lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=c1[nH]c(CCCCN2CCN(Cc3ccccc3)CC2)nc2c1sc1ccccc12
InChIKey: IZWYRHFYSOFNMK-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]-8-OH-DPAT from human 5-HT1A receptor expressed in CHO-K1 cells incubated for 60 mins by liquid scintillation counting method
Measurement: Ki = 964 nM (pChEMBL 6.019999980926514)
Descriptors: MW 432.59, ALogP 4.28, HBA 5, HBD 1, PSA 52.23, QED 0.44
Compound (SMILES): OCCNc1ccn2ncc(-c3ccc4c(c3)OCO4)c2n1
InChIKey: ZCPFRXHHHDGQRP-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase receptor Ret (SINGLE PROTEIN), Homo sapiens
UniProt: P07949
Assay: Inhibition of recombinant N-Terminal GST-tagged human RET V804M mutant (658 to end residues) incubated for 15 mins followed by substrate addition and measured after 30 mins by TR-FRET assay
Measurement: IC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 298.3, ALogP 1.53, HBA 7, HBD 2, PSA 80.91, QED 0.76
Compound (SMILES): CC(=O)Nc1ccc(N2CC[C@](O)(C(=O)NCc3cc(F)cc(Cl)c3)C2=O)cc1
InChIKey: AHRJDYRLVWITBE-FQEVSTJZSA-N
Target: Methionine aminopeptidase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P50579
Assay: Inhibition of recombinant human N-terminal His-tagged MetAP2 (2 to 478 residues) using Met-Ala-Ser as substrate and manganese as co-facor preincubated for 15 mins followed by substrate addition and measured after 45 mins by AAO/horse radish peroxidase enzyme coupled assay
Measurement: IC50 = 80 nM (pChEMBL 7.099999904632568)
Descriptors: MW 419.84, ALogP 2.22, HBA 4, HBD 3, PSA 98.74, QED 0.65
Compound (SMILES): COc1cccc(C2CS(=O)(=O)Oc3c2c(C)nn3-c2ccccc2)c1
InChIKey: UPMCMHNJWBLBMF-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE using butyrylthiocholine iodide as substrate preincubated with enzyme for 20 mins followed by substrate addition by Ellman's method
Measurement: IC50 = 10980 nM (pChEMBL 4.960000038146973)
Descriptors: MW 370.43, ALogP 3.04, HBA 6, HBD 0, PSA 70.42, QED 0.66
Compound (SMILES): C[C@@H](NC(=O)c1cc(-c2ccccc2)nn1C)c1ccc(N)cc1
InChIKey: DFVLRIRWLWEFHX-CYBMUJFWSA-N
Target: D-3-phosphoglycerate dehydrogenase (SINGLE PROTEIN), Homo sapiens
UniProt: O43175
Assay: Inhibition of N-terminal His6-tagged human PHGDH (4 to 315 residues) assessed as effect on NADH fluorescence incubated for 2 hrs using 3-PG substrate in presence of 19 uM NAD+ and PSAT1 by diaphorase based luminescence assay
Measurement: IC50 = 38100 nM (pChEMBL 4.420000076293945)
Descriptors: MW 320.4, ALogP 3.16, HBA 4, HBD 2, PSA 72.94, QED 0.73
Compound (SMILES): CN1C(=O)S/C(=C\c2cc(OCc3cn(-c4ccccc4)nn3)c(O)cc2Br)C1=O
InChIKey: GZLCIAAEDIEMDE-LSCVHKIXSA-N
Target: Cyclic GMP-AMP synthase (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N884
Assay: Inhibition of recombinant His6-SUMO tagged human CGAS expressed in Escherichia coli BL21/pLys cells incubated for 20 mins by Kinase Glo chemiluminescence assay
Measurement: IC50 >= 10000 nM (pChEMBL 5)
Descriptors: MW 487.34, ALogP 3.98, HBA 8, HBD 1, PSA 97.55, QED 0.54
Compound (SMILES): NCCCc1nnc(CCc2c[nH]c3ccccc23)n1Cc1ccccc1
InChIKey: MPJRDLNRQFRHJB-UHFFFAOYSA-N
Target: Somatostatin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P30874
Assay: Displacement of [125I]-Tyr-SRIF from recombinant human SST2A receptor expressed in CHOK1 cell membranes after 90 mins by gamma counting method
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 359.48, ALogP 3.48, HBA 4, HBD 2, PSA 72.52, QED 0.51
Compound (SMILES): Nc1nc(-c2ccccc2)nc2sc(-c3ccco3)nc12
InChIKey: DPPYADKHEBSKOL-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of [3H]HEMADO from human adenosine A3 receptor expressed in CHO cells after 3 hrs by scintillation counting method
Measurement: Ki = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 294.34, ALogP 3.6, HBA 6, HBD 1, PSA 77.83, QED 0.61
Compound (SMILES): CC[C@H](C(=O)O)c1ccc2cc(OC)ccc2c1
InChIKey: LSDAHSHHKKHOKE-AWEZNQCLSA-N
Target: Aldo-keto reductase family 1 member C3 (SINGLE PROTEIN), Homo sapiens
UniProt: P42330
Assay: Inhibition of human recombinant AKR1C3 using S-tetralol as substrate assessed as reduction in NADP+-dependent S-tetralol oxidation preincubated for 10 mins followed by protein addition by fluorometric assay
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 244.29, ALogP 3.43, HBA 2, HBD 1, PSA 46.53, QED 0.9
Compound (SMILES): COc1ccc(CNS(=O)(=O)c2[nH]c3ccc(Cl)cc3c2C)cc1
InChIKey: WCJCYNDCNOJHGS-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Negative allosteric modulation of human CB1 receptor expressed in CHO-K1 cells assessed as inhibition of CP55940 induced beta arrestin recruitment preincubated for 30 mins followed by addition of CP55940 for 90 mins by chemiluminescence assay
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 364.85, ALogP 3.62, HBA 3, HBD 2, PSA 71.19, QED 0.73
Compound (SMILES): COc1cc(C(=O)N2CCC(O)CC2)ccc1Nc1ccc2c(n1)N(C1CCCC1)[C@H](C)C(=O)N2C
InChIKey: WDUULYPCWOELII-QGZVFWFLSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of Bio-JQ1 from recombinant human His6 tagged BRD4 bromodomain 1 by alphascreen assay
Measurement: IC50 = 47 nM (pChEMBL 7.329999923706055)
Descriptors: MW 493.61, ALogP 3.54, HBA 7, HBD 2, PSA 98.24, QED 0.66
Compound (SMILES): COc1cc(O)ccc1-c1nnc(-c2ccc(-c3nnc(-c4cccc(Cl)c4)s3)cc2)o1
InChIKey: GYGLOANGWNHQIM-UHFFFAOYSA-N
Target: Beta-glucuronidase (SINGLE PROTEIN), Homo sapiens
UniProt: P08236
Assay: Inhibition of human beta-glucuronidase pre-incubated for 30 mins before p-nitrophenyl-beta-D-glucuronide substrate addition by spectrophotometry
Measurement: IC50 = 56100 nM (pChEMBL 4.25)
Descriptors: MW 462.92, ALogP 5.96, HBA 8, HBD 1, PSA 94.16, QED 0.34
Compound (SMILES): CC1=NN(c2ccc(C(=O)O)cc2)C(=O)/C1=C\c1ccc(-c2cc(C)c(C)cc2[N+](=O)[O-])[nH]1
InChIKey: NRJQSTDTLZMQFA-UNOMPAQXSA-N
Target: Histone acetyltransferase p300 (SINGLE PROTEIN), Homo sapiens
UniProt: Q09472
Assay: Inhibition of p300 (unknown origin) using biotinylated histone H3 (1 to 21 residues) as substrate measured after 90 mins in presence of Acetyl CoA by AlphaLISA assay
Measurement: IC50 = 1950 nM (pChEMBL 5.710000038146973)
Descriptors: MW 444.45, ALogP 4.71, HBA 5, HBD 2, PSA 128.9, QED 0.33
Compound (SMILES): N#CN1CC[C@@H](NC(=O)c2cc(-c3cccnc3)no2)C1
InChIKey: YZDDSFXRMVHPRG-LLVKDONJSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 30 (SINGLE PROTEIN), Homo sapiens
UniProt: Q70CQ3
Assay: Biochemical Fluorescence Intensity Assay: Dilution plates were prepared at 21 times the final concentration (2100 μM for a final concentration of 100 μM) in 50% DMSO in a 96-well polypropylene V-bottom plate (Greiner #651201). A typical 8-point dilution series would be 100, 30, 10, 3, 1, 0.3, 0.1, 0.03 μM final. Reactions were performed in duplicate in black 384 well plates (small volume, Greiner 784076) in a final reaction volume of 21 μl.Either 1 μl of 50% DMSO or diluted compound was added to the plate. USP30 was diluted in reaction buffer (40 mM Tris, pH 7.5, 0.005% Tween 20, 0.5 mg/ml BSA, 5 mMbeta-mercaptoethanol) to the equivalent of 0.001 μl/well and 10 μl of diluted USP30 was added to the compound. Enzyme and compound were incubated for 30 min at room temp. Reactions were initiated by the addition of Ubiquitin-Rhodamine 110 (U-555; Boston Biochem) at a final concentration of 100 nM. Reactions were read immediately after addition of substrate and following a 2 h incubation at room temperature. Readings were performed on a Pherastar Plus (BMG Labtech). λ Excitation 487 nm; λ Emission 535 nm.
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 283.29, ALogP 1.02, HBA 6, HBD 1, PSA 95.05, QED 0.84
Compound (SMILES): COc1cccc2nc(C(=O)N(CCN(C)C)C3CCc4c3ccc(Cl)c4Cl)c(-c3ccc(F)c(C)c3)n12
InChIKey: BWYYHFIZGSMZRY-UHFFFAOYSA-N
Target: Centromere-associated protein E (SINGLE PROTEIN), Homo sapiens
UniProt: Q02224
Assay: Inhibition of human CENP-E motor domain assessed as ADP levels preincubated with protein motor domain/microtubule for 60 mins followed by ATP addition measured after 20 mins by ADPglo assay
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 555.48, ALogP 6.46, HBA 5, HBD 0, PSA 50.08, QED 0.26
Compound (SMILES): COc1ccc(Nc2ncc3c(n2)n([C@H]2CC[C@H](O)CC2)c(=O)n3C)cc1
InChIKey: NUWUOZZMEMRKGH-HDJSIYSDSA-N
Target: DNA-dependent protein kinase catalytic subunit (SINGLE PROTEIN), Homo sapiens
UniProt: P78527
Assay: Inhibition of human HeLa cell-derived full length DNA-PK catalytic subunit using fluorescein-EPPLSQEAFADLWKK as substrate preincubated for 30 mins followed by substrate addition and measured after 40 mins TR-FRET assay
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 369.43, ALogP 2.36, HBA 8, HBD 2, PSA 94.2, QED 0.73
Compound (SMILES): C[C@@H](O)Cc1ccc(-c2ccc(N3C[C@H](C[C@](C)(C(=O)NO)S(C)(=O)=O)OC3=O)cc2)cc1
InChIKey: DDOYNQFIQRQZRM-ZNRXUEPQSA-N
Target: UDP-3-O-acyl-N-acetylglucosamine deacetylase (SINGLE PROTEIN), Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG12228)
UniProt: P47205
Assay: Binding affinity to Pseudomonas aeruginosa PAO1 NB52019 LpxC after 60 to 420 secs by SPR method
Measurement: Kd = 0.12 nM (pChEMBL 9.920000076293945)
Descriptors: MW 476.55, ALogP 2.3, HBA 7, HBD 3, PSA 133.24, QED 0.39
Compound (SMILES): CSCC[C@@H]1NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CO)NC(C)=O)CSSC[C@H](C(=O)N[C@H](C(=O)N[C@@H](Cc2c[nH]c3ccccc23)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc2ccccc2)C(N)=O)C(C)C)C(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCSC)NC(=O)[C@H]([C@@H](C)O)NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC1=O
InChIKey: FBNHDCVDNRWGTR-ZDJTXHLJSA-N
Target: Tissue factor pathway inhibitor (SINGLE PROTEIN), Homo sapiens
UniProt: P10646
Assay: Binding affinity to TFPI (unknown origin) incubated for 1.5 hrs using tracer peptide JBT0131 by screening ELISA
Measurement: IC50 = 3470 nM (pChEMBL 5.460000038146973)
Descriptors: MW 2886.52
Compound (SMILES): CCCn1c(=O)[nH]c2nc(-c3ccc(S(=O)(=O)N4CCN(c5cccc(Br)c5)CC4)cc3)[nH]c2c1=O
InChIKey: KVRGNXSLUZKBTA-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Displacement of [3H]PSB-603 from recombinant human A2B adenosine receptor expressed in CHO cell membranes measured after 75 mins in presence of adenosine deaminase by liquid scintillation counting method
Measurement: Ki = 0.234 nM (pChEMBL 9.630000114440918)
Descriptors: MW 573.47, ALogP 2.76, HBA 7, HBD 2, PSA 124.16, QED 0.37
Compound (SMILES): O=c1c([N+](=O)[O-])c(NCC(O)CO)nc2scnn12
InChIKey: YOZBDPWEYRYNOM-UHFFFAOYSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Inhibition of DPP4 in human serum assessed as decrease in p-nitroaniline formation using Gly-Pro-p-nitroanilide as substrate preincubated for 5 mins followed by incubation with substrate for 15 mins by microplate reader analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 287.26, ALogP -1.18, HBA 10, HBD 3, PSA 142.89, QED 0.46
Compound (SMILES): Cc1ccc(S(=O)(=O)N[C@@H](CC(=O)NC(C)(C)C)C(=O)NCCNC(=O)c2cccc(C#N)c2)cc1
InChIKey: PTZGUXXLZVHWFC-NRFANRHFSA-N
Target: Proteasome Macropain subunit MB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28074
Assay: Inhibition of human beta5 20S constitutive proteasome using suc-LLVY-AMC as substrate
Measurement: IC50 = 40190 nM (pChEMBL 4.400000095367432)
Descriptors: MW 513.62, ALogP 1.36, HBA 6, HBD 4, PSA 157.26, QED 0.35
Compound (SMILES): Cn1c2c(cc(Nc3ccc(C(=O)N4CCOCC4)cn3)c1=O)-c1cccc(-n3ncc4cc(C(C)(C)C)cc(F)c4c3=O)c1C[C@@H](O)C2
InChIKey: ACFBKRAWAGNCMP-XMMPIXPASA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Bruton's Tyrosine Kinase (BTK) Inhibition Assay: The assay is a capture of radioactive 33P phosphorylated product through filtration. The interactions of BTK, biotinylated SH2 peptide substrate (Src homology), and ATP lead to phosphorylation of the peptide substrate. Biotinylated product is bound streptavidin sepharose beads. All bound, radiolabeled products are detected by scintillation counter.Plates assayed are 96-well polypropylene (Greiner) and 96-well 1.2 μm hydrophilic PVDF filter plates (Millipore). Concentrations reported here are final assay concentrations: 10-100 μM compounds in DMSO (Burdick and Jackson), 5-10 nM BTK enzyme (His-tagged, full-length), 30 μM peptide substrate (Biotin-Aca-AAAEEIYGEI-NH2), 100 μM ATP (Sigma), 8 mM imidazole (Sigma, pH 7.2), 8 mM glycerol-2-phosphate (Sigma), 200 μM EGTA (Roche Diagnostics), 1 mM MnCl2 (Sigma), 20 mM MgCl2 (Sigma), 0.1 mg/ml BSA (Sigma), 2 mM DTT (Sigma), 1 μCi 33P ATP (Amersham), 20% streptavidin sepharose beads (Amersham), 50 mM EDTA (Gibco), 2 M NaCl (Gibco), 2 M NaCl w/1% phosphoric acid (Gibco), microscint-20 (Perkin Elmer).
Measurement: IC50 = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 664.74, ALogP 4.26, HBA 10, HBD 2, PSA 131.58, QED 0.29
Compound (SMILES): CCCN(CC)[C@H](c1ccccn1)[C@@H](c1ccccn1)N(CCOC)C[C@H](C)CO
InChIKey: VOVVOYNEQIHWDR-TUACAJSNSA-N
Target: Potassium voltage-gated channel subfamily A member 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P22460
Assay: Inhibition of recombinant human Kv1.5 expressed in CHO cells by IonWork high-throughput electrophysiology assay
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 414.59, ALogP 3.57, HBA 6, HBD 1, PSA 61.72, QED 0.51
Compound (SMILES): Cc1nnc2n1-c1ccc(-c3ccc(N(C)C)cc3)cc1C(Nc1ccc(Cl)cc1)CC2
InChIKey: BDYDYXUOQPJZFO-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to human recombinant BRD4 BD1 (44 to 168 residues) by fluorescence polarization assay
Measurement: Ki = 466 nM (pChEMBL 6.329999923706055)
Descriptors: MW 443.98, ALogP 6.06, HBA 5, HBD 1, PSA 45.98, QED 0.42
Compound (SMILES): Cc1cccc([C@@H](C)Nc2nc(C)nc3cc(C)c(C4CCNCC4)cc23)c1
InChIKey: RPRVSEMRMSMXLT-QGZVFWFLSA-N
Target: Son of sevenless homolog 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07889
Assay: Inhibition of GST-tagged SOS1 (564 to 1049 amino acids) (unknown origin) assessed as reduction SOS1/6xHis-Tev-tagged K-Ras G12D mutant (1 to 169 residues) interaction incubated for 30 mins by AlphaLISA method
Measurement: IC50 = 46 nM (pChEMBL 7.340000152587891)
Descriptors: MW 374.53, ALogP 5.2, HBA 4, HBD 2, PSA 49.84, QED 0.66
Compound (SMILES): O=C(Nc1cccnc1)c1ccccc1OCc1cccc(F)c1
InChIKey: ANAFAHZDDIMSJV-UHFFFAOYSA-N
Target: Phosphatidylcholine:ceramide cholinephosphotransferase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NHU3
Assay: Inhibition of SMS2 (unknown origin) over-expressed in H5 insect cell lysate using C6-NBD-Ceramide and DMPC as substrates preincubated for 30 mins followed by substrate addition and measured after 2 hrs by TLC or HPLC method
Measurement: IC50 = 1600 nM (pChEMBL 5.800000190734863)
Descriptors: MW 322.34, ALogP 4.05, HBA 3, HBD 1, PSA 51.22, QED 0.77
Compound (SMILES): CC(C)CN(C)C(=O)NC1CCN(c2ncnc3c2nc(-c2ccccc2Cl)n3-c2ccc(Cl)cc2)CC1
InChIKey: CWBWBKVFAHDHEO-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Displacement of [3H]CP55940 from human CB1 receptor expressed in HEK293 cell membranes
Measurement: Ki = 0.8 nM (pChEMBL 9.100000381469727)
Descriptors: MW 552.51, ALogP 6.06, HBA 6, HBD 1, PSA 79.18, QED 0.31
Compound (SMILES): O=C(NCCN1CCOCC1)Nc1nc2ccc(Sc3nnc4ccc(NC5CCCCC5)nn34)cc2s1
InChIKey: VBIKDDWKDFQSGC-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of wild type phosphorylated MET (unknown origin) pre-incubated for 30 mins before biotinylated poly(glutamate-alanine-tyrosine) peptide addition and measured after 5 mins by HTRF assay
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 553.72, ALogP 4.08, HBA 11, HBD 3, PSA 121.6, QED 0.3
Compound (SMILES): OCCC1c2ccccc2-c2cncn21
InChIKey: VQGLVXRSMONFQT-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Enzymatic IDO Assay: The IC50 values for each compound were determined by testing the activity of IDO in a mixture containing 50 mM potassium phosphate buffer at pH 6.5; 70 nM purified human IDO protein, 200 μM L-tryptophan, 20 mM ascorbate, 20 μM methylene blue, 0.1% DMSO. The inhibitors were initially diluted in DMSO at 100 mM and were diluted in potassium phosphate 50 mM, added to the reaction mixture at final concentrations raging from 1 mM to 5 nM and preincubated with the enzyme for 5 min at 25° C. The reaction was started by addition of L-tryptophan to 200 μM and incubated 15 min at 37° C. The reaction was stopped by addition of 0.5 vol of 30% trichloroacetic acid and incubated 30 min at 60° C. to hydrolyze N-formylkynurenine to kynurenine. The reaction was centrifuged at 3400 g for 5 min to remove precipitated protein and the supernatant was reacted with 2% (w/v) of p-dimethylaminobenzaldehyde in acetic acid. The reaction was incubated 10 min at 25° C. and read at 480 nm in a spectrophotometer. Control samples with no IDO inhibitor, or with no IDO enzyme or with the reference inhibitors 1-methyl-tryptophan (200 μM) and menadione (1.2 μM) were used as controls to set the parameters for the non-linear regressions necessary for determination of the IC50 for each compound. Nonlinear regressions and determination of the IC50 values were performed using the GraphPad Prism 4 software. Compounds with an IC50 of less than 500 μM were considered as active inhibitors in this assay.
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 200.24, ALogP 1.84, HBA 3, HBD 1, PSA 38.05, QED 0.8
Compound (SMILES): C#C[C@@H](CC[C@H](N)C(=O)O)C[C@H]1O[C@@H](n2cnc3c(N)ncnc32)[C@H](O)[C@@H]1O
InChIKey: XWVQVRRCQQSPDU-WHUDRKENSA-N
Target: Nicotinamide N-methyltransferase (SINGLE PROTEIN), Homo sapiens
UniProt: P40261
Assay: Inhibition of N-terminal His6-tagged wild type human NNMT expressed in Escherichia coli NiCo21(DE3) assessed as reduction in 1-methylquinolinium level using quinoline as substrate in presence of SAM and measured every 27 seconds for 5.5 mins by fluorescence-based assay
Measurement: Ki = 47863.01 nM (pChEMBL 4.320000171661377)
Descriptors: MW 390.4, ALogP -1.14, HBA 10, HBD 5, PSA 182.63, QED 0.36
Compound (SMILES): CC1(C)[N+]([O-])=c2ccc(S(=O)(=O)C(F)(F)F)cc2=[N+]1[O-]
InChIKey: WAAZQPBRMWWBKM-UHFFFAOYSA-N
Target: Separin (SINGLE PROTEIN), Homo sapiens
UniProt: Q14674
Assay: Inhibition of epitope-tagged separase (unknown origin) using Rad21-MCA as substrate preincubated for 1 hr followed by substrate addition measured after 3 hrs by fluorescence assay
Measurement: IC50 = 50100 nM (pChEMBL 4.300000190734863)
Descriptors: MW 310.25, ALogP -0.29, HBA 4, HBD 0, PSA 86.28, QED 0.53
Compound (SMILES): COc1cc2oc(-c3ccc(NCCCNc4c5c(nc6cc(Cl)ccc46)CCCC5)cc3)cc(=O)c2c(OC)c1OC
InChIKey: FRHTWDFXZBLZBU-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human erythrocyte acetylcholinesterase using acetylthiocholine as substrate preincubated for 5 mins followed by substrate addition by Ellman's method
Measurement: IC50 = 1.9 nM (pChEMBL 8.720000267028809)
Descriptors: MW 600.12, ALogP 7.48, HBA 8, HBD 2, PSA 94.85, QED 0.16
Compound (SMILES): N#Cc1c(C(F)(F)F)cc(NCc2ccco2)n2c1nc1cc(Cl)c(Cl)cc12
InChIKey: NQPRDTNENNRERF-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in CHO cells assessed as reduction in peak channel current by IonWork patch-clamp electrophysiology method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 425.2, ALogP 5.89, HBA 5, HBD 1, PSA 66.26, QED 0.44
Compound (SMILES): C=C1C(=O)O[C@H]2[C@H]1CC/C(C(=O)OCCOCCOC(=O)/C1=C/CC[C@@]3(C)O[C@H]3[C@H]3OC(=O)C(=C)[C@@H]3CC1)=C\CC[C@@]1(C)O[C@@H]21
InChIKey: GWPIZLOXKPAPCU-RXQFCVLDSA-N
Target: Pyruvate kinase PKM (SINGLE PROTEIN), Homo sapiens
UniProt: P14618
Assay: Activation of recombinant human N-terminal 6His-tagged PKM2 expressed in Escherichia coli BL21 cells after 50 mins by fluorescence based analysis
Measurement: AC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 626.7, ALogP 3.6, HBA 11, HBD 0, PSA 139.49, QED 0.13
Compound (SMILES): CC(C)C[C@H](NC(=O)OCc1ccccc1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)CF
InChIKey: BCSYRUDRFKMLLR-ACRUOGEOSA-N
Target: Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UDY8
Assay: Biological Assay: For exemplary compounds of the disclosure, Ki for inhibition of MALT1 was measured (Table E11). A concentration of 100 nM MALT1 was used for the assay.
Measurement: Ki = 93 nM (pChEMBL 7.03000020980835)
Descriptors: MW 534.63, ALogP 1.61, HBA 6, HBD 5, PSA 166.71, QED 0.14
Compound (SMILES): O=c1cc(NCCc2cccs2)[nH]c(=O)[nH]1
InChIKey: ZSZHKLPMEHZSSD-UHFFFAOYSA-N
Target: G-protein coupled receptor 84 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NQS5
Assay: Displacement of [3H]PSB-1584 from recombinant human GPR84 expressed in CHO cell membranes co-expressing beta-arrestin2 measured after 6 hrs by scintillation counting method
Measurement: Ki = 49.4 nM (pChEMBL 7.309999942779541)
Descriptors: MW 237.28, ALogP 0.78, HBA 4, HBD 3, PSA 77.75, QED 0.73
Compound (SMILES): CSCC[C@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]1CCCN1C(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)CNC(=O)[C@H](CO)NC(=O)CCC(=O)NCCCOCCOCCOCCCNC(=O)CCCC[C@@H]1SC[C@@H]2NC(=O)N[C@@H]21)C(C)C)C(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N[C@@H](CO)C(N)=O)[C@@H](C)O
InChIKey: AALSSVNTHMZCKK-LNHNLLCTSA-N
Target: Tissue factor pathway inhibitor (SINGLE PROTEIN), Homo sapiens
UniProt: P10646
Assay: Inhibition of C-terminus 10x-His-taged human TFPI-1 (29 to 282 residues) assessed as suppression of TFPI-mediated inhibition of extrinsic tenase complex by measuring factor 10a activation using S-2222 substrate in presence of FVIIa, lipidated TF, phospholipid vesicles by micro-plate reader based assay
Measurement: EC50 = 5050 nM (pChEMBL 5.300000190734863)
Descriptors: MW 4030.78
Compound (SMILES): Cc1cc(-c2cc(S(=O)(=O)N(C)C)ccc2Oc2ccc(F)cc2F)n2cc[nH]c(=O)c12
InChIKey: HLJKSGJUPKVYRB-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of SGRG-K(Ac)-GG-K(Ac)-GLG-K(Ac)-GGA-K(Ac)-RHRKVGG-K-Biotin binding to N-terminal His6-tagged BRD4 bromodomain 1 (49 to 170 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) preincubated for 15 mins followed by biotin-labeled H4 peptide addition and measured after 10 mins by Alphascreen assay
Measurement: IC50 = 198 nM (pChEMBL 6.699999809265137)
Descriptors: MW 459.47, ALogP 3.92, HBA 5, HBD 1, PSA 83.88, QED 0.49
Compound (SMILES): O=C(/C=C/c1sc(N2CCOCC2)nc1-c1ccc([N+](=O)[O-])cc1)Nc1ccc(Br)cc1
InChIKey: WDMALLAYTYBPIW-MDZDMXLPSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of recombinant human carbonic anhydrase1 preincubated for 10 mins followed by CO2 solution addition by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 515.39, ALogP 4.97, HBA 7, HBD 1, PSA 97.6, QED 0.28
Compound (SMILES): C=C1CC[C@@H]2[C@](C)(CO)[C@H](O)CC[C@@]2(C)[C@@H]1C/C=C1/C(=O)OC[C@@H]1Oc1ccc([N+](=O)[O-])cc1
InChIKey: YKRZOZUJNQKHNW-NCBWJJKVSA-N
Target: Bile acid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RI1
Assay: Antagonist activity at FXR (unknown origin)
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 471.55, ALogP 3.96, HBA 7, HBD 2, PSA 119.13, QED 0.21
Compound (SMILES): O=C(O)c1ccc(NC(=O)c2cc(-c3ccccc3)cn2Cc2csc(N3CCCCC3)n2)cc1
InChIKey: KMIRSRBLZSUGQB-UHFFFAOYSA-N
Target: Dynamin-1-like protein (SINGLE PROTEIN), Homo sapiens
UniProt: O00429
Assay: Inhibition of DRP1 (unknown origin) using GTP as substrate incubated for 20 mins by malachite green reagent based colorimetric assay
Measurement: IC50 = 1800 nM (pChEMBL 5.75)
Descriptors: MW 486.6, ALogP 5.6, HBA 6, HBD 2, PSA 87.46, QED 0.36
Compound (SMILES): O=C1NC2(CCCCC2)n2c1c(Cl)cc(Nc1ccon1)c2=O
InChIKey: VFSUAKYNPKYPLY-UHFFFAOYSA-N
Target: MAP kinase-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BUB5
Assay: Inhibition of recombinant GST-tagged MNK1 (unknown origin) using eIF4E-derived peptide as substrate in presence of ATP at km concentration by ADP-Glo assay
Measurement: Ki = 341 nM (pChEMBL 6.46999979019165)
Descriptors: MW 334.76, ALogP 2.59, HBA 6, HBD 2, PSA 89.16, QED 0.88
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CSC1CC(=O)N(CCCCCCCCCCCC(=O)N[C@@H](CCC(=O)O)C(=O)O)C1=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)CNC(=O)[C@@H](N)Cc1cnc[nH]1)[C@@H](C)O)[C@@H](C)O)C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(=O)O)C(=O)NCC(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(N)=O
InChIKey: CTFQVQYMYMXBAD-JTDPODAYSA-N
Target: Glucagon-like peptide 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P43220
Assay: Agonist activity at human GLP1 receptor expressed in HEK293 cells assessed as induction of cAMP levels after 20 mins by time-resolved fluorescence analysis
Measurement: EC50 = 0.0182 nM (pChEMBL 10.739999771118164)
Descriptors: MW 4701.24
Compound (SMILES): COc1ccccc1C(=O)CN1C(=O)NC(C)(c2ccc(S(N)(=O)=O)cc2)C1=O
InChIKey: OJVATLAXHQXUFX-UHFFFAOYSA-N
Target: Decaprenylphosphoryl-beta-D-ribose oxidase (SINGLE PROTEIN), Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
UniProt: P9WJF1
Assay: Inhibition of Mycobacterium tuberculosis DprE1 expressed in Escherichia coli BL21(DE3) cells
Measurement: IC50 = 2511.89 nM (pChEMBL 5.599999904632568)
Descriptors: MW 417.44, ALogP 0.99, HBA 6, HBD 2, PSA 135.87, QED 0.53
Compound (SMILES): COc1ccc(C2(C(=O)NCCCn3cncc3C)CCCCC2)cc1OC
InChIKey: GVWGRGAXTFLLGH-UHFFFAOYSA-N
Target: Glutaminyl-peptide cyclotransferase (SINGLE PROTEIN), Homo sapiens
UniProt: Q16769
Assay: Inhibition of recombinant human N-terminal His6-tagged glutaminyl cyclase (Ala33 to Leu361 residues) expressed in baculovirus infected Sf21 insect cells using H-Gln-AMC hydrobromide as substrate measured in presence of pGAPase by fluorometric assay
Measurement: IC50 = 77.5 nM (pChEMBL 7.110000133514404)
Descriptors: MW 385.51, ALogP 3.62, HBA 5, HBD 1, PSA 65.38, QED 0.71
Compound (SMILES): FC(F)(F)c1ccc(OCc2cc(OC[C@@H]3CCCN3)no2)cc1.O=C(O)C(F)(F)F
InChIKey: ANEOOROEEJBZOQ-YDALLXLXSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9R0C9
Assay: Displacement of [3H]-pentazocine from rat brain sigma1 receptor by PDSP assay
Measurement: Ki = 13.3 nM (pChEMBL 7.880000114440918)
Descriptors: MW 342.32, ALogP 3.4, HBA 5, HBD 1, PSA 56.52, QED 0.87
Compound (SMILES): COc1nnc2ccc(N3CCC(c4ccc(OCCCN5CCN(C)C(=O)[C@H]5C)cc4)CC3)nn12
InChIKey: PRSHWIPDPJVWMF-LJQANCHMSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of Alexa647-labeled JQ1 derivative from wild type BRD4 tandem domain (44 to 460 residues) (unknown origin) incubated for 1 hr by fluorescence polarization assay
Measurement: Ki = 3.981 nM (pChEMBL 8.399999618530273)
Descriptors: MW 493.61, ALogP 2.45, HBA 9, HBD 0, PSA 88.33, QED 0.44
Compound (SMILES): COc1ccccc1N1CCN(CC2COCC(c3ccccc3)(c3ccccc3)O2)CC1
InChIKey: FBWZMWVPZRCOTO-UHFFFAOYSA-N
Target: Alpha-1A adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35348
Assay: Displacement of [3H]Prazosin from human recombinant alpha 1A adrenergic receptor expressed in CHO cells incubated for 30 mins by radioligand competition binding assay
Measurement: Ki = 2.63 nM (pChEMBL 8.579999923706055)
Descriptors: MW 444.58, ALogP 4.18, HBA 5, HBD 0, PSA 34.17, QED 0.57
Compound (SMILES): Cn1c(=O)n(CCC(C)(C)O)c2cc(Nc3nc(N4CCCC(C#N)C4)ncc3Cl)ccc21
InChIKey: OJWXEUBUPGPNEN-UHFFFAOYSA-N
Target: B-cell lymphoma 6 protein (SINGLE PROTEIN), Homo sapiens
UniProt: P41182
Assay: Inhibition of recombinant His-tagged human BCL6 expressed in Escherichia coli BL21 AI cell incubated for 2 hrs by TR-FRET assay
Measurement: IC50 = 390 nM (pChEMBL 6.409999847412109)
Descriptors: MW 469.98, ALogP 3.43, HBA 9, HBD 2, PSA 112, QED 0.57
Compound (SMILES): CC(=O)N[C@H](Cc1ccccc1)C(=O)N[C@H]1CCSC[C@@H](C(=O)N[C@@H](Cc2ccc(OCCN)cc2)C(=O)N[C@@H](Cc2ccc3ccccc3c2)C(=O)NC2(C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(N)=O)CCOCC2)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC1=O
InChIKey: BNPFEMHTPIPXCV-CVTAPTCVSA-N
Target: Interleukin-23 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q5VWK5
Assay: Inhibition of interleukin-23 receptor in human natural killer cells assessed as reduction in IL23/IL18-induced IFNgamma production incubated for 20 to 24 hrs by ELISA
Measurement: IC50 < 25 nM (pChEMBL 7.6020002365112305)
Descriptors: MW 1824.01
Compound (SMILES): Cc1cc(=O)oc2cc(OCC3CCN(Cc4ccc(CO)cc4)CC3)ccc12
InChIKey: NFCWFFSVKPHRMZ-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of recombinant human MAO-A expressed in baculovirus infected insect cell microsomes using kynuramine as substrate measured after 30 mins by fluorescence based assay
Measurement: IC50 = 11000 nM (pChEMBL 4.960000038146973)
Descriptors: MW 393.48, ALogP 3.88, HBA 5, HBD 1, PSA 62.91, QED 0.64
Compound (SMILES): COc1ccc2c(c1)c(C1=C(c3nn(C)c4ncccc34)C(=O)NC1=O)cn2CCCn1ccnc1
InChIKey: OHXRWTJVZNRZAW-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of recombinant human N-terminal GST-fused IDH1 R132H mutant expressed in Escherichia coli using alpha-ketoglutarate as substrate preincubated for 15 mins followed by substrate addition
Measurement: IC50 = 13620 nM (pChEMBL 4.869999885559082)
Descriptors: MW 481.52, ALogP 2.79, HBA 9, HBD 1, PSA 108.86, QED 0.36
Compound (SMILES): CCCS(=O)(=O)c1cnc(CN)s1
InChIKey: OZYJJMNLSHTWAP-UHFFFAOYSA-N
Target: Lysyl oxidase homolog 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y4K0
Assay: Inhibition of human C-terminal His10-tagged LOXL2 (Met1 to Gln774 residues) expressed in mouse NS0 cells using cadaverine hydrochloride as substrate preincubated for 1 hr followed by substrate addition by ROS-Glo assay
Measurement: IC50 = 554 nM (pChEMBL 6.260000228881836)
Descriptors: MW 220.32, ALogP 0.79, HBA 5, HBD 1, PSA 73.05, QED 0.81
Compound (SMILES): NC(=O)c1cc(-c2ccc(F)cc2)c2sc(COc3ccc(F)cc3)cc2n1
InChIKey: ABCQFRDVTDOGPC-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P31421
Assay: Negative allosteric modulation of rat mGlu2R expressed in HEK293 cells co-expressing Galpha15 assessed as decrease in glutamate-induced calcium mobilization preincubated for 2.3 mins followed by glutamate addition and measured after 1.7 mins by Fluo-4-AM dye based fluorescence assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 396.42, ALogP 4.92, HBA 4, HBD 1, PSA 65.21, QED 0.52
Compound (SMILES): COc1ccc(CCCNC(C)=O)cc1F
InChIKey: YRAQXUSPBHYZMV-UHFFFAOYSA-N
Target: Melatonin receptor type 1C (SINGLE PROTEIN), Xenopus laevis
UniProt: P49219
Assay: Agonist activity at Melatonin receptor type 1C in Xenopus laevis melanophores assessed as induction of pigment aggregation response by microtiter plate reader based absorbance detection assay
Measurement: EC50 = 1819.7 nM (pChEMBL 5.739999771118164)
Descriptors: MW 225.26, ALogP 1.9, HBA 2, HBD 1, PSA 38.33, QED 0.78
Compound (SMILES): COC(=O)N[C@H](C(=O)N1CCC[C@H]1c1ncc(-c2cc3ccc4cc(-c5cnc([C@@H]6CCCN6C(=O)[C@@H](NC(=O)OC)C(C)C)[nH]5)cc5c(=O)c(c2)c3c45)[nH]1)C(C)C
InChIKey: FDSZEUUPPNPVLA-VOIOCNMVSA-N
Target: Nonstructural protein 5A (SINGLE PROTEIN), Hepatitis C virus
UniProt: Q5L478
Assay: Inhibition of NS5A in HCV genotype 1a H77 infected in human HuH7 replicon cells assessed as reduction in viral replication after 3 days by luciferase reporter gene assay
Measurement: EC50 = 0.22 nM (pChEMBL 9.65999984741211)
Descriptors: MW 788.91, ALogP 6.25, HBA 9, HBD 4, PSA 191.71, QED 0.12
Compound (SMILES): Cn1cc(-c2cc3nccnc3c(NC[C@@H]3CNCCO3)n2)cn1
InChIKey: UAUJVWLUSNTVTA-LBPRGKRZSA-N
Target: Tyrosine-protein kinase SYK (SINGLE PROTEIN), Homo sapiens
UniProt: P43405
Assay: Inhibition of N-terminal 6His-tagged full length human recombinant SYK expressed in baculovirus using Biotin-AAAEEIYGEI as substrate after 60 mins by TR-FRET assay
Measurement: IC50 = 63.1 nM (pChEMBL 7.199999809265137)
Descriptors: MW 325.38, ALogP 0.83, HBA 8, HBD 2, PSA 89.78, QED 0.73
Compound (SMILES): Cc1ccc(C(c2ccc(C)cc2)[S+]([O-])Cc2nccs2)cc1
InChIKey: HRIZROVEMSCCBM-UHFFFAOYSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q01959
Assay: Inhibition of wild type human dopamine transporter expressed in HEK293 cells assessed as inhibition of [3H]dopamine reuptake preincubated for 5 mins followed by [3H]dopamine addition and measured after 1 min by liquid scintillation analysis
Measurement: IC50 = 29390 nM (pChEMBL 4.53000020980835)
Descriptors: MW 341.5, ALogP 4.8, HBA 3, HBD 0, PSA 35.95, QED 0.63
Compound (SMILES): CCCCCOc1ccc(S(=O)(=O)Nc2ccc(F)c(C(=O)O)c2)c2ccccc12
InChIKey: UNBNHHUEAAIBDO-UHFFFAOYSA-N
Target: Fatty acid-binding protein, adipocyte (SINGLE PROTEIN), Homo sapiens
UniProt: P15090
Assay: Displacement of 1,8-ANS from human recombinant full length N-terminal his-tagged FABP4 expressed in Escherichia coli BL21 (DE3) incubated for 3 mins by fluorescence based assay
Measurement: IC50 = 2990 nM (pChEMBL 5.519999980926514)
Descriptors: MW 431.49, ALogP 5.05, HBA 4, HBD 2, PSA 92.7, QED 0.46
Compound (SMILES): CNC1CN(c2ccnc(N)n2)C1.O=C(O)/C=C/C(=O)O
InChIKey: GPGGZCNINXEKPN-WLHGVMLRSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of [3H]NAMH from human H3R expressed in HEK293T cells incubated for 2 hrs by microbeta scintillation counting analysis
Measurement: Ki = 6.31 nM (pChEMBL 8.199999809265137)
Descriptors: MW 179.23, ALogP -0.53, HBA 5, HBD 2, PSA 67.07, QED 0.64
Compound (SMILES): COCCN1C(=O)C2(CCN(c3nc4c(c(=O)[nH]3)CCCN4C)CC2)c2c(F)cc(F)cc21
InChIKey: GNQFITKNHVZOAH-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase tankyrase-1 (SINGLE PROTEIN), Homo sapiens
UniProt: O95271
Assay: Inhibition of recombinant human N-terminal TEV cleavage site-fused/FLAG-poly his-tagged TNKS SAM-PARP domain (1024 to 1327 residues) expressed in Escherichia coli assessed as reduction in auto-PARylation preincubated for 10 mins followed by biotinylated-NAD+ addition and measured after 45 mins by ELISA
Measurement: IC50 = 10.3 nM (pChEMBL 7.989999771118164)
Descriptors: MW 459.5, ALogP 1.96, HBA 6, HBD 1, PSA 81.77, QED 0.75
Compound (SMILES): COC(=O)N[C@H](C(=O)N1[C@H](c2ncc(-c3ccc4c5ccc(-c6cnc([C@@H]7C[C@@H]8CCC[C@@H]8N7C(=O)[C@@H](NC(=O)OC)[C@@H](C)OC)[nH]6)cc5n(C)c4c3)[nH]2)C[C@@H]2CCC[C@@H]21)[C@@H](C)OC
InChIKey: KCIXCDPQMJNLAF-UTXFPBNYSA-N
Target: Nonstructural protein 5A (SINGLE PROTEIN), Hepatitis C virus
UniProt: Q5L478
Assay: Inhibition of NS5A in HCV genotype 1a infected in HuH-Lcu-Neo cells assessed as reduction in viral replication incubated for 48 hrs by luciferase reporter gene assay
Measurement: EC50 = 0.1479 nM (pChEMBL 9.829999923706055)
Descriptors: MW 878.04, ALogP 6.51, HBA 11, HBD 4, PSA 198.03, QED 0.11
Compound (SMILES): C[C@]1(c2ccc(Cl)cc2Cl)OC[C@@H](COc2ccc(N3CCN(c4ccc(NC(=O)c5ccsc5)cc4)CC3)cc2)O1
InChIKey: ARNVLGVFTIJNRD-NSJVFKKDSA-N
Target: Protein smoothened (SINGLE PROTEIN), Mus musculus
UniProt: P56726
Assay: Inhibition of smo-mediated hedgehog signaling pathway in mouse ASZ001 cells assessed as decrease in Gli1 mRNA expression after 48 hrs by qPCR method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 624.59, ALogP 7.3, HBA 7, HBD 1, PSA 63.27, QED 0.22
Compound (SMILES): COc1cc(N(CC(C)(C)O)c2cccc(C(F)(F)F)c2)cnc1C(=O)[C@H]1C[C@@H]1C(=O)O
InChIKey: UOUATSQRYUKYDM-HOTGVXAUSA-N
Target: Leukotriene C4 synthase (SINGLE PROTEIN), Homo sapiens
UniProt: Q16873
Assay: Inhibition of human N-terminal His6-tagged LTC4S expressed in Pichia pastoris X33 using LTA4 methyl ester and glutathione as substrate preincubated for 15 mins followed by substrate addition and measured after 30 mins by LC-MS/MS analysis
Measurement: IC50 = 31.8 nM (pChEMBL 7.5)
Descriptors: MW 452.43, ALogP 3.92, HBA 6, HBD 2, PSA 99.96, QED 0.59
Compound (SMILES): CCCCCCC(Sc1nc2ccc(NS(=O)(=O)c3ccc(Cl)cc3Cl)cc2s1)C(=O)O
InChIKey: GTNKAJJMCCFDIU-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q07869
Assay: Partial agonist activity at Gal4-fused PPARalpha LBD (unknown origin) expressed in HEK293T cells after 14 to 16 hrs by dual-Glo luciferase assay
Measurement: EC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 533.52, ALogP 6.92, HBA 6, HBD 2, PSA 96.36, QED 0.21
Compound (SMILES): C[C@@H](N)C(=O)NCc1cccnc1Oc1ccc(F)cc1F
InChIKey: UJKUHMOJMZFIAO-SECBINFHSA-N
Target: Histone-arginine methyltransferase CARM1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86X55
Assay: Inhibition of full-length Halo-tagged human CARM1 (1 to 608 residues) expressed in 293-F cells using [3H]-SAM and biotinylated histone peptides by scintillation proximity based radiometric assay
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 307.3, ALogP 2.12, HBA 4, HBD 2, PSA 77.24, QED 0.89
Compound (SMILES): CCCCN1CCC2(CCC(c3cccs3)(N(C)C)CC2)C1=O
InChIKey: PLYOHNHGRVMVDF-UHFFFAOYSA-N
Target: Nociceptin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41146
Assay: Displacement of [3H]-nociceptin/orphanin FQ from recombinant ORL1 receptor (unknown origin) expressed in CHO cell membranes measured after 1 hr by scintillation counter method
Measurement: Ki = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 334.53, ALogP 4.1, HBA 3, HBD 0, PSA 23.55, QED 0.81
Compound (SMILES): CSCC[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)C(C)(C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccncc1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](Cc1ccncc1)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)Cc1cnc[nH]1)[C@@H](C)O)[C@@H](C)O)C(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)O)[C@@H](C)O
InChIKey: PKCKLTULFGTCMF-AHHJYCKTSA-N
Target: Glucagon receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P47871
Assay: Activation of glucagon receptor (unknown origin) transfected in HEK293 cells coinfected with luciferase reporter gene linked CRE element assessed as cAMP accumulation after 5 hrs in presence of luclite substrate by liquid scintillation counting
Measurement: EC50 = 0.0309 nM (pChEMBL 10.510000228881836)
Descriptors: MW 3450.81
Compound (SMILES): O=C(NC1=NN(c2ccc(Cl)c(Cl)c2)CC1)c1c(F)cccc1F
InChIKey: ILWYJEABNLXHGZ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Activation of full length human 6His-tagged c-Abl expressed in baculovirus expression system using abltide as substrate after 2 hrs by IMAP assay
Measurement: IC50 = 630.96 nM (pChEMBL 6.199999809265137)
Descriptors: MW 370.19, ALogP 4.23, HBA 3, HBD 1, PSA 44.7, QED 0.86
Compound (SMILES): COc1ccc2[nH]cc(C3CCCN(CCCCn4c(=O)c(-c5ccccc5C)c5ccccn5c4=O)C3)c2c1
InChIKey: VZVCIHLSJDBPFI-UHFFFAOYSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: P31652
Assay: Displacement of [3H]-citalopram from SERT in rat cortex tissue measured after 60 mins by microbeta scintillation counting analysis
Measurement: Ki = 87 nM (pChEMBL 7.059999942779541)
Descriptors: MW 536.68, ALogP 5.59, HBA 6, HBD 1, PSA 71.74, QED 0.26
Compound (SMILES): Cc1c(C)c2ccc(OC3CCN(Cc4cccc(Cl)c4)CC3)cc2oc1=O
InChIKey: HWTRGPWDQGKEJX-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of human recombinant MAOA expressed in microsomes of baculovirus-infected insect cell using kynuramine as substrate preincubated for 20 mins followed by protein addition measured after 30 mins by fluorescence assay
Measurement: IC50 = 870 nM (pChEMBL 6.059999942779541)
Descriptors: MW 397.9, ALogP 5.11, HBA 4, HBD 0, PSA 42.68, QED 0.57
Compound (SMILES): C#C[C@H](CC(=O)OC)NC(=O)c1cccc(Oc2cc(CN)ncn2)c1.Cl
InChIKey: YWNSRKVUMLQOEO-BTQNPOSSSA-N
Target: Lysyl oxidase homolog 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y4K0
Assay: Inhibition of human LOXL2 expressed in CHO cells assessed as reduction in amine oxidase activity incubated for 2 hrs by Amplex red based fluorescence assay
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 354.37, ALogP 1.02, HBA 7, HBD 2, PSA 116.43, QED 0.56
Compound (SMILES): NC(=O)c1ccccc1Nc1cc(Nc2ccc(F)cn2)ncc1C(=O)NC1CC1
InChIKey: JFPFBEVJXBIYCZ-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of fluorescein-labeled kinase tracer binding to His-TVMV-fused TYK2 JH2 domain (575 to 869 residues) (unknown origin) measured after 90 mins by HTRF assay
Measurement: IC50 = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 406.42, ALogP 3.09, HBA 6, HBD 4, PSA 122.03, QED 0.48
Compound (SMILES): CC(C)[C@H](NC(=O)[C@@H]1C[C@@H](NC(=O)Cc2cccnc2)CN1C(=O)[C@@H](CC1CCCCC1)NC(=O)c1ccc2ccccc2c1)B(O)O
InChIKey: HVQONGVEMPMJLB-QFBUMDDISA-N
Target: Serine protease HTRA1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92743
Assay: Inhibition of full length His-tagged human HTRA1 using Mca-H20PT as substrate preincubated for 10 mins followed by substrate addition and measured after 10 mins by spectrofluorometry
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 655.61
Compound (SMILES): Cc1cn(C23CCC(Nc4nc5n(n4)CCCC[C@H]5c4ccc(F)c(F)c4)(CC2)CC3)cn1
InChIKey: SHMFPLIJEKPQEZ-CCYWVKEMSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Cellular gamma-Secretase Assay: Human neuroglioma H4 cells overexpressing human APP695 with the Swedish double mutation (K595N/M596L) were plated at 30,000 cells/well/100 μl in 96-well plates in IMDM media containing 10% FCS, 0.2 mg/l Hygromycin B and incubated at 37° C., 5% CO2.3-4 hr post plating, compounds are a diluted in media and 50 μl is added as 1.5-fold concentrate to achieve the final concentration. Compound incubation is performed for 24 hr. Final doses typically range from 4 μM down to 0.001 μM in half-log steps resulting in a eight point dose response curve.Appropriate controls using vehicle only and reference compound were applied to this assay. The final concentration of Me2SO was 0.4%.After incubation at 37° C., 5% CO2, the supernatant was subjected to quantification of secreted Aβ42 by the means of an AlphaLisa assay kit (Human Amyloid beta 1-42 Kit: Cat #AL203C, Perkin Elmer). 20 μl of the cell culture supernatant was transferred to an assay plate. Then 10 μl of a mixture of the AlphaLisa coupled capture antibody and the biotinylated detection antibody was added and incubated for 3 hours at room temperature while softly shaking the assay plate. After a further addition of 20 μl of the Donor beads the assay plate was incubated for 30 min at room temperature and constant shaking without exposure to direct light. The assay plate was then read on a Paradigm AlphaLisa Reader using the build-in program with excitation at 680 nm and emission at 570 nm.The measured signals were then used to calculate IC50 values for inhibition of Aβ42 secretion by nonlinear regression fit analysis using XLfit 5.3 software (IDBS).
Measurement: EC50 = 49 nM (pChEMBL 7.309999942779541)
Descriptors: MW 452.55, ALogP 5.29, HBA 6, HBD 1, PSA 60.56, QED 0.58
Compound (SMILES): COc1ccc(N2CN=c3s/c(=C/c4ccc(Cl)cc4)c(=O)n3C2)cc1
InChIKey: PLSRDSGHHGDMEV-LICLKQGHSA-N
Target: RNA-directed RNA polymerase (SINGLE PROTEIN), Hepacivirus hominis
UniProt: O39930
Assay: Inhibition of recombinant HCV genotype 1a NS5B polymerase coincubated with HCV international ribosome entry site template sequence containing nucleotide residues 21-371 of HCV 5'-untranslated Escherichia coli DNA polymerase I region incubated for 3 hrs by scintillation/luminescence counter method
Measurement: IC50 = 3531.83 nM (pChEMBL 5.449999809265137)
Descriptors: MW 385.88, ALogP 2.46, HBA 6, HBD 0, PSA 46.83, QED 0.7
Compound (SMILES): N#Cc1ccc(CS(=O)(=O)c2ccc3nc(N)sc3c2)cc1
InChIKey: IJWKBZSTSGACBS-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of human CYP1A2 expressed in baculovirus infected insect cells using beetle D-luciferin as substrate preincubated for 30 mins followed by NADPH addition and measured after 30 mins by CYP450-Glo assay
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 329.41, ALogP 2.72, HBA 6, HBD 1, PSA 96.84, QED 0.8
Compound (SMILES): C[C@@]12COc3c(Br)cccc3[C@@H]1CCN2
InChIKey: GKALLXNUCAXRAR-JOYOIKCWSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Displacement of [3H]-LSD from human recombinant 5-HT2B receptor stably expressed in HEK cells after 90 mins by microbeta scintillation counting method
Measurement: Ki = 19.95 nM (pChEMBL 7.699999809265137)
Descriptors: MW 268.15, ALogP 2.68, HBA 2, HBD 1, PSA 21.26, QED 0.78
Compound (SMILES): NS(=O)(=O)Oc1ccc(NC(=O)N2CCN(Cc3cc4ccccc4o3)CC2)cc1
InChIKey: WBJBLYZJVUELNX-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 incubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 32700 nM (pChEMBL 4.489999771118164)
Descriptors: MW 430.49, ALogP 2.36, HBA 6, HBD 2, PSA 118.11, QED 0.64
Compound (SMILES): CCCC[C@H](NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)CNC(=O)[C@@H](CCCNC(=O)COCCOCCNC(=O)COCCOCCNC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCCCC(=O)O)C(=O)O)NC(=O)Cc1ccc(O)cc1)C(=O)N(C)[C@H](CC(=O)O)C(=O)N(C)[C@@H](Cc1ccccc1)C(N)=O
InChIKey: FDDCPVCEEAPPMX-OUMKONITSA-N
Target: Gastrin/cholecystokinin type B receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P32239
Assay: Displacement of [125I]-CCK-8 from human CCK2R expressed in human 1321N1 cell membranes after 2 hrs by SPA assay
Measurement: IC50 = 8317.64 nM (pChEMBL 5.079999923706055)
Descriptors: MW 1627.94
Compound (SMILES): Nc1ncc(N2CCN(c3cccc(-c4ccnnc4)c3)CC2)c(N)n1
InChIKey: UNGXAKLKRHIMSF-UHFFFAOYSA-N
Target: Bifunctional dihydrofolate reductase-thymidylate synthase (SINGLE PROTEIN), Toxoplasma gondii
UniProt: Q07422
Assay: Inhibition of Toxoplasma gondii DHFR-TS expressed in Escherichia coli BL21 competent cells using DHF as substrate preincubated for 15 mins followed by substrate and NADPH addition and measured after 60 mins by resazurin dye based diaphorase-coupled assay
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 348.41, ALogP 1.42, HBA 8, HBD 2, PSA 110.08, QED 0.73
Compound (SMILES): O=C(O)[C@H]1CC[C@H](C(=O)N2CC[C@@]3(S(=O)(=O)c4ccc(F)cc4)c4ccc(C(F)(C(F)(F)F)C(F)(F)F)cc4NC[C@@H]23)CC1
InChIKey: WCICLOUJTXBWJG-KBLCWGLDSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at full length human RORgammat expressed in human Jurkat cells assessed as inhibition of constitutive receptor activity incubated for 18 hrs by Gal4-Luc reporter gene assay
Measurement: EC50 = 29 nM (pChEMBL 7.539999961853027)
Descriptors: MW 654.58, ALogP 5.7, HBA 5, HBD 2, PSA 103.78, QED 0.32