lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): C[C@@H]1CCCN1c1cc2c(N)ncnc2n1C
InChIKey: HJAJWIUCEYNBJM-MRVPVSSYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of recombinant human GST tagged truncated LRRK2 G2019S mutant using fluorescein-labeled LRRKtide as substrate in presence of ATP preincubated for 50 mins followed by anti-phospho-LRRKtide antibody addition and measured after 30 mins by TR-FRET based Lanthascreen kinase activity assay
Measurement: IC50 = 6387 nM (pChEMBL 5.199999809265137)
Descriptors: MW 231.3, ALogP 1.54, HBA 5, HBD 1, PSA 59.97, QED 0.81
Compound (SMILES): CCCC[C@@H]1NC(=O)[C@@H](N)C/C=C\C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N2CCC[C@H]2C(=O)N[C@@H](CCCC)C(=O)N2CCC[C@H]2C(=O)N[C@@H](Cc2ccccc2)C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC1=O
InChIKey: NNYWSHZCWMAGJQ-REGFRKHLSA-N
Target: Apelin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35414
Assay: Displacement of [125I]-[Nle75,Tyr77][Pyr1]-Ape13 from YFP-tagged human APJ expressed in HEK293 cell membranes assessed as inhibition constant incubated for 1 hr by scintillation counting method
Measurement: Ki = 343 nM (pChEMBL 6.460000038146973)
Descriptors: MW 1137.39
Compound (SMILES): Cc1cc(-c2ccnc(C(F)(F)F)c2)cc(C)c1Nc1ccnc(Nc2ccc(C#N)cc2)n1
InChIKey: HYNSNZMNPFBJGM-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of recombinant wild type p66/p51 HIV1 reverse transcriptase incubated for 40 mins by picogreen dye-based spectrofluorometric analysis
Measurement: IC50 = 68.5 nM (pChEMBL 7.159999847412109)
Descriptors: MW 460.46, ALogP 6.53, HBA 6, HBD 2, PSA 86.52, QED 0.35
Compound (SMILES): CC(C)(C)NS(=O)(=O)c1cccc(NC(=O)c2ccc(NC(C)(C)CO)nc2N2CCC3(CC2)CC3)c1
InChIKey: LANBPKZWGQQXCW-UHFFFAOYSA-N
Target: Kinesin-like protein KIF18A (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NI77
Assay: Inhibition of recombinant His-tagged human KIF18A (1 to 467 residues) expressed in baculovirus expression system assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 15 mins followed by ATP addition and further incubated for 15 mins and measured after 40 mins by ADP-Glo reagent based assay
Measurement: IC50 = 70 nM (pChEMBL 7.159999847412109)
Descriptors: MW 529.71, ALogP 3.97, HBA 7, HBD 4, PSA 123.66, QED 0.41
Compound (SMILES): CC(NCc1cc2ccc(CNC(=O)c3cc(=O)n4ccccc4n3)cc2[nH]1)C12CC(F)(C1)C2
InChIKey: YUORQJPNKZSTOG-UHFFFAOYSA-N
Target: METTL3/METTL14 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9HCE5
Assay: Inhibition of full-length His-tagged METTL3 (unknown origin) coexpressed with full-length FLAG-tagged METTL14 (unknown origin) expressed in baculovirus expression system using 5'P-uacacucgaucuggacuaaagcugcuc-3' RNA as substrate pre-incubated for 10 mins and followed by substrate addition and measured after 60 mins by methyltransferase assay
Measurement: IC50 = 6.1 nM (pChEMBL 8.210000038146973)
Descriptors: MW 459.53, ALogP 3.48, HBA 5, HBD 3, PSA 91.29, QED 0.39
Compound (SMILES): c1cc(-c2cn(Cc3ccc4cc(CNCC5CCC5)[nH]c4c3)nn2)c2cn[nH]c2c1
InChIKey: RBMMWSMSWCZWGC-UHFFFAOYSA-N
Target: METTL3/METTL14 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9HCE5
Assay: Inhibition of full-length His-tagged METTL3 (unknown origin) coexpressed with full-length FLAG-tagged METTL14 (unknown origin) expressed in baculovirus expression system using 5'P-uacacucgaucuggacuaaagcugcuc-3' RNA as substrate pre-incubated for 10 mins and followed by substrate addition and measured after 60 mins by methyltransferase assay
Measurement: IC50 = 6.1 nM (pChEMBL 8.210000038146973)
Descriptors: MW 411.51, ALogP 4.24, HBA 5, HBD 3, PSA 87.21, QED 0.37
Compound (SMILES): COc1cnc(Nc2ccc(C(=O)N3CCNCC3)cn2)nc1-c1ccc2ncc(N(C)C)nc2c1
InChIKey: NNWSGVSQWRVOIZ-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00534
Assay: Inhibition of CDK6 (unknown origin) by TR-FRET analysis
Measurement: IC50 = 1385 nM (pChEMBL 5.860000133514404)
Descriptors: MW 485.55, ALogP 2.35, HBA 10, HBD 2, PSA 121.29, QED 0.42
Compound (SMILES): CCc1cccc2cccc(-c3ncc4c(N5C[C@H]6CC[C@@H](C5)N6)nc(OCC56CCCN5CCC6)nc4c3F)c12
InChIKey: SAMGEKOCFLHABC-PSWAGMNNSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Inhibition of KRAS G12D mutant in human AGS cells assessed as reduction in ERK phosphorylation measured after 3 hrs by In-Cell Western assay
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 552.7, ALogP 5.49, HBA 7, HBD 1, PSA 66.41, QED 0.34
Compound (SMILES): C[C@H](Sc1nncn1C)c1ccnc(NC(=O)c2nc3ccccc3s2)c1
InChIKey: AJBIINWCSZQXOM-NSHDSACASA-N
Target: E3 ubiquitin-protein ligase CBL-B (SINGLE PROTEIN), Homo sapiens
UniProt: Q13191
Assay: Inhibition of N-terminal Avi-tagged human CBL-B (36 to 427 residues) incubated with 60 nM Src kinase for 1.5 hrs followed by incubation with fluorescently labeled UbcH5B-Ub for 1 hr and measured by TR-FRET assay
Measurement: IC50 = 3001 nM (pChEMBL 5.519999980926514)
Descriptors: MW 396.5, ALogP 3.93, HBA 8, HBD 1, PSA 85.59, QED 0.51
Compound (SMILES): Cc1cc(NC(=O)c2ccc(NS(=O)(=O)CCO)cc2N2CCC3(CC2)CC3)cc(N2CCC(F)(F)CC2)n1
InChIKey: LFLJMXCTMOQMSW-UHFFFAOYSA-N
Target: Kinesin-like protein KIF18A (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NI77
Assay: Inhibition of recombinant His-tagged human KIF18A (1 to 467 residues) expressed in baculovirus expression system assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 15 mins followed by ATP addition and further incubated for 15 mins and measured after 40 mins by ADP-Glo reagent based assay
Measurement: IC50 = 38.4 nM (pChEMBL 7.420000076293945)
Descriptors: MW 563.67, ALogP 3.99, HBA 7, HBD 3, PSA 114.87, QED 0.44
Compound (SMILES): CCOc1cc2[nH]c(Cc3nn(CC(=O)N4CCOCC4)c(=O)c4ccccc34)nc2cc1Cl
InChIKey: AJNJARPEJYGMNO-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O95136
Assay: Antagonist activity at human S1P2 receptor expressed in CHO cells assessed as inhibition of calcium flux
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 481.94, ALogP 2.77, HBA 7, HBD 1, PSA 102.34, QED 0.45
Compound (SMILES): O=C(CNC(=O)c1cccc(NC2=NCC(F)(F)CN2)c1)NC[C@H](NC(=O)c1c(Cl)cc(N2CCOCC2)cc1Cl)C(=O)O
InChIKey: OPQCIIAMSOTDQL-FQEVSTJZSA-N
Target: Integrin alpha-5/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P05556
Assay: Cell Adhesion Assay: Evaluation of cell attachment to extracellular matrix proteins was performed as previously described by Yokosaki et al, J. Biol. Chem., 271: (39): 24144-24150 (1996). Briefly, wells of non-tissue culture-treated polystyrene 96-well flat-bottom microtiter plates (Linbro/Titertek, Flow Laboratories, McLean, Va.) were coated by incubation with 100 μl of each substrate in PBS at 37° C. for 1 hour. 96-well flat-bottomed tissue culture plates were coated with human plasma fibronectin for 1 hour at 37° C. After incubation, wells were washed with PBS, then blocked with 1% bovine serum albumin (BSA) for one hour. Control wells were filled with 1% BSA. SW480 cells were detached using 10 mM EDTA and resuspended in serum-free DMEM. For blocking experiments, cells were incubated with 10 μg/ml of the antibody for 15 minutes at 4° C. before plating. The plates were centrifuged at 10 g for 5 minutes before incubation for 1 hour at 37° C. in humidified 5% CO2. Nonadherent cells were removed by centrifugation (top side down) at 10 g for 5 minutes. Attached cells were stained with 0.5% crystal violet, and the wells were washed with PBS. The relative number of cells in each well was evaluated after solubilization in 40 μl of 2% Triton X-100 by measuring absorbance at 595 nm in a microplate reader. All determinations were carried out in triplicate.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 656.47, ALogP 1.57, HBA 9, HBD 6, PSA 173.49, QED 0.22
Compound (SMILES): C[C@H](CC(=O)N1CCC(O)(Cn2cc(-c3ccccc3)c(-c3ccccc3)cc2=O)CC1)c1ccccc1
InChIKey: CZWNOIWMYUORDB-RUZDIDTESA-N
Target: Ubiquitin carboxyl-terminal hydrolase 19 (SINGLE PROTEIN), Homo sapiens
UniProt: O94966
Assay: USP19 Activity Assay: USP19 activity was monitored in a fluorescence polarisation (FP) homogeneous assay using the isopeptide Ubiquitin-Lys-TAMRA substrate (either AUB-101, Almac Sciences Scotland Limited, or U-558, Boston Biochem, both of which gave identical results). Full-length USP19 was purchased from Boston Biochem (E-576). Unless otherwise stated, all other reagents were purchased from Sigma. Enzymatic reactions were conducted in black flat bottom polystyrene 384-well plates (Nunc) and 30 μL total volume. USP19 (2.5 nM, 10 μL) was incubated in assay buffer (50 mM HEPES (pH 7.4), 150 mM NaCl, 5 mM DTT, 0.05% BSA (w/v), 0.05% CHAPS) in the presence or absence of inhibitor (10 μL). Inhibitors were stored as 10 mM DMSO stocks in an inert environment (low humidity, dark, low oxygen, room temperature) using the Storage Pod System and serial dilutions were prepared in buffer just prior to the assay (from 200 μM to 2 pM, 8-18 data point curve). Following incubation at RT for 30 min, the enzymatic reactions were initiated by dispensing the Ub substrate (500 nM, 10 μL). FP was measured every 15 min over a period of 90 min (within the linear range of the assay) using a Synergy 4 plate reader (BioTek) exciting at 530 nm and measuring the amount of parallel and perpendicular light at 575 nm. The FP signal was subsequently normalised to the no compound control. Data were plotted and fitted, and the concentrations resulting in 50% inhibition (IC50) were calculated using the non-linear regression curve fitting model using GraphPad (Prism).
Measurement: IC50 = 27500 nM (pChEMBL 4.559999942779541)
Descriptors: MW 506.65, ALogP 5.73, HBA 4, HBD 1, PSA 62.54, QED 0.35
Compound (SMILES): COc1ccccc1Oc1c(N)nc(-c2ccc(Br)cc2)nc1Cl
InChIKey: GBTXLCFBIYCONW-UHFFFAOYSA-N
Target: Deoxyhypusine synthase (SINGLE PROTEIN), Homo sapiens
UniProt: P49366
Assay: Inhibition of DHPS (unknown origin ) incubated for 30 mins by NAD/NADH-Glow assay
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 406.67, ALogP 4.94, HBA 5, HBD 1, PSA 70.26, QED 0.62
Compound (SMILES): CCc1ccc(-c2nc(NC(C)(C)CO)cnc2C(=O)Nc2cccc(S(=O)(=O)NC(C)(C)C)c2)cc1
InChIKey: ILPFGTJHUBJILV-UHFFFAOYSA-N
Target: Kinesin-like protein KIF18A (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NI77
Assay: Inhibition of recombinant His-tagged human KIF18A (1 to 467 residues) expressed in baculovirus expression system assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 15 mins followed by ATP addition and further incubated for 15 mins and measured after 40 mins by ADP-Glo reagent based assay
Measurement: IC50 = 146 nM (pChEMBL 6.840000152587891)
Descriptors: MW 525.68, ALogP 4.22, HBA 7, HBD 4, PSA 133.31, QED 0.33
Compound (SMILES): COC(C(=O)N1CC2=C(C1)CN(S(=O)(=O)c1cnc3c(c1)OCCO3)C2)c1cccc2oc(C)nc12
InChIKey: JUMFMQRWAPUWRG-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 9X (SINGLE PROTEIN), Homo sapiens
UniProt: Q93008
Assay: Inhibition of USP9X (unknown origin) using Ubiquitin-Rhoadmine 110 as substrate preincubated for 30 mins followed by substrate addition and measured after 11 mins by fluorescence assay
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 512.54, ALogP 1.83, HBA 9, HBD 0, PSA 124.3, QED 0.47
Compound (SMILES): O=C1CCCc2nn(C(=O)C3CC3)cc21
InChIKey: GKDODFNEXITXEL-UHFFFAOYSA-N
Target: Neutrophil elastase (SINGLE PROTEIN), Homo sapiens
UniProt: P08246
Assay: Inhibition of human neutrophil elastase
Measurement: Ki = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 204.23, ALogP 1.45, HBA 4, HBD 0, PSA 51.96, QED 0.7
Compound (SMILES): CC(C)(C)NC(=O)Nc1ccc(Nc2ncnc3c2OC(C)(C)C(=O)N3)cc1
InChIKey: KFACNDRHPRGUQS-UHFFFAOYSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: Inhibition of wild type TrkA (unknown origin) using poly(Glu: Tyr) as substrate preincubated for 15 mins followed by substrate addition and further incubated for 30 mins in presence of [gamma-33P]ATP by scintillation counting method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 384.44, ALogP 3.25, HBA 6, HBD 4, PSA 117.27, QED 0.65
Compound (SMILES): O=C1CCC(N2Cc3cc(C4CCN(Cc5ccc(F)cc5)CC4)ccc3C2=O)C(=O)N1.O=CO
InChIKey: MUXPNHZWLVWTGK-UHFFFAOYSA-N
Target: DNA-binding protein Ikaros (SINGLE PROTEIN), Homo sapiens
UniProt: Q13422
Assay: Induction of IKZF1 degradation in human GripTite 293 MSR cells assessed as reduction in IKZF1 level measured by PathHunter assay
Measurement: EC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 435.5, ALogP 2.97, HBA 4, HBD 1, PSA 69.72, QED 0.75
Compound (SMILES): CC[C@@H]1CN(C(=O)c2cc(Cn3c(=O)[nH]c(=O)c4ccccc43)ccc2F)CCN1C
InChIKey: SCZPGKAQAVZXIX-MRXNPFEDSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Inhibition of recombinant human PARP1 using NAD+ as substrate incubated for 1 hr by ELISA
Measurement: IC50 = 39.58 nM (pChEMBL 7.400000095367432)
Descriptors: MW 424.48, ALogP 2.04, HBA 5, HBD 1, PSA 78.41, QED 0.7
Compound (SMILES): CN(C)C(=O)N1CC[C@H](NC2=Nc3cc(F)ccc3N(CC(F)F)c3ccc(Cl)cc32)C1
InChIKey: RVHZFZVJXGIAJF-HNNXBMFYSA-N
Target: Serine/threonine-protein kinase PAK 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13153
Assay: Affinity Biochemical interaction: (Caliper in vitro dephosphorylation assay (PAK1 phos.)) EUB0001075a PAK1
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 465.91, ALogP 4.62, HBA 4, HBD 1, PSA 51.18, QED 0.72
Compound (SMILES): COc1ccc(-c2cccc(C(=O)N(C)C)c2)cc1S(=O)(=O)Nc1cccc(CCNC(=O)c2ccccc2-n2nccn2)c1
InChIKey: AMTAVIZAVFJXIJ-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Agonist activity at human OX1R stably expressed in CHO cells
Measurement: EC50 < 35481.34 nM (pChEMBL 4.449999809265137)
Descriptors: MW 624.72, ALogP 4.42, HBA 8, HBD 2, PSA 135.52, QED 0.22
Compound (SMILES): Nc1nc2c(ncn2[C@@H]2O[C@@H]3COP(=O)(S)O[C@@H]4[C@@H](COP(=O)(S)O[C@@H]2[C@@H]3O)C[C@@H](Oc2ccncn2)[C@@H]4F)c(=O)[nH]1
InChIKey: NBTGHBHVPPFXTL-OMXPKPSISA-N
Target: Stimulator of interferon genes protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q86WV6
Assay: Binding affinity to human STING incubated for 60 mins measured by competitive TR-FRET assay
Measurement: EC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 667.53, ALogP 1.45, HBA 16, HBD 5, PSA 225.12, QED 0.2
Compound (SMILES): CCCCNc1nc(N)nc2ccc(Cc3ccccc3CN(C)C)nc12
InChIKey: COESQVJWHNEPPM-UHFFFAOYSA-N
Target: Toll-like receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYK1
Assay: Agonist activity at human TLR7 expressed in HEK293 cells incubated for 6 to 16 hrs by SEAP reporter gene assay
Measurement: EC50 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 364.5, ALogP 3.47, HBA 6, HBD 2, PSA 79.96, QED 0.6
Compound (SMILES): Cn1cnnc1CC1(c2cccc(NC(=O)c3cc(CN4CC[C@H](F)C4)nc(C4CC4)n3)c2)COC1
InChIKey: OIAAQGHQMQYZEB-IBGZPJMESA-N
Target: E3 ubiquitin-protein ligase CBL-B (SINGLE PROTEIN), Homo sapiens
UniProt: Q13191
Assay: Inhibition of N-terminal Avi-tagged human CBL-B (36 to 427 residues) incubated with 60 nM Src kinase for 1.5 hrs followed by incubation with fluorescently labeled UbcH5B-Ub for 1 hr and measured by TR-FRET assay
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 491.57, ALogP 2.79, HBA 8, HBD 1, PSA 98.06, QED 0.52
Compound (SMILES): [2H]C([2H])([2H])c1nnn(C)c1-c1cc2c(cc1F)c1ncc(C(C)(C)O)cc1n2[C@H](c1ccccc1)C1CCOCC1
InChIKey: AIWLOFZSVQLGOB-GNUZTRDVSA-N
Target: Myc proto-oncogene protein (SINGLE PROTEIN), Homo sapiens
UniProt: P01106
Assay: Inhibition of c-MYC (unknown origin)
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 513.62, ALogP 5.68, HBA 7, HBD 1, PSA 77.99, QED 0.33
Compound (SMILES): C=CC(=O)N1C(=O)CC(c2ccc(OC)cc2)Sc2ccccc21
InChIKey: HILKMLIHQJPADV-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of recombinant human GSK-3beta using GS-2 peptide as substrate incubated for 30 mins in presence of ATP by kinase-glo luminescence assay
Measurement: IC50 = 6200 nM (pChEMBL 5.210000038146973)
Descriptors: MW 339.42, ALogP 3.98, HBA 4, HBD 0, PSA 46.61, QED 0.79
Compound (SMILES): Oc1cccc([C@]23CCC[C@H](NCC2)[C@H]3O)c1
InChIKey: SCLHPUJRNBPHLE-MJBXVCDLSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-N-methylspiperone from human dopamine D2 receptor expressed in HEK293 cell membranes incubated for 60 mins by microbeta scintillation counting analysis
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 233.31, ALogP 1.54, HBA 3, HBD 3, PSA 52.49, QED 0.69
Compound (SMILES): Cn1cnnc1CC1(c2cccc(NC(=O)c3cc(CN4CCC5CC54)cc(C4CC4)n3)c2)COC1
InChIKey: DFMVTXPBVBJBAQ-UHFFFAOYSA-N
Target: E3 ubiquitin-protein ligase CBL-B (SINGLE PROTEIN), Homo sapiens
UniProt: Q13191
Assay: Inhibition of N-terminal Avi-tagged human CBL-B (36 to 427 residues) incubated with 60 nM Src kinase for 1.5 hrs followed by incubation with fluorescently labeled UbcH5B-Ub for 1 hr and measured by TR-FRET assay
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 484.6, ALogP 3.44, HBA 7, HBD 1, PSA 85.17, QED 0.53
Compound (SMILES): Nc1nc(-c2cccc(-n3ccc4cc(C5CC5)cc(F)c4c3=O)c2CO)c2cc(-c3cccnc3)[nH]c2n1
InChIKey: QKYCGTAINHHWEB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of human BTK-A using phosphorylated substrate in presence of ATP by microplate reader assay
Measurement: IC50 = 2.1 nM (pChEMBL 8.680000305175781)
Descriptors: MW 518.55, ALogP 5.08, HBA 7, HBD 3, PSA 122.71, QED 0.29
Compound (SMILES): Cn1cnnc1C(F)(F)C1(c2cccc(N3Cc4c(cc(CN5CC[C@H](F)C5)cc4C(F)(F)F)C3=O)c2)CC1
InChIKey: GZNCMBTVLMVMQO-SFHVURJKSA-N
Target: E3 ubiquitin-protein ligase CBL-B (SINGLE PROTEIN), Homo sapiens
UniProt: Q13191
Assay: Inhibition of N-terminal Avi-tagged human CBL-B (36 to 427 residues) incubated with 60 nM Src kinase for 1.5 hrs followed by incubation with fluorescently labeled UbcH5B-Ub for 1 hr and measured by TR-FRET assay
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 549.52, ALogP 5.36, HBA 5, HBD 0, PSA 54.26, QED 0.39
Compound (SMILES): Cc1c(O[C@H](C(=O)O)c2ccccc2)ccc2c1oc(=O)c1ccccc12
InChIKey: NFQYAASIUHLEDX-FQEVSTJZSA-N
Target: Polymerase basic protein 2 (SINGLE PROTEIN), Influenza A virus (strain A/Puerto Rico/8/1934 H1N1)
UniProt: P03428
Assay: Binding affinity to CM5 immobilized N-terminal His/Sumo tagged Influenza A virus (A/WSN/1933(H1N1)) PB2 CBD (318 to 486 residues) expressed in Escherichia coli by surface plasmon resonance assay
Measurement: Kd = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 360.37, ALogP 4.46, HBA 4, HBD 1, PSA 76.74, QED 0.43
Compound (SMILES): CS(=O)(=O)NC(=O)c1cc(C2CC2)c(OCC2CCN(C(c3ccccc3)c3ccccc3)CC2)cc1F
InChIKey: XVGMRZRHSRQQFG-UHFFFAOYSA-N
Target: Sodium channel protein type 7 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q01118
Assay: Displacement of [3H]GX-545 Nav1.7 (unknown origin) expressed in HEK cells by liquid scintillation counting based radioligand competition assay
Measurement: IC50 = 3.6 nM (pChEMBL 8.4399995803833)
Descriptors: MW 536.67, ALogP 5.27, HBA 5, HBD 1, PSA 75.71, QED 0.4
Compound (SMILES): Cc1nc(N)c2c(C#N)c(-c3cccnc3)[nH]c2n1
InChIKey: AWVFEGNSWDVVKZ-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Binding affinity to DYRK1A (unknown origin) assessed as inhibition constant by ADP hunter plus assay
Measurement: Ki = 32 nM (pChEMBL 7.5)
Descriptors: MW 250.26, ALogP 1.78, HBA 5, HBD 2, PSA 104.27, QED 0.68
Compound (SMILES): O=C(N1CCC(O)(Cn2cnc(-c3ccccc3)cc2=O)CC1)N1CCOC[C@H]1c1ccccc1
InChIKey: MWOPCHILKMMGPB-DEOSSOPVSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 19 (SINGLE PROTEIN), Homo sapiens
UniProt: O94966
Assay: Inhibition of C-terminal His6-tagged recombinant human USP19 using iso-peptide ubiquitin-Lys-TAMRA as substrate incubated for 30 mins and measured after 90 mins by fluorescent polarization assay
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 474.56, ALogP 2.93, HBA 6, HBD 1, PSA 87.9, QED 0.63
Compound (SMILES): COc1ccc(/C=C/c2n[nH]c(=O)o2)cc1OC
InChIKey: IVRQNGSTDFTVSO-GQCTYLIASA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of human recombinant MAO-A by fluorescence assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 248.24, ALogP 1.55, HBA 5, HBD 1, PSA 77.35, QED 0.89
Compound (SMILES): O=C(Nc1ccc(/C=C/c2ccc(F)cc2)cc1)c1ccccc1
InChIKey: VWHBXOXKVRZVMJ-VOTSOKGWSA-N
Target: Alpha-synuclein (SINGLE PROTEIN), Homo sapiens
UniProt: P37840
Assay: Binding affinity to recombinant human alpha-syn aggregates assessed as dissociation constant by SPR analysis
Measurement: Kd > 10000 nM (pChEMBL 5)
Descriptors: MW 317.36, ALogP 5.25, HBA 1, HBD 1, PSA 29.1, QED 0.65
Compound (SMILES): CC(C)[C@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](C)N)[C@@H](C)O)C(=O)N[C@@H](Cc1ccc(OP(=O)(O)O)cc1)C(=O)NCC(=O)O
InChIKey: KNYSLGYWRXBXHS-NQGNDLBJSA-N
Target: Tyrosine-protein phosphatase non-receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P54829
Assay: Inhibition of TAM-3Y-F2Pmp peptide binding to N-terminal His6-fused STEP32 (282 to 563 residues) (unknown origin) expressed in Escherichia coli BL21(DE3) measured for 30 mins by fluorescence polarization method
Measurement: Ki = 5350 nM (pChEMBL 5.269999980926514)
Descriptors: MW 1252.24
Compound (SMILES): COc1ccc(OC)c(NC(=O)c2sc(=S)n3c2[nH]c(=O)c2cc(OC)c(OC)cc23)c1
InChIKey: QFJYZNBZFSRWCL-UHFFFAOYSA-N
Target: Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UDY8
Assay: Inhibition of N-terminal his-tagged GCN4 leucine zipper fused human MALT1 (340-281 residues) expressed in Escherichia coli using Ac-LVSR-AMC as substrate by HTS assay
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 473.53, ALogP 3.86, HBA 9, HBD 2, PSA 103.29, QED 0.41
Compound (SMILES): O=C([C@H]1C[C@H](c2c(-c3ccc(F)cc3)[nH]c3c(F)cc(F)cc32)C1)N1CCOC(CO)C1
InChIKey: QAZNIOFYQCKYIP-OSPTYYIOSA-N
Target: Apolipoprotein L1 (SINGLE PROTEIN), Homo sapiens
UniProt: O14791
Assay: Inhibition of APOL1 G1 variant in human HEK293-T-REx cells measured by Thallium assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 444.45, ALogP 3.97, HBA 3, HBD 2, PSA 65.56, QED 0.64
Compound (SMILES): C=CCN1CC#CCN(NC(=O)[C@H](C)N)C(=O)N[C@@H](C)C(=O)N[C@@H](Cc2c[nH]c3ccccc23)C(=O)N[C@H](Cc2ccccc2)C(=O)N[C@H](C(N)=O)CCC1
InChIKey: YIMYPOCGLSYDMK-FNPJULINSA-N
Target: Platelet glycoprotein 4 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q07969
Assay: Displacement of [125I]-Tyr-Bpa-Ala-hexarelin from rat CD36 receptor in heart tissue membrane incubated for 60 mins by competitive receptor binding assay
Measurement: IC50 = 22800 nM (pChEMBL 4.639999866485596)
Descriptors: MW 754.89, ALogP -0.04, HBA 8, HBD 8, PSA 236.88, QED 0.11
Compound (SMILES): COc1cccc(NC(=O)[C@H]2CC[C@@H](n3cnc4c(N)nc(Nc5cccnc5)nc43)CC2)c1
InChIKey: QQQDPDYWXPNIQA-RHNCMZPLSA-N
Target: Choline kinase alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P35790
Assay: Inhibition of ChoKalpha (unknown origin) by HTS assay
Measurement: IC50 = 3075 nM (pChEMBL 5.510000228881836)
Descriptors: MW 458.53, ALogP 3.93, HBA 9, HBD 3, PSA 132.87, QED 0.4
Compound (SMILES): CC(C)n1cc(-c2nc(Nc3ccc(C(=O)N4CCN(C(=O)OC(C)(C)C)CC4)cn3)ncc2F)c2cc(F)cnc21
InChIKey: ACRARLRPFDXNGU-UHFFFAOYSA-N
Target: CDK6/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24385
Assay: Inhibition of CDK6/Cyclin D1 (unknown origin) using ULight-MBP peptide substrate in presence of ATP by TR-FRET assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 578.62, ALogP 5.18, HBA 9, HBD 1, PSA 118.37, QED 0.34
Compound (SMILES): Cc1n[nH]c(C)c1N1CCN(c2cc(C(=O)O)ccc2Cl)CC1
InChIKey: HSSORIGMNUFCNX-UHFFFAOYSA-N
Target: Transthyretin (SINGLE PROTEIN), Homo sapiens
UniProt: P02766
Assay: Binding affinity to human plasma TTR tetramer assessed as displacement of diclofenac-coupled FITC by fluorescence polarization assay
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 334.81, ALogP 2.7, HBA 4, HBD 2, PSA 72.46, QED 0.9
Compound (SMILES): NC(=O)CNC[C@H]1C[C@@H](c2c(-c3ccc(F)cc3)[nH]c3c(F)cc(F)cc32)C1
InChIKey: PHFXFXHTZZXZSW-BJHJDKERSA-N
Target: Apolipoprotein L1 (SINGLE PROTEIN), Homo sapiens
UniProt: O14791
Assay: Inhibition of APOL1 G1 variant in human HEK293-T-REx cells measured by Thallium assay
Measurement: IC50 < 250 nM (pChEMBL 6.6020002365112305)
Descriptors: MW 387.41, ALogP 3.82, HBA 2, HBD 3, PSA 70.91, QED 0.6
Compound (SMILES): CNCCc1ccc(Cl)c(-c2ccccc2OC)c1.Cl
InChIKey: MXZLWDMMDSHACB-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Displacement of [3H] D-lysergic acid diethylamide from 5-HT7R (unknown origin) transfected in HEK293 cells incubated for 1.5 hrs by microbeta scintillation counter analysis
Measurement: Ki = 2.818 nM (pChEMBL 8.550000190734863)
Descriptors: MW 275.78, ALogP 3.78, HBA 2, HBD 1, PSA 21.26, QED 0.9
Compound (SMILES): CO[C@@H]1[C@@H](n2cc(-c3cc(F)c(F)c(F)c3)nn2)[C@@H](O)[C@@H](CO)O[C@H]1S[C@@H]1COC[C@H](n2cc(-c3ccccc3)nn2)[C@H]1O
InChIKey: HZNVFMVXUOADJM-XBSVYHDWSA-N
Target: Galectin-3 (SINGLE PROTEIN), Homo sapiens
UniProt: P17931
Assay: Inhibition of biotin-asialofetuin binding to human Gal3 measured after 90 mins by HTRF competition assay
Measurement: IC50 = 42 nM (pChEMBL 7.380000114440918)
Descriptors: MW 634.64, ALogP 1.99, HBA 13, HBD 3, PSA 149.8, QED 0.24
Compound (SMILES): NC(=O)[C@H]1CCN(C(=O)[C@H]2C[C@H](c3c(-c4ccc(F)cc4)[nH]c4c(F)cc(F)cc43)C2)C1
InChIKey: AHFBWHGDUQQTSP-KKUMJFAQSA-N
Target: Apolipoprotein L1 (SINGLE PROTEIN), Homo sapiens
UniProt: O14791
Assay: Inhibition of APOL1 G1 variant in human HEK293-T-REx cells measured by Thallium assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 441.45, ALogP 4.08, HBA 2, HBD 2, PSA 79.19, QED 0.64
Compound (SMILES): CCCS(=O)(=O)N[C@H]1CCCN(C(C)=O)[C@H]1CO[C@H]1CC[C@@H](C(C)C)CC1
InChIKey: PGPHOCNBEFFTNM-YRPNKDGESA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Agonist activity at human OX2R expressed in CHO-K1 cells by FLIPR calcium flux assay
Measurement: EC50 = 2500 nM (pChEMBL 5.599999904632568)
Descriptors: MW 402.6, ALogP 2.93, HBA 4, HBD 1, PSA 75.71, QED 0.68
Compound (SMILES): N#CC1CCCN(C(=O)c2cnc(NC3(c4cncnc4)CC3)nc2)C1
InChIKey: CDTXEVWHMGPGKZ-UHFFFAOYSA-N
Target: Biotinidase (SINGLE PROTEIN), Homo sapiens
UniProt: P43251
Assay: Inhibition of N-terminal FLAG/His6-tagged human biotinidase expressed in COS cells using biotinyl-7-amino-4-trifluoromethylcoumarin as substrate preincubated for 10 mins followed by substrate addition and measured after 90 mins
Measurement: IC50 = 53000 nM (pChEMBL 4.28000020980835)
Descriptors: MW 349.4, ALogP 1.74, HBA 7, HBD 1, PSA 107.69, QED 0.9
Compound (SMILES): CCC(CO)(CO)NC(=O)[C@@H]1CCCN1Cc1ccc(OCc2cccc(-c3ccccc3)c2C)c([N+](=O)[O-])c1
InChIKey: ZZBCMEXCGGSSOT-MHZLTWQESA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NZQ7
Assay: Inhibition of human PD-1/PD-L1 interaction assessed as disruption of PD-1/PD-L1 complex incubated for 2 hrs by Tag-1 Eu3+ and anti-Tag2-XL665 based HTRF assay
Measurement: IC50 = 82.3 nM (pChEMBL 7.079999923706055)
Descriptors: MW 547.65, ALogP 4.36, HBA 7, HBD 3, PSA 125.17, QED 0.23
Compound (SMILES): C[C@@H](c1cccc(N2Cc3c(cccc3C(F)(F)F)C2=O)c1)[C@@H](F)c1nncn1C
InChIKey: GQVRIESWPBYISN-KPZWWZAWSA-N
Target: E3 ubiquitin-protein ligase CBL-B (SINGLE PROTEIN), Homo sapiens
UniProt: Q13191
Assay: Inhibition of N-terminal Avi-tagged human CBL-B (36 to 427 residues) incubated with 60 nM Src kinase for 1.5 hrs followed by incubation with fluorescently labeled UbcH5B-Ub for 1 hr and measured by TR-FRET assay
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 418.39, ALogP 4.81, HBA 4, HBD 0, PSA 51.02, QED 0.57
Compound (SMILES): CC1(COc2cccc(NC(=O)c3ccc(NS(=O)(=O)CCO)cc3N3CCC4(CC3)CC4)n2)COC1
InChIKey: JIRCYYBXUUJBNM-UHFFFAOYSA-N
Target: Kinesin-like protein KIF18A (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NI77
Assay: Inhibition of recombinant His-tagged human KIF18A (1 to 467 residues) expressed in baculovirus expression system assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 15 mins followed by ATP addition and further incubated for 15 mins and measured after 40 mins by ADP-Glo reagent based assay
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 530.65, ALogP 2.86, HBA 8, HBD 3, PSA 130.09, QED 0.43
Compound (SMILES): Cc1ccc(-c2nc(N)nc3c2ncc(=O)n3Cc2ccccc2)o1
InChIKey: KHYXCTKKSFTXSV-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Antagonist activity at human A2aR expressed in HEK293 cells assessed as reduction in cAMP production incubated for 60 mins by ultra LANCE cAMP detection assay
Measurement: IC50 = 481.7 nM (pChEMBL 6.320000171661377)
Descriptors: MW 333.35, ALogP 2.39, HBA 7, HBD 1, PSA 99.83, QED 0.62
Compound (SMILES): C=CC[C@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](N)CC=C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCC)C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1ccccc1)C(=O)O
InChIKey: PKRWGTWQTMCAMO-AGVBWZICSA-N
Target: Apelin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35414
Assay: Displacement of [125I]-[Nle75,Tyr77][Pyr1]-Ape13 from YFP-tagged human APJ expressed in HEK293 cell membranes assessed as inhibition constant incubated for 1 hr by scintillation counting method
Measurement: Ki = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 1208.47
Compound (SMILES): CCc1cc(NC)c2ccc(CCc3cncc(-n4cc(-c5ccn(C)n5)c5c(N)ncnc54)c3)cc2n1
InChIKey: ALMAFGMURQMISC-UHFFFAOYSA-N
Target: Protein arginine N-methyltransferase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: O14744
Assay: Inhibition of PRMT5 (unknown origin) using Ac-SGRGKGGKGLGKGGAKRHRKVGGK-Biotin and 3H-SAM as substrates preincubated for 5 mins followed by substrate addition incubated for 60 mins by TopCount scintillation counting method
Measurement: IC50 >= 1000 nM (pChEMBL 6)
Descriptors: MW 503.61, ALogP 4.74, HBA 9, HBD 2, PSA 112.36, QED 0.32
Compound (SMILES): CN(C)C(=O)c1c(N)ccc(-c2cnc3c(c2Cl)[C@]2(CC[C@@]4(CCCNC4=O)C2)CN3)c1F
InChIKey: GTDGSURDWQAKFW-ZEQRLZLVSA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92918
Assay: Inhibition of HPK1 in human Jurkat E6.1 cells assessed as SLP76 phosphorylation incubated for 30 mins followed by anti-CD3, biotinylated anti-SLP76 and TMB substrate addition measured after 3 hrs by ELISA assay
Measurement: IC50 = 1700 nM (pChEMBL 5.769999980926514)
Descriptors: MW 471.96, ALogP 3.57, HBA 5, HBD 3, PSA 100.35, QED 0.58
Compound (SMILES): CC(C)c1ccnc(-c2nc3nc(C(=O)O)nc(N[C@H](C)C4CCC4)c3n2Cc2ccc(OC(F)(F)F)c(F)c2)c1
InChIKey: LNMKUQHCQKKGKH-OAHLLOKOSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: FRET Assay: An HDM2 FRET assay was developed to assess the compounds' inhibitory activity towards binding of p53 protein. A truncated version of HDM2 with residues 17 to 125 (containing p53 binding surface, Science (1994) 265, 346-355), with N-terminal His and Thioredoxin tag was generated in pET32a expression vector and expressed in E. coli strain BL21(DE3)Rosetta. Protein was purified using Ni-affinity chromatography, followed by size exclusion chromatography using Superdex 75 26/60 column. To assess inhibition of p53 binding to HDM2, a FITC labeled 8-mer peptide (sequence: Ac-Phe-Arg-Dpr-Ac6c-(6-Br)Trp-Glu-Glu-Leu-NH2; Anal Biochem. 2004 Aug. 1; 331(1):138-46) with strong affinity towards p53 binding pocket of HDM2 was used. The HDM2 assay buffer contained 1× Phosphate Buffered Saline (Invitrogen, Cat#14190), 0.01% BSA (Jackson ImmunoResearch, Cat#001-000-162), 0.01% Tween-20. In the 1× assay buffer recombinant HDM2 protein, peptide and Lumi4-Tb Cryptate-conjugate mouse anti-6×His antibody (cisbio, Cat# Tb61HISTLB) were added and transferred to ProxiPlate PLUS (PerkinElmer, Cat#6008269), containing compounds so that final DMSO concentration is 0.1%. Final concentrations of reagents in the assay wells are 0.5 nM HDM2, 0.25 nM anti HIS (Tb label) antibody and 3 nM peptide. After two hour incubation at room temperature in a humidified chamber plates were read on EnVision plate reader with the following settings: excitation: UV, 340 nM, two emission filters: 520 nm and 495 nm respectively. Ratio of em520/em495 was used to calculate % inhibition and to obtain IC50 with 4-parameter logistic equation.
Measurement: IC50 = 9.507 nM (pChEMBL 8.020000457763672)
Descriptors: MW 572.56, ALogP 6.4, HBA 8, HBD 2, PSA 115.05, QED 0.22
Compound (SMILES): C[C@H](CC1CCCCC1)C(=O)N1CC[C@](O)(Cn2cc(C(=O)N3CCNCC3)c(-c3ccccc3)cc2=O)C(C)(C)C1
InChIKey: RCKRBLQTXSFTRS-GZGVDWRWSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 19 (SINGLE PROTEIN), Homo sapiens
UniProt: O94966
Assay: USP19 Activity Assay: USP19 activity was monitored in a fluorescence polarisation (FP) homogeneous assay using the isopeptide Ubiquitin-Lys-TAMRA substrate (either AUB-101, Almac Sciences Scotland Limited, or U-558, Boston Biochem, both of which gave identical results). Full-length USP19 was purchased from Boston Biochem (E-576). Unless otherwise stated, all other reagents were purchased from Sigma. Enzymatic reactions were conducted in black flat bottom polystyrene 384-well plates (Nunc) and 30 μL total volume. USP19 (2.5 nM, 10 μL) was incubated in assay buffer (50 mM HEPES (pH 7.4), 150 mM NaCl, 5 mM DTT, 0.05% BSA (w/v), 0.05% CHAPS) in the presence or absence of inhibitor (10 μL). Inhibitors were stored as 10 mM DMSO stocks in an inert environment (low humidity, dark, low oxygen, room temperature) using the Storage Pod System and serial dilutions were prepared in buffer just prior to the assay (from 200 μM to 2 pM, 8-18 data point curve). Following incubation at RT for 30 min, the enzymatic reactions were initiated by dispensing the Ub substrate (500 nM, 10 μL). FP was measured every 15 min over a period of 90 min (within the linear range of the assay) using a Synergy 4 plate reader (BioTek) exciting at 530 nm and measuring the amount of parallel and perpendicular light at 575 nm. The FP signal was subsequently normalised to the no compound control. Data were plotted and fitted, and the concentrations resulting in 50% inhibition (IC50) were calculated using the non-linear regression curve fitting model using GraphPad (Prism).
Measurement: IC50 = 27500 nM (pChEMBL 4.559999942779541)
Descriptors: MW 576.78, ALogP 4.16, HBA 6, HBD 2, PSA 94.88, QED 0.52
Compound (SMILES): CCS(=O)(=O)N1CCOc2ccc(F)cc2CN(C)c2ccn3ncc(c3n2)C1
InChIKey: JMJNHMVQWSMBRO-UHFFFAOYSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: Inhibition of TRKA G595R mutant (unknown origin)
Measurement: IC50 = 99.9 nM (pChEMBL 7)
Descriptors: MW 419.48, ALogP 2.05, HBA 7, HBD 0, PSA 80.04, QED 0.63
Compound (SMILES): NC(=O)c1ccc(Nc2ncc(C(F)(F)F)c(N[C@H]3CC[C@H](N)CC3)n2)cc1
InChIKey: ASLOBMSYWWVZKE-HAQNSBGRSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of N-terminal GST tagged human recombinant wild type FLT-3 (564-993 residues) expressed in baculovirus infected Sf21 insect cells using TK peptide as substrate incubated for 1 hrs by HTRF KinEASE TK assay
Measurement: IC50 = 12.25 nM (pChEMBL 7.909999847412109)
Descriptors: MW 394.4, ALogP 3.02, HBA 6, HBD 4, PSA 118.95, QED 0.62
Compound (SMILES): O=C(N1CCC(O)(Cn2cnc(-c3ccccc3)cc2=O)C2(CCCCC2)C1)N1CCNC[C@H]1c1ccccc1
InChIKey: VFZYQVKRJBSERP-MLAKCTNMSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 19 (SINGLE PROTEIN), Homo sapiens
UniProt: O94966
Assay: Inhibition of C-terminal His6-tagged recombinant human USP19 using iso-peptide ubiquitin-Lys-TAMRA as substrate incubated for 30 mins and measured after 90 mins by fluorescent polarization assay
Measurement: IC50 < 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 541.7, ALogP 4.06, HBA 6, HBD 2, PSA 90.7, QED 0.52
Compound (SMILES): COc1cccc(C2CNCCN2C(=O)N2CCC(O)(Cn3cnc(-c4ccccc4)cc3=O)C3(CCCC3)C2)c1
InChIKey: UFXPDBXXRQENSQ-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 19 (SINGLE PROTEIN), Homo sapiens
UniProt: O94966
Assay: Inhibition of C-terminal His6-tagged recombinant human USP19 using iso-peptide ubiquitin-Lys-TAMRA as substrate incubated for 30 mins and measured after 90 mins by fluorescent polarization assay
Measurement: IC50 = 5000 nM (pChEMBL 5.300000190734863)
Descriptors: MW 557.7, ALogP 3.68, HBA 7, HBD 2, PSA 99.93, QED 0.5
Compound (SMILES): N#Cc1cccc(-c2cnc(Nc3cccc(C(=O)N4CCCC4)c3)nc2N[C@H]2[C@@H](C(N)=O)[C@@H]3C=C[C@H]2C3)c1
InChIKey: ZFLJQOGIHBIDNZ-YGKRLXNZSA-N
Target: Interleukin-1 receptor-associated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWZ3
Assay: Inhibition of IRAK4 (unknown origin) in presence of MBP as substrate by ADP-Glo assay
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 519.61, ALogP 4.08, HBA 7, HBD 3, PSA 137.03, QED 0.4
Compound (SMILES): Cc1ccc(NC(=O)c2nccc(C(F)(F)F)n2)cc1-c1ccc2c(c1)OC1(CCOCC1)CC(=O)N2
InChIKey: WASYUHBPAZRREF-UHFFFAOYSA-N
Target: RAF proto-oncogene serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P04049
Assay: Inhibition of human recombinant cRAF measured after 60 mins by TR-FRET assay
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 512.49, ALogP 4.99, HBA 6, HBD 2, PSA 102.44, QED 0.51
Compound (SMILES): C[C@@H](O)[C@@H]1NC(=O)[C@@H]2CSSC[C@@H](C(=O)N[C@@H](Cc3ccc(O)cc3)C(=O)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc3ccc(O)c(I)c3)NC(=O)[C@H](CCCNC(N)=O)NC(=O)[C@H](CSCS[C@@H](NC(=O)CN)C(=O)N2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CC(=O)O)NC1=O
InChIKey: HFSGGAQSIXRBQM-LNUJUBLCSA-N
Target: Neuronal acetylcholine receptor; alpha9/alpha10 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9GZZ6
Assay: Inhibition of human alpha9alpha10 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response by two-electrode voltage-clamp method
Measurement: IC50 = 882 nM (pChEMBL 6.050000190734863)
Descriptors: MW 1690.67
Compound (SMILES): C[C@H](CC1CCCCC1)C(=O)N1CCC(O)(Cn2cc(C(=O)O)c(-c3ccccc3)cc2=O)C(C)(C)C1
InChIKey: VELNUIZXDNMOQK-BPADPFCFSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 19 (SINGLE PROTEIN), Homo sapiens
UniProt: O94966
Assay: USP19 Activity Assay: USP19 activity was monitored in a fluorescence polarisation (FP) homogeneous assay using the isopeptide Ubiquitin-Lys-TAMRA substrate (either AUB-101, Almac Sciences Scotland Limited, or U-558, Boston Biochem, both of which gave identical results). Full-length USP19 was purchased from Boston Biochem (E-576). Unless otherwise stated, all other reagents were purchased from Sigma. Enzymatic reactions were conducted in black flat bottom polystyrene 384-well plates (Nunc) and 30 μL total volume. USP19 (2.5 nM, 10 μL) was incubated in assay buffer (50 mM HEPES (pH 7.4), 150 mM NaCl, 5 mM DTT, 0.05% BSA (w/v), 0.05% CHAPS) in the presence or absence of inhibitor (10 μL). Inhibitors were stored as 10 mM DMSO stocks in an inert environment (low humidity, dark, low oxygen, room temperature) using the Storage Pod System and serial dilutions were prepared in buffer just prior to the assay (from 200 μM to 2 pM, 8-18 data point curve). Following incubation at RT for 30 min, the enzymatic reactions were initiated by dispensing the Ub substrate (500 nM, 10 μL). FP was measured every 15 min over a period of 90 min (within the linear range of the assay) using a Synergy 4 plate reader (BioTek) exciting at 530 nm and measuring the amount of parallel and perpendicular light at 575 nm. The FP signal was subsequently normalised to the no compound control. Data were plotted and fitted, and the concentrations resulting in 50% inhibition (IC50) were calculated using the non-linear regression curve fitting model using GraphPad (Prism).
Measurement: IC50 = 2750 nM (pChEMBL 5.559999942779541)
Descriptors: MW 508.66, ALogP 4.81, HBA 5, HBD 2, PSA 99.84, QED 0.56
Compound (SMILES): CCCCC#Cc1ccc(NC2CCN(C(=O)CC3CC3)CC2)c(C(N)=O)c1
InChIKey: PUKQFVJDNGORJO-UHFFFAOYSA-N
Target: Endoplasmin (SINGLE PROTEIN), Canis lupus familiaris
UniProt: P41148
Assay: Inhibition of GST-tagged dog GRP94 (69 to 337 residues) expressed in Escherichia coli BL21 (DE3) measured after 4 hrs by fluorescent polarization assay
Measurement: IC50 = 797 nM (pChEMBL 6.099999904632568)
Descriptors: MW 381.52, ALogP 3.53, HBA 3, HBD 2, PSA 75.43, QED 0.56
Compound (SMILES): Cc1c(-c2cc(=O)n(CC3(O)CCN(C(=O)C[C@@H](C)c4ccccc4)CC3)cn2)cnn1C
InChIKey: LZDMKSNLVPBHNX-GOSISDBHSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 19 (SINGLE PROTEIN), Homo sapiens
UniProt: O94966
Assay: Inhibition of C-terminal His6-tagged recombinant human USP19 using iso-peptide ubiquitin-Lys-TAMRA as substrate incubated for 30 mins and measured after 90 mins by fluorescent polarization assay
Measurement: IC50 = 50000 nM (pChEMBL 4.300000190734863)
Descriptors: MW 449.56, ALogP 2.5, HBA 7, HBD 1, PSA 93.25, QED 0.62
Compound (SMILES): C[C@H](CC1CCCCC1)C(=O)N1CCC(O)(Cn2cnc3cc(Cl)ccc3c2=O)C2(CCCC2)C1
InChIKey: NKTZLKNQMYOIMD-HFLPEKOISA-N
Target: Ubiquitin carboxyl-terminal hydrolase 19 (SINGLE PROTEIN), Homo sapiens
UniProt: O94966
Assay: Inhibition of C-terminal His6-tagged recombinant human USP19 using iso-peptide ubiquitin-Lys-TAMRA as substrate incubated for 30 mins and measured after 90 mins by fluorescent polarization assay
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 500.08, ALogP 5.18, HBA 5, HBD 1, PSA 75.43, QED 0.61
Compound (SMILES): Clc1cc(Cl)cc(Oc2nccc(-c3c(-c4ccc(I)cc4)ncn3C3CCNCC3)n2)c1
InChIKey: JZBMVXXCSVPZPB-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of BRD4 D1 (unknown origin) by competitive fluorescence anisotropy assay
Measurement: IC50 = 430 nM (pChEMBL 6.369999885559082)
Descriptors: MW 592.27, ALogP 6.64, HBA 6, HBD 1, PSA 64.86, QED 0.26
Compound (SMILES): O/N=C(\Nc1ccc(F)c(Br)c1)c1nonc1NCCn1cc(C2(O)CCCCC2)nn1
InChIKey: WCQVJFBGCFNOBE-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 (unknown origin) assessed as reduction in kynurenine formation using L-tryptophan as substrate by methylene blue reagent based assay
Measurement: IC50 = 62 nM (pChEMBL 7.210000038146973)
Descriptors: MW 509.34, ALogP 3.07, HBA 10, HBD 4, PSA 146.51, QED 0.16
Compound (SMILES): CN1CCCC1CNC(=O)c1cccn2c(=O)c3cc4ccccc4cc3nc12
InChIKey: WFUAXNSUEKKLNA-UHFFFAOYSA-N
Target: DNA-directed RNA polymerase I subunit RPA1 (SINGLE PROTEIN), Homo sapiens
UniProt: O95602
Assay: Inhibition of RNA polymerase 1 in human A-375 assessed as RPA194 degradation measured after 4 hrs by Hoechst 33342 staining based assay
Measurement: IC50 = 3940 nM (pChEMBL 5.409999847412109)
Descriptors: MW 386.46, ALogP 2.82, HBA 5, HBD 1, PSA 66.71, QED 0.55
Compound (SMILES): O=C(COc1ccc2cc(/C=C3/SC(=O)NC3=O)ccc2c1)Nc1ccc(Br)cc1
InChIKey: HBKXKIGCMXKNTC-VXLYETTFSA-N
Target: Histone deacetylase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56524
Assay: Inhibition of recombinant human HDAC4 using Boc-Lys (trifluoroacetyl)-AMC as substrate preincubated for 1 hr followed by substrate addition and measured after 1 hr by micro plate reader analysis
Measurement: IC50 = 2900 nM (pChEMBL 5.539999961853027)
Descriptors: MW 483.34, ALogP 4.94, HBA 5, HBD 2, PSA 84.5, QED 0.5
Compound (SMILES): CCC(=C(c1ccc(O)cc1)c1ccc(/C=C/C(=O)NCCCCCCNC(=O)CCc2nc3cc(OC)ccc3[nH]2)cc1)c1ccccc1
InChIKey: HQJAAMFRZYIEQD-LKSPLNBLSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Displacement of fluorescent-labeled E2 from LBD of ERalpha (unknown origin) by TR-FRET assay
Measurement: IC50 = 2.61 nM (pChEMBL 8.579999923706055)
Descriptors: MW 670.85, ALogP 8.09, HBA 5, HBD 4, PSA 116.34, QED 0.05
Compound (SMILES): c1ccc([C@H]2CN(c3cc(O[C@H]4C[C@@H](n5ccnn5)C4)ncn3)CCO2)cc1
InChIKey: QJUYMEBMFILZDE-FGTMMUONSA-N
Target: Very long chain fatty acid elongase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BW60
Assay: Inhibition of ELOVL1 in HEK293 cells assessed as reduction of C26:0 lipo phosphatidyl choline synthesis
Measurement: IC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 378.44, ALogP 2.43, HBA 8, HBD 0, PSA 78.19, QED 0.67
Compound (SMILES): CC1=C(C(=O)Nc2nnc(-c3cccnc3)s2)C(c2ccccc2Cl)N=C(Nc2nc3cc(N)ccc3o2)N1
InChIKey: FXIKSLOIAPNLAO-UHFFFAOYSA-N
Target: Galactokinase (SINGLE PROTEIN), Homo sapiens
UniProt: P51570
Assay: Inhibition of recombinant human GALK1 using ATP as substrate incubated for 1 hr and measured by Kinase-Glo assay
Measurement: IC50 = 10860 nM (pChEMBL 4.960000038146973)
Descriptors: MW 558.03, ALogP 5, HBA 11, HBD 4, PSA 156.24, QED 0.22
Compound (SMILES): C[C@@H]1CN(c2cccc(NC(=O)c3ccc(C(C)(O)CO)nc3N3CCC4(CC3)CC4)n2)CCO1
InChIKey: JACFYFFFFZJVJK-YDONVPIESA-N
Target: Kinesin-like protein KIF18A (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NI77
Assay: Inhibition of recombinant His-tagged human KIF18A (1 to 467 residues) expressed in baculovirus expression system assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 15 mins followed by ATP addition and further incubated for 15 mins and measured after 40 mins by ADP-Glo reagent based assay
Measurement: IC50 = 62.5 nM (pChEMBL 7.199999809265137)
Descriptors: MW 481.6, ALogP 2.53, HBA 8, HBD 3, PSA 111.05, QED 0.58
Compound (SMILES): O=C(N1CC[C@@](O)(Cn2cnc(-c3ccc(Cl)cc3)cc2=O)C2(CCCC2)C1)N1CCNC[C@H]1c1ccccc1
InChIKey: AMSJPXMLJKZMIY-JTSJOTPCSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 19 (SINGLE PROTEIN), Homo sapiens
UniProt: O94966
Assay: Inhibition of C-terminal His6-tagged recombinant human USP19 using iso-peptide ubiquitin-Lys-TAMRA as substrate incubated for 30 mins and measured after 90 mins by fluorescent polarization assay
Measurement: IC50 < 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 562.11, ALogP 4.33, HBA 6, HBD 2, PSA 90.7, QED 0.49
Compound (SMILES): Cn1cnnc1CC1(c2cccc(NC(=O)c3ccnc(C(F)(F)F)n3)c2)COC1
InChIKey: LMXOQVRBOSXEEN-UHFFFAOYSA-N
Target: E3 ubiquitin-protein ligase CBL-B (SINGLE PROTEIN), Homo sapiens
UniProt: Q13191
Assay: Inhibition of N-terminal Avi-tagged human CBL-B (36 to 427 residues) incubated with 60 nM Src kinase for 1.5 hrs followed by incubation with fluorescently labeled UbcH5B-Ub for 1 hr and measured by TR-FRET assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 418.38, ALogP 2.39, HBA 7, HBD 1, PSA 94.82, QED 0.68
Compound (SMILES): Cc1cc(NC(=O)c2ccc(NS(=O)(=O)CCO)cc2N2CCC3(CC2)CC3)nc(N2CCO[C@H](C)C2)n1
InChIKey: POKANPPMADPXNT-LJQANCHMSA-N
Target: Kinesin-like protein KIF18A (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NI77
Assay: Inhibition of recombinant His-tagged human KIF18A (1 to 467 residues) expressed in baculovirus expression system assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 15 mins followed by ATP addition and further incubated for 15 mins and measured after 40 mins by ADP-Glo reagent based assay
Measurement: IC50 = 57 nM (pChEMBL 7.239999771118164)
Descriptors: MW 544.68, ALogP 2.38, HBA 9, HBD 3, PSA 136.99, QED 0.46
Compound (SMILES): C[C@H](Cc1nncn1C)c1cccc(NC(=O)c2cc(C(=O)N3CC[C@H](C#N)C3)ccn2)c1
InChIKey: VGFNCEKJKJJCMQ-IAGOWNOFSA-N
Target: E3 ubiquitin-protein ligase CBL-B (SINGLE PROTEIN), Homo sapiens
UniProt: Q13191
Assay: Inhibition of N-terminal Avi-tagged human CBL-B (36 to 427 residues) incubated with 60 nM Src kinase for 1.5 hrs followed by incubation with fluorescently labeled UbcH5B-Ub for 1 hr and measured by TR-FRET assay
Measurement: IC50 = 1001 nM (pChEMBL 6)
Descriptors: MW 443.51, ALogP 2.79, HBA 7, HBD 1, PSA 116.8, QED 0.63
Compound (SMILES): CCC(C)C1CCN(c2nc(NC(C)(C)CO)cnc2C(=O)Nc2cccc(S(=O)(=O)NC(C)(C)C)c2)CC1
InChIKey: OEHHUKFAPIKGFL-UHFFFAOYSA-N
Target: Kinesin-like protein KIF18A (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NI77
Assay: Inhibition of recombinant His-tagged human KIF18A (1 to 467 residues) expressed in baculovirus expression system assessed as inhibition of microtubule-stimulated ATPase activity preincubated for 15 mins followed by ATP addition and further incubated for 15 mins and measured after 40 mins by ADP-Glo reagent based assay
Measurement: IC50 = 163 nM (pChEMBL 6.789999961853027)
Descriptors: MW 560.77, ALogP 4.25, HBA 8, HBD 4, PSA 136.55, QED 0.34