek hybrid reader. The dispensing of NOS enzyme and hemoglobin were automated, and after 30 sec (maximum delay), NO production was read by monitoring the absorbance at 401 nm (resulting from conversion of oxyhemoglobin to methemoglobin). Kinetic readouts were performed for 5 min. Each compound was assayed at least in duplicate, and six to nine concentrations (500 μM-50 nM or 100 μM-10 nM for eNOS and iNOS; 50 μM to 5 nM for rat and human nNOS) were used to construct dose-response curves. IC50 values were calculated by non-linear regression (variable slope, four parameters) using GraphPad Prism software, and Ki values were obtained using the Cheng-Prusoff equation [Ki=IC50/(1+[S]/Km)] with the following Km values: 1.3 μM (rat nNOS), 1.6 μM (human nNOS), 8.2 μM (murine macrophage iNOS), and 3.9 (human eNOS).
Measurement: Ki = 7410 nM (pChEMBL 5.130000114440918)
Descriptors: MW 307.4, ALogP 3.46, HBA 4, HBD 1, PSA 51.38, QED 0.78
Compound (SMILES): CNCc1cncc(OCc2ccc3ccc(N)nc3c2)c1
InChIKey: CCVIETYDINGXSM-UHFFFAOYSA-N
Target: Nitric oxide synthase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P29475
Assay: Enzyme Assay: Rat and human nNOS, murine macrophage iNOS, and human eNOS were recombinant enzymes (expressed in E. coli and purified as reported previously in the literature). To test for NOS inhibition, the hemoglobin capture assay was used to measure nitric oxide production. The assay was performed at 37° C. in HEPES buffer (100 mM with 10% glycerol, pH 7.4) in the presence of 10 μM L-arginine. Also included were 100 μM NADPH, 0.83 mM CaCl2, approximately 320 units/mL of calmodulin, 10 μM H4B, and human oxyhemoglobin (3 μM). For iNOS, the CaCl2 and calmodulin were omitted and replaced with HEPES buffer (neither are required for activation of iNOS). The assay was performed in 96-well plates using a Synergy 4 BioTek hybrid reader. The dispensing of NOS enzyme and hemoglobin were automated, and after 30 sec (maximum delay), NO production was read by monitoring the absorbance at 401 nm (resulting from conversion of oxyhemoglobin to methemoglobin). Kinetic readouts were performed for 5 min. Each compound was assayed at least in duplicate, and six to nine concentrations (500 μM-50 nM or 100 μM-10 nM for eNOS and iNOS; 50 μM to 5 nM for rat and human nNOS) were used to construct dose-response curves. IC50 values were calculated by non-linear regression (variable slope, four parameters) using GraphPad Prism software, and Ki values were obtained using the Cheng-Prusoff equation [Ki=IC50/(1+[S]/Km)] with the following Km values: 1.3 μM (rat nNOS), 1.6 μM (human nNOS), 8.2 μM (murine macrophage iNOS), and 3.9 (human eNOS).
Measurement: Ki = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 294.36, ALogP 2.51, HBA 5, HBD 2, PSA 73.06, QED 0.76
Compound (SMILES): CS(=O)(=O)Cc1cccc(Nc2nccc(Oc3ccc4c(C(=O)Nc5ccccc5)cccc4c3)n2)c1
InChIKey: KOFXELGVKHKUJR-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of human recombinant EGFR T790M/L858R mutant expressed in baculovirus using Poly (Glu,Tyr) as substrate after 60 mins by ELISA
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 524.6, ALogP 5.96, HBA 7, HBD 2, PSA 110.28, QED 0.26
Compound (SMILES): CS(=O)(=O)Cc1cccc(Nc2nccc(Oc3ccc4c(C(=O)Nc5cccc(F)c5)cccc4c3)n2)c1
InChIKey: GUUYUIDTJAWAHO-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of human recombinant EGFR T790M/L858R mutant expressed in baculovirus using Poly (Glu,Tyr) as substrate after 60 mins by ELISA
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 542.59, ALogP 6.1, HBA 7, HBD 2, PSA 110.28, QED 0.24
Compound (SMILES): CS(=O)(=O)Cc1cccc(Nc2nccc(Oc3ccc4c(C(=O)Nc5cccnc5)cccc4c3)n2)c1
InChIKey: HAWQJVUHZAYNCF-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of human recombinant EGFR T790M/L858R mutant expressed in baculovirus using Poly (Glu,Tyr) as substrate after 60 mins by ELISA
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 525.59, ALogP 5.36, HBA 8, HBD 2, PSA 123.17, QED 0.28
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 = 19014 nM (pChEMBL 4.71999979019165)
Descriptors: MW 719.79, ALogP 2.06, HBA 9, HBD 8, PSA 240.43, QED 0.05
Compound (SMILES): COc1cc(Br)cc2c1nc(C)c1c(C)nc(-c3ccc(F)nc3)n12
InChIKey: PZAJISDCIZCGIB-UHFFFAOYSA-N
Target: Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HCR9
Assay: Inhibition of human PDE11A using [3H]cAMP as substrate after 30 mins by scintillation proximity assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 401.24, ALogP 4.47, HBA 5, HBD 0, PSA 52.31, QED 0.47
Compound (SMILES): COc1cc(-c2ccc(F)nc2)cc2c1nc(C)c1c(C)nc(-c3ccc(F)nc3)n12
InChIKey: OTKDXQUDAQCPRM-UHFFFAOYSA-N
Target: Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HCR9
Assay: Inhibition of human PDE11A using [3H]cAMP as substrate after 30 mins by scintillation proximity assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 417.42, ALogP 4.91, HBA 6, HBD 0, PSA 65.2, QED 0.39
Compound (SMILES): COc1cc(Br)cc2c1nc(C)c1c(C)nc(-c3cccnc3F)n12
InChIKey: RMWWNYKNAPEPNW-UHFFFAOYSA-N
Target: Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HCR9
Assay: Inhibition of human PDE11A using [3H]cAMP as substrate after 30 mins by scintillation proximity assay
Measurement: IC50 = 494 nM (pChEMBL 6.309999942779541)
Descriptors: MW 401.24, ALogP 4.47, HBA 5, HBD 0, PSA 52.31, QED 0.47
Compound (SMILES): COc1cc(-c2cccnc2)cc2c1nc(C)c1c(C)nc(-c3cccnc3)n12
InChIKey: JOJOWCOCCMULDU-UHFFFAOYSA-N
Target: Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HCR9
Assay: Inhibition of human PDE11A using [3H]cAMP as substrate after 30 mins by scintillation proximity assay
Measurement: IC50 = 286 nM (pChEMBL 6.539999961853027)
Descriptors: MW 381.44, ALogP 4.63, HBA 6, HBD 0, PSA 65.2, QED 0.46
Compound (SMILES): COc1cc(-c2ccc(F)nc2)cc2c1nc(C)c1c(C)nc(-c3ccncc3)n12
InChIKey: VEYWHNZHTOXBLT-UHFFFAOYSA-N
Target: Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HCR9
Assay: Inhibition of human PDE11A using [3H]cAMP as substrate after 30 mins by scintillation proximity assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 399.43, ALogP 4.77, HBA 6, HBD 0, PSA 65.2, QED 0.41
Compound (SMILES): COc1cc(-c2ccc(F)nc2)cc2c1nc(C)c1c(C)nc(-c3cccnc3)n12
InChIKey: ZTLRRRPDWBCINJ-UHFFFAOYSA-N
Target: Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HCR9
Assay: Inhibition of human PDE11A using [3H]cAMP as substrate after 30 mins by scintillation proximity assay
Measurement: IC50 = 286 nM (pChEMBL 6.539999961853027)
Descriptors: MW 399.43, ALogP 4.77, HBA 6, HBD 0, PSA 65.2, QED 0.41
Compound (SMILES): COc1cc(-c2ccncc2)cc2c1nc(C)c1c(C)nc(-c3ccc(F)nc3)n12
InChIKey: JAWKANDWMZNIHM-UHFFFAOYSA-N
Target: Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HCR9
Assay: Inhibition of human PDE11A using [3H]cAMP as substrate after 30 mins by scintillation proximity assay
Measurement: IC50 = 413 nM (pChEMBL 6.380000114440918)
Descriptors: MW 399.43, ALogP 4.77, HBA 6, HBD 0, PSA 65.2, QED 0.41
Compound (SMILES): COc1cc(-c2cccnc2)cc2c1nc(C)c1c(C)nc(-c3ccc(F)nc3)n12
InChIKey: MTAOOMYAOJQXKB-UHFFFAOYSA-N
Target: Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HCR9
Assay: Inhibition of human PDE11A using [3H]cAMP as substrate after 30 mins by scintillation proximity assay
Measurement: IC50 = 395 nM (pChEMBL 6.400000095367432)
Descriptors: MW 399.43, ALogP 4.77, HBA 6, HBD 0, PSA 65.2, QED 0.41
Compound (SMILES): COc1cc(-c2cccnc2)cc2c1nc(C)c1c(C)nc(-c3cccnc3F)n12
InChIKey: JOKHDDDMDHGDNV-UHFFFAOYSA-N
Target: Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HCR9
Assay: Inhibition of human PDE11A using [3H]cAMP as substrate after 30 mins by scintillation proximity assay
Measurement: IC50 = 457 nM (pChEMBL 6.340000152587891)
Descriptors: MW 399.43, ALogP 4.77, HBA 6, HBD 0, PSA 65.2, QED 0.41
Compound (SMILES): Cc1ccc(C(=O)O)c(C)c1NC(=O)c1cc(-c2cccc(Cl)c2)cc2ccccc12
InChIKey: SIIGKILIYGRIJN-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 429.9, ALogP 6.73, HBA 2, HBD 2, PSA 66.4, QED 0.38
Compound (SMILES): O=C(O)C1CN(Cc2ccc(OCc3ccc(Cl)c(Cl)c3)cc2)C1
InChIKey: WAAWETUDFSIYSD-UHFFFAOYSA-N
Target: RAC-gamma serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y243
Assay: Inhibition of AKT3 (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): CCOC(=O)C1=C(CN2CCOCC2)NC(c2nccs2)=NC1c1ccc(F)cc1Br
InChIKey: SQGRDKSRFFUBBU-UHFFFAOYSA-N
Target: Core antigen (SINGLE PROTEIN), Hepatitis B virus
UniProt: Q03732
Assay: Inhibition of reverse transcriptase M204I mutant expressing lamivudine-resistant hepatitis B virus capsid assembly in human Huh7 cells assessed as reduction in intracellular DNA levels measured on day 7 by real-time PCR analysis
Measurement: EC50 = 92 nM (pChEMBL 7.039999961853027)
Descriptors: MW 509.4, ALogP 3.29, HBA 8, HBD 1, PSA 76.05, QED 0.6
Compound (SMILES): CC1(C)c2cc(C3CCN(CC4CCOCC4)CC3)ccc2C(=O)c2c1[nH]c1cc(C#N)ccc21
InChIKey: VWCZORWQNKCYGE-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P16234
Assay: Inhibition of N-terminal His6-tagged recombinant human PDGFRalpha (550 residues) expressed in insect Sf21 cells using poly(Glu,Tyr)4:1 as substrate incubated for 60 mins by ELISA
Measurement: IC50 = 402 nM (pChEMBL 6.400000095367432)
Descriptors: MW 467.61, ALogP 5.52, HBA 4, HBD 1, PSA 69.12, QED 0.55
Compound (SMILES): CCc1cc2c(cc1-c1cnn(CC(=O)N(C)C)c1)C(C)(C)c1[nH]c3cc(C#N)ccc3c1C2=O
InChIKey: IDGNCVHQDDOPND-UHFFFAOYSA-N
Target: Casein kinase II subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P68400
Assay: Inhibition of CSNK2A1 (unknown origin)
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 465.56, ALogP 4.42, HBA 5, HBD 1, PSA 94.78, QED 0.48
Compound (SMILES): COCCN1CCC(CNC(=O)c2n[nH]c3ccc(-c4cccc(F)c4F)cc23)CC1
InChIKey: QCLXNOBXQUWUEW-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in CHOK1 cells assessed as reduction in tail current by measuring tail current amplitude measured after deploarization to +20 mV for 2s followed by 1s pulse to -40 mV by whole cell patch clamp assay
Measurement: IC50 = 44 nM (pChEMBL 7.360000133514404)
Descriptors: MW 428.48, ALogP 3.6, HBA 4, HBD 2, PSA 70.25, QED 0.6
Compound (SMILES): CN(C)Cc1cccc(OCc2ccc3ccc(N)nc3c2)c1
InChIKey: NTASSNARMLLQTN-UHFFFAOYSA-N
Target: Nitric oxide synthase 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P29476
Assay: Enzyme Assay: Rat and human nNOS, murine macrophage iNOS, and human eNOS were recombinant enzymes (expressed in E. coli and purified as reported previously in the literature). To test for NOS inhibition, the hemoglobin capture assay was used to measure nitric oxide production. The assay was performed at 37° C. in HEPES buffer (100 mM with 10% glycerol, pH 7.4) in the presence of 10 μM L-arginine. Also included were 100 μM NADPH, 0.83 mM CaCl2, approximately 320 units/mL of calmodulin, 10 μM H4B, and human oxyhemoglobin (3 μM). For iNOS, the CaCl2 and calmodulin were omitted and replaced with HEPES buffer (neither are required for activation of iNOS). The assay was performed in 96-well plates using a Synergy 4 BioTek hybrid reader. The dispensing of NOS enzyme and hemoglobin were automated, and after 30 sec (maximum delay), NO production was read by monitoring the absorbance at 401 nm (resulting from conversion of oxyhemoglobin to methemoglobin). Kinetic readouts were performed for 5 min. Each compound was assayed at least in duplicate, and six to nine concentrations (500 μM-50 nM or 100 μM-10 nM for eNOS and iNOS; 50 μM to 5 nM for rat and human nNOS) were used to construct dose-response curves. IC50 values were calculated by non-linear regression (variable slope, four parameters) using GraphPad Prism software, and Ki values were obtained using the Cheng-Prusoff equation [Ki=IC50/(1+[S]/Km)] with the following Km values: 1.3 μM (rat nNOS), 1.6 μM (human nNOS), 8.2 μM (murine macrophage iNOS), and 3.9 (human eNOS).
Measurement: Ki = 39 nM (pChEMBL 7.409999847412109)
Descriptors: MW 307.4, ALogP 3.46, HBA 4, HBD 1, PSA 51.38, QED 0.78
Compound (SMILES): CNCc1cncc(OCc2ccc3ccc(N)nc3c2)c1
InChIKey: CCVIETYDINGXSM-UHFFFAOYSA-N
Target: Nitric oxide synthase 1 (SINGLE PROTEIN), Mus musculus
UniProt: Q9Z0J4
Assay: Enzyme Assay: Rat and human nNOS, murine macrophage iNOS, and human eNOS were recombinant enzymes (expressed in E. coli and purified as reported previously in the literature). To test for NOS inhibition, the hemoglobin capture assay was used to measure nitric oxide production. The assay was performed at 37° C. in HEPES buffer (100 mM with 10% glycerol, pH 7.4) in the presence of 10 μM L-arginine. Also included were 100 μM NADPH, 0.83 mM CaCl2, approximately 320 units/mL of calmodulin, 10 μM H4B, and human oxyhemoglobin (3 μM). For iNOS, the CaCl2 and calmodulin were omitted and replaced with HEPES buffer (neither are required for activation of iNOS). The assay was performed in 96-well plates using a Synergy 4 BioTek hybrid reader. The dispensing of NOS enzyme and hemoglobin were automated, and after 30 sec (maximum delay), NO production was read by monitoring the absorbance at 401 nm (resulting from conversion of oxyhemoglobin to methemoglobin). Kinetic readouts were performed for 5 min. Each compound was assayed at least in duplicate, and six to nine concentrations (500 μM-50 nM or 100 μM-10 nM for eNOS and iNOS; 50 μM to 5 nM for rat and human nNOS) were used to construct dose-response curves. IC50 values were calculated by non-linear regression (variable slope, four parameters) using GraphPad Prism software, and Ki values were obtained using the Cheng-Prusoff equation [Ki=IC50/(1+[S]/Km)] with the following Km values: 1.3 μM (rat nNOS), 1.6 μM (human nNOS), 8.2 μM (murine macrophage iNOS), and 3.9 (human eNOS).
Measurement: Ki = 25700 nM (pChEMBL 4.590000152587891)
Descriptors: MW 294.36, ALogP 2.51, HBA 5, HBD 2, PSA 73.06, QED 0.76
Compound (SMILES): CS(=O)(=O)Cc1cccc(Nc2nccc(Oc3ccc4c(C(=O)Nc5ccccc5)cccc4c3)n2)c1
InChIKey: KOFXELGVKHKUJR-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase Src (SINGLE PROTEIN), Homo sapiens
UniProt: P12931
Assay: Inhibition of c-Src (unknown origin) using Poly (Glu,Tyr) as substrate after 60 mins by ELISA
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 524.6, ALogP 5.96, HBA 7, HBD 2, PSA 110.28, QED 0.26
Compound (SMILES): CS(=O)(=O)Cc1cccc(Nc2nccc(Oc3ccc4c(C(=O)Nc5cccc(F)c5)cccc4c3)n2)c1
InChIKey: GUUYUIDTJAWAHO-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase Src (SINGLE PROTEIN), Homo sapiens
UniProt: P12931
Assay: Inhibition of c-Src (unknown origin) using Poly (Glu,Tyr) as substrate after 60 mins by ELISA
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 542.59, ALogP 6.1, HBA 7, HBD 2, PSA 110.28, QED 0.24
Compound (SMILES): CS(=O)(=O)Cc1cccc(Nc2nccc(Oc3ccc4c(C(=O)Nc5cccnc5)cccc4c3)n2)c1
InChIKey: HAWQJVUHZAYNCF-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase Src (SINGLE PROTEIN), Homo sapiens
UniProt: P12931
Assay: Inhibition of c-Src (unknown origin) using Poly (Glu,Tyr) as substrate after 60 mins by ELISA
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 525.59, ALogP 5.36, HBA 8, HBD 2, PSA 123.17, QED 0.28
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 = 1535 nM (pChEMBL 5.809999942779541)
Descriptors: MW 719.79, ALogP 2.06, HBA 9, HBD 8, PSA 240.43, QED 0.05
Compound (SMILES): Cc1ccc(C(=O)O)c(C)c1NC(=O)c1cc(-c2cccc(Cl)c2)cc2ccccc12
InChIKey: SIIGKILIYGRIJN-UHFFFAOYSA-N
Target: Cytochrome P450 2B6 (SINGLE PROTEIN), Homo sapiens
UniProt: P20813
Assay: Inhibition of CYP2B6 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 429.9, ALogP 6.73, HBA 2, HBD 2, PSA 66.4, QED 0.38
Compound (SMILES): O=C(O)C1CN(Cc2ccc(OCc3ccc(Cl)c(Cl)c3)cc2)C1
InChIKey: WAAWETUDFSIYSD-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of ALK (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): CCOC(=O)C1=C(CN2CCOCC2)NC(c2nccs2)=NC1c1ccc(F)cc1Br
InChIKey: SQGRDKSRFFUBBU-UHFFFAOYSA-N
Target: Core antigen (SINGLE PROTEIN), Hepatitis B virus
UniProt: Q03732
Assay: Inhibition of lamivudine-resistant wild type hepatitis B virus capsid assembly in human Huh7 cells assessed as reduction in intracellular DNA levels measured on day 7 by real-time PCR analysis
Measurement: EC50 = 34 nM (pChEMBL 7.46999979019165)
Descriptors: MW 509.4, ALogP 3.29, HBA 8, HBD 1, PSA 76.05, QED 0.6
Compound (SMILES): CC1(C)c2cc(C3CCN(CC4CCOCC4)CC3)ccc2C(=O)c2c1[nH]c1cc(C#N)ccc21
InChIKey: VWCZORWQNKCYGE-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Inhibition of N-terminal His6-tagged recombinant human PDGFRbeta (557 residues) expressed in insect Sf21 cells using poly(Glu,Tyr)4:1 as substrate incubated for 60 mins by ELISA
Measurement: IC50 = 64.2 nM (pChEMBL 7.190000057220459)
Descriptors: MW 467.61, ALogP 5.52, HBA 4, HBD 1, PSA 69.12, QED 0.55
Compound (SMILES): CCc1cc2c(cc1-c1cnn(CC(=O)N(C)C)c1)C(C)(C)c1[nH]c3cc(C#N)ccc3c1C2=O
InChIKey: IDGNCVHQDDOPND-UHFFFAOYSA-N
Target: Interleukin-1 receptor-associated kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P51617
Assay: Inhibition of IRAK1 (unknown origin)
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 465.56, ALogP 4.42, HBA 5, HBD 1, PSA 94.78, QED 0.48
Compound (SMILES): COCCN1CCC(CNC(=O)c2n[nH]c3ccc(-c4cccc(F)c4F)cc23)CC1
InChIKey: QCLXNOBXQUWUEW-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: In Vitro Assay: Activity on human GSK-3β was assessed using the following methods (according to Meijer et al., Chem. Biol., 2003-10:1255-1266).In a first screening assay, compounds were tested in duplicate at a concentration of 10 μM.Human recombinant enzyme GSK-3β was incubated for 90 minutes at 22° C. in the presence of compounds or vehicle in a reaction buffer containing ATP plus 100 nM unphosphorylated specific substrate peptide (Ulight-CFFKNIVTPRTPPPSQG K-amide). Substrate phosphorylation was measured by LANCE technology (PerkinElmer, Conn., USA).The results, reported in the following Table 4, are expressed as a percentage of inhibition of control specific activity obtained in the presence of the test compounds (as % inhibition at 10 μm).In a second assay, the same compounds were assayed at five concentrations ranging from 100 μM to 10 nM with ten-fold dilutions in duplicate. Compounds 1 to 15 were tested using the same first assay, compounds 16 to 41 were tested in another assay based on the binding and displacement of AlexaFluor® 647 labeled, ATP-competitive Kinase inhibitor scaffold using LanthaScreen TR-FRET technology Eu Kinase assay packet according to manufacturer's instruction (Life Technologies, Italy). The results of the two assays are comparable.
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 428.48, ALogP 3.6, HBA 4, HBD 2, PSA 70.25, QED 0.6
Compound (SMILES): CN(C)Cc1cccc(OCc2ccc3ccc(N)nc3c2)c1
InChIKey: NTASSNARMLLQTN-UHFFFAOYSA-N
Target: Nitric oxide synthase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P29475
Assay: Enzyme Assay: Rat and human nNOS, murine macrophage iNOS, and human eNOS were recombinant enzymes (expressed in E. coli and purified as reported previously in the literature). To test for NOS inhibition, the hemoglobin capture assay was used to measure nitric oxide production. The assay was performed at 37° C. in HEPES buffer (100 mM with 10% glycerol, pH 7.4) in the presence of 10 μM L-arginine. Also included were 100 μM NADPH, 0.83 mM CaCl2, approximately 320 units/mL of calmodulin, 10 μM H4B, and human oxyhemoglobin (3 μM). For iNOS, the CaCl2 and calmodulin were omitted and replaced with HEPES buffer (neither are required for activation of iNOS). The assay was performed in 96-well plates using a Synergy 4 BioTek hybrid reader. The dispensing of NOS enzyme and hemoglobin were automated, and after 30 sec (maximum delay), NO production was read by monitoring the absorbance at 401 nm (resulting from conversion of oxyhemoglobin to methemoglobin). Kinetic readouts were performed for 5 min. Each compound was assayed at least in duplicate, and six to nine concentrations (500 μM-50 nM or 100 μM-10 nM for eNOS and iNOS; 50 μM to 5 nM for rat and human nNOS) were used to construct dose-response curves. IC50 values were calculated by non-linear regression (variable slope, four parameters) using GraphPad Prism software, and Ki values were obtained using the Cheng-Prusoff equation [Ki=IC50/(1+[S]/Km)] with the following Km values: 1.3 μM (rat nNOS), 1.6 μM (human nNOS), 8.2 μM (murine macrophage iNOS), and 3.9 (human eNOS).
Measurement: Ki = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 307.4, ALogP 3.46, HBA 4, HBD 1, PSA 51.38, QED 0.78
Compound (SMILES): CNCc1cncc(OCc2ccc3ccc(N)nc3c2)c1
InChIKey: CCVIETYDINGXSM-UHFFFAOYSA-N
Target: Nitric oxide synthase, inducible (SINGLE PROTEIN), Homo sapiens
UniProt: P35228
Assay: Enzyme Assay: Rat and human nNOS, murine macrophage iNOS, and human eNOS were recombinant enzymes (expressed in E. coli and purified as reported previously in the literature). To test for NOS inhibition, the hemoglobin capture assay was used to measure nitric oxide production. The assay was performed at 37° C. in HEPES buffer (100 mM with 10% glycerol, pH 7.4) in the presence of 10 μM L-arginine. Also included were 100 μM NADPH, 0.83 mM CaCl2, approximately 320 units/mL of calmodulin, 10 μM H4B, and human oxyhemoglobin (3 μM). For iNOS, the CaCl2 and calmodulin were omitted and replaced with HEPES buffer (neither are required for activation of iNOS). The assay was performed in 96-well plates using a Synergy 4 BioTek hybrid reader. The dispensing of NOS enzyme and hemoglobin were automated, and after 30 sec (maximum delay), NO production was read by monitoring the absorbance at 401 nm (resulting from conversion of oxyhemoglobin to methemoglobin). Kinetic readouts were performed for 5 min. Each compound was assayed at least in duplicate, and six to nine concentrations (500 μM-50 nM or 100 μM-10 nM for eNOS and iNOS; 50 μM to 5 nM for rat and human nNOS) were used to construct dose-response curves. IC50 values were calculated by non-linear regression (variable slope, four parameters) using GraphPad Prism software, and Ki values were obtained using the Cheng-Prusoff equation [Ki=IC50/(1+[S]/Km)] with the following Km values: 1.3 μM (rat nNOS), 1.6 μM (human nNOS), 8.2 μM (murine macrophage iNOS), and 3.9 (human eNOS).
Measurement: Ki = 18900 nM (pChEMBL 4.71999979019165)
Descriptors: MW 294.36, ALogP 2.51, HBA 5, HBD 2, PSA 73.06, QED 0.76
Compound (SMILES): CS(=O)(=O)Cc1cccc(Nc2nccc(Oc3ccc4c(C(=O)Nc5ccccc5)cccc4c3)n2)c1
InChIKey: KOFXELGVKHKUJR-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Inhibition of human recombinant Abl using Poly (Glu,Tyr) as substrate after 60 mins by ELISA
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 524.6, ALogP 5.96, HBA 7, HBD 2, PSA 110.28, QED 0.26
Compound (SMILES): CS(=O)(=O)Cc1cccc(Nc2nccc(Oc3ccc4c(C(=O)Nc5cccc(F)c5)cccc4c3)n2)c1
InChIKey: GUUYUIDTJAWAHO-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Inhibition of human recombinant Abl using Poly (Glu,Tyr) as substrate after 60 mins by ELISA
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 542.59, ALogP 6.1, HBA 7, HBD 2, PSA 110.28, QED 0.24
Compound (SMILES): CS(=O)(=O)Cc1cccc(Nc2nccc(Oc3ccc4c(C(=O)Nc5cccnc5)cccc4c3)n2)c1
InChIKey: HAWQJVUHZAYNCF-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Inhibition of human recombinant Abl using Poly (Glu,Tyr) as substrate after 60 mins by ELISA
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 525.59, ALogP 5.36, HBA 8, HBD 2, PSA 123.17, QED 0.28
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 = 1096 nM (pChEMBL 5.960000038146973)
Descriptors: MW 719.79, ALogP 2.06, HBA 9, HBD 8, PSA 240.43, QED 0.05
Compound (SMILES): Cc1ccc(C(=O)O)c(C)c1NC(=O)c1cc(-c2cccc(Cl)c2)cc2ccccc12
InChIKey: SIIGKILIYGRIJN-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 429.9, ALogP 6.73, HBA 2, HBD 2, PSA 66.4, QED 0.38
Compound (SMILES): O=C(O)C1CN(Cc2ccc(OCc3ccc(Cl)c(Cl)c3)cc2)C1
InChIKey: WAAWETUDFSIYSD-UHFFFAOYSA-N
Target: Aurora kinase B (SINGLE PROTEIN), Homo sapiens
UniProt: Q96GD4
Assay: Inhibition of Aurora1 (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): CCOC(=O)C1=C(CN2CCOCC2)NC(c2nccs2)=NC1c1ccc(F)cc1Br
InChIKey: SQGRDKSRFFUBBU-UHFFFAOYSA-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 = 1 nM (pChEMBL 9)
Descriptors: MW 509.4, ALogP 3.29, HBA 8, HBD 1, PSA 76.05, QED 0.6
Compound (SMILES): CC1(C)c2cc(C3CCN(CC4CCOCC4)CC3)ccc2C(=O)c2c1[nH]c1cc(C#N)ccc21
InChIKey: VWCZORWQNKCYGE-UHFFFAOYSA-N
Target: Receptor tyrosine-protein kinase erbB-4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15303
Assay: Inhibition of N-terminal His6-tagged recombinant human ErbB4 (709 to 991 residues) expressed in insect Sf21 cells using poly(Glu,Tyr)4:1 as substrate incubated for 60 mins by ELISA
Measurement: IC50 = 213 nM (pChEMBL 6.670000076293945)
Descriptors: MW 467.61, ALogP 5.52, HBA 4, HBD 1, PSA 69.12, QED 0.55
Compound (SMILES): CCc1cc2c(cc1-c1cnn(CC(=O)N(C)C)c1)C(C)(C)c1[nH]c3cc(C#N)ccc3c1C2=O
InChIKey: IDGNCVHQDDOPND-UHFFFAOYSA-N
Target: Interleukin-1 receptor-associated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWZ3
Assay: Inhibition of IRAK4 (unknown origin)
Measurement: IC50 = 465 nM (pChEMBL 6.329999923706055)
Descriptors: MW 465.56, ALogP 4.42, HBA 5, HBD 1, PSA 94.78, QED 0.48
Compound (SMILES): COCCN1CCC(CNC(=O)c2n[nH]c3ccc(-c4cccc(F)c4F)cc23)CC1
InChIKey: QCLXNOBXQUWUEW-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Activity on Human GSK-3beta: The activity on human GSK-3β of the compounds of the invention listed in the following Table 1 and of the comparison compound C was assessed at five concentrations ranging from 10 μM to 1 nM with ten-fold dilutions in duplicate using the following methods (according to Meijer et al., Chem. Biol., 2003-10:1255-1266).Human recombinant enzyme GSK-3β was incubated for 90 minutes at 22° C. in the presence of compounds or vehicle in a reaction buffer containing ATP plus 100 nM unphosphorylated specific substrate peptide (Ulight-CFFKNIVTPRTPPPSQGK-amide). Substrate phosphorylation was measured by LANCE technology (PerkinElmer, CT, USA).The IC50 values (concentration causing a half maximal inhibition of control specific activity) were determined by non-linear regression analysis of the inhibition curves generated with mean replicate values using Hill equation curve fitting.
Measurement: IC50 = 21.6 nM (pChEMBL 7.670000076293945)
Descriptors: MW 428.48, ALogP 3.6, HBA 4, HBD 2, PSA 70.25, QED 0.6
Compound (SMILES): CN(C)Cc1cccc(OCc2ccc3ccc(N)nc3c2)c1
InChIKey: NTASSNARMLLQTN-UHFFFAOYSA-N
Target: Nitric oxide synthase 1 (SINGLE PROTEIN), Mus musculus
UniProt: Q9Z0J4
Assay: Enzyme Assay: Rat and human nNOS, murine macrophage iNOS, and human eNOS were recombinant enzymes (expressed in E. coli and purified as reported previously in the literature). To test for NOS inhibition, the hemoglobin capture assay was used to measure nitric oxide production. The assay was performed at 37° C. in HEPES buffer (100 mM with 10% glycerol, pH 7.4) in the presence of 10 μM L-arginine. Also included were 100 μM NADPH, 0.83 mM CaCl2, approximately 320 units/mL of calmodulin, 10 μM H4B, and human oxyhemoglobin (3 μM). For iNOS, the CaCl2 and calmodulin were omitted and replaced with HEPES buffer (neither are required for activation of iNOS). The assay was performed in 96-well plates using a Synergy 4 BioTek hybrid reader. The dispensing of NOS enzyme and hemoglobin were automated, and after 30 sec (maximum delay), NO production was read by monitoring the absorbance at 401 nm (resulting from conversion of oxyhemoglobin to methemoglobin). Kinetic readouts were performed for 5 min. Each compound was assayed at least in duplicate, and six to nine concentrations (500 μM-50 nM or 100 μM-10 nM for eNOS and iNOS; 50 μM to 5 nM for rat and human nNOS) were used to construct dose-response curves. IC50 values were calculated by non-linear regression (variable slope, four parameters) using GraphPad Prism software, and Ki values were obtained using the Cheng-Prusoff equation [Ki=IC50/(1+[S]/Km)] with the following Km values: 1.3 μM (rat nNOS), 1.6 μM (human nNOS), 8.2 μM (murine macrophage iNOS), and 3.9 (human eNOS).
Measurement: Ki = 5750 nM (pChEMBL 5.239999771118164)
Descriptors: MW 307.4, ALogP 3.46, HBA 4, HBD 1, PSA 51.38, QED 0.78
Compound (SMILES): CS(=O)(=O)Cc1cccc(Nc2nccc(Oc3ccc4c(C(=O)Nc5ccccc5)cccc4c3)n2)c1
InChIKey: KOFXELGVKHKUJR-UHFFFAOYSA-N
Target: Ephrin type-A receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29317
Assay: Inhibition of human recombinant EPHA2 using Poly (Glu,Tyr) as substrate after 60 mins by ELISA
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 524.6, ALogP 5.96, HBA 7, HBD 2, PSA 110.28, QED 0.26
Compound (SMILES): CS(=O)(=O)Cc1cccc(Nc2nccc(Oc3ccc4c(C(=O)Nc5cccc(F)c5)cccc4c3)n2)c1
InChIKey: GUUYUIDTJAWAHO-UHFFFAOYSA-N
Target: Ephrin type-A receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29317
Assay: Inhibition of human recombinant EPHA2 using Poly (Glu,Tyr) as substrate after 60 mins by ELISA
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 542.59, ALogP 6.1, HBA 7, HBD 2, PSA 110.28, QED 0.24
Compound (SMILES): CS(=O)(=O)Cc1cccc(Nc2nccc(Oc3ccc4c(C(=O)Nc5cccnc5)cccc4c3)n2)c1
InChIKey: HAWQJVUHZAYNCF-UHFFFAOYSA-N
Target: Ephrin type-A receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29317
Assay: Inhibition of human recombinant EPHA2 using Poly (Glu,Tyr) as substrate after 60 mins by ELISA
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 525.59, ALogP 5.36, HBA 8, HBD 2, PSA 123.17, QED 0.28
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 = 4989 nM (pChEMBL 5.300000190734863)
Descriptors: MW 719.79, ALogP 2.06, HBA 9, HBD 8, PSA 240.43, QED 0.05
Compound (SMILES): Cc1ccc(C(=O)O)c(C)c1NC(=O)c1cc(-c2cccc(Cl)c2)cc2ccccc12
InChIKey: SIIGKILIYGRIJN-UHFFFAOYSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of CYP2C8 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 429.9, ALogP 6.73, HBA 2, HBD 2, PSA 66.4, QED 0.38
Compound (SMILES): O=C(O)C1CN(Cc2ccc(OCc3ccc(Cl)c(Cl)c3)cc2)C1
InChIKey: WAAWETUDFSIYSD-UHFFFAOYSA-N
Target: Aurora kinase A (SINGLE PROTEIN), Homo sapiens
UniProt: O14965
Assay: Inhibition of Aurora2 (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): CCOC(=O)C1=C(CN2CCOCC2)NC(c2nccs2)=NC1c1ccc(F)cc1Br
InChIKey: SQGRDKSRFFUBBU-UHFFFAOYSA-N
Target: Core antigen (SINGLE PROTEIN), Hepatitis B virus
UniProt: Q03732
Assay: Inhibition of reverse transcriptase M204I/S202G/M250V triple mutant expressing entecavir-resistant hepatitis B virus capsid assembly in human Huh7 cells assessed as reduction in intracellular DNA levels measured on day 7 by real-time PCR analysis
Measurement: EC50 = 46 nM (pChEMBL 7.340000152587891)
Descriptors: MW 509.4, ALogP 3.29, HBA 8, HBD 1, PSA 76.05, QED 0.6
Compound (SMILES): CC1(C)c2cc(C3CCN(CC4CCOCC4)CC3)ccc2C(=O)c2c1[nH]c1cc(C#N)ccc21
InChIKey: VWCZORWQNKCYGE-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P17948
Assay: Inhibition of N-terminal GST-tagged recombinant human FLT1 (783 residues) expressed in insect Sf21 cells using poly(Glu,Tyr)4:1 as substrate incubated for 60 mins by ELISA
Measurement: IC50 = 159 nM (pChEMBL 6.800000190734863)
Descriptors: MW 467.61, ALogP 5.52, HBA 4, HBD 1, PSA 69.12, QED 0.55
Compound (SMILES): CCc1cc2c(cc1-c1cnn(CC(=O)N(C)C)c1)C(C)(C)c1[nH]c3cc(C#N)ccc3c1C2=O
InChIKey: IDGNCVHQDDOPND-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HAZ1
Assay: Inhibition of CLK4 (unknown origin)
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 465.56, ALogP 4.42, HBA 5, HBD 1, PSA 94.78, QED 0.48
Compound (SMILES): COCCN1CCC(CNC(=O)c2n[nH]c3ccc(-c4cccc(F)c4F)cc23)CC1
InChIKey: QCLXNOBXQUWUEW-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Selectivity on hERG Channel : Confirmation of interaction with the potassium channels of the compounds of the invention listed in the following Table 1 and of the comparison compound C was made by means of the automated whole-cell patch clamp test described in Mathes, C. (2006), Expert Opin. Ther. Targets, 10 (2): 230-241 using the recombinant human cell line CHO-K1, which stably expresses the hERG ion channel.The IC50 values (concentration causing a half maximal inhibition of control specific activity) were determined at five concentrations ranging from 100 μM to 10 nM with ten-fold dilutions in duplicate.The degree of inhibition (%) was obtained by measuring the tail current amplitude, which is induced by a one second test pulse to −40 mV after a two second pulse to +20 mV, before and after drug incubation (the difference current was normalized to control and multiplied by 100 to obtain the percent of inhibition). Concentration (log) response curves were fitted to a logistic equation (three parameters assuming complete block of the current at very high test compound concentrations) to generate estimates of the 50% inhibitory concentration (IC50).
Measurement: IC50 = 49.9 nM (pChEMBL 7.300000190734863)
Descriptors: MW 428.48, ALogP 3.6, HBA 4, HBD 2, PSA 70.25, QED 0.6
Compound (SMILES): CN(C)Cc1cccc(OCc2ccc3ccc(N)nc3c2)c1
InChIKey: NTASSNARMLLQTN-UHFFFAOYSA-N
Target: Nitric oxide synthase, inducible (SINGLE PROTEIN), Homo sapiens
UniProt: P35228
Assay: Enzyme Assay: Rat and human nNOS, murine macrophage iNOS, and human eNOS were recombinant enzymes (expressed in E. coli and purified as reported previously in the literature). To test for NOS inhibition, the hemoglobin capture assay was used to measure nitric oxide production. The assay was performed at 37° C. in HEPES buffer (100 mM with 10% glycerol, pH 7.4) in the presence of 10 μM L-arginine. Also included were 100 μM NADPH, 0.83 mM CaCl2, approximately 320 units/mL of calmodulin, 10 μM H4B, and human oxyhemoglobin (3 μM). For iNOS, the CaCl2 and calmodulin were omitted and replaced with HEPES buffer (neither are required for activation of iNOS). The assay was performed in 96-well plates using a Synergy 4 BioTek hybrid reader. The dispensing of NOS enzyme and hemoglobin were automated, and after 30 sec (maximum delay), NO production was read by monitoring the absorbance at 401 nm (resulting from conversion of oxyhemoglobin to methemoglobin). Kinetic readouts were performed for 5 min. Each compound was assayed at least in duplicate, and six to nine concentrations (500 μM-50 nM or 100 μM-10 nM for eNOS and iNOS; 50 μM to 5 nM for rat and human nNOS) were used to construct dose-response curves. IC50 values were calculated by non-linear regression (variable slope, four parameters) using GraphPad Prism software, and Ki values were obtained using the Cheng-Prusoff equation [Ki=IC50/(1+[S]/Km)] with the following Km values: 1.3 μM (rat nNOS), 1.6 μM (human nNOS), 8.2 μM (murine macrophage iNOS), and 3.9 (human eNOS).
Measurement: Ki = 6660 nM (pChEMBL 5.179999828338623)
Descriptors: MW 307.4, ALogP 3.46, HBA 4, HBD 1, PSA 51.38, QED 0.78
Compound (SMILES): CS(=O)(=O)Cc1cccc(Nc2nccc(Oc3ccc4c(C(=O)Nc5ccccc5)cccc4c3)n2)c1
InChIKey: KOFXELGVKHKUJR-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: Inhibition of human recombinant IGF1R expressed in baculovirus using Poly (Glu,Tyr) as substrate after 60 mins by ELISA
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 524.6, ALogP 5.96, HBA 7, HBD 2, PSA 110.28, QED 0.26
Compound (SMILES): CS(=O)(=O)Cc1cccc(Nc2nccc(Oc3ccc4c(C(=O)Nc5cccc(F)c5)cccc4c3)n2)c1
InChIKey: GUUYUIDTJAWAHO-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: Inhibition of human recombinant IGF1R expressed in baculovirus using Poly (Glu,Tyr) as substrate after 60 mins by ELISA
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 542.59, ALogP 6.1, HBA 7, HBD 2, PSA 110.28, QED 0.24
Compound (SMILES): CS(=O)(=O)Cc1cccc(Nc2nccc(Oc3ccc4c(C(=O)Nc5cccnc5)cccc4c3)n2)c1
InChIKey: HAWQJVUHZAYNCF-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: Inhibition of human recombinant IGF1R expressed in baculovirus using Poly (Glu,Tyr) as substrate after 60 mins by ELISA
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 525.59, ALogP 5.36, HBA 8, HBD 2, PSA 123.17, QED 0.28
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 = 4446 nM (pChEMBL 5.349999904632568)
Descriptors: MW 719.79, ALogP 2.06, HBA 9, HBD 8, PSA 240.43, QED 0.05
Compound (SMILES): Cc1ccc(C(=O)O)c(C)c1NC(=O)c1cc(-c2cccc(Cl)c2)cc2ccccc12
InChIKey: SIIGKILIYGRIJN-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 429.9, ALogP 6.73, HBA 2, HBD 2, PSA 66.4, QED 0.38
Compound (SMILES): O=C(O)C1CN(Cc2ccc(OCc3ccc(Cl)c(Cl)c3)cc2)C1
InChIKey: WAAWETUDFSIYSD-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Blk (SINGLE PROTEIN), Homo sapiens
UniProt: P51451
Assay: Inhibition of BLK (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): CCOC(=O)C1=C(CN2CCOCC2)NC(c2nccs2)=NC1c1ccc(F)cc1Br
InChIKey: SQGRDKSRFFUBBU-UHFFFAOYSA-N
Target: Core antigen (SINGLE PROTEIN), Hepatitis B virus
UniProt: Q03732
Assay: Inhibition of reverse transcriptase M204I/S202G double mutant expressing entecavir-resistant hepatitis B virus capsid assembly in human Huh7 cells assessed as reduction in secreted DNA levels measured on day 7 by real-time PCR analysis
Measurement: EC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 509.4, ALogP 3.29, HBA 8, HBD 1, PSA 76.05, QED 0.6
Compound (SMILES): CC1(C)c2cc(C3CCN(CC4CCOCC4)CC3)ccc2C(=O)c2c1[nH]c1cc(C#N)ccc21
InChIKey: VWCZORWQNKCYGE-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of N-terminal GST-tagged recombinant human FLT3 (564 residues) expressed in insect Sf21 cells using poly(Glu,Tyr)4:1 as substrate incubated for 60 mins by ELISA
Measurement: IC50 = 85.7 nM (pChEMBL 7.070000171661377)
Descriptors: MW 467.61, ALogP 5.52, HBA 4, HBD 1, PSA 69.12, QED 0.55
Compound (SMILES): CCc1cc2c(cc1-c1cnn(CC(=O)N(C)C)c1)C(C)(C)c1[nH]c3cc(C#N)ccc3c1C2=O
InChIKey: IDGNCVHQDDOPND-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase receptor Ret (SINGLE PROTEIN), Homo sapiens
UniProt: P07949
Assay: Inhibition of RET (unknown origin)
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 465.56, ALogP 4.42, HBA 5, HBD 1, PSA 94.78, QED 0.48
Compound (SMILES): CS(=O)(=O)Cc1cccc(Nc2nccc(Oc3ccc4c(C(=O)Nc5ccccc5)cccc4c3)n2)c1
InChIKey: KOFXELGVKHKUJR-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human recombinant FGFR1 expressed in baculovirus using Poly (Glu,Tyr) as substrate after 60 mins by ELISA
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 524.6, ALogP 5.96, HBA 7, HBD 2, PSA 110.28, QED 0.26
Compound (SMILES): CS(=O)(=O)Cc1cccc(Nc2nccc(Oc3ccc4c(C(=O)Nc5cccc(F)c5)cccc4c3)n2)c1
InChIKey: GUUYUIDTJAWAHO-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human recombinant FGFR1 expressed in baculovirus using Poly (Glu,Tyr) as substrate after 60 mins by ELISA
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 542.59, ALogP 6.1, HBA 7, HBD 2, PSA 110.28, QED 0.24
Compound (SMILES): CS(=O)(=O)Cc1cccc(Nc2nccc(Oc3ccc4c(C(=O)Nc5cccnc5)cccc4c3)n2)c1
InChIKey: HAWQJVUHZAYNCF-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human recombinant FGFR1 expressed in baculovirus using Poly (Glu,Tyr) as substrate after 60 mins by ELISA
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 525.59, ALogP 5.36, HBA 8, HBD 2, PSA 123.17, QED 0.28
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 = 18997 nM (pChEMBL 4.71999979019165)
Descriptors: MW 719.79, ALogP 2.06, HBA 9, HBD 8, PSA 240.43, QED 0.05
Compound (SMILES): Cc1ccc(C(=O)O)c(C)c1NC(=O)c1cc(-c2cccc(Cl)c2)cc2ccccc12
InChIKey: SIIGKILIYGRIJN-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 429.9, ALogP 6.73, HBA 2, HBD 2, PSA 66.4, QED 0.38