lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1cc(C)cc(C(=O)NC(=S)Nc2cc(-c3ccccc3)ccc2O)c1
InChIKey: VPDLRGFVKFCAKS-UHFFFAOYSA-N
Target: 3-phosphoinositide-dependent protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O15530
Assay: Fluorescence Polarization Assay: In order to identify compounds that disrupt the interaction between PIP3 and PH domains, a high-throughput fluorescence polarization (FP)-binding assay was developed using recombinant 1-123 amino acid N-terminal fragment of human Akt1 (also referred to herein simply as Akt), encompassing the PH domain (PH123 protein), and fluorescent NBD-labeled PIP3 molecule. The amino acid sequence of human Akt1 is publicly available as, for example, GenBank Accession No. NP001014432.1 (SEQ ID NO:1), and the corresponding DNA sequence is publicly available as, for example, GenBank Accession No. NM001014432. Briefly, 5 μM recombinant GST fusion proteins containing 1-123 a.a. N-terminal fragment of human Akt1 (PH 123) or 100 nM 441-551 a.a. region of human PDK1 were incubated with 15 nM TMR-labeled PIP3, PIP2, or PIP5 in buffer containing 50 mM Tris-HCl (pH 7.5), 150 mM NaCl, and 5 mM b-ME for 15 min at room temperature in the dark.
Measurement: IC50 = 52300 nM (pChEMBL 4.28000020980835)
Descriptors: MW 376.48, ALogP 4.8, HBA 3, HBD 3, PSA 61.36, QED 0.45
Compound (SMILES): CNC(=O)[C@@H]1NC2(CCNCC2)[C@@]2(C(=O)Nc3cc(Cl)ccc32)[C@H]1c1cccc(Cl)c1F
InChIKey: HVIFZQHAQKSDBI-GEQKSPFYSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: Inhibition of FAM-tagged p53-based PMDM6-F peptide binding to human recombinant His-tagged MDM2 (1 to 118 residues) after 30 mins by fluorescence polarization assay
Measurement: IC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 477.37, ALogP 2.95, HBA 4, HBD 4, PSA 82.26, QED 0.54
Compound (SMILES): CNC(=O)[C@@H]1NC2(CCN(C)CC2)[C@@]2(C(=O)Nc3cc(Cl)ccc32)[C@H]1c1cccc(Cl)c1F
InChIKey: APXGCNZUGJHYPE-MFSJNOQSSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: Inhibition of FAM-tagged p53-based PMDM6-F peptide binding to human recombinant His-tagged MDM2 (1 to 118 residues) after 30 mins by fluorescence polarization assay
Measurement: IC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 491.39, ALogP 3.29, HBA 4, HBD 3, PSA 73.47, QED 0.6
Compound (SMILES): CNC(=O)[C@@H]1NC2(CCN(C(C)=O)CC2)[C@@]2(C(=O)Nc3cc(Cl)ccc32)[C@H]1c1cccc(Cl)c1F
InChIKey: REHJJNQNQSNLAN-PIBDYAPNSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: Inhibition of FAM-tagged p53-based PMDM6-F peptide binding to human recombinant His-tagged MDM2 (1 to 118 residues) after 30 mins by fluorescence polarization assay
Measurement: Ki = 525 nM (pChEMBL 6.28000020980835)
Descriptors: MW 519.4, ALogP 3.21, HBA 4, HBD 3, PSA 90.54, QED 0.57
Compound (SMILES): CNC(=O)[C@@H]1NC2(CCCCC2)[C@@]2(C(=O)Nc3cc(Cl)ccc32)[C@H]1c1cccc(Cl)c1F
InChIKey: LHBZDASUSDFFIL-MFSJNOQSSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: Inhibition of FAM-tagged p53-based PMDM6-F peptide binding to human recombinant His-tagged MDM2 (1 to 118 residues) after 30 mins by fluorescence polarization assay
Measurement: Ki = 4.3 nM (pChEMBL 8.369999885559082)
Descriptors: MW 476.38, ALogP 4.53, HBA 3, HBD 3, PSA 70.23, QED 0.6
Compound (SMILES): O=C(O)CCCNC(=O)[C@@H]1NC2(CCCCC2)[C@@]2(C(=O)Nc3cc(Cl)ccc32)[C@H]1c1cccc(Cl)c1F
InChIKey: FYGISHSSTLYWEA-VBANMALSSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: Inhibition of FAM-tagged p53-based PMDM6-F peptide binding to human recombinant His-tagged MDM2 (1 to 118 residues) after 30 mins by fluorescence polarization assay
Measurement: Ki < 1 nM (pChEMBL 9)
Descriptors: MW 548.44, ALogP 4.76, HBA 4, HBD 4, PSA 107.53, QED 0.39
Compound (SMILES): O=C(O)c1ccc(CNC(=O)[C@@H]2NC3(CCCCC3)[C@@]3(C(=O)Nc4cc(Cl)ccc43)[C@H]2c2cccc(Cl)c2F)cc1
InChIKey: YGDUAQBHMIIUNT-UZXRVZLOSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: Inhibition of FAM-tagged p53-based PMDM6-F peptide binding to human recombinant His-tagged MDM2 (1 to 118 residues) after 30 mins by fluorescence polarization assay
Measurement: Ki < 1 nM (pChEMBL 9)
Descriptors: MW 596.49, ALogP 5.8, HBA 4, HBD 4, PSA 107.53, QED 0.3
Compound (SMILES): CS(=O)(=O)NC(=O)[C@@H]1NC2(CCCCC2)[C@@]2(C(=O)Nc3cc(Cl)ccc32)[C@H]1c1cccc(Cl)c1F
InChIKey: AVQYUHKLFSSGRH-MFSJNOQSSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: Inhibition of FAM-tagged p53-based PMDM6-F peptide binding to human recombinant His-tagged MDM2 (1 to 118 residues) after 30 mins by fluorescence polarization assay
Measurement: Ki = 12.8 nM (pChEMBL 7.889999866485596)
Descriptors: MW 540.44, ALogP 3.86, HBA 5, HBD 3, PSA 104.37, QED 0.55
Compound (SMILES): COc1cc(C(=O)O)ccc1NC(=O)[C@@H]1NC2(CCCCC2)[C@@]2(C(=O)Nc3cc(Cl)ccc32)[C@H]1c1cccc(Cl)c1F
InChIKey: BWIALTALKVTEJS-UZXRVZLOSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: Inhibition of FAM-tagged p53-based PMDM6-F peptide binding to human recombinant His-tagged MDM2 (1 to 118 residues) after 30 mins by fluorescence polarization assay
Measurement: Ki < 1 nM (pChEMBL 9)
Descriptors: MW 612.49, ALogP 6.13, HBA 5, HBD 4, PSA 116.76, QED 0.28
Compound (SMILES): O=C(O)c1ccc(NC(=O)[C@@H]2NC3(CCCCC3)[C@@]3(C(=O)Nc4cc(Cl)ccc43)[C@H]2c2cccc(Cl)c2F)cn1
InChIKey: YRQMWWJYNFOFFG-IQANXLHVSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: Inhibition of FAM-tagged p53-based PMDM6-F peptide binding to human recombinant His-tagged MDM2 (1 to 118 residues) after 30 mins by fluorescence polarization assay
Measurement: Ki = 1 nM (pChEMBL 9)
Descriptors: MW 583.45, ALogP 5.51, HBA 5, HBD 4, PSA 120.42, QED 0.32
Compound (SMILES): O=C(O)CN1CCC(NC(=O)[C@@H]2NC3(CCCCC3)[C@@]3(C(=O)Nc4cc(Cl)ccc43)[C@H]2c2cccc(Cl)c2F)CC1
InChIKey: IQBSUVGURXIBHW-RFJFUGTDSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: Inhibition of FAM-tagged p53-based PMDM6-F peptide binding to human recombinant His-tagged MDM2 (1 to 118 residues) after 30 mins by fluorescence polarization assay
Measurement: Ki = 3.4 nM (pChEMBL 8.470000267028809)
Descriptors: MW 603.52, ALogP 4.45, HBA 5, HBD 4, PSA 110.77, QED 0.4
Compound (SMILES): CC(=O)N1CC(NC(=O)[C@@H]2NC3(CCCCC3)[C@@]3(C(=O)Nc4cc(Cl)ccc43)[C@H]2c2cccc(Cl)c2F)C1
InChIKey: SDCCOKXGHZANMZ-ZQIDGUAPSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: Inhibition of FAM-tagged p53-based PMDM6-F peptide binding to human recombinant His-tagged MDM2 (1 to 118 residues) after 30 mins by fluorescence polarization assay
Measurement: Ki = 3.4 nM (pChEMBL 8.470000267028809)
Descriptors: MW 559.47, ALogP 4.13, HBA 4, HBD 3, PSA 90.54, QED 0.53
Compound (SMILES): O=C(N[C@H]1CC[C@H](O)CC1)[C@@H]1NC2(CCCCC2)[C@@]2(C(=O)Nc3cc(Cl)ccc32)[C@H]1c1cncc(Cl)c1
InChIKey: WLGWITVWSYJSBH-ZEKBRLKRSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: Inhibition of FAM-tagged p53-based PMDM6-F peptide binding to human recombinant His-tagged MDM2 (1 to 118 residues) after 30 mins by fluorescence polarization assay
Measurement: Ki = 77 nM (pChEMBL 7.110000133514404)
Descriptors: MW 543.5, ALogP 4.46, HBA 5, HBD 4, PSA 103.35, QED 0.46
Compound (SMILES): O=C(O)c1cccc(NC(=O)[C@@H]2NC3(CCCCC3)[C@@]3(C(=O)Nc4cc(Cl)ccc43)[C@H]2c2cccc(Cl)c2F)c1
InChIKey: OBRQIAOWJAIPGR-LOLKONATSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: Inhibition of FAM-tagged p53-based PMDM6-F peptide binding to human recombinant His-tagged MDM2 (1 to 118 residues) after 30 mins by fluorescence polarization assay
Measurement: Ki < 1 nM (pChEMBL 9)
Descriptors: MW 582.46, ALogP 6.12, HBA 4, HBD 4, PSA 107.53, QED 0.3
Compound (SMILES): Cn1c2c(c3ccc(-n4ccc(OCc5ccccc5)cc4=O)cc31)C1CCC(C2)N1
InChIKey: COJKEZKAKAGCDA-UHFFFAOYSA-N
Target: Melanin-concentrating hormone receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99705
Assay: Binding Assay: Evaluation of the affinity of compounds for the human MCH-1 receptor was accomplished using 4-(3,4,5-tritritiumbenzyloxy)-1-(1-(2-(pyrrolidin-1-yl)ethyl)-1H-indazol-5-yl)pyridin-2(1H)-one and membranes prepared from stable CHO-K1 cells expressing the human MCH1 receptor obtained from Euroscreen (Batch 1138). Cell membrane homogenates (8.92 μg protein) were incubated for 60 min at 25° C. with 1.4 μM of the [3H]-labeled compound in the absence or presence of the test compound in 50 mM Tris-HCl buffer, pH 7.4. Nonspecific binding was determined in the presence of 50 μM 1-(5-(4-cyanophenyl)bicyclo[3.1.0]hexan-2-yl)-3-(4-fluoro 3-(trifluoromethyl)phenyl)-1-(3-(4-methylpiperazin-1-yl)propyl)urea. Following incubation, the samples were filtered rapidly under vacuum through Skatron 11731 filters, pre-soaked in 0.5% polyethylenimine, and washed with ice-cold 50 mM Tris-HCl buffer, pH 7.4, (wash setting 9,9,0) using a Skatron cell harvester.
Measurement: Ki = 15.8 nM (pChEMBL 7.800000190734863)
Descriptors: MW 411.51, ALogP 4.26, HBA 5, HBD 1, PSA 48.19, QED 0.55
Compound (SMILES): Cn1c2c(c3ccc(-n4ccc(-c5ccc(C(F)(F)F)cn5)cc4=O)cc31)C1CCC(C2)N1
InChIKey: WSPSSCWJQMVPSM-UHFFFAOYSA-N
Target: Melanin-concentrating hormone receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99705
Assay: Binding Assay: Evaluation of the affinity of compounds for the human MCH-1 receptor was accomplished using 4-(3,4,5-tritritiumbenzyloxy)-1-(1-(2-(pyrrolidin-1-yl)ethyl)-1H-indazol-5-yl)pyridin-2(1H)-one and membranes prepared from stable CHO-K1 cells expressing the human MCH1 receptor obtained from Euroscreen (Batch 1138). Cell membrane homogenates (8.92 μg protein) were incubated for 60 min at 25° C. with 1.4 μM of the [3H]-labeled compound in the absence or presence of the test compound in 50 mM Tris-HCl buffer, pH 7.4. Nonspecific binding was determined in the presence of 50 μM 1-(5-(4-cyanophenyl)bicyclo[3.1.0]hexan-2-yl)-3-(4-fluoro 3-(trifluoromethyl)phenyl)-1-(3-(4-methylpiperazin-1-yl)propyl)urea. Following incubation, the samples were filtered rapidly under vacuum through Skatron 11731 filters, pre-soaked in 0.5% polyethylenimine, and washed with ice-cold 50 mM Tris-HCl buffer, pH 7.4, (wash setting 9,9,0) using a Skatron cell harvester.
Measurement: Ki = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 450.46, ALogP 4.76, HBA 5, HBD 1, PSA 51.85, QED 0.48
Compound (SMILES): Cn1c2c(c3ccc(-n4ccc(OCc5ccc(F)cn5)cc4=O)cc31)C1CCC(C2)N1
InChIKey: WIHBSZQMVJUBGL-UHFFFAOYSA-N
Target: Melanin-concentrating hormone receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99705
Assay: Binding Assay: Evaluation of the affinity of compounds for the human MCH-1 receptor was accomplished using 4-(3,4,5-tritritiumbenzyloxy)-1-(1-(2-(pyrrolidin-1-yl)ethyl)-1H-indazol-5-yl)pyridin-2(1H)-one and membranes prepared from stable CHO-K1 cells expressing the human MCH1 receptor obtained from Euroscreen (Batch 1138). Cell membrane homogenates (8.92 μg protein) were incubated for 60 min at 25° C. with 1.4 μM of the [3H]-labeled compound in the absence or presence of the test compound in 50 mM Tris-HCl buffer, pH 7.4. Nonspecific binding was determined in the presence of 50 μM 1-(5-(4-cyanophenyl)bicyclo[3.1.0]hexan-2-yl)-3-(4-fluoro 3-(trifluoromethyl)phenyl)-1-(3-(4-methylpiperazin-1-yl)propyl)urea. Following incubation, the samples were filtered rapidly under vacuum through Skatron 11731 filters, pre-soaked in 0.5% polyethylenimine, and washed with ice-cold 50 mM Tris-HCl buffer, pH 7.4, (wash setting 9,9,0) using a Skatron cell harvester.
Measurement: Ki = 7.4 nM (pChEMBL 8.130000114440918)
Descriptors: MW 430.48, ALogP 3.79, HBA 6, HBD 1, PSA 61.08, QED 0.54
Compound (SMILES): O=c1cc(OCc2ccccc2)ccn1-c1ccc2c3c([nH]c2c1)CC1CCC3N1
InChIKey: DOUMNJOBZGMSMH-UHFFFAOYSA-N
Target: Melanin-concentrating hormone receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99705
Assay: Binding Assay: Evaluation of the affinity of compounds for the human MCH-1 receptor was accomplished using 4-(3,4,5-tritritiumbenzyloxy)-1-(1-(2-(pyrrolidin-1-yl)ethyl)-1H-indazol-5-yl)pyridin-2(1H)-one and membranes prepared from stable CHO-K1 cells expressing the human MCH1 receptor obtained from Euroscreen (Batch 1138). Cell membrane homogenates (8.92 μg protein) were incubated for 60 min at 25° C. with 1.4 μM of the [3H]-labeled compound in the absence or presence of the test compound in 50 mM Tris-HCl buffer, pH 7.4. Nonspecific binding was determined in the presence of 50 μM 1-(5-(4-cyanophenyl)bicyclo[3.1.0]hexan-2-yl)-3-(4-fluoro 3-(trifluoromethyl)phenyl)-1-(3-(4-methylpiperazin-1-yl)propyl)urea. Following incubation, the samples were filtered rapidly under vacuum through Skatron 11731 filters, pre-soaked in 0.5% polyethylenimine, and washed with ice-cold 50 mM Tris-HCl buffer, pH 7.4, (wash setting 9,9,0) using a Skatron cell harvester.
Measurement: Ki = 9.3 nM (pChEMBL 8.029999732971191)
Descriptors: MW 397.48, ALogP 4.25, HBA 4, HBD 2, PSA 59.05, QED 0.54
Compound (SMILES): Fc1cc(I)ccc1Nc1ccnc2cc(Cl)ccc12
InChIKey: SGYXYQQGWNUEIG-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (SINGLE PROTEIN), Plasmodium falciparum
UniProt: Q54A96
Assay: Enzymatic Assays: Type 2 DHODH activity was monitored with either the direct assay measuring the formation of orotate or via a chromogen reduction assay using DCIP. Although the extinction coefficient and absorption wavelength are preferable for the chromogen reduction assay, the inorganic electron acceptor DCIP can be utilized by DHODH as the final electron acceptor in lieu of CoQn when the endogenous substrate is at a low concentration. As such, the direct assay was used to measure the binding affinity of pfDHODH to CoQD and L-DHO. The enzymatic reaction was performed by varying the L-DHO concentration (1-400 μM) or CoQD concentration (1-200 μM) while keeping the other substrate constant and in excess. Inhibition of DHODH by small molecules was evaluated using the chromogen based assay with a final substrate concentration of 200 μM L-DHO, 18 μM CoQD, and 100 μM DCIP, unless otherwise noted.
Measurement: IC50 = 580 nM (pChEMBL 6.239999771118164)
Descriptors: MW 398.61, ALogP 5.38, HBA 2, HBD 1, PSA 24.92, QED 0.59
Compound (SMILES): Cc1ccccc1/C=C/c1cc(O)c2ccccc2n1
InChIKey: NUTJRCJUMGYLIV-ZHACJKMWSA-N
Target: Dihydroorotate dehydrogenase (SINGLE PROTEIN), Plasmodium falciparum
UniProt: Q54A96
Assay: Enzymatic Assays: Type 2 DHODH activity was monitored with either the direct assay measuring the formation of orotate or via a chromogen reduction assay using DCIP. Although the extinction coefficient and absorption wavelength are preferable for the chromogen reduction assay, the inorganic electron acceptor DCIP can be utilized by DHODH as the final electron acceptor in lieu of CoQn when the endogenous substrate is at a low concentration. As such, the direct assay was used to measure the binding affinity of pfDHODH to CoQD and L-DHO. The enzymatic reaction was performed by varying the L-DHO concentration (1-400 μM) or CoQD concentration (1-200 μM) while keeping the other substrate constant and in excess. Inhibition of DHODH by small molecules was evaluated using the chromogen based assay with a final substrate concentration of 200 μM L-DHO, 18 μM CoQD, and 100 μM DCIP, unless otherwise noted.
Measurement: IC50 = 930 nM (pChEMBL 6.03000020980835)
Descriptors: MW 261.32, ALogP 4.42, HBA 2, HBD 1, PSA 33.12, QED 0.74
Compound (SMILES): CCCCCC1CCCc2c1nc1ccccc1c2O
InChIKey: BLBSNYYRLAWWDS-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (quinone), mitochondrial (SINGLE PROTEIN), Plasmodium berghei (strain Anka)
UniProt: A0A0Y9T855
Assay: Enzymatic Assays: Type 2 DHODH activity was monitored with either the direct assay measuring the formation of orotate or via a chromogen reduction assay using DCIP. Although the extinction coefficient and absorption wavelength are preferable for the chromogen reduction assay, the inorganic electron acceptor DCIP can be utilized by DHODH as the final electron acceptor in lieu of CoQn when the endogenous substrate is at a low concentration. As such, the direct assay was used to measure the binding affinity of pfDHODH to CoQD and L-DHO. The enzymatic reaction was performed by varying the L-DHO concentration (1-400 μM) or CoQD concentration (1-200 μM) while keeping the other substrate constant and in excess. Inhibition of DHODH by small molecules was evaluated using the chromogen based assay with a final substrate concentration of 200 μM L-DHO, 18 μM CoQD, and 100 μM DCIP, unless otherwise noted.
Measurement: IC50 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 269.39, ALogP 4.94, HBA 2, HBD 1, PSA 33.12, QED 0.8
Compound (SMILES): CCCNC(=O)c1ccc(-n2c(C)cc3ccccc32)s1
InChIKey: OQYMMMMIAASALW-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (SINGLE PROTEIN), Plasmodium falciparum
UniProt: Q54A96
Assay: Enzymatic Assays: Type 2 DHODH activity was monitored with either the direct assay measuring the formation of orotate or via a chromogen reduction assay using DCIP. Although the extinction coefficient and absorption wavelength are preferable for the chromogen reduction assay, the inorganic electron acceptor DCIP can be utilized by DHODH as the final electron acceptor in lieu of CoQn when the endogenous substrate is at a low concentration. As such, the direct assay was used to measure the binding affinity of pfDHODH to CoQD and L-DHO. The enzymatic reaction was performed by varying the L-DHO concentration (1-400 μM) or CoQD concentration (1-200 μM) while keeping the other substrate constant and in excess. Inhibition of DHODH by small molecules was evaluated using the chromogen based assay with a final substrate concentration of 200 μM L-DHO, 18 μM CoQD, and 100 μM DCIP, unless otherwise noted.
Measurement: IC50 = 42 nM (pChEMBL 7.380000114440918)
Descriptors: MW 298.41, ALogP 4.14, HBA 3, HBD 1, PSA 34.03, QED 0.77
Compound (SMILES): O=C(NC1CC1)c1ccc(N2CCSc3ccccc32)s1
InChIKey: RNLKPTOJCXLFDG-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (SINGLE PROTEIN), Plasmodium falciparum
UniProt: Q54A96
Assay: Enzymatic Assays: Type 2 DHODH activity was monitored with either the direct assay measuring the formation of orotate or via a chromogen reduction assay using DCIP. Although the extinction coefficient and absorption wavelength are preferable for the chromogen reduction assay, the inorganic electron acceptor DCIP can be utilized by DHODH as the final electron acceptor in lieu of CoQn when the endogenous substrate is at a low concentration. As such, the direct assay was used to measure the binding affinity of pfDHODH to CoQD and L-DHO. The enzymatic reaction was performed by varying the L-DHO concentration (1-400 μM) or CoQD concentration (1-200 μM) while keeping the other substrate constant and in excess. Inhibition of DHODH by small molecules was evaluated using the chromogen based assay with a final substrate concentration of 200 μM L-DHO, 18 μM CoQD, and 100 μM DCIP, unless otherwise noted.
Measurement: IC50 = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 316.45, ALogP 3.88, HBA 4, HBD 1, PSA 32.34, QED 0.93
Compound (SMILES): Cc1nc(CN(C)C(=O)c2cccc(C(=O)N[C@@H](Cc3ccccc3)[C@H](O)C3NCCN(Cc4ccccc4)C3=O)c2)cs1
InChIKey: JCNCCHUDAASMSY-GAVYTZHXSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition Assay: The potencies of compounds were determined by measurement of their inhibition of memapsin 2 catalytic activity toward a fluorescent substrate. Kinetic inhibition experiments were performed using the procedure as described in Ermolieff, et al. Biochemistry 39:12450-12456 (2000), the teachings of which are incorporated hereby in their entirety. Briefly, assays were performed at pH 4, 37° C., by pre-incubation of memapsin 2 enzyme with compound for 20 minutes. Activity measure was initiated by addition of a fluorogenic substrate FS-2 (Bachem Americas, Torrance, Calif.).
Measurement: IC50 < 10000 nM (pChEMBL 5)
Descriptors: MW 611.77, ALogP 3.43, HBA 7, HBD 3, PSA 114.87, QED 0.24
Compound (SMILES): CC(C)CN1CCN[C@@H]([C@@H](O)[C@H](Cc2ccccc2)NC(=O)c2cc(C(=O)N[C@H](C)c3ccccc3)cc(N(C)S(C)(=O)=O)c2)C1=O
InChIKey: XVHBFKBJMOUAGF-GCJCAGDSSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of recombinant human BACE1 (Ala8P to Ala326 residues) expressed in Escherichia coli BL21(DE3) using Arg-Glu(EDANS)-Glu-Val-Asn-Leu-Asp-Ala-Glu-Phe-Lys (Dabcyl)-Arg as substrate by fluorescence assay
Measurement: Ki = 12.9 nM (pChEMBL 7.889999866485596)
Descriptors: MW 663.84, ALogP 2.73, HBA 7, HBD 4, PSA 148.15, QED 0.22
Compound (SMILES): COc1ccc(CN2CCN[C@@H]([C@@H](O)[C@H](Cc3ccccc3)NC(=O)c3cc(C(=O)N[C@H](C)c4ccccc4)cc(N(C)S(C)(=O)=O)c3)C2=O)cc1
InChIKey: LAYJOTDSIADFSB-FBCAFTLCSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of recombinant human BACE1 (Ala8P to Ala326 residues) expressed in Escherichia coli BL21(DE3) using Arg-Glu(EDANS)-Glu-Val-Asn-Leu-Asp-Ala-Glu-Phe-Lys (Dabcyl)-Arg as substrate by fluorescence assay
Measurement: Ki = 81.4 nM (pChEMBL 7.090000152587891)
Descriptors: MW 727.88, ALogP 3.28, HBA 8, HBD 4, PSA 157.38, QED 0.15
Compound (SMILES): COc1cccc(CN2CCN[C@@H]([C@@H](O)[C@H](Cc3ccccc3)NC(=O)c3cc(C(=O)N[C@H](C)c4ccccc4)cc(N(C)S(C)(=O)=O)c3)C2=O)c1
InChIKey: LXVLCSGCXPGNLZ-FBCAFTLCSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of recombinant human BACE1 (Ala8P to Ala326 residues) expressed in Escherichia coli BL21(DE3) using Arg-Glu(EDANS)-Glu-Val-Asn-Leu-Asp-Ala-Glu-Phe-Lys (Dabcyl)-Arg as substrate by fluorescence assay
Measurement: Ki = 129 nM (pChEMBL 6.889999866485596)
Descriptors: MW 727.88, ALogP 3.28, HBA 8, HBD 4, PSA 157.38, QED 0.15
Compound (SMILES): Cc1ccc(-n2nccn2)c(C(=O)N2C[C@H](Nc3nccc4ccccc34)CC[C@H]2C)c1
InChIKey: NTCHIMSKJJOQPB-UYAOXDASSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Radioligand Binding Assay: Compound potency can be assessed by a radioligand binding assay (described in Bergman et. al. Bioorg. Med. Chem. Lett. 2008, 18, 1425-1430) in which the inhibition constant (Ki) is determined in membranes prepared from CHO cells expressing either the orexin-1 (OX1) or orexin-2 (OX2) receptor.
Measurement: Ki = 0.56 nM (pChEMBL 9.25)
Descriptors: MW 426.52, ALogP 4.23, HBA 6, HBD 1, PSA 75.94, QED 0.53
Compound (SMILES): C[C@@H]1CC[C@@H](Oc2cccc3ocnc23)CN1C(=O)c1ccccc1-n1nccn1
InChIKey: KCSVKKJYYFTKCU-HZPDHXFCSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Radioligand Binding Assay: Compound potency can be assessed by a radioligand binding assay (described in Bergman et. al. Bioorg. Med. Chem. Lett. 2008, 18, 1425-1430) in which the inhibition constant (Ki) is determined in membranes prepared from CHO cells expressing either the orexin-1 (OX1) or orexin-2 (OX2) receptor.
Measurement: Ki = 18.33 nM (pChEMBL 7.739999771118164)
Descriptors: MW 403.44, ALogP 3.48, HBA 7, HBD 0, PSA 86.28, QED 0.52
Compound (SMILES): COc1ccccc1-c1cc(NC(=O)C2CCC(=O)NC2)ncn1
InChIKey: NFQWUUWZHAEWSA-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: In Vitro Kinase Inhibition Assays: All kinase assays were performed in 96-well FlashPlates from Perkin Elmer/NEN (Boston, Mass., USA) in a 50 μl reaction volume. The reaction mixture was pipetted in four steps in the following order:20 μl of assay buffer (standard buffer),5 μl of ATP solution (in H2O),5 μl of test compound (in 10% DMSO),10 μl of substrate/10 μl of enzyme solution (premixed),The assay for all enzymes contained 60 mM HEPES-NaOH, pH 7.5, 3 mM MgCl2, 3 mM MnCl2, 3 μM Na-Orthovanadate, 1.2 mM DTT, 50 μg/ml PEG20000, 1 μM [-33P]-ATP (approx. 5×1005 cpm per well).
Measurement: IC50 = 0.173 nM (pChEMBL 9.760000228881836)
Descriptors: MW 326.36, ALogP 1.62, HBA 5, HBD 2, PSA 93.21, QED 0.89
Compound (SMILES): CC(C)OCCOc1nc(Oc2ccc3c(c2)COB3O)c(Cl)cc1C#N
InChIKey: BKBBEYMNJXXDAQ-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: P27815
Assay: Inhibition Assay: Inhibition of the human PDE4 enzyme, using semi-purified enzyme from human U937 cells. The PDE4 enzyme was partially purified from human U937 myeloid leukemia cells and activity was assayed using a method optimized from Cortijo et al (10, Cortijo 1993) and Nicholson et al. (11, Nicholson, 1991). Test article and/or vehicle was incubated with 0.2 mg of enzyme and 1 μM cAMP containing 0.01 μM [3H]cAMP in Tris buffer (50 mM Tris-HCl pH 7.5, 5 mM MgCl2) for 20 minutes at 25° C. The reaction was terminated by boiling for 2 minutes and the resulting AMP was converted to adenosine by addition of 10 mg/ml snake venom nucleotidase and further incubation at 37° C. for 10 min. Unhydrolyzed cAMP was bound to AG1-X2 resin, and the remaining [3H] adenosine in the aqueous phase was quantitated by scintillation counting.
Measurement: IC50 = 5.2 nM (pChEMBL 8.279999732971191)
Descriptors: MW 388.62
Compound (SMILES): CC(=O)CCCOc1nc(Oc2ccc3c(c2)COB3O)c(Cl)cc1C#N
InChIKey: BEYCUVURKUGSEQ-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: P27815
Assay: Inhibition Assay: Inhibition of the human PDE4 enzyme, using semi-purified enzyme from human U937 cells. The PDE4 enzyme was partially purified from human U937 myeloid leukemia cells and activity was assayed using a method optimized from Cortijo et al (10, Cortijo 1993) and Nicholson et al. (11, Nicholson, 1991). Test article and/or vehicle was incubated with 0.2 mg of enzyme and 1 μM cAMP containing 0.01 μM [3H]cAMP in Tris buffer (50 mM Tris-HCl pH 7.5, 5 mM MgCl2) for 20 minutes at 25° C. The reaction was terminated by boiling for 2 minutes and the resulting AMP was converted to adenosine by addition of 10 mg/ml snake venom nucleotidase and further incubation at 37° C. for 10 min. Unhydrolyzed cAMP was bound to AG1-X2 resin, and the remaining [3H] adenosine in the aqueous phase was quantitated by scintillation counting.
Measurement: IC50 = 0.8 nM (pChEMBL 9.100000381469727)
Descriptors: MW 386.6
Compound (SMILES): COCC(COc1nc(Oc2ccc3c(c2)COB3O)c(Cl)cc1C#N)OC
InChIKey: WLRPIEXEHDHNIW-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4B (SINGLE PROTEIN), Homo sapiens
UniProt: Q07343
Assay: Inhibition Assay: Inhibition of the human PDE4 enzyme, using semi-purified enzyme from human U937 cells. The PDE4 enzyme was partially purified from human U937 myeloid leukemia cells and activity was assayed using a method optimized from Cortijo et al (10, Cortijo 1993) and Nicholson et al. (11, Nicholson, 1991). Test article and/or vehicle was incubated with 0.2 mg of enzyme and 1 μM cAMP containing 0.01 μM [3H]cAMP in Tris buffer (50 mM Tris-HCl pH 7.5, 5 mM MgCl2) for 20 minutes at 25° C. The reaction was terminated by boiling for 2 minutes and the resulting AMP was converted to adenosine by addition of 10 mg/ml snake venom nucleotidase and further incubation at 37° C. for 10 min. Unhydrolyzed cAMP was bound to AG1-X2 resin, and the remaining [3H] adenosine in the aqueous phase was quantitated by scintillation counting.
Measurement: IC50 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 404.62
Compound (SMILES): N#Cc1cc(Cl)c(Oc2ccc3c(c2)COB3O)nc1OCCOC1CC1
InChIKey: JXQLQPODTZFKHM-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: P27815
Assay: Inhibition Assay: Inhibition of the human PDE4 enzyme, using semi-purified enzyme from human U937 cells. The PDE4 enzyme was partially purified from human U937 myeloid leukemia cells and activity was assayed using a method optimized from Cortijo et al (10, Cortijo 1993) and Nicholson et al. (11, Nicholson, 1991). Test article and/or vehicle was incubated with 0.2 mg of enzyme and 1 μM cAMP containing 0.01 μM [3H]cAMP in Tris buffer (50 mM Tris-HCl pH 7.5, 5 mM MgCl2) for 20 minutes at 25° C. The reaction was terminated by boiling for 2 minutes and the resulting AMP was converted to adenosine by addition of 10 mg/ml snake venom nucleotidase and further incubation at 37° C. for 10 min. Unhydrolyzed cAMP was bound to AG1-X2 resin, and the remaining [3H] adenosine in the aqueous phase was quantitated by scintillation counting.
Measurement: IC50 = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 386.6
Compound (SMILES): CC(C)OCCOc1nc(Oc2ccc3c(c2)COB3O)cc(C(F)(F)F)c1C#N
InChIKey: DSHINXNFGWBHRA-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: P27815
Assay: Inhibition Assay: Inhibition of the human PDE4 enzyme, using semi-purified enzyme from human U937 cells. The PDE4 enzyme was partially purified from human U937 myeloid leukemia cells and activity was assayed using a method optimized from Cortijo et al (10, Cortijo 1993) and Nicholson et al. (11, Nicholson, 1991). Test article and/or vehicle was incubated with 0.2 mg of enzyme and 1 μM cAMP containing 0.01 μM [3H]cAMP in Tris buffer (50 mM Tris-HCl pH 7.5, 5 mM MgCl2) for 20 minutes at 25° C. The reaction was terminated by boiling for 2 minutes and the resulting AMP was converted to adenosine by addition of 10 mg/ml snake venom nucleotidase and further incubation at 37° C. for 10 min. Unhydrolyzed cAMP was bound to AG1-X2 resin, and the remaining [3H] adenosine in the aqueous phase was quantitated by scintillation counting.
Measurement: IC50 = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 422.17
Compound (SMILES): CC(C)OCCOc1nc(Oc2ccc3c(c2)COB3O)c(C#N)cc1C#N
InChIKey: VUKLRTNDLAMXGZ-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: P27815
Assay: Inhibition Assay: Inhibition of the human PDE4 enzyme, using semi-purified enzyme from human U937 cells. The PDE4 enzyme was partially purified from human U937 myeloid leukemia cells and activity was assayed using a method optimized from Cortijo et al (10, Cortijo 1993) and Nicholson et al. (11, Nicholson, 1991). Test article and/or vehicle was incubated with 0.2 mg of enzyme and 1 μM cAMP containing 0.01 μM [3H]cAMP in Tris buffer (50 mM Tris-HCl pH 7.5, 5 mM MgCl2) for 20 minutes at 25° C. The reaction was terminated by boiling for 2 minutes and the resulting AMP was converted to adenosine by addition of 10 mg/ml snake venom nucleotidase and further incubation at 37° C. for 10 min. Unhydrolyzed cAMP was bound to AG1-X2 resin, and the remaining [3H] adenosine in the aqueous phase was quantitated by scintillation counting.
Measurement: IC50 = 6.5 nM (pChEMBL 8.1899995803833)
Descriptors: MW 379.18
Compound (SMILES): CC(=O)CCCOc1nc(Oc2cc(C)c3c(c2)COB3O)c(Cl)cc1C#N
InChIKey: KRPGYDWKKKFLRX-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: P27815
Assay: Inhibition Assay: Inhibition of the human PDE4 enzyme, using semi-purified enzyme from human U937 cells. The PDE4 enzyme was partially purified from human U937 myeloid leukemia cells and activity was assayed using a method optimized from Cortijo et al (10, Cortijo 1993) and Nicholson et al. (11, Nicholson, 1991). Test article and/or vehicle was incubated with 0.2 mg of enzyme and 1 μM cAMP containing 0.01 μM [3H]cAMP in Tris buffer (50 mM Tris-HCl pH 7.5, 5 mM MgCl2) for 20 minutes at 25° C. The reaction was terminated by boiling for 2 minutes and the resulting AMP was converted to adenosine by addition of 10 mg/ml snake venom nucleotidase and further incubation at 37° C. for 10 min. Unhydrolyzed cAMP was bound to AG1-X2 resin, and the remaining [3H] adenosine in the aqueous phase was quantitated by scintillation counting.
Measurement: IC50 = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 400.63
Compound (SMILES): CC(C)OCCOc1nc(Oc2cc(F)c3c(c2)COB3O)c(Cl)cc1C#N
InChIKey: UPBKTTZHNZAEQA-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4B (SINGLE PROTEIN), Homo sapiens
UniProt: Q07343
Assay: Inhibition Assay: Inhibition of the human PDE4 enzyme, using semi-purified enzyme from human U937 cells. The PDE4 enzyme was partially purified from human U937 myeloid leukemia cells and activity was assayed using a method optimized from Cortijo et al (10, Cortijo 1993) and Nicholson et al. (11, Nicholson, 1991). Test article and/or vehicle was incubated with 0.2 mg of enzyme and 1 μM cAMP containing 0.01 μM [3H]cAMP in Tris buffer (50 mM Tris-HCl pH 7.5, 5 mM MgCl2) for 20 minutes at 25° C. The reaction was terminated by boiling for 2 minutes and the resulting AMP was converted to adenosine by addition of 10 mg/ml snake venom nucleotidase and further incubation at 37° C. for 10 min. Unhydrolyzed cAMP was bound to AG1-X2 resin, and the remaining [3H] adenosine in the aqueous phase was quantitated by scintillation counting.
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 406.61
Compound (SMILES): CC(=O)CCCOc1nc(Oc2cc(F)c3c(c2)COB3O)c(Cl)cc1C#N
InChIKey: XONFIBGUKUGPPG-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: P27815
Assay: Inhibition Assay: Inhibition of the human PDE4 enzyme, using semi-purified enzyme from human U937 cells. The PDE4 enzyme was partially purified from human U937 myeloid leukemia cells and activity was assayed using a method optimized from Cortijo et al (10, Cortijo 1993) and Nicholson et al. (11, Nicholson, 1991). Test article and/or vehicle was incubated with 0.2 mg of enzyme and 1 μM cAMP containing 0.01 μM [3H]cAMP in Tris buffer (50 mM Tris-HCl pH 7.5, 5 mM MgCl2) for 20 minutes at 25° C. The reaction was terminated by boiling for 2 minutes and the resulting AMP was converted to adenosine by addition of 10 mg/ml snake venom nucleotidase and further incubation at 37° C. for 10 min. Unhydrolyzed cAMP was bound to AG1-X2 resin, and the remaining [3H] adenosine in the aqueous phase was quantitated by scintillation counting.
Measurement: IC50 = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 404.59
Compound (SMILES): CC(=O)CCCOc1nc(Oc2ccc3c(c2)COB3O)c(C#N)cc1Cl
InChIKey: CGGDBFMTDWNCOY-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4B (SINGLE PROTEIN), Homo sapiens
UniProt: Q07343
Assay: Inhibition Assay: Inhibition of the human PDE4 enzyme, using semi-purified enzyme from human U937 cells. The PDE4 enzyme was partially purified from human U937 myeloid leukemia cells and activity was assayed using a method optimized from Cortijo et al (10, Cortijo 1993) and Nicholson et al. (11, Nicholson, 1991). Test article and/or vehicle was incubated with 0.2 mg of enzyme and 1 μM cAMP containing 0.01 μM [3H]cAMP in Tris buffer (50 mM Tris-HCl pH 7.5, 5 mM MgCl2) for 20 minutes at 25° C. The reaction was terminated by boiling for 2 minutes and the resulting AMP was converted to adenosine by addition of 10 mg/ml snake venom nucleotidase and further incubation at 37° C. for 10 min. Unhydrolyzed cAMP was bound to AG1-X2 resin, and the remaining [3H] adenosine in the aqueous phase was quantitated by scintillation counting.
Measurement: IC50 = 0.25 nM (pChEMBL 9.600000381469727)
Descriptors: MW 386.6
Compound (SMILES): O[C@H]1CCC[C@H](c2cccnc2Oc2ccc(Nc3nc4ccccc4s3)cc2)C1
InChIKey: HHGBPGARRHXTDJ-WMZOPIPTSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Enzyme Inhibition Assay: To check the inhibition profile, 5 μL of serial diluted compounds were incubated with 5 μL of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.) for 30 min at room temperature. After incubation, 10 μL of diluted fluorescein labeled cAMP or cGMP substrate were added and incubated for 60 min at room temperature. The reaction was stopped by adding 60 μL of diluted binding reagents and plates were read on an Envision (Perkin Elmer, Waltham, Mass.) for time resolved fluorescence resonance energy transfer. The data were analyzed with GraphPad Prism (La Jolla, Calif.).
Measurement: IC50 = 9.93 nM (pChEMBL 8)
Descriptors: MW 417.53, ALogP 6.25, HBA 6, HBD 2, PSA 67.27, QED 0.4
Compound (SMILES): O=C(c1ccc(Oc2ncccc2[C@@H]2CCC[C@@H](O)C2)cc1)c1nc2ccccc2[nH]1
InChIKey: ULRZEXNCMHFJNG-QZTJIDSGSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Enzyme Inhibition Assay: To check the inhibition profile, 5 μL of serial diluted compounds were incubated with 5 μL of diluted PDE10 enzyme (BPS Bioscience, San Diego, Calif.) or tissue homogenate in a 384-well polystyrene assay plate (Corning, Corning, N.Y.) for 30 min at room temperature. After incubation, 10 μL of diluted fluorescein labeled cAMP or cGMP substrate were added and incubated for 60 min at room temperature. The reaction was stopped by adding 60 μL of diluted binding reagents and plates were read on an Envision (Perkin Elmer, Waltham, Mass.) for time resolved fluorescence resonance energy transfer. The data were analyzed with GraphPad Prism (La Jolla, Calif.).
Measurement: IC50 = 0.585 nM (pChEMBL 9.229999542236328)
Descriptors: MW 413.48, ALogP 5, HBA 5, HBD 2, PSA 88.1, QED 0.45
Compound (SMILES): Cn1c(Nc2c(Cl)ccc(CNC(=O)C(C)(C)C)c2Cl)nc2cc(C(=O)Nc3ccc(Cl)cc3F)c(OCC(F)F)cc21
InChIKey: BPHPOXOCKDIPBH-UHFFFAOYSA-N
Target: Prostaglandin E synthase (SINGLE PROTEIN), Homo sapiens
UniProt: O14684
Assay: Inhibition of recombinant human mPGES1 using PGH2 as substrate pretreated for 25 mins followed by substrate addition measured after 60 secs by HTRF assay
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 656.92, ALogP 7.97, HBA 6, HBD 3, PSA 97.28, QED 0.17
Compound (SMILES): Clc1cnc2nc1NCc1cccc(c1)OCc1cccc(c1)N2
InChIKey: PKOKZOVQUJMMJL-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: In Vitro Kinase Assay: One or more compounds herein were tested for inhibitory activity of JAK targets according to the following in vitro assay described in Park et al., Analytical Biochemistry 1999, 269, 94-104. The catalytic domains of human JAK1 (a.a. 837-1142), JAK2 (a.a. 828-1132) and JAK3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. The ATP concentration in the reactions was 90 uM for JAK1, 30 uM for JAK2 and 3 uM for JAK3. Reactions were carried out at room temperature for 1 hr and then stopped with 20 uL 45 mM EDTA.
Measurement: IC50 = 51 nM (pChEMBL 7.289999961853027)
Descriptors: MW 338.8, ALogP 4.38, HBA 5, HBD 2, PSA 59.07, QED 0.64
Compound (SMILES): Clc1cnc2nc1NCc1cccc(c1)OCCc1cccc(c1)N2
InChIKey: HOLZGQKSANGENU-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: TYK2 Assay: TYK2 assays described by James E. Thompson et. al, Photochemical preparation of a pyridone containing tetracycle: A JAK protein kinase inhibitor, Bioorganic & Medicinal Chemistry Letters, Volume 12, Issue 8, 22 Apr. 2002, Pages 1219-1223].
Measurement: IC50 = 35 nM (pChEMBL 7.460000038146973)
Descriptors: MW 352.83, ALogP 4.42, HBA 5, HBD 2, PSA 59.07, QED 0.63
Compound (SMILES): O=S1(=O)Nc2cccc(c2)CNc2nc(ncc2Cl)Nc2cccc1c2
InChIKey: ARCKFUMURBKDRR-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: In Vitro Kinase Assay: One or more compounds herein were tested for inhibitory activity of JAK targets according to the following in vitro assay described in Park et al., Analytical Biochemistry 1999, 269, 94-104. The catalytic domains of human JAK1 (a.a. 837-1142), JAK2 (a.a. 828-1132) and JAK3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. The ATP concentration in the reactions was 90 uM for JAK1, 30 uM for JAK2 and 3 uM for JAK3. Reactions were carried out at room temperature for 1 hr and then stopped with 20 uL 45 mM EDTA.
Measurement: IC50 = 325 nM (pChEMBL 6.489999771118164)
Descriptors: MW 387.85, ALogP 3.6, HBA 6, HBD 3, PSA 96.01, QED 0.55
Compound (SMILES): O=C1Nc2cccc(c2)CNc2nc(ncc2Cl)Nc2cccc1c2
InChIKey: WKFDYXPIKYJBDD-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: In Vitro Kinase Assay: One or more compounds herein were tested for inhibitory activity of JAK targets according to the following in vitro assay described in Park et al., Analytical Biochemistry 1999, 269, 94-104. The catalytic domains of human JAK1 (a.a. 837-1142), JAK2 (a.a. 828-1132) and JAK3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. The ATP concentration in the reactions was 90 uM for JAK1, 30 uM for JAK2 and 3 uM for JAK3. Reactions were carried out at room temperature for 1 hr and then stopped with 20 uL 45 mM EDTA.
Measurement: IC50 = 104 nM (pChEMBL 6.980000019073486)
Descriptors: MW 351.8, ALogP 4.05, HBA 5, HBD 3, PSA 78.94, QED 0.57
Compound (SMILES): Clc1cnc2nc1NCc1cccc(c1)OCCCc1cccc(c1)N2
InChIKey: WILMKMPUMOSDLH-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: In Vitro Kinase Assay: One or more compounds herein were tested for inhibitory activity of JAK targets according to the following in vitro assay described in Park et al., Analytical Biochemistry 1999, 269, 94-104. The catalytic domains of human JAK1 (a.a. 837-1142), JAK2 (a.a. 828-1132) and JAK3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. The ATP concentration in the reactions was 90 uM for JAK1, 30 uM for JAK2 and 3 uM for JAK3. Reactions were carried out at room temperature for 1 hr and then stopped with 20 uL 45 mM EDTA.
Measurement: IC50 = 2.4 nM (pChEMBL 8.619999885559082)
Descriptors: MW 366.85, ALogP 4.81, HBA 5, HBD 2, PSA 59.07, QED 0.6
Compound (SMILES): C[C@H]1Nc2nc(ncc2Cl)Nc2cccc(c2)COc2cccc1c2
InChIKey: OMIMDZMFZXMMGS-GFCCVEGCSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: In Vitro Kinase Assay: One or more compounds herein were tested for inhibitory activity of JAK targets according to the following in vitro assay described in Park et al., Analytical Biochemistry 1999, 269, 94-104. The catalytic domains of human JAK1 (a.a. 837-1142), JAK2 (a.a. 828-1132) and JAK3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. The ATP concentration in the reactions was 90 uM for JAK1, 30 uM for JAK2 and 3 uM for JAK3. Reactions were carried out at room temperature for 1 hr and then stopped with 20 uL 45 mM EDTA.
Measurement: IC50 = 140 nM (pChEMBL 6.849999904632568)
Descriptors: MW 352.83, ALogP 4.94, HBA 5, HBD 2, PSA 59.07, QED 0.6
Compound (SMILES): Clc1cnc2nc1NCc1cccc(c1)OCCOc1cccc(c1)N2
InChIKey: JRMWFZSAQXNBSZ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: In Vitro Kinase Assay: One or more compounds herein were tested for inhibitory activity of JAK targets according to the following in vitro assay described in Park et al., Analytical Biochemistry 1999, 269, 94-104. The catalytic domains of human JAK1 (a.a. 837-1142), JAK2 (a.a. 828-1132) and JAK3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. The ATP concentration in the reactions was 90 uM for JAK1, 30 uM for JAK2 and 3 uM for JAK3. Reactions were carried out at room temperature for 1 hr and then stopped with 20 uL 45 mM EDTA.
Measurement: IC50 = 6.4 nM (pChEMBL 8.1899995803833)
Descriptors: MW 368.82, ALogP 4.26, HBA 6, HBD 2, PSA 68.3, QED 0.62
Compound (SMILES): Clc1cnc2nc1NCCc1cccc(c1)OCc1cccc(c1)N2
InChIKey: BBVOVZFYMUEXGT-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: TYK2 Assay: TYK2 assays described by James E. Thompson et. al, Photochemical preparation of a pyridone containing tetracycle: A JAK protein kinase inhibitor, Bioorganic & Medicinal Chemistry Letters, Volume 12, Issue 8, 22 Apr. 2002, Pages 1219-1223].
Measurement: IC50 = 438 nM (pChEMBL 6.360000133514404)
Descriptors: MW 352.83, ALogP 4.42, HBA 5, HBD 2, PSA 59.07, QED 0.63
Compound (SMILES): Clc1cnc2nc1NCCc1cccc(c1)OCCc1cccc(c1)N2
InChIKey: DDEPHNOBUQYIBZ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: In Vitro Kinase Assay: One or more compounds herein were tested for inhibitory activity of JAK targets according to the following in vitro assay described in Park et al., Analytical Biochemistry 1999, 269, 94-104. The catalytic domains of human JAK1 (a.a. 837-1142), JAK2 (a.a. 828-1132) and JAK3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. The ATP concentration in the reactions was 90 uM for JAK1, 30 uM for JAK2 and 3 uM for JAK3. Reactions were carried out at room temperature for 1 hr and then stopped with 20 uL 45 mM EDTA.
Measurement: IC50 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 366.85, ALogP 4.46, HBA 5, HBD 2, PSA 59.07, QED 0.61