lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): N#Cc1ccc(CN2CCC(NC(=O)c3ccc(C(=O)N4CCC(C(F)c5ccc(F)cc5)CC4)cn3)CC2)cc1
InChIKey: FJNHSBVZTQFKEF-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) in presence of NADPH
Measurement: IC50 = 9800 nM (pChEMBL 5.010000228881836)
Descriptors: MW 557.65, ALogP 5.05, HBA 5, HBD 1, PSA 89.33, QED 0.44
Compound (SMILES): N#Cc1ccc2[nH]cc(CCCCN3CCC(c4cn(-c5ccc(Oc6ccc(Cl)cc6)cc5)c(C5CCCCC5)n4)CC3)c2c1
InChIKey: JTLLNPQSUHMCED-UHFFFAOYSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P31645
Assay: Inhibition of SERT (unknown origin) expressed in human HEK293 cells
Measurement: IC50 = 14.17 nM (pChEMBL 7.849999904632568)
Descriptors: MW 632.25, ALogP 9.92, HBA 5, HBD 1, PSA 69.87, QED 0.16
Compound (SMILES): O=C1COc2ccc(CN[C@H]3CO[C@H](CC4Cn5c(=O)ccc6ncc(F)c4c65)OC3)nc2N1
InChIKey: DTODKLZFABOOOA-CWJUMGKGSA-N
Target: DNA gyrase (PROTEIN COMPLEX), Staphylococcus aureus
UniProt: P0A0K8
Assay: Inhibition of Staphylococcus aureus DNA gyrase supercoiling activity incubated for 25 min by ethidium bromide/bromophenol blue staining based agarose gel electrophoresis analysis
Measurement: IC50 = 4200 nM (pChEMBL 5.380000114440918)
Descriptors: MW 467.46, ALogP 1.28, HBA 9, HBD 2, PSA 116.6, QED 0.58
Compound (SMILES): Cc1ccccc1C1C(=O)N(C)c2cnc(Nc3ccc(S(N)(=O)=O)cc3)nc2N1C
InChIKey: FWEIAKDAIDQPRK-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13188
Assay: Inhibition of recombinant full length N-terminal GST -tagged human MST2 expressed in baculovirus infected Sf9 insect cells using KKSRGDYMTMQIG as substrate incubated for 1 hr in presence of ATP by ADP-Glo luminescent assay
Measurement: IC50 = 652 nM (pChEMBL 6.190000057220459)
Descriptors: MW 438.51, ALogP 2.33, HBA 7, HBD 2, PSA 121.52, QED 0.64
Compound (SMILES): COc1cc(N2CCN(C)CC2)ccc1Nc1ncc(C)c(Nc2ccc3cn[nH]c3c2)n1
InChIKey: KHZNPBYKXJANSV-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Inhibition of PDGFRbeta (unknown origin) by caliper mobility shift assay
Measurement: IC50 = 44.1 nM (pChEMBL 7.360000133514404)
Descriptors: MW 444.54, ALogP 3.91, HBA 8, HBD 3, PSA 94.23, QED 0.41
Compound (SMILES): CC(C)NC[C@@H](C(=O)N1CCN(c2ncnc3c2[C@H]2C[C@H]2C(=O)N3)CC1)c1ccc(Cl)cc1
InChIKey: KBKHULLGXKATKS-IPMKNSEASA-N
Target: RAC-beta serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31751
Assay: Inhibition of recombinant AKT2 (120 to 481 end residues) (unknown origin) catalytic domain expressed in Sf21 cells using peptide substrate incubated for 1 hr in presence of ATP by caliper off-chip mobility shift assay
Measurement: IC50 = 475 nM (pChEMBL 6.320000171661377)
Descriptors: MW 468.99, ALogP 2.62, HBA 6, HBD 2, PSA 90.46, QED 0.68
Compound (SMILES): COc1cc(CCc2cc(-c3nc4ccc(C(=O)N5CCN(C)CC5)cc4[nH]3)n[nH]2)cc(OC)c1
InChIKey: HIRADXZLYXUWGK-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition Kinases In Vitro Assay: The compounds were dissolved in 100% DMSO, and obtained solutions were serially diluted in reaction buffer (50 mM Tris pH 7.5, 10 mM MgCl2, 0.25 mM EGTA, 0.1 mM Na3VO4, 0.01% Triton X-100, 2.5 mM DTT). Recombinant FGFR1, FGFR2, FGFR3 or KDR kinase (Carna Biosciences) was diluted to final concentration of 0.1 ng/μL in the dilution buffer (50 mM Tris-HCl pH 7.5, 150 mM NaCl, 10% glycerol, 0.05% Triton X-100, 1 mM DTT). 5 μL of prepared solutions of the compounds along with 5 μL of selected kinase solution were added to each well of a 96-well plate. The plate was incubated for 10 minutes at 25° C. in plate shaker thermostat with orbital shaking at 400 rpm. To negative control wells all reagents were added except compounds and kinase, while to positive control wells all reagents except tested compounds. The reaction was initiated by adding 15 μL of solution consisting of 5× concentrated reaction buffer (50 mM Tris pH 7.5, 10 mM MgCl2, 0.25 mM EGTA, 0.1 mM Na3VO4, 0.01% Triton X-100, 2.5 mM DTT), water, 50 μM ATP, 16.67 μM IGF-1Rtide peptide (Milipore). Than the plate was incubated for 1 hour at 25° C. in plate shaker thermostat with orbital shaking at 400 rpm. Detection of ADP obtained in enzymatic reaction was performed with ADP-Glo Kinase Assay (Promega). 25 μL of ADP-Glo Reagent was added to each well of 96-well plate and the plate was incubated for 40 minutes at 25° C. in plate shaker thermostat with orbital shaking at 400 rpm. Then 50 μL of Kinase Detection Reagent was added to each well of 96-well plate and the plate was incubated for 30 minutes at 25° C. in plate shaker thermostat with orbital shaking at 400 rpm. Finally, the intensity of luminescence was measured using Victor Light luminometer (Perkin Elmer, Inc.).
Measurement: IC50 = 2.13 nM (pChEMBL 8.670000076293945)
Descriptors: MW 474.57, ALogP 3.14, HBA 6, HBD 2, PSA 99.37, QED 0.43
Compound (SMILES): COc1ccc(S(=O)(=O)n2cc(C)c3cc(Br)ccc32)cc1N1CCNCC1
InChIKey: AOAOBXLWOLIEQK-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Biological Assay: The binding affinity of the compound of this invention to human 5-HT6 receptor expressed in CHO cell was evaluated by radioligand binding assay as follows.32 μg membrane proteins of CHO cell expressing human 5-HT6 receptor, 2 nM of radioactive marker [3H]LSD, the compound of the present invention having different test concentrations and a buffer solution were mixed uniformly, and the resulting mixture was incubated at 37° C. for 120 mins, in which the buffer solution was comprised of 50 mM Tris-HCl (pH 7.4), 10 mM MgCl2, 0.5 mM EDTA, 10 μM pargyline and 20 mg/L protease inhibitor.100 μM of 5-HT was added to the mixture to eliminate nonspecific binding sites. After incubation, the resulting mixture was filtered with glassfabricfilter in vacuo, and the glassfabricfilter should be preimpregnated with 0.3% PEI before filtering and washed with 50 mM of Tris-HCl several times after filtering. After the filter was dried, the radioactivity of the scintillation mixture was determined by liquid scintillation counting with a scintillometer. The reference standard was 5-HT, and IC50 values were calculated from plots of competitive inhibition curves formed based on several inhibition ratios and the corresponding compound concentrations.
Measurement: IC50 = 0.87 nM (pChEMBL 9.0600004196167)
Descriptors: MW 464.39, ALogP 3.37, HBA 6, HBD 1, PSA 63.57, QED 0.64
Compound (SMILES): C=CC(=O)Nc1cc(C)ccc1Nc1nc(Nc2cc(OC)ncc2C)ncc1C(F)(F)F
InChIKey: ILUKRINUNLAVMH-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P27361
Assay: Inhibition of ERK1 (unknown origin)
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 458.44, ALogP 5.13, HBA 7, HBD 3, PSA 101.06, QED 0.42
Compound (SMILES): OC[C@H]1O[C@@H](c2nncn2-c2cccc(Cl)c2)[C@H](O)[C@@H](n2cc(-c3cc(F)c(F)c(F)c3)nn2)[C@H]1O
InChIKey: LJDBMNRBJWMZIZ-OBJCFNGXSA-N
Target: Galectin-3 (SINGLE PROTEIN), Mus musculus
UniProt: P16110
Assay: Inhibition of His-tagged recombinant mouse Gal-3 preincubated for 30 mins followed by B-ASF addition measured after 1 hr by time resolved fluorescence based assay
Measurement: IC50 = 1700 nM (pChEMBL 5.769999980926514)
Descriptors: MW 522.87, ALogP 1.99, HBA 10, HBD 3, PSA 131.34, QED 0.34
Compound (SMILES): Cn1cc(-c2cccc(C(=O)Nc3cnn(C4CCC4)c3)c2F)cn1
InChIKey: XBTMBRMHZRXXHS-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of human LRRK2 G2019S mutant expressed in human SH-SY5Y cells assessed as inhibition of tetracycline induced LRRK2 phosphorylation at Ser935 residue incubated for 90 mins by MSD assay
Measurement: IC50 = 1647 nM (pChEMBL 5.78000020980835)
Descriptors: MW 339.37, ALogP 3.4, HBA 5, HBD 1, PSA 64.74, QED 0.79
Compound (SMILES): CCCCCC[Si](C)(C)c1cc(O)c(C2CCCC2)c(O)c1
InChIKey: BUOLDJDFLFOZNY-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]-CP55940 from recombinant human CB2 receptor expressed in CHO cells assessed as inhibition constant incubated for 120 mins by radioligand binding assay
Measurement: Ki = 42.26 nM (pChEMBL 7.369999885559082)
Descriptors: MW 320.55
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)CCCCNC(=O)CCCCNC(=O)CCCCNC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](N)Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CO)C(N)=O
InChIKey: HGHNUWUJDKODLA-DDFWIJSPSA-N
Target: Neuropeptides B/W receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P48145
Assay: Antagonist activity at human NPBWR1 expressed in CHO-RD-HGA16 cells measured by calcium mobilization assay
Measurement: IC50 = 1060 nM (pChEMBL 5.96999979019165)
Descriptors: MW 1475.76
Compound (SMILES): O[C@H]1CCC[C@@H]1N1CCN(CCCc2ccccc2Br)CC1
InChIKey: POXGMEPFJHVKBM-ROUUACIJSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q5U3Y7
Assay: Displacement of [3H]DTG from sigma-2 receptor in Sprague-Dawley rat liver membrane incubated for 90 mins in presence of by liquid scintillation counter analysis (+)-pentazocine by liquid scintillation counter analysis
Measurement: Ki = 116.1 nM (pChEMBL 6.929999828338623)
Descriptors: MW 367.33, ALogP 2.91, HBA 3, HBD 1, PSA 26.71, QED 0.87
Compound (SMILES): Nc1ncc(-c2cn(CCCCCC(=O)NO)c(=O)c(N3CCOCC3)n2)cn1
InChIKey: VSACYDKVAQRIQI-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin)
Measurement: IC50 = 109 nM (pChEMBL 6.960000038146973)
Descriptors: MW 403.44, ALogP 0.18, HBA 10, HBD 3, PSA 148.49, QED 0.32
Compound (SMILES): CC(C)(C)NC(=O)NC1CCN(C(=O)[C@H](Cc2cccc(C(=N)N)c2)NS(=O)(=O)c2cccc(-c3ccc(F)c(CO)c3)c2)CC1
InChIKey: QAHHZFAADGSYIF-LJAQVGFWSA-N
Target: Prothrombin (SINGLE PROTEIN), Bos taurus
UniProt: P00735
Assay: Binding affinity to bovine thrombin assessed as inhibition constant using tosyl-Gly-Pro-Arg-AMC as substrate
Measurement: Ki = 1070 nM (pChEMBL 5.96999979019165)
Descriptors: MW 652.79, ALogP 3.25, HBA 6, HBD 6, PSA 177.71, QED 0.14
Compound (SMILES): C/C(=N\NC(=O)c1ccc(S(N)(=O)=O)cc1)c1ccc(N2C(=O)C3CC=CCC3C2=O)cc1
InChIKey: QDSKIEIEFNHCMV-AFUMVMLFSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Binding affinity to human recombinant CA9 assessed as inhibition constant incubated for 15 mins prior to testing by phenol red based stopped-flow CO2 hydration assay
Measurement: Ki = 17.3 nM (pChEMBL 7.760000228881836)
Descriptors: MW 466.52, ALogP 1.94, HBA 6, HBD 2, PSA 139, QED 0.3
Compound (SMILES): CCc1ccc(-c2nc3cc(NC(=O)c4cc([N+](=O)[O-])ccc4Cl)ccc3n2C)cc1
InChIKey: XRQPGICIGLQHJP-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Inverse agonist activity at PPARgamma in human RT112/84-FABP4 cells assessed as reduction in PPARgamma transactivation measured by Nanoluciferase reporter gene assay
Measurement: IC50 = 4.4 nM (pChEMBL 8.359999656677246)
Descriptors: MW 434.88, ALogP 5.62, HBA 5, HBD 1, PSA 90.06, QED 0.33
Compound (SMILES): C=CC[Si](C)(C)c1ccc(C(O)(C(F)(F)F)C(F)(F)F)cc1
InChIKey: ULUFHBNVVKMYSI-UHFFFAOYSA-N
Target: Oxysterols receptor LXR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: P55055
Assay: Agonist activity against human LXRbeta expressed in human HEK293T cells co-expressing CMX-GAL4N-hLXRbeta incubated for 24 hrs by reporter gene assay
Measurement: EC50 = 450 nM (pChEMBL 6.349999904632568)
Descriptors: MW 342.36
Compound (SMILES): CC(C)(C)c1cc(NC(=O)Nc2ccc(Oc3ccc4ncncc4c3)cc2)n(-c2ccc3ncccc3c2)n1
InChIKey: VZSXRPCZRQJQFY-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: In Vitro Biochemical Assay: The biochemical assays were carried out using the non-phosphorylated kinase domain of c-Abl, Bcr-Abl in Ba/F3 cells is in the phosphorylated state.
Measurement: Ki = 3.4 nM (pChEMBL 8.470000267028809)
Descriptors: MW 529.6, ALogP 7.1, HBA 7, HBD 2, PSA 106.85, QED 0.25
Compound (SMILES): C=CC(=O)N1CCC(Oc2nc(Nc3ccc(N4CCN(C)CC4)cc3)ncc2Cl)CC1
InChIKey: XVULRMAVBIKLQU-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of N-terminal GST-tagged human recombinant wild type EGFR (695 to end residues) expressed in baculovirus-infected Sf9 cells using poly (4:1 Glu,Tyr) peptide as substrate incubated for 60 mins in presence of ATP by ADP-Glo kinase assay
Measurement: IC50 = 30.26 nM (pChEMBL 7.519999980926514)
Descriptors: MW 456.98, ALogP 3.18, HBA 7, HBD 1, PSA 73.83, QED 0.67
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(CCCCCCCC(=O)NO)c4)nc3c2)c1
InChIKey: BLJSCYQVOWYZMS-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of FGFR1 (unknown origin)
Measurement: IC50 = 95 nM (pChEMBL 7.019999980926514)
Descriptors: MW 558.68, ALogP 5.9, HBA 9, HBD 2, PSA 114.63, QED 0.11
Compound (SMILES): CCCCCCSC[C@H](NC(=O)[C@H](CO)NC(=O)CN)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](Cc1c[nH]cn1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)O)C(C)C
InChIKey: CQXIEOVFWXPEIO-RXONAPBBSA-N
Target: Appetite-regulating hormone (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBU3
Assay: Displacement of C-terminal Cys-tagged human LEAP2-SmBiT tracer from C-terminal Cys-tagged human Ghrelin expressed in HEK293T cells by microplate reader based NanoBiT-binding assay
Measurement: IC50 = 20.4 nM (pChEMBL 7.690000057220459)
Descriptors: MW 3344.95
Compound (SMILES): O=C(NCCNc1cc(-c2cn(-c3ccccc3)nc2-c2cccc(O)c2)ccn1)Nc1ccc(Cl)c(Cl)c1
InChIKey: HZYXNQSQNJIKGP-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 10 (SINGLE PROTEIN), Homo sapiens
UniProt: P53779
Assay: Inhibition of JNK3 (unknown origin)
Measurement: IC50 = 524.81 nM (pChEMBL 6.28000020980835)
Descriptors: MW 559.46, ALogP 6.85, HBA 6, HBD 4, PSA 104.1, QED 0.16
Compound (SMILES): CC(C)(C)c1cc(NC(=O)Nc2ccc(-c3cn4c5c(sc4n3)CCc3c[nH]cc3-5)cc2)no1
InChIKey: OAMPOKDQUZAAKE-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 ITD mutant (unknown orgin) by ADP-glo kinase assay
Measurement: IC50 = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 472.57, ALogP 6.09, HBA 6, HBD 3, PSA 100.25, QED 0.3
Compound (SMILES): Nc1nc2ccc(-c3cn([C@@H]4CN[C@H](C(=O)Nc5ccc(Cl)c(C(F)(F)F)c5)C4)nn3)nc2s1
InChIKey: QPEWSVDGDKWHMX-BONVTDFDSA-N
Target: Bcr/Abl fusion protein (CHIMERIC PROTEIN), Homo sapiens
UniProt: P11274
Assay: Inhibition of Bcr-Abl T315I mutant (unknown origin) incubated for 1 hr in presence of ATP by ADP-Glo kinase assay
Measurement: IC50 = 24.69 nM (pChEMBL 7.610000133514404)
Descriptors: MW 508.92, ALogP 3.75, HBA 9, HBD 3, PSA 123.64, QED 0.38
Compound (SMILES): O=C(/C=C/c1ccccc1Br)c1ccc(N2C(=O)[C@@H]3[C@H](C2=O)[C@@H]2C=C[C@H]3C2)cc1
InChIKey: IGBRQJSXDSFSJZ-RVSZZEMNSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Binding affinity to human CA2 assessed as inhibition constant using 4-nitrophenylacetate as substrate by spectrophotometrical analysis
Measurement: Ki = 0.2454 nM (pChEMBL 9.609999656677246)
Descriptors: MW 448.32, ALogP 4.66, HBA 3, HBD 0, PSA 54.45, QED 0.3
Compound (SMILES): CCCN1CCN(c2cccc(C3CCCCN3C(=O)/C=C/c3ccccc3)c2)CC1
InChIKey: LPOOUTTZIAYDSP-CCEZHUSRSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99720
Assay: Displacement of [3H](+)-pentazocine from human sigma 1 receptor transfected in human HEK293T cells assessed as inhibition constant by radioligand competition binding assay
Measurement: Ki = 4.8 nM (pChEMBL 8.319999694824219)
Descriptors: MW 417.6, ALogP 4.99, HBA 3, HBD 0, PSA 26.79, QED 0.62
Compound (SMILES): NOCc1cccc(-c2ccc(F)cc2)c1
InChIKey: LZGMZRSJRFHHSW-UHFFFAOYSA-N
Target: Alanine--glyoxylate aminotransferase (SINGLE PROTEIN), Homo sapiens
UniProt: P21549
Assay: Inhibition of recombinant wild type His-tagged AGT (unknown origin) expressed in Escherichia coli BL21 assessed as inhibition constant using L-alanine and glyoxylate as a substrate in presence of PLP
Measurement: Ki = 3500 nM (pChEMBL 5.460000038146973)
Descriptors: MW 217.24, ALogP 2.88, HBA 2, HBD 1, PSA 35.25, QED 0.8
Compound (SMILES): O=S(=O)(c1cccc(Cl)c1)n1ccc2c(N[C@H]3CCOC3)nc3ccccc3c21
InChIKey: KXYKGHPPJVXDFH-HNNXBMFYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human recombinant MAO-B using p-tyramine as substrate preincubated for 30 mins followed by substrate addition and measured after 1 hr by fluorometric analysis
Measurement: IC50 = 1142 nM (pChEMBL 5.940000057220459)
Descriptors: MW 427.91, ALogP 4.28, HBA 6, HBD 1, PSA 73.22, QED 0.53
Compound (SMILES): COc1cc(CCc2cc(-c3nc4ccc(C(=O)N5CCOCC5)cc4[nH]3)n[nH]2)cc(OC)c1
InChIKey: UTHRHKGJHFUFBP-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition Kinases In Vitro Assay: The compounds were dissolved in 100% DMSO, and obtained solutions were serially diluted in reaction buffer (50 mM Tris pH 7.5, 10 mM MgCl2, 0.25 mM EGTA, 0.1 mM Na3VO4, 0.01% Triton X-100, 2.5 mM DTT). Recombinant FGFR1, FGFR2, FGFR3 or KDR kinase (Carna Biosciences) was diluted to final concentration of 0.1 ng/μL in the dilution buffer (50 mM Tris-HCl pH 7.5, 150 mM NaCl, 10% glycerol, 0.05% Triton X-100, 1 mM DTT). 5 μL of prepared solutions of the compounds along with 5 μL of selected kinase solution were added to each well of a 96-well plate. The plate was incubated for 10 minutes at 25° C. in plate shaker thermostat with orbital shaking at 400 rpm. To negative control wells all reagents were added except compounds and kinase, while to positive control wells all reagents except tested compounds. The reaction was initiated by adding 15 μL of solution consisting of 5× concentrated reaction buffer (50 mM Tris pH 7.5, 10 mM MgCl2, 0.25 mM EGTA, 0.1 mM Na3VO4, 0.01% Triton X-100, 2.5 mM DTT), water, 50 μM ATP, 16.67 μM IGF-1Rtide peptide (Milipore). Than the plate was incubated for 1 hour at 25° C. in plate shaker thermostat with orbital shaking at 400 rpm. Detection of ADP obtained in enzymatic reaction was performed with ADP-Glo Kinase Assay (Promega). 25 μL of ADP-Glo Reagent was added to each well of 96-well plate and the plate was incubated for 40 minutes at 25° C. in plate shaker thermostat with orbital shaking at 400 rpm. Then 50 μL of Kinase Detection Reagent was added to each well of 96-well plate and the plate was incubated for 30 minutes at 25° C. in plate shaker thermostat with orbital shaking at 400 rpm. Finally, the intensity of luminescence was measured using Victor Light luminometer (Perkin Elmer, Inc.).
Measurement: IC50 = 7.8 nM (pChEMBL 8.109999656677246)
Descriptors: MW 461.52, ALogP 3.23, HBA 6, HBD 2, PSA 105.36, QED 0.44
Compound (SMILES): COc1cc(CCc2cc(-c3nc4ccc(C(=O)NC5CCOCC5)cc4[nH]3)n[nH]2)cc(OC)c1
InChIKey: WRLCMSJRWBXEIO-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition Kinases In Vitro Assay: The compounds were dissolved in 100% DMSO, and obtained solutions were serially diluted in reaction buffer (50 mM Tris pH 7.5, 10 mM MgCl2, 0.25 mM EGTA, 0.1 mM Na3VO4, 0.01% Triton X-100, 2.5 mM DTT). Recombinant FGFR1, FGFR2, FGFR3 or KDR kinase (Carna Biosciences) was diluted to final concentration of 0.1 ng/μL in the dilution buffer (50 mM Tris-HCl pH 7.5, 150 mM NaCl, 10% glycerol, 0.05% Triton X-100, 1 mM DTT). 5 μL of prepared solutions of the compounds along with 5 μL of selected kinase solution were added to each well of a 96-well plate. The plate was incubated for 10 minutes at 25° C. in plate shaker thermostat with orbital shaking at 400 rpm. To negative control wells all reagents were added except compounds and kinase, while to positive control wells all reagents except tested compounds. The reaction was initiated by adding 15 μL of solution consisting of 5× concentrated reaction buffer (50 mM Tris pH 7.5, 10 mM MgCl2, 0.25 mM EGTA, 0.1 mM Na3VO4, 0.01% Triton X-100, 2.5 mM DTT), water, 50 μM ATP, 16.67 μM IGF-1Rtide peptide (Milipore). Than the plate was incubated for 1 hour at 25° C. in plate shaker thermostat with orbital shaking at 400 rpm. Detection of ADP obtained in enzymatic reaction was performed with ADP-Glo Kinase Assay (Promega). 25 μL of ADP-Glo Reagent was added to each well of 96-well plate and the plate was incubated for 40 minutes at 25° C. in plate shaker thermostat with orbital shaking at 400 rpm. Then 50 μL of Kinase Detection Reagent was added to each well of 96-well plate and the plate was incubated for 30 minutes at 25° C. in plate shaker thermostat with orbital shaking at 400 rpm. Finally, the intensity of luminescence was measured using Victor Light luminometer (Perkin Elmer, Inc.).
Measurement: IC50 = 1.07 nM (pChEMBL 8.970000267028809)
Descriptors: MW 475.55, ALogP 3.66, HBA 6, HBD 3, PSA 114.15, QED 0.36
Compound (SMILES): CC[C@@H]1c2nnc(C)n2-c2cnc(Nc3ccc(C(=O)NC4CCN(CCCCNC(=O)COc5cccc6c5C(=O)C(C5CCC(=O)NC5=O)C6=O)CC4)cc3OC)nc2N1CC1CCCCC1
InChIKey: HWCCWYQDFQTRHY-ZKGBFYIRSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of BRD4 (unknown origin) by alpha-screen assay
Measurement: IC50 = 219 nM (pChEMBL 6.659999847412109)
Descriptors: MW 944.11, ALogP 5.19, HBA 16, HBD 4, PSA 231.97, QED 0.06
Compound (SMILES): Cc1ccc(NC(=O)CCc2cccc(-c3cnc4[nH]ccc4c3)c2)cc1C(F)(F)F
InChIKey: MCCKGEPZYYKAEX-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: P49336
Assay: Inhibition of CDK8 in human HCT-116 cells transfected with TOPFlash luciferase reporter plasmid assessed as reduction in TCF/LEF transcriptional activity
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 423.44, ALogP 6.13, HBA 2, HBD 2, PSA 57.78, QED 0.41
Compound (SMILES): O=C(c1ccco1)N(Cc1ccc(F)cc1)C1CCN(CCc2ccccc2)CC1
InChIKey: DTGGEYAEKFSEMP-UHFFFAOYSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Displacement of [3H]-DAMGO from human MOR expressed in CHO-K1 cell membranes incubated for 90 mins measured by MicroBeta scintillation counter method
Measurement: Ki = 7.9 nM (pChEMBL 8.100000381469727)
Descriptors: MW 406.5, ALogP 4.77, HBA 3, HBD 0, PSA 36.69, QED 0.57
Compound (SMILES): NC(=O)c1ccc(OCC2CCC2)cc1F
InChIKey: VLOWWMKTNSPEAY-UHFFFAOYSA-N
Target: Protein mono-ADP-ribosyltransferase PARP10 (SINGLE PROTEIN), Homo sapiens
UniProt: Q53GL7
Assay: Inhibition of human PARP-10 using NAD+ as substrate incubated for 10 mins by fluorescence based analysis
Measurement: IC50 = 616.6 nM (pChEMBL 6.210000038146973)
Descriptors: MW 223.25, ALogP 2.1, HBA 2, HBD 1, PSA 52.32, QED 0.85
Compound (SMILES): O=c1[nH]cc(CSc2ccc(S(F)(F)(F)(F)F)cc2)[nH]c1=O
InChIKey: MGJOQYMLLCTZSD-UHFFFAOYSA-N
Target: D-amino-acid oxidase (SINGLE PROTEIN), Homo sapiens
UniProt: P14920
Assay: Inhibition of full length human DAO transfected in CHO-K1 cells incubated for 30 mins by Amplex red and horseradish peroxidase based fluorescence assay
Measurement: EC50 = 710 nM (pChEMBL 6.150000095367432)
Descriptors: MW 360.33, ALogP 4.01, HBA 3, HBD 2, PSA 65.72, QED 0.49
Compound (SMILES): COc1cc(CCNc2nc(OCC(C)C)nc3c2ncn3[C@H]2[C@H](O)[C@H](O)[C@@H]3C[C@@H]32)ccc1O
InChIKey: RMSPTRHMWVZXTN-LFDFRMOKSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of [125I] N6-(4-amino-3-iodobenzyl)adenosine-5'-N-methyluronamide from human A3A receptor stably expressed in HEK293 cell membrane by radioligand inhibition assay
Measurement: Ki = 13.1 nM (pChEMBL 7.880000114440918)
Descriptors: MW 469.54, ALogP 2.14, HBA 10, HBD 4, PSA 134.78, QED 0.37
Compound (SMILES): CCOc1nc(N)c2nc(-c3cncc(F)c3)n(Cc3ccc(CN4C[C@@H]5C[C@H]4CN5C)cc3)c2n1
InChIKey: NHZSWKDFGUWVJJ-SFTDATJTSA-N
Target: Toll-like receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYK1
Assay: Inhibition of the Activation Assay: As human TLR7 expressing cell line, HEK293 cell line was bought from IMGENEX Corporation (TLR7/NF-ηB/SEAPorter HEK293 cell), which is human embryonic kidney cell line and stably expresses full-length human TLR7 gene and secreted alkaline phosphatase (SEAP) reporter gene under the transcriptional control of an NE-ηB response element. The TLR7/NF-ηB/SEAPorter HEK293 cell was cultivated with DMEM containing 10% fetal bovine serum (FBS) and 10 μg/mL blasticidin S at 37° C. in the presence of 5% CO2. The TLR7/NF-ηB/SEAPorter HEK293 cell was seeded into 96-well microtiter plate at 5×104 cell/90 μL/well, and the place was cultivated at 37° C. in a CO2 incubator overnight. Each test compound that was diluted with the medium was added to the wells (10 μL/well), wherein each final concentration was adjusted to 0.001, 0.003, 0.01, 0.03, 0.1, 0.3, 1, 3, and 10 μmol/L, or 0.01, 0.03, 0.1, 0.3, 1, 3, 10, 30, and 100 μmol/L. After 0.5 hour, R-848 that is TLR7/8 ligand was added to each well (10 μL/well), wherein each final concentration was adjusted to 200 nmol/L. The total volume was adjusted to 110 μL/well, the test samples were incubated in CO2 incubator for 20±1 hours, and then the SEAP activity was measured as activation of TLR7. The SEAP activity was evaluated as follows: p-nitro-phenyl phosphate (pNPP) (Invitrogen) was added to the incubated sample (50 μL/well); after 15 minutes, 4 mol/L sodium hydroxide solution (nacalai tesque) was added thereto (50 μL/well) to quench the reaction; and the absorbance of each sample was measured at 405 nm with microplate reader Elx808 (BioTek). The 50% inhibitory concentration (IC50 value) of each sample compound was calculated based on 100% of the SEAP activity wherein the test sample comprises no sample compound.
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 488.57, ALogP 2.94, HBA 9, HBD 1, PSA 98.22, QED 0.42
Compound (SMILES): O=C(O)c1cn(Cc2ccc(F)cc2)c2ccc(OCc3ccc4c(c3)OCO4)cc2c1=O
InChIKey: VUMOKRMKAPAPNR-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of HIV-1 reverse transcriptase associated RNA-dependent DNA polymerase activity using poly(A)-oligo(dT) as template/primer incubated for 30 mins by multilabel counter plate reader analysis
Measurement: IC50 = 5100 nM (pChEMBL 5.289999961853027)
Descriptors: MW 447.42, ALogP 4.19, HBA 6, HBD 1, PSA 86.99, QED 0.48
Compound (SMILES): CC(C)(C)[C@H](NC(=O)OCc1ccccc1)C(=O)N1C[C@H]2[C@@H]([C@H]1C(=O)N[C@H](C=O)C[C@@H]1CCNC1=O)C2(C)C
InChIKey: BDHVPCDBFSBZMM-RCTKEMKKSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of eGFP fused SARS-CoV2 main protease transfected in HEK293T/17 cells incubated for 72 hrs by fluorescence based flow cytometry analysis
Measurement: EC50 = 310 nM (pChEMBL 6.510000228881836)
Descriptors: MW 540.66, ALogP 2.02, HBA 6, HBD 3, PSA 133.91, QED 0.41
Compound (SMILES): Cc1cc(NC(=O)COc2ccccc2C(F)(F)F)n(C2CCS(=O)(=O)C2)n1
InChIKey: LVQJVRVRSGRQES-UHFFFAOYSA-N
Target: Kir3.1/Kir3.4 (PROTEIN COMPLEX), Homo sapiens
UniProt: P48544
Assay: Activation of GIRK1/4 channel (unknown origin) expressed in HEK293 cells incubated for 6 mins by thallium flux assay
Measurement: EC50 = 1286 nM (pChEMBL 5.889999866485596)
Descriptors: MW 417.41, ALogP 2.59, HBA 6, HBD 1, PSA 90.29, QED 0.81
Compound (SMILES): C[C@@H]1OCC2(CCN(c3nc4[nH]nc(-c5cccc(Cl)c5Cl)c4nc3CO)CC2)[C@@H]1N
InChIKey: WRHXPUBAPLIIDL-BBATYDOGSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: Inhibition of human SHP2 assessed as downregulation of PERK level in human KYSE520 cells incubated for 2 hrs by Alpha screen assay
Measurement: IC50 = 0.4 nM (pChEMBL 9.399999618530273)
Descriptors: MW 463.37, ALogP 3.15, HBA 7, HBD 3, PSA 113.18, QED 0.55
Compound (SMILES): COc1cc(N=S(C)(=O)C(C)(C)C)cc2ncnc(Nc3ccc(F)cc3O[C@H]3COC[C@H]3O)c12
InChIKey: FRWDDDSGEGTXIY-KSJUYSEISA-N
Target: MAP kinase-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BUB5
Assay: MNK1 In Vitro Kinase Assay (Assay 3): MNK1 Data can be obtained from the MNK1 Z′-LYTE® assay. The MNK1 Z′-LYTE® screening protocol and assay conditions are also described on www.invitrogen.com.
Measurement: IC50 = 329 nM (pChEMBL 6.480000019073486)
Descriptors: MW 504.58, ALogP 4.19, HBA 9, HBD 2, PSA 115.16, QED 0.51
Compound (SMILES): COC(=O)C1CCN(C(=O)Cc2ccc(NCc3cnc4nc(N)nc(N)c4n3)cc2)CC1
InChIKey: NQLDZGLJAMJTPQ-UHFFFAOYSA-N
Target: Pteridine reductase 1 (SINGLE PROTEIN), Leishmania major
UniProt: Q01782
Assay: Inhibition of recombinant Leishmania major PTR1 expressed in Escherichia coli BL21 (DE3) cells using H2B as substrate in presence of cytochrome c and NADPH by envision multilabel reader
Measurement: IC50 = 1140 nM (pChEMBL 5.940000057220459)
Descriptors: MW 450.5, ALogP 1.15, HBA 10, HBD 3, PSA 162.24, QED 0.46
Compound (SMILES): COc1cccc([C@@H](C)NC(=O)N2CCN(c3ccncc3F)CC2)c1
InChIKey: RLYKEFWBHJQJPK-CQSZACIVSA-N
Target: cGMP-dependent protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13976
Assay: Inhibition of full length recombinant N-terminal GST-tagged human PKG expressed in baculovirus infected Sf9 insect cells using RSK as substrate preincubated for 15 mins followed by substrate addition and measured after 30 mins in presence of ATP by ADP Glo kinase assay
Measurement: IC50 = 1830 nM (pChEMBL 5.739999771118164)
Descriptors: MW 358.42, ALogP 2.82, HBA 4, HBD 1, PSA 57.7, QED 0.91
Compound (SMILES): COC(=O)C1CN(Cc2ccc(-c3cn(-c4ccc(C(C)(C)C)cc4)nn3)cc2)C1
InChIKey: XWUFCNIGWPRUMJ-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21453
Assay: Agonist activity at S1P1 receptor (unknown origin) expressed in PathHunter HEK 293 EDG1 Total GPCR Internalization cells assessed as receptor internalization incubated for 90 mins by measuring chemiluminescence signal by microplate reader method
Measurement: EC50 = 209 nM (pChEMBL 6.679999828338623)
Descriptors: MW 404.51, ALogP 3.84, HBA 6, HBD 0, PSA 60.25, QED 0.6
Compound (SMILES): COC(=O)CCCCCNC(=O)[C@@H]1CN(C(=O)c2ccc(C(=O)N3C[C@@H](C(=O)N[C@H]4C[C@@H]4c4ccccc4)[C@H](C(=O)N[C@H]4C[C@@H]4c4ccccc4)C3)cc2)C[C@H]1C(=O)N[C@H]1C[C@@H]1c1ccccc1
InChIKey: GVYYNIQEMHJOLI-LJAQFQLOSA-N
Target: Toll-like receptor 1/2 (PROTEIN COMPLEX), Mus musculus
UniProt: Q9EPQ1
Assay: Agonist activity at TLR1/TLR2 in wild type C57BL/6J mouse macrophages assessed as stimulation of TNF alpha release measured for 4 hrs by ELISA based assay
Measurement: EC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 921.11, ALogP 4.93, HBA 8, HBD 4, PSA 183.32, QED 0.08
Compound (SMILES): CCc1cc2ccc(CN3CCN(c4cnc(C(=O)NC)nc4)CC3)cc2[nH]c1=O
InChIKey: IFWBMCSAZFPFMU-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGN5
Assay: Inhibition of human recombinant N-terminal Avi-6His-TEV tagged PARP2 full length expressed in pFastBac expression system incubated for 4 hrs by fluorescence anisotropy binding assay
Measurement: IC50 = 2400 nM (pChEMBL 5.619999885559082)
Descriptors: MW 406.49, ALogP 1.56, HBA 6, HBD 2, PSA 94.22, QED 0.67
Compound (SMILES): CC(C)[C@H](NC(=O)OCc1ccccc1)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@H](C=O)C[C@@H]1CCNC1=O
InChIKey: WOAWOVDMMGJUQG-QORCZRPOSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of N-terminal His/SUMO tagged recombinant SARS-CoV2 main protease expressed in Escherichia coli BL21 (DE3) cells using DABCYL-Lys-Thr-Ser-Ala-Val-Leu-Gln-Ser-Gly-Phe-Arg-Lys-MetGlu-EDANS as substrate preincubated with enzyme for 30 mins followed by substrate addition and measured after 30 mins by fluorescence based assay
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 536.63, ALogP 1.87, HBA 6, HBD 4, PSA 142.7, QED 0.29
Compound (SMILES): COc1cc2c(N3CC4(CCN4)C3)ccnc2cc1OCCCN1CCCC1
InChIKey: ATENUHBFGBAHLE-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase EHMT1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H9B1
Assay: Inhibition of GLP (unknown origin)
Measurement: IC50 = 2177.5 nM (pChEMBL 5.659999847412109)
Descriptors: MW 382.51, ALogP 2.66, HBA 6, HBD 1, PSA 49.86, QED 0.74
Compound (SMILES): COc1cccc(Cc2nnc(Cc3c[nH]c4ccccc34)n2CCCc2c[nH]cn2)c1
InChIKey: ROQQXMSADWNTHG-UHFFFAOYSA-N
Target: Somatostatin receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P31391
Assay: Agonist activity at recombinant human SST4 receptor expressed in CHO-K1 cells assessed as inhibition of forskolin-stimulated cAMP production measured after 2.5 to 20 hrs in presence of 3-isobutyl-1-methylxanthine by TR-FRET LANCE assay
Measurement: EC50 = 0.5 nM (pChEMBL 9.300000190734863)
Descriptors: MW 426.52, ALogP 4.31, HBA 5, HBD 2, PSA 84.41, QED 0.37
Compound (SMILES): CC(C)Oc1ccc(C2CC(c3ccc(CN4CC(C(=O)[O-])C4)cc3)=NO2)cc1C(F)(F)F.[Na+]
InChIKey: FGDSVJCKZKRYBF-UHFFFAOYSA-M
Target: Sphingosine 1-phosphate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21453
Assay: Agonist activity at S1P1 receptor (unknown origin) expressed in PathHunter HEK 293 EDG1 Total GPCR Internalization cells assessed as receptor internalization incubated for 90 mins by measuring chemiluminescence signal by microplate reader method
Measurement: EC50 = 5.09 nM (pChEMBL 8.289999961853027)
Descriptors: MW 462.47, ALogP 4.87, HBA 5, HBD 1, PSA 71.36, QED 0.64
Compound (SMILES): O=C(O)COc1ccc(OCc2cccc(-c3ccc(OCC4CC4)cc3)c2)cc1F
InChIKey: FOJUJKWUPWKPPX-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor delta (SINGLE PROTEIN), Homo sapiens
UniProt: Q03181
Assay: Agonist activity at pBIND tagged human PPARdelta expressed in human HepG2 cells incubated for 18 hrs by dual luciferase reporter assay
Measurement: EC50 = 540 nM (pChEMBL 6.269999980926514)
Descriptors: MW 422.45, ALogP 5.32, HBA 4, HBD 1, PSA 64.99, QED 0.48
Compound (SMILES): CNCc1cn(C[C@H](NC(=O)[C@@H](C)c2ccccc2)c2ccc(OCC3CCC3)cc2)nn1
InChIKey: FWAICBIPKQVSQB-DFBJGRDBSA-N
Target: G protein-coupled receptor 88 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9GZN0
Assay: Agonist activity at GPR88 (unknown origin) expressed in CHO cells coexpressing PPLS-HA assessed as reduction in forskolin-stimulated cAMP production and measured after 90 mins by Lance TR-FRET cAMP assay
Measurement: EC50 = 1995.26 nM (pChEMBL 5.699999809265137)
Descriptors: MW 447.58, ALogP 3.84, HBA 6, HBD 2, PSA 81.07, QED 0.47
Compound (SMILES): O=C(O)Cc1cn(-c2ccccc2-c2nc(-c3ccc(Cl)cc3)c(-c3ccccc3)s2)nn1
InChIKey: AAIBURXAPRUOHH-UHFFFAOYSA-N
Target: Fatty acid-binding protein, adipocyte (SINGLE PROTEIN), Homo sapiens
UniProt: P15090
Assay: Inhibition of FABP4 (unknown origin) incubated for 10 mins by fluorescence based analysis
Measurement: IC50 = 4310 nM (pChEMBL 5.369999885559082)
Descriptors: MW 472.96, ALogP 6.01, HBA 6, HBD 1, PSA 80.9, QED 0.33
Compound (SMILES): OC[C@]1(c2cccc(F)c2)NC[C@H](O)[C@H]1O
InChIKey: AIOMIFPYWRTSMA-HBNTYKKESA-N
Target: Sucrase-isomaltase, intestinal (SINGLE PROTEIN), Rattus norvegicus
UniProt: P23739
Assay: Inhibition of rat intestinal sucrase assessed as release of p-nitrophenol using p-nitrophenyl glycoside as substrate by spectrometric assay
Measurement: IC50 = 950 nM (pChEMBL 6.019999980926514)
Descriptors: MW 227.24, ALogP -0.66, HBA 4, HBD 4, PSA 72.72, QED 0.54
Compound (SMILES): CN1CCN(CCCCOc2cc3c4c(nccc4c2)-c2ccccc2C3=O)CC1
InChIKey: OHDNWGYICAQWLV-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BchE using S-butyryl thiocholine iodide as substrate incubated for 10 mins followed by substrate addition measured at 0 to 180 secs by Ellman's method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 401.51, ALogP 3.85, HBA 5, HBD 0, PSA 45.67, QED 0.46
Compound (SMILES): COC1=C(Br)[C@H](O)[C@@]2(C=C1Br)CC(C(=O)NCCCOc1c(Br)cc(C[C@H](N)C(=O)O)cc1Br)=NO2
InChIKey: RPGUXLHCNCEFRX-OSGPJOMKSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of horse BuChE using butyrylthiocholine as substrate preincubated with enzyme for 30 mins followed by substrate addition by Ellman's method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 761.06, ALogP 3.47, HBA 8, HBD 4, PSA 152.7, QED 0.26
Compound (SMILES): CCCCCOc1cc2c3c(c1OC)-c1cc(OC)c(OC)cc1C[C@@H]3N(C)CC2
InChIKey: HPOSZPFSZXKXGA-IBGZPJMESA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Displacement of [3H]LSD from 5-HT2B receptor (unknown origin) assessed as inhibition constant incubated for 90 mins by MicroBeta scintillation counting method
Measurement: Ki = 47 nM (pChEMBL 7.329999923706055)
Descriptors: MW 411.54, ALogP 5.03, HBA 5, HBD 0, PSA 40.16, QED 0.57
Compound (SMILES): O=S1(=Nc2cc(Cl)c3c(Nc4ccc(F)cc4O[C@H]4COC[C@@H]4O)ncnc3c2)CCC1
InChIKey: XCQQKYFEUUGRAR-HKUYNNGSSA-N
Target: MAP kinase-interacting serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HBH9
Assay: MNK2a In Vitro Kinase Assay (Assay 2): ASSAY SETUP: The inhibition of kinase activity of MNK2a was assessed using pre-activated GST-MNK2a. The white, 384-well OptiPlate F plates were purchased from PerkinElmer. The ADP-Glo Kinase Assay (including ultra pure ATP) was purchased from Promega (V9103). Activated MNK2a was obtained as described in WO2011/104340. The unlabeled eIF4E peptide (NH2-TATKSGSTTKNR-CONH2), differing from Seq. ID No. 5 of WO 2011/104340 by the C-terminal CONH2 group, was purchased from Thermo Fisher Scientific. All other materials were of highest grade commercially available. Compounds are tested in either serial dilutions or single dose concentrations. The compound stock solutions are 10 mM in 100% DMSO The serial compound dilutions are prepared in 100% DMSO followed by 1:27.3 intermediate dilution in assay buffer. The final DMSO concentration in assay will be <3%.In the 384-well plates 3 μl of test compound from the intermediate dilutionis mixed with 4 μl of the activated MNK2 enzyme (final concentration of 10 nM) and 4 μl of the peptide (final concentration of 25 μM)/ultra pure ATP (final concentration of 20 μM), all dissolved in assay buffer. This step is followed by an incubation time of 90 min, then 10 μl of ADP Glo reagent are added, followed by 40 min of incubation. Then 20 μl of kinase detection reagent are admixed. The plates are sealed and after an incubation period of 30 min, the luminescence signal is measured in an Envision reader to determine the amount of produced ADP. All incubation steps are performed at room temperature.The assay buffer consists of 20 mM HEPES, 2 mM DTT, 0.01% BSA, 20 mM MgCl2 and 0.1% Pluronic F-127.Each assay microtiter plate contains wells with vehicle controls instead of compound (1% DMSO in water) as reference for the high signal (100% CTL, high signal), and wells containing a potent MNK2 inhibitor (final 20 μM, 1% DMSO) as reference for low signal (0% CTL, low signal).The luminescent signal generated is proportional to the ADP concentration produced and is correlated with activated MNK2 activity. The analysis of the data is performed by the calculation of the percentage of ATP consumption of activated MNK2 in the presence of the test compound compared to the consumption of ATP in the presence of activated MNK2 without compound. RLU(sample)−RLU(low control))*100/(RLU(high value)−RLU(low control)) [RLU=relative luminescence units]An inhibitor of the MNK2 enzyme will give values between 100% CTL (no inhibition) and 0% CTL (complete inhibition). Values of more than 100% CTL are normally related to compound/sample specific physico-chemical properties (e.g. solubility, light absorbance, fluorescence).IC50 values based on dose response curves are calculated with the AssayExplorer software.
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 478.93, ALogP 3.81, HBA 8, HBD 2, PSA 105.93, QED 0.57
Compound (SMILES): N#C/C(=C/C1CC1)C(=O)N1CCC[C@@H]1Cn1nc(-c2ccc(Oc3ccccc3)cc2F)c2c(N)ncnc21
InChIKey: JVLRCXYMHHEMSN-QRRJMBGHSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of biotinylated-labeled BTK-selective probe binding to BTK in human Ramos assessed as target occupancy pretreated for 1 hr followed by probe addition measured for 18 hrs by AlphaScreen assay
Measurement: IC50 = 17.2 nM (pChEMBL 7.760000228881836)
Descriptors: MW 523.57, ALogP 4.86, HBA 8, HBD 1, PSA 122.95, QED 0.27
Compound (SMILES): N[C@@H](Cc1ccccc1)C(=O)NC[C@@H]1CC[C@@H](CCB(O)O)C[C@]1(N)C(=O)O
InChIKey: HXHPFEIBPKEEPB-IUVQAAGXSA-N
Target: Arginase-2, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P78540
Assay: Inhibition of recombinant human ARG2 expressed in Escherichia coli using L-arginine hydrochloride as substrate incubated for 1 hr by colorimetric assay
Measurement: IC50 > 300 nM (pChEMBL 6.5229997634887695)
Descriptors: MW 391.28
Compound (SMILES): COC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](O)[C@H](N)CCOc1ccc(O)cc1
InChIKey: PBYNWRKJSAGRFG-SBFWRKJZSA-N
Target: Endoplasmic reticulum aminopeptidase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6P179
Assay: Inhibition of recombinant ERAP2 (unknown origin) expressed in baculovirus infected Hi-5 insect cells using R-AMC as substrate by flourescence assay
Measurement: IC50 = 2300 nM (pChEMBL 5.639999866485596)
Descriptors: MW 531.61, ALogP 0.99, HBA 9, HBD 6, PSA 180.44, QED 0.19
Compound (SMILES): CCc1ncc(-c2nc(C(F)(F)F)sc2N2CCN(C(=O)Cn3nc(C)nc3C)[C@H](C)C2)cn1
InChIKey: IZNYLAAYGQFRQK-GFCCVEGCSA-N
Target: C-X-C chemokine receptor type 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49682
Assay: Inhibition of CXCR3 receptor internalization in human venous whole blood incubated for 30 mins by flow cytometer analysis
Measurement: IC50 = 567 nM (pChEMBL 6.25)
Descriptors: MW 494.55, ALogP 3.13, HBA 9, HBD 0, PSA 92.93, QED 0.54
Compound (SMILES): O=C(O)c1ccc(CN2CCC[C@H](O[C@H](CO)c3cc(Cl)cc(Cl)c3)[C@@H]2c2ccccc2)c([N+](=O)[O-])c1
InChIKey: REDPQDQMPNUDEP-NXCFDTQHSA-N
Target: cGMP-dependent protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13976
Assay: Activation of cGMP induced partially activated state recombinant PKG1alpha (unknown origin) using Glass-tide peptide substrate incubated for 30 mins followed by ATP addition and measured after 2 hr in presence of cGMP by ADP-GLO Max Assay
Measurement: EC50 = 520 nM (pChEMBL 6.28000020980835)
Descriptors: MW 545.42, ALogP 6.06, HBA 6, HBD 2, PSA 113.14, QED 0.25
Compound (SMILES): Fc1ccc(-c2cnn3ccc(N4CCC[C@@H]4c4cc(F)ccc4F)nc23)cc1
InChIKey: FZDBUWPPVZCIKN-HXUWFJFHSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: Inhibition of TRKA G667C mutant (unknown origin) using TK-sub biotin peptide substrate preincubated for 30 mins followed by substrate addition and measured after 40 mins by FRET assay
Measurement: IC50 = 40.6 nM (pChEMBL 7.389999866485596)
Descriptors: MW 394.4, ALogP 5.16, HBA 4, HBD 0, PSA 33.43, QED 0.48
Compound (SMILES): C=CC(=O)Nc1cccc(-n2c(=O)cc(C)c3cnc(Nc4ccc(N5CCN(C(=O)CCCCCCCCCCCNC(=O)CC67CC8CC(CC(C8)C6)C7)CC5)cc4OC)nc32)c1
InChIKey: KIOCSJVBFXPDNN-UHFFFAOYSA-N
Target: RAC-gamma serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y243
Assay: Induction of AKT3 degradation in human NCI-H1975 cells assessed as reduction in AKT3 protein level incubated for 24 hrs under serum free medium by Western blot analysis
Measurement: EC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 885.17, ALogP 9.24, HBA 10, HBD 3, PSA 150.79, QED 0.05
Compound (SMILES): Cc1cc(Br)cc2c(=O)[nH]c(CSc3ncccn3)nc12
InChIKey: UYAVGZOEYLNVKI-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Inhibition of N-terminal His-tagged full length human PARP1 expressed in Escherichia coli BL21 (DE3) preincubated with 6-a-NAD+ for 5 to 10 mins followed by enzyme addition and measured after 60 mins using NAD+ as substrate byHRP based chemiluminescence assay
Measurement: IC50 = 2500 nM (pChEMBL 5.599999904632568)
Descriptors: MW 363.24, ALogP 3.08, HBA 5, HBD 1, PSA 71.53, QED 0.57
Compound (SMILES): C=CC(=O)Nc1ccccc1Nc1n[nH]c2cc(-c3c(Cl)c(OC)cc(OC)c3Cl)ccc12
InChIKey: IWLDGFXTOCUENF-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of FGFR2 (unknown orgin) using Tyr 04 peptide as substrate incubated for 1 hr in presence of 5 uM ATP by FRET based Z'-LYTE assay
Measurement: IC50 = 4770 nM (pChEMBL 5.320000171661377)
Descriptors: MW 483.36, ALogP 6.42, HBA 5, HBD 3, PSA 88.27, QED 0.26
Compound (SMILES): COc1cc(CCc2cc(-c3nc4ccc(C(=O)NCCN5CCOCC5)cc4[nH]3)n[nH]2)cc(OC)c1
InChIKey: VQCLOXLEVFZMAT-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition Kinases In Vitro Assay: The compounds were dissolved in 100% DMSO, and obtained solutions were serially diluted in reaction buffer (50 mM Tris pH 7.5, 10 mM MgCl2, 0.25 mM EGTA, 0.1 mM Na3VO4, 0.01% Triton X-100, 2.5 mM DTT). Recombinant FGFR1, FGFR2, FGFR3 or KDR kinase (Carna Biosciences) was diluted to final concentration of 0.1 ng/μL in the dilution buffer (50 mM Tris-HCl pH 7.5, 150 mM NaCl, 10% glycerol, 0.05% Triton X-100, 1 mM DTT). 5 μL of prepared solutions of the compounds along with 5 μL of selected kinase solution were added to each well of a 96-well plate. The plate was incubated for 10 minutes at 25° C. in plate shaker thermostat with orbital shaking at 400 rpm. To negative control wells all reagents were added except compounds and kinase, while to positive control wells all reagents except tested compounds. The reaction was initiated by adding 15 μL of solution consisting of 5× concentrated reaction buffer (50 mM Tris pH 7.5, 10 mM MgCl2, 0.25 mM EGTA, 0.1 mM Na3VO4, 0.01% Triton X-100, 2.5 mM DTT), water, 50 μM ATP, 16.67 μM IGF-1Rtide peptide (Milipore). Than the plate was incubated for 1 hour at 25° C. in plate shaker thermostat with orbital shaking at 400 rpm. Detection of ADP obtained in enzymatic reaction was performed with ADP-Glo Kinase Assay (Promega). 25 μL of ADP-Glo Reagent was added to each well of 96-well plate and the plate was incubated for 40 minutes at 25° C. in plate shaker thermostat with orbital shaking at 400 rpm. Then 50 μL of Kinase Detection Reagent was added to each well of 96-well plate and the plate was incubated for 30 minutes at 25° C. in plate shaker thermostat with orbital shaking at 400 rpm. Finally, the intensity of luminescence was measured using Victor Light luminometer (Perkin Elmer, Inc.).
Measurement: IC50 = 29.8 nM (pChEMBL 7.53000020980835)
Descriptors: MW 504.59, ALogP 2.82, HBA 7, HBD 3, PSA 117.39, QED 0.3
Compound (SMILES): Cc1nc([C@@H]2O[C@H](CO)[C@H](O)[C@H](n3cc(-c4ccc(Br)c(F)c4F)nn3)[C@H]2O)n(-c2cc(Cl)ccc2C(F)(F)F)n1
InChIKey: VVVKRADBWKMYOO-WIXLDOGYSA-N
Target: Galectin-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09382
Assay: Inhibition of His-tagged recombinant human Gal-1 preincubated for 30 mins followed by B-ASF addition measured after 1 hr by time resolved fluorescence based assay
Measurement: IC50 = 2660 nM (pChEMBL 5.579999923706055)
Descriptors: MW 665.8, ALogP 3.94, HBA 10, HBD 3, PSA 131.34, QED 0.22
Compound (SMILES): NS(=O)(=O)c1ccc(Nc2nc(N/N=C/c3ccc(C(F)(F)F)cc3)nc(Nc3ccccc3)n2)cc1
InChIKey: TZPKUKKCIXSTTM-CCVNUDIWSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human CA 9 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 29.7 nM (pChEMBL 7.53000020980835)
Descriptors: MW 528.52, ALogP 4.47, HBA 9, HBD 4, PSA 147.28, QED 0.19
Compound (SMILES): C#Cc1nc(/C=C\CCCCCC(=O)NO)cs1
InChIKey: KAKCYHAHFMDCRW-VURMDHGXSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of full length C-terminal FLAG-tagged human recombinant HDAC6 expressed inSf9 insect cells
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 264.35, ALogP 2.59, HBA 4, HBD 2, PSA 62.22, QED 0.34