lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): C[C@H](CC1CCCCC1)C(=O)N1CCC(O)(Cn2cc(-c3ccccn3)c(-c3ccccc3F)cc2=O)C(C)(C)C1
InChIKey: KKKREGKIJYHSPR-CPPKSAKYSA-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 559.73, ALogP 6.31, HBA 5, HBD 1, PSA 75.43, QED 0.37
Compound (SMILES): Cc1ccc(/C=C2/N=C(c3cccc(Cl)c3Cl)OC2=O)o1
InChIKey: JBORAKUIWHKMFB-KPKJPENVSA-N
Target: Palmitoleoyl-protein carboxylesterase NOTUM (SINGLE PROTEIN), Homo sapiens
UniProt: Q6P988
Assay: Inhibition of human Notum (81 to 451 Cys330Ser) using OPTS as substrate incubated for 40 mins by fluorescence based assay
Measurement: IC50 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 322.15, ALogP 4.24, HBA 4, HBD 0, PSA 51.8, QED 0.61
Compound (SMILES): Cn1cnnc1CC(C)(C)c1cccc(N2Cc3c(cccc3C(F)(F)F)C2=O)c1
InChIKey: GEBIVTJQIPRAIN-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 414.43, ALogP 4.51, HBA 4, HBD 0, PSA 51.02, QED 0.63
Compound (SMILES): CON(C)C(=O)Oc1ccccc1C(=O)NCCc1c[nH]c2ccccc12
InChIKey: HMRQNXQTMJUDBQ-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of electric eel AChE using acetylthiocholine iodide as substrate assessed as inhibition constant at 0.78 to 12.5 uM preincubated for 10 mins followed by substrate addition and measured for 15 mins by Lineweaver-Burk plot analysis
Measurement: Ki = 1596 nM (pChEMBL 5.800000190734863)
Descriptors: MW 367.41, ALogP 3.13, HBA 4, HBD 2, PSA 83.66, QED 0.66
Compound (SMILES): Cn1cnnc1CC1(c2cccc(N3Cc4c(cc(CN5CCOC(CCF)C5)cc4C(F)(F)F)C3=O)c2)COC1
InChIKey: WDRRIHYTAPMNIV-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 573.59, ALogP 4.07, HBA 7, HBD 0, PSA 72.72, QED 0.38
Compound (SMILES): Cc1ccc(C(O)c2cc3c(cn2)CN(S(=O)(=O)c2ccc(-c4ncco4)cc2)C3)cc1N1CCN(C)CC1
InChIKey: QNAGSYZQXNTVKY-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 = 1 nM (pChEMBL 9)
Descriptors: MW 545.67, ALogP 3.58, HBA 8, HBD 1, PSA 103.01, QED 0.39
Compound (SMILES): CC(C)(C)NS(=O)(=O)c1cccc(NC(=O)c2ccc(N3CC(O)(C(F)(F)F)C3)nc2N2CCC3(CC2)CC3)c1
InChIKey: HZWLHXZKHRFLKJ-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 = 280 nM (pChEMBL 6.550000190734863)
Descriptors: MW 581.66, ALogP 3.9, HBA 7, HBD 3, PSA 114.87, QED 0.47
Compound (SMILES): Cc1nnc(C(C)C)n1C1C[C@H]2CC[C@@H](C1)N2CC[C@H](NC(=O)C1CCC(F)(F)CC1)c1ccc(NC(=O)COCC(=O)NCCCCCCCNC(=O)COCC(=O)N[C@@H]2CC[C@@]3(O)[C@H]4Cc5ccc(O)c6c5[C@@]3(CCN4CC3CC3)[C@H]2O6)cc1
InChIKey: BAVVASQPMQMZER-DUSRTOIOSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Mus musculus
UniProt: P42866
Assay: Displacement of [3H]-naloxone from mouse MOR expressed in CHO cells incubated for 1.5 hrs by competitive radioligand binding assay
Measurement: Ki = 51.8 nM (pChEMBL 7.289999961853027)
Descriptors: MW 1197.48
Compound (SMILES): CC(C)(CO)Nc1ccc(C(=O)Nc2cc(Cl)cc(N3CCOCC3)n2)c(N2CCC3(CC2)CC3)n1
InChIKey: HPDUSSUFRURUPY-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 = 74.3 nM (pChEMBL 7.130000114440918)
Descriptors: MW 515.06, ALogP 3.78, HBA 8, HBD 3, PSA 102.85, QED 0.51
Compound (SMILES): Cn1ccc(-c2cc(Cl)c(Cl)c3[nH]c4c(c23)CN(C(=O)CNC(=O)C2=C[C@H](O)[C@H](O)[C@@H](O)C2)CC4)n1
InChIKey: LEPRZSBIUGRQMB-BSRJHKFKSA-N
Target: Cyclic GMP-AMP synthase (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N884
Assay: Inhibition of human cGAS expressed in THP1-Dual cells transfected with HT-DNA assessed as suppression of lipofectamine 2000:ds-DNA complex induced activation of cGAS incubated for 1 hr by Quanti-luc reagent based assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 534.4, ALogP 1.29, HBA 7, HBD 5, PSA 143.71, QED 0.34
Compound (SMILES): O=C(NCc1ccc2cc(CN3CCCC3CO)[nH]c2c1)c1cc(=O)n2ccccc2n1
InChIKey: FXNNSNRGNUOUKG-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 = 228 nM (pChEMBL 6.639999866485596)
Descriptors: MW 431.5, ALogP 2.06, HBA 6, HBD 3, PSA 102.73, QED 0.43
Compound (SMILES): O=C(CSc1nccn1-c1ccc(Cl)cc1)Nc1ccc(Br)cc1
InChIKey: HYUPPBCXHUNYFH-UHFFFAOYSA-N
Target: Chloride anion exchanger (SINGLE PROTEIN), Mus musculus
UniProt: Q9WVC8
Assay: Inhibition of mouse Slc26a3 transfected in rat FRT cells preincubated with forskolin, 8-Br-cGMP and PMA and measured by fluorescence assay
Measurement: IC50 = 1800 nM (pChEMBL 5.75)
Descriptors: MW 422.74, ALogP 5.02, HBA 4, HBD 1, PSA 46.92, QED 0.59
Compound (SMILES): CNc1ccc2ccc(OC(C)c3cncc(-n4ccc5c(N)ncnc54)c3)cc2n1
InChIKey: RGLBTOWRPKOSKJ-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 411.47, ALogP 4.13, HBA 8, HBD 2, PSA 103.77, QED 0.45
Compound (SMILES): Cl.OC1CCC(NCc2cc(Cl)c(OCc3cccc(-c4ccccc4)c3Br)cc2OCc2ccc3nonc3c2)CC1
InChIKey: NLRBJRMQHYWLTE-UHFFFAOYSA-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 blockade activity incubated for 15 mins by HTRF assay
Measurement: IC50 = 57.2 nM (pChEMBL 7.239999771118164)
Descriptors: MW 648.98, ALogP 7.86, HBA 7, HBD 2, PSA 89.64, QED 0.16
Compound (SMILES): C[C@H](NC(=O)c1ccc(NC(=O)Nc2ccc(-c3nc(N4CCOCC4)nc(N4CCOC[C@@H]4C)n3)cc2)cc1)C(N)=O
InChIKey: LMXYZMNDIFPRCF-OALUTQOASA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of PI3Kalpha (unknown origin) using PIP2 as substrate in presence of ATP incubated for 60 mins by ADP-glo based luminescence assay
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 589.66, ALogP 1.85, HBA 10, HBD 4, PSA 176.93, QED 0.3
Compound (SMILES): C[C@]1([C@H](O)C[C@H]2c3c(F)cccc3-c3cncn32)CC[C@H](O)CC1
InChIKey: LZEDJAODAMNCQE-FRXJQCMVSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of human IDO1
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 330.4, ALogP 3.28, HBA 4, HBD 2, PSA 58.28, QED 0.91
Compound (SMILES): Cn1cc(NC(=O)c2cc(NC(=O)CCS(C)(=O)=O)cn2C)cc1C(=O)NCC(=O)NCCCCCC[C@@H]1Cc2cc(O)ccc2[C@H]2CC[C@]3(C)[C@@H](O)CC[C@H]3[C@H]12
InChIKey: DDHOKPZNHNTILT-MBCOJTBISA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Binding affinity of ERalpha LBD (unknown origin) incubated for 2 hrs by LanthaScreen TR-FRET assay
Measurement: IC50 = 0.99 nM (pChEMBL 9)
Descriptors: MW 807.03, ALogP 4.63, HBA 10, HBD 6, PSA 200.86, QED 0.11
Compound (SMILES): Nc1nonc1-c1nc2ccccc2n1CC(=O)Nc1ccc([N+](=O)[O-])cc1
InChIKey: WAUUCBKSBSQKCF-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BChE using butyrylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition and measured after 2 mins by DTNB-reagent based Ellman's method
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 379.34, ALogP 2.22, HBA 9, HBD 2, PSA 155, QED 0.39
Compound (SMILES): N#CCCN1CCC2CCN(c3ncnc4[nH]c5cc(I)ccc5c34)C2C1
InChIKey: LGSGQFAHYFBAGY-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of recombinant human GSK-3-beta using YRRAAVPPSPSLSRHSSPHQ(pS)EDEEE as substrate preincubated for 10 mins followed by substrate addition and measured after 1 hr in presence of ATP by ADP Glo kinase assay
Measurement: IC50 = 132 nM (pChEMBL 6.880000114440918)
Descriptors: MW 472.33, ALogP 3.53, HBA 5, HBD 1, PSA 71.84, QED 0.59
Compound (SMILES): O=C1CCC(N2C(=O)c3cccc(NCCOCCOCCOCCOCCOCCNC(=O)N[C@H]4CC[C@@H](Nc5ncnc6[nH]cc(C(=O)c7ccc(Oc8ccccc8)cc7Cl)c56)CC4)c3C2=O)C(=O)N1
InChIKey: OIAOFDRZXBDDRR-HYKUANOISA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of full length N-terminal GST fusion tagged human BTK expressed in baculovirus expression system using FAM-P2 peptide solution as substrate incubated for 10 mins in presence of ATP by microplate reader assay
Measurement: IC50 = 56.4 nM (pChEMBL 7.25)
Descriptors: MW 1024.53
Compound (SMILES): CC#CCCNCc1cc2ccc(CNC(=O)c3cc(=O)n4ccccc4n3)cc2[nH]1
InChIKey: GHPDGAWBKYHSSO-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 = 185 nM (pChEMBL 6.730000019073486)
Descriptors: MW 413.48, ALogP 2.61, HBA 5, HBD 3, PSA 91.29, QED 0.32
Compound (SMILES): CC(CC(C)(C)C)C(=O)N1CCC(O)(Cn2cnc(-c3ccccc3F)cc2=O)C(C)(C)C1
InChIKey: JYBCTUBGJXZZCE-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 = 50000 nM (pChEMBL 4.300000190734863)
Descriptors: MW 457.59, ALogP 4.11, HBA 5, HBD 1, PSA 75.43, QED 0.73
Compound (SMILES): CCOC(=O)[C@@H](CCC(=O)NC(CCCCN)C(=O)OC)NC(=O)[C@@H](NC(=O)CNC(=O)/C=C/c1ccc(O)c(OC)c1)C(C)C
InChIKey: OYNPOYHWXQPREH-NYDMZULMSA-N
Target: Nucleotide-binding oligomerization domain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HC29
Assay: Agonist activity at NOD2 in HEK-Blue hNOD2 cells assessed as increase in NFkappaB transactivation-mediated SEAP activity measured after 18 hrs by spectrophotometric method
Measurement: EC50 = 10220 nM (pChEMBL 4.989999771118164)
Descriptors: MW 649.74, ALogP 0.29, HBA 11, HBD 6, PSA 224.48, QED 0.06
Compound (SMILES): COc1ccc(-c2cccc(C(=O)Nc3ccc(CNCCNC(C)=O)cn3)c2Cl)cc1OC
InChIKey: QFGKFHMHWHFFOD-UHFFFAOYSA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NZQ7
Assay: Inhibition of PD-1/PDL-1 (unknown origin) interaction incubated for 15 mins by TR-FRET assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 482.97, ALogP 3.9, HBA 6, HBD 3, PSA 101.58, QED 0.38
Compound (SMILES): NC(=O)[C@@H]1[C@H](Nc2nc(Nc3cccc(C(=O)N4CCCC4)c3)ncc2-c2ccncc2)[C@H]2C=C[C@@H]1C2
InChIKey: SMIIJPDEPOIIHO-RJADORODSA-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 = 10 nM (pChEMBL 8)
Descriptors: MW 495.59, ALogP 3.61, HBA 7, HBD 3, PSA 126.13, QED 0.43
Compound (SMILES): CCc1cc(C)[nH]c(=O)c1CN1CCN(C)c2c(Cl)cc(-c3c(C)noc3C)c(Cl)c2C1=O
InChIKey: NZHVFZFNLVEEFS-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Inhibition of EZH2 (unknown origin) using 3H-SAM as substrate incubated for 1 hour by filter binding method
Measurement: IC50 = 1.8 nM (pChEMBL 8.739999771118164)
Descriptors: MW 489.4, ALogP 4.92, HBA 5, HBD 1, PSA 82.44, QED 0.56
Compound (SMILES): O=C(NC1(CO)CC(F)(F)C1)C1CC(Cc2c(-c3ccc(F)cc3)[nH]c3c(F)cc(F)cc23)C1
InChIKey: LAKFPQDVDOKBHC-UHFFFAOYSA-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 478.46, ALogP 5.1, HBA 2, HBD 3, PSA 65.12, QED 0.43
Compound (SMILES): CNC1CCN(c2ncnc3[nH]cc(-c4cccc(Cl)c4)c23)CC1
InChIKey: XZKDYHDTDSBKKV-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13043
Assay: Inhibition of recombinant N-terminal His6-tagged human STK4 (43 to 431 residues) expressed in Escherichia coli using myelin basic protein as substrate in presence of ATP by ADP-Glo luminescence kinase assay
Measurement: IC50 = 148 nM (pChEMBL 6.829999923706055)
Descriptors: MW 341.85, ALogP 3.47, HBA 4, HBD 2, PSA 56.84, QED 0.77
Compound (SMILES): C[C@@H](Cn1c(=O)[nH]/c(=N\c2ccc(OC3CCC3)cc2)n(Cc2ccc(Cl)cc2)c1=O)C(=O)O
InChIKey: NEQUTLFYLILHFN-HNNXBMFYSA-N
Target: P2X purinoceptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P56373
Assay: Human P2X3 Receptor Inhibition Assay: Stably expressing cell line (C6BU-1 transfected with human P2X3 receptor gene (GenBank accession number Y07683) was used. The cells were seeded in a 96-well microtiter plate at a concentration of 8000 cells/well and cultured in the medium (8.3% fetal bovine serum, 8.3% horse serum, 1% antibiotic and antifungal in DMEM) for one day at 37° C. under 5% carbon dioxide atmosphere. The medium was replaced with 4 μM Fluo-3-AM solution (20 mM HEPES, 137 mM NaCl, 2.7 mM KCl, 0.9 mM MgCl2, 5.0 mM CaCl2, 5.6 mM D-glucose, 2.5 mM probenecid, 10% BSA, and 0.08% Pluronic F-127, pH 7.5) and incubated at 37° C. under 5% dioxide carbon atmosphere for one hour. The plate was washed with washing buffer (20 mM HEPES, 137 mM NaCl, 2.7 KCl, 0.9 mM MgCl2, 5.0 mM CaCl2, 5.6 mM D-glucose, 2.5 mM probenecid, pH 7.5), each well was added with 40 μL of this buffer. The plate was placed in High-Throughput Screening System FDSS 3000 (Hamamatsu Photonics K.K.). Measurement of fluorescence intensity by FDSS 3000 was started, and 40 μl, of DMSO solutions containing different concentrations of the test, compound as prepared by dilution with dilution buffer (20 mM HEPES, 137 mM NaCl, 2.7 mM KCl, 0.9 mM MgCl2, 5.0 mM CaCl2, 5.6 mM D-glucose, 2.5 mM probenecid, 0.1.% Pluronic F-127, pH 7.5) were dispensed to each well through the built-in automatic dispenser. Five minutes after, 50 nM ATP solution (50 μL) prepared by dilution with the dilution buffer was dispensed through the built-in automatic dispenser, and the measurement of fluorescence intensity was continued for 3 min. For each well, the specific maximum fluorescence intensity was calculated as the ratio of the maximum fluorescence intensity after addition of the ATP solution to the fluorescence intensity at the starting of the measurement. The 50% inhibitory concentration (IC50) was calculated under the assumption that the specific maximum fluorescence intensity without test compound is 0% inhibition and that the specific maximum fluorescence intensity when the dilution buffer was added in place of ATP solution is 100% inhibition, to evaluate the inhibitory activity of the test compound. FDSS software (Hamamatsu Photonics K.K.) was used for calculation of the specific maximum fluorescence intensity. IC50 was calculated using Microsoft Excel (Microsoft Corporation) and Ltd.).
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 484.94, ALogP 2.92, HBA 7, HBD 2, PSA 118.68, QED 0.51
Compound (SMILES): C[C@@H](Sc1nncn1C)c1cccc(NC(=O)c2cc3ccccc3cn2)c1
InChIKey: ISYOOTUPLKWBDU-CQSZACIVSA-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 389.48, ALogP 4.47, HBA 6, HBD 1, PSA 72.7, QED 0.51
Compound (SMILES): N#Cc1c(-c2ccccc2)nc(Nc2ccccc2)nc1-c1ccco1
InChIKey: PMGRDIKEQFHCSA-UHFFFAOYSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30542
Assay: Displacement of [3H]DPCPX from human A1AR expressed in CHO cell membrane incubated for 60 mins by microbeta trilux scintillation counter analysis
Measurement: Ki = 33.7 nM (pChEMBL 7.46999979019165)
Descriptors: MW 338.37, ALogP 5.02, HBA 5, HBD 1, PSA 74.74, QED 0.57
Compound (SMILES): C=CC(=O)Nc1cc(Nc2nccc(Nc3cnn(C)c3)n2)c(OC)cc1N(C)CCN(C)C
InChIKey: GGMCKPMWBJESJY-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR del19 (unknown origin) using flurogenic substrate in presence of ATP by HTRF assay
Measurement: IC50 = 54.35 nM (pChEMBL 7.260000228881836)
Descriptors: MW 465.56, ALogP 2.83, HBA 10, HBD 3, PSA 112.47, QED 0.37
Compound (SMILES): Nc1ccccc1Nc1ccc2c(c1)CCc1ccc(C(=O)NCCN3CCNCC3)cc1C2=O
InChIKey: OBYRMFNIDHAEAX-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Inhibition of human p38 MAPK alpha incubated for 1 hr by photometric method
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 469.59, ALogP 2.98, HBA 6, HBD 4, PSA 99.49, QED 0.41
Compound (SMILES): c1ccc(C2CCN(c3cnc4c(N5CCOCC5)nccn34)CC2)cc1
InChIKey: OKTXMSSTNJXZII-UHFFFAOYSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q01959
Assay: GPCRScan assay: inhibition of DAT
Measurement: Ki = 4168.69 nM (pChEMBL 5.380000114440918)
Descriptors: MW 363.47, ALogP 2.95, HBA 6, HBD 0, PSA 45.9, QED 0.72
Compound (SMILES): Cc1ccc(C(=O)Nc2ccc(CN)cc2)c(O)c1
InChIKey: GKPOHSSTLWSOGV-UHFFFAOYSA-N
Target: Kallikrein-6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92876
Assay: Activities on KLK6 (Boc-QAR-AMC): In a typical test, 100 μl of reaction medium contains the buffer, 1 μl of recombinant enzyme, 1 μl of substrate (Boc-QAR-AMC) and 1 μl of the compound tested at 10 μM (in the control, 1 μl of DMSO). In each well, the inhibitor is deposited in the presence of the enzyme-buffer mixture for preincubation for 15 minutes at 37° C. The enzymatic reaction is then triggered by adding the buffer-substrate mixture (100 μM). The release of the 7-amino-4-methylcoumarin fluorescent group (AMC, λex=360 nm, λem=460 nm) following the hydrolysis of the substrate catalyzed by the enzyme is monitored for 30 minutes at 37° C. using a FLUOstar spectrofluorimeter.
Measurement: Ki = 1920 nM (pChEMBL 5.71999979019165)
Descriptors: MW 256.31, ALogP 2.41, HBA 3, HBD 3, PSA 75.35, QED 0.79
Compound (SMILES): NCc1ccc(NC(=O)c2cc3ccccc3cc2O)cc1
InChIKey: VRZLGSXKZZLNLO-UHFFFAOYSA-N
Target: Kallikrein-6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92876
Assay: Activities on KLK6 (Boc-QAR-AMC): In a typical test, 100 μl of reaction medium contains the buffer, 1 μl of recombinant enzyme, 1 μl of substrate (Boc-QAR-AMC) and 1 μl of the compound tested at 10 μM (in the control, 1 μl of DMSO). In each well, the inhibitor is deposited in the presence of the enzyme-buffer mixture for preincubation for 15 minutes at 37° C. The enzymatic reaction is then triggered by adding the buffer-substrate mixture (100 μM). The release of the 7-amino-4-methylcoumarin fluorescent group (AMC, λex=360 nm, λem=460 nm) following the hydrolysis of the substrate catalyzed by the enzyme is monitored for 30 minutes at 37° C. using a FLUOstar spectrofluorimeter.
Measurement: Ki = 790 nM (pChEMBL 6.099999904632568)
Descriptors: MW 292.34, ALogP 3.26, HBA 3, HBD 3, PSA 75.35, QED 0.69
Compound (SMILES): NCc1ccc(NC(=O)c2ccc3ccccc3c2O)cc1
InChIKey: QANBHYSEYDYUTP-UHFFFAOYSA-N
Target: Kallikrein-6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92876
Assay: Activities on KLK6 (Boc-QAR-AMC): In a typical test, 100 μl of reaction medium contains the buffer, 1 μl of recombinant enzyme, 1 μl of substrate (Boc-QAR-AMC) and 1 μl of the compound tested at 10 μM (in the control, 1 μl of DMSO). In each well, the inhibitor is deposited in the presence of the enzyme-buffer mixture for preincubation for 15 minutes at 37° C. The enzymatic reaction is then triggered by adding the buffer-substrate mixture (100 μM). The release of the 7-amino-4-methylcoumarin fluorescent group (AMC, λex=360 nm, λem=460 nm) following the hydrolysis of the substrate catalyzed by the enzyme is monitored for 30 minutes at 37° C. using a FLUOstar spectrofluorimeter.
Measurement: Ki = 2260 nM (pChEMBL 5.650000095367432)
Descriptors: MW 292.34, ALogP 3.26, HBA 3, HBD 3, PSA 75.35, QED 0.69
Compound (SMILES): CC(C)(O)c1ccc2c(c1)C(=O)N(Cc1ccc(Cl)cc1S(C)(=O)=O)[C@@]2(OCC1(CO)CC1)c1ccc(Cl)cc1
InChIKey: RXUWUIRMPWZSAR-SSEXGKCCSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: Binding Assay (ELISA): The ELISA assay was performed in streptavidin coated plates which were preincubated with 200 ul per well of 1 μg ml−1 biotinylated IP3 peptide. The plates were ready to use for MDM2 binding after washing the plate with PBS.Compounds and control solutions in DMSO aliquoted in 96-well plates were pre-incubated in a final 2.5-5% (v/v) DMSO concentration at room temperature (for example 20C.) for 20 min with 190 ul aliquots of optimized concentrations of in vitro translated MDM2, before transfer of the MDM2-compound mixture to the b-IP3 streptavidin plates, and incubation at 4C. for 90 min. After washing three times with PBS to remove unbound MDM2, each well was incubated at 20C. for 1 hour with a TBS-Tween (50 mM Tris pH7.5; 150 mM NaCl; 0.05% Tween 20 nonionic detergent) buffered solution of primary mouse monoclonal anti-MDM2 antibody (Ab-5, Calbiochem, used at a 1/10000 or 1/200 dilution depending on the antibody stock solution used), then washed three times with TBS-Tween before incubation for 45 mins at 20C. with a TBS-Tween buffered solution of a goat-anti-mouse horseradish peroxidase (HRP) conjugated secondary antibody (used at 1/20000 or 1/2000 depending on the antibody stock solution). The unbound secondary antibody was removed by washing three times with TBS-Tween. The bound HRP activity was measured by enhanced chemiluminesence (ECL, Amersham Biosciences) using the oxidation of the diacylhydrazide substrate, luminol, to generate a quantifiable light signal. The percentage of MDM2 inhibition at a given concentration is calculated as the [1−(RLU detected in the compound treated sample−RLU negative DMSO control)÷(RLU of DMSO positive and negative controls)]x100 or as the (RLU detected in the compound treated sample ÷ RLU of DMSO controls)x100.
Measurement: IC50 = 5.1 nM (pChEMBL 8.289999961853027)
Descriptors: MW 604.55, ALogP 5.27, HBA 6, HBD 2, PSA 104.14, QED 0.35
Compound (SMILES): COc1ccc2c(O)c(C(=O)Nc3ccc(CN)cc3)ccc2c1
InChIKey: TUCBVMZLIZJSTJ-UHFFFAOYSA-N
Target: Kallikrein-6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92876
Assay: Activities on KLK6 (Boc-QAR-AMC): In a typical test, 100 μl of reaction medium contains the buffer, 1 μl of recombinant enzyme, 1 μl of substrate (Boc-QAR-AMC) and 1 μl of the compound tested at 10 μM (in the control, 1 μl of DMSO). In each well, the inhibitor is deposited in the presence of the enzyme-buffer mixture for preincubation for 15 minutes at 37° C. The enzymatic reaction is then triggered by adding the buffer-substrate mixture (100 μM). The release of the 7-amino-4-methylcoumarin fluorescent group (AMC, λex=360 nm, λem=460 nm) following the hydrolysis of the substrate catalyzed by the enzyme is monitored for 30 minutes at 37° C. using a FLUOstar spectrofluorimeter.
Measurement: Ki = 1000 nM (pChEMBL 6)
Descriptors: MW 322.36, ALogP 3.27, HBA 4, HBD 3, PSA 84.58, QED 0.69
Compound (SMILES): CC(C)c1ccc(C(=O)Nc2ccc(CN)cc2)c(O)c1
InChIKey: LERYNNIOTWZURB-UHFFFAOYSA-N
Target: Kallikrein-6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92876
Assay: Activities on KLK6 (Boc-QAR-AMC): In a typical test, 100 μl of reaction medium contains the buffer, 1 μl of recombinant enzyme, 1 μl of substrate (Boc-QAR-AMC) and 1 μl of the compound tested at 10 μM (in the control, 1 μl of DMSO). In each well, the inhibitor is deposited in the presence of the enzyme-buffer mixture for preincubation for 15 minutes at 37° C. The enzymatic reaction is then triggered by adding the buffer-substrate mixture (100 μM). The release of the 7-amino-4-methylcoumarin fluorescent group (AMC, λex=360 nm, λem=460 nm) following the hydrolysis of the substrate catalyzed by the enzyme is monitored for 30 minutes at 37° C. using a FLUOstar spectrofluorimeter.
Measurement: Ki = 1750 nM (pChEMBL 5.760000228881836)
Descriptors: MW 284.36, ALogP 3.23, HBA 3, HBD 3, PSA 75.35, QED 0.81
Compound (SMILES): Cc1cccc(C)c1-c1ccc2nc(NC(=O)[C@@H]3C[C@@H]3F)sc2c1
InChIKey: AEZMREWUYWLTQN-KGLIPLIRSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: c-abl Kinase Assay: ADP-Glo assay kit was purchased from Promega. Magnesium chloride (MgCl2), bovine serum albumin (BSA), ethylene glycol-bis(β-aminoethyl ether)-N,N′,N′-tetraacetic acid (EGTA), tween-20, 1,4-dithiothreitol (DTT) and dimethyl sulfoxide (DMSO) were purchased from Sigma-Aldrich. HEPES buffer was purchased from Gibco. ABL1 kinase and Abltide were purchased from Signalchem.c-abl kinase activity was measured by Promega's ADP-Glo Assay. In this assay, His-tagged recombinant human ABL1 (0.25 ng/μl) is incubated with 5 μL of compounds (0.5% DMSO), 5 μL of Abltide (0.01 μg/μl) and 5 μL of ATP (25 μM) in buffer (50 mM HEPES, 7.5; 10 mM MgCl2; 1 mM EGTA; 0.05% BSA; 0.01% Tween-20; 2 mM DTT). The assay was started by incubating the reaction mixture in a 96-well plate at 30° C. for 30-min. After the incubation, 25 μL ADP-Glo reagent was added and the reaction was incubated at room temperature for 40-min to stop the reaction and degrade residual ATP. The ADP product was then converted to ATP by adding 50 μL per well of detection reagent. Luminescence was detected after 30-min room temperature incubation with the Molecular device I3X plate reader. The IC50 values were calculated from a series of percent inhibition values determined at a range of inhibitor concentration using software routines as implemented in the GraphPad Prism 7 software or SigmaPlot 13.0.
Measurement: IC50 = 11.9 nM (pChEMBL 7.920000076293945)
Descriptors: MW 340.42, ALogP 4.88, HBA 3, HBD 1, PSA 41.99, QED 0.74
Compound (SMILES): COc1cccc(OC)c1-c1cc(C(=O)N[C@@H](CCN2CCCCC2)CC(=O)NC2CCC2)nn1C1CCCC1
InChIKey: FQHBCDRUCUFIPW-QHCPKHFHSA-N
Target: Apelin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35414
Assay: Agonist activity at human APJ receptor expressed in CHO cells co-expressing Galphaq16 assessed as stimulation of Ca2+ mobilization measured at 1 sec interval for 90 sec by fluorescent Calcium 5-dye based FLIPR-calcium mobilization assay
Measurement: EC50 = 136 nM (pChEMBL 6.869999885559082)
Descriptors: MW 551.73, ALogP 4.72, HBA 7, HBD 2, PSA 97.72, QED 0.4
Compound (SMILES): Cn1cc(C(=O)Nc2ccc([C@@H]3C[C@H]3NCC3CC3)cc2)cn1
InChIKey: NTRMVYTYDOLCRU-DLBZAZTESA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Inhibition of LSD1 (unknown origin)
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 310.4, ALogP 2.53, HBA 4, HBD 2, PSA 58.95, QED 0.86
Compound (SMILES): CC(C)(O)c1cc(F)c2c(c1)C(=O)N(Cc1ccc(C#N)cc1)[C@@]2(OCC1(CO)CC1)c1ccc(Cl)cc1
InChIKey: DIVMTXBUDOMYFO-SSEXGKCCSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: Binding Assay (ELISA): The ELISA assay was performed in streptavidin coated plates which were preincubated with 200 ul per well of 1 μg ml−1 biotinylated IP3 peptide. The plates were ready to use for MDM2 binding after washing the plate with PBS.Compounds and control solutions in DMSO aliquoted in 96-well plates were pre-incubated in a final 2.5-5% (v/v) DMSO concentration at room temperature (for example 20C.) for 20 min with 190 ul aliquots of optimized concentrations of in vitro translated MDM2, before transfer of the MDM2-compound mixture to the b-IP3 streptavidin plates, and incubation at 4C. for 90 min. After washing three times with PBS to remove unbound MDM2, each well was incubated at 20C. for 1 hour with a TBS-Tween (50 mM Tris pH7.5; 150 mM NaCl; 0.05% Tween 20 nonionic detergent) buffered solution of primary mouse monoclonal anti-MDM2 antibody (Ab-5, Calbiochem, used at a 1/10000 or 1/200 dilution depending on the antibody stock solution used), then washed three times with TBS-Tween before incubation for 45 mins at 20C. with a TBS-Tween buffered solution of a goat-anti-mouse horseradish peroxidase (HRP) conjugated secondary antibody (used at 1/20000 or 1/2000 depending on the antibody stock solution). The unbound secondary antibody was removed by washing three times with TBS-Tween. The bound HRP activity was measured by enhanced chemiluminesence (ECL, Amersham Biosciences) using the oxidation of the diacylhydrazide substrate, luminol, to generate a quantifiable light signal. The percentage of MDM2 inhibition at a given concentration is calculated as the [1−(RLU detected in the compound treated sample−RLU negative DMSO control)÷(RLU of DMSO positive and negative controls)]x100 or as the (RLU detected in the compound treated sample ÷ RLU of DMSO controls)x100.
Measurement: IC50 = 7.7 nM (pChEMBL 8.109999656677246)
Descriptors: MW 535.02, ALogP 5.22, HBA 5, HBD 2, PSA 93.79, QED 0.41
Compound (SMILES): O=C(Nc1ccc(NS(=O)(=O)c2ccccc2Cl)cc1)c1ccc([N+](=O)[O-])o1
InChIKey: KFYCQSKVLBXKCI-UHFFFAOYSA-N
Target: Urea transporter 1 (SINGLE PROTEIN), Mus musculus
UniProt: Q8VHL0
Assay: Inhibition of mouse UT-B expressed in MDCK cells
Measurement: IC50 = 1050 nM (pChEMBL 5.980000019073486)
Descriptors: MW 421.82, ALogP 3.89, HBA 6, HBD 2, PSA 131.55, QED 0.46
Compound (SMILES): CC(C)C[C@@H]1NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)CSC[C@@H](C(N)=O)NC(=O)CNC(=O)CNC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CCCNC(=N)N)NC1=O
InChIKey: IOYPAQFESXRNJZ-CUZNLEPHSA-N
Target: Coagulation factor XII (SINGLE PROTEIN), Homo sapiens
UniProt: P00748
Assay: Inhibition of human factor 12a using H-D-Pro-Phe-Arg-p-nitroanilide as chromogenic substrate assessed as liberation of p-nitroaniline in presence of BSA measured every 5 mins for 60 min by multimode plate reader analysis
Measurement: IC50 = 61 nM (pChEMBL 7.210000038146973)
Descriptors: MW 1506.76
Compound (SMILES): NC1(C(=O)N[C@@H](CCN2CCN(C(=O)CCOCCOCCOCCOCCOCCNc3cccc4c3C(=O)N(C3CCC(=O)NC3=O)C4=O)CC2)c2ccc(Cl)cc2)CCN(c2ncnc3[nH]ccc23)CC1
InChIKey: CGNFOQWXOLLQAR-JFKYFZFSSA-N
Target: RAC-beta serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31751
Assay: Binding affinity to DNA-tagged AKT2 (unknown origin) assessed as dissociation constant by q-PCR based competitive binding assay
Measurement: Kd = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 1044.61
Compound (SMILES): C[C@H](Cn1cnc2c(N)ncnc21)OCP(=O)(O)OCCCCCCCCCCCCCCCCCC#CC(F)(F)F.N
InChIKey: JWFOQRIDJPTNPH-VQIWEWKSSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of human recombinant CYP3A4 expressed in insect microsome using 7-benzyloxy-4-trifluoromethylcoumarin as a substrate incubated for 30 mins followed by addition of NADPH regenerating system measured immediately by fluorescence based analysis
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 617.69, ALogP 7.78, HBA 8, HBD 2, PSA 125.38, QED 0.07
Compound (SMILES): CSCC[C@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@@H](N)CS)C(C)C)C(=O)N[C@@H](Cc1ccccc1)C(=O)NCC(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(=N)N)C(=O)O
InChIKey: JTOQZGHBKXEVAQ-OWTLXNSISA-N
Target: Interleukin-17A (SINGLE PROTEIN), Homo sapiens
UniProt: Q16552
Assay: Inhibition of IL-17A (unknown origin) measured by AlphaLISA assay
Measurement: IC50 = 190 nM (pChEMBL 6.71999979019165)
Descriptors: MW 1935.29
Compound (SMILES): Cc1ccc2c(c1)Oc1ccncc1C2NC(=O)c1ccc(C(F)(F)F)[nH]c1=O
InChIKey: FMVPKFUTPDKTAQ-UHFFFAOYSA-N
Target: 17-beta-hydroxysteroid dehydrogenase type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P37059
Assay: Inhibition of HSD17B2 (unknown origin) using estradiol as substrate incubated for 45 mins and measured after 1 hr by NADH Glo luminescence assay
Measurement: IC50 = 22100 nM (pChEMBL 4.659999847412109)
Descriptors: MW 401.34, ALogP 3.72, HBA 4, HBD 2, PSA 84.08, QED 0.69
Compound (SMILES): Cc1cc(N)c2ccc(OCc3cncc(-n4cc(Cl)c5c(N)ncnc54)c3)cc2n1
InChIKey: CMPUNYUTNUCFTA-UHFFFAOYSA-N
Target: N6-adenosine-methyltransferase catalytic subunit (SINGLE PROTEIN), Homo sapiens
UniProt: Q86U44
Assay: Inhibition of METTL3 (unknown origin) using UCUGGACUAAA-biotin and 3H-SAM as substrates preincubated for 5 mins followed by substrate addition incubated for 30 mins by TopCount scintillation counting method
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 431.89, ALogP 4.07, HBA 8, HBD 2, PSA 117.76, QED 0.44
Compound (SMILES): [2H]C1([2H])Oc2ccc(S(=O)(=O)N3CC4=C(CN(C(=O)C(O)c5cccc6oc(C)nc56)C4)C3)cc2OC1([2H])[2H]
InChIKey: JVLLOOJUXDLXDR-OSEHSPPNSA-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 = 1 nM (pChEMBL 9)
Descriptors: MW 497.53, ALogP 1.78, HBA 8, HBD 1, PSA 122.41, QED 0.54
Compound (SMILES): CN(C)C(=O)c1c(-c2ccc(O)cc2)oc2ccc(O)c(CN3CCC4(COC4)C3)c12
InChIKey: JBRQXQCBBPWWAR-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG ion channel by Q patch-clamp method
Measurement: IC50 = 10700 nM (pChEMBL 4.96999979019165)
Descriptors: MW 422.48, ALogP 3.44, HBA 6, HBD 2, PSA 86.38, QED 0.67
Compound (SMILES): CCOC(=O)N1C[C@H]2[C@H](C)[C@@H](C)[C@H](/C=C/c3ccc(-c4ccccc4C#N)cn3)[C@@H]3[C@@H](C)OC(=O)[C@@]32C1
InChIKey: BAFRFQOCCOJJAY-IDKUMADTSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of [35S]MK-499 binding to hERG expressed in HEK293 cells
Measurement: IC50 = 1600 nM (pChEMBL 5.800000190734863)
Descriptors: MW 499.61, ALogP 5.17, HBA 6, HBD 0, PSA 92.52, QED 0.54
Compound (SMILES): COc1ccc(-c2ncc(/C=C/C(=O)NO)s2)c(OC)c1OC
InChIKey: WLURIJZBBHRHBR-QPJJXVBHSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of recombinant human His-tagged HDAC3 expressed in baculovirus insect cells using Ac-Leu-Gly-Lys (Ac)-AMC as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by fluorescence microtiter plate reader assay
Measurement: IC50 = 6230 nM (pChEMBL 5.210000038146973)
Descriptors: MW 336.37, ALogP 2.35, HBA 7, HBD 2, PSA 89.91, QED 0.48
Compound (SMILES): O=C1c2nc3cccc(Br)c3n2CCN1Cc1ccc(F)cc1
InChIKey: FJEZUMNREBEZPG-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by patch clamp electrophysiology assay
Measurement: IC50 = 8600 nM (pChEMBL 5.070000171661377)
Descriptors: MW 374.21, ALogP 3.59, HBA 3, HBD 0, PSA 38.13, QED 0.69
Compound (SMILES): CN(C)C(=O)c1cn([C@@H]2O[C@H](COc3ccc4ccc(N5CCC5)nc4c3)[C@@H](O)[C@@H]2F)c2ncnc(N)c12
InChIKey: ZUKGOODIBJXZNH-PVFWEKFRSA-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 = 100 nM (pChEMBL 7)
Descriptors: MW 521.55, ALogP 2.15, HBA 10, HBD 2, PSA 131.86, QED 0.39
Compound (SMILES): CN(C)C(=O)c1cn(CC2(O)CCN(C(=O)c3nc(C(F)(F)F)cs3)CC23CCCC3)c(=O)cc1-c1ccccc1
InChIKey: MXCQCJWRUCKUPX-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 588.65, ALogP 4.53, HBA 7, HBD 1, PSA 95.74, QED 0.47
Compound (SMILES): Cc1ccc2c(c1)C(NC(=O)c1ccc(C(F)(F)F)[nH]c1=O)c1ccccc1-2
InChIKey: DNEUYQMCOKTEGP-UHFFFAOYSA-N
Target: 17-beta-hydroxysteroid dehydrogenase type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P37059
Assay: Inhibition of HSD17B2 (unknown origin) using estradiol as substrate incubated for 45 mins and measured after 1 hr by NADH Glo luminescence assay
Measurement: IC50 = 47900 nM (pChEMBL 4.320000171661377)
Descriptors: MW 384.36, ALogP 4.2, HBA 2, HBD 2, PSA 61.96, QED 0.7
Compound (SMILES): CC(c1cccc(NC(=O)c2ccc(CO)c(C3CC3)n2)c1)C(F)(F)c1nncn1C
InChIKey: CSSMAEABQURSLV-UHFFFAOYSA-N
Target: E3 ubiquitin-protein ligase CBL-B (SINGLE PROTEIN), Homo sapiens
UniProt: Q13191
Assay: Binding affinity towards N-terminal biotinylated Avi-tagged human CBL-B (36 to 427 residues) measured by surface plasmon resonance assay
Measurement: Kd = 1001 nM (pChEMBL 6)
Descriptors: MW 427.46, ALogP 3.73, HBA 6, HBD 2, PSA 92.93, QED 0.6
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(-c3cnc(C(F)(F)F)nc3)nn2)[C@H]1O
InChIKey: YMPKEQXHXKVPFF-HZCDSYHLSA-N
Target: Galectin-3 (SINGLE PROTEIN), Mus musculus
UniProt: P16110
Assay: Inhibition of biotin-asialofetuin binding to mouse Gal3 measured after 90 mins by HTRF competition assay
Measurement: IC50 = 493 nM (pChEMBL 6.309999942779541)
Descriptors: MW 704.61, ALogP 1.8, HBA 15, HBD 3, PSA 175.58, QED 0.18
Compound (SMILES): Clc1ccc(C2(Cn3cncn3)COC(c3cc4ccc(Cl)cc4s3)=N2)cc1
InChIKey: HDRXGGWSEWGELG-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes incubated for 10 mins in presence of NADPH by LC/MS/MS analysis
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 429.33, ALogP 5.17, HBA 6, HBD 0, PSA 52.3, QED 0.45
Compound (SMILES): C=CC(=O)Nc1cccc(-n2c(=O)c(-c3ccccc3F)nc3cnc(Nc4ccc(OCCOC)cc4)nc32)c1
InChIKey: IJONDZVYIBNTDX-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ITK/TSK (SINGLE PROTEIN), Homo sapiens
UniProt: Q08881
Assay: Inhibition of human ITK using poly-Glu-Tyr (4:1) as substrate incubated for 1 hr by ELISA
Measurement: IC50 = 199.3 nM (pChEMBL 6.699999809265137)
Descriptors: MW 552.57, ALogP 4.88, HBA 9, HBD 2, PSA 120.26, QED 0.19
Compound (SMILES): CN(C)C(=O)c1cc(-c2cnc3c(c2)C2(CCCC2)CN3)ccc1N
InChIKey: DGAUFASKKMUKJE-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92918
Assay: Inhibition of HPK1 (unknown origin) followed by anti-GST antibody incubated for 60 mins measured after 1 hr by TR-FRET based LanthaScreen Eu-Kinase binding assay
Measurement: Ki = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 336.44, ALogP 3.27, HBA 4, HBD 2, PSA 71.25, QED 0.83
Compound (SMILES): CNc1ccc2ccc(CC[C@H]3C[C@@H](n4cc(CO)c5c(N)ncnc54)[C@H](O)[C@@H]3O)cc2n1
InChIKey: YONOTRKVJDBWHH-OZPQRRJYSA-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 < 10 nM (pChEMBL 8)
Descriptors: MW 448.53, ALogP 2.01, HBA 9, HBD 5, PSA 142.34, QED 0.3
Compound (SMILES): CNC(=O)c1c(-c2ccc(O)c(F)c2)oc2ccc(O)c(CN3CCC4(COC4)C3)c12
InChIKey: CLGYBKWKICSQGN-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG ion channel by Q patch-clamp method
Measurement: IC50 = 2700 nM (pChEMBL 5.570000171661377)
Descriptors: MW 426.44, ALogP 3.23, HBA 6, HBD 3, PSA 95.17, QED 0.59
Compound (SMILES): C[C@H](Sc1nncn1C)c1ccnc(NC(=O)c2cccc(S(F)(F)(F)(F)F)c2)c1
InChIKey: FMNCLHKEOWGVKX-NSHDSACASA-N
Target: E3 ubiquitin-protein ligase CBL-B (SINGLE PROTEIN), Homo sapiens
UniProt: Q13191
Assay: Binding affinity towards N-terminal biotinylated Avi-tagged human CBL-B (36 to 427 residues) measured by surface plasmon resonance assay
Measurement: Kd = 3001 nM (pChEMBL 5.519999980926514)
Descriptors: MW 465.47, ALogP 5.97, HBA 6, HBD 1, PSA 72.7, QED 0.36
Compound (SMILES): CC(C)c1nc(SCC(=O)c2ccccc2)nc(Nc2ccc(S(N)(=O)=O)cc2)c1C#N
InChIKey: WEJWYQDHVCEHPX-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human CA2 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 46.2 nM (pChEMBL 7.329999923706055)
Descriptors: MW 467.58, ALogP 3.84, HBA 8, HBD 2, PSA 138.83, QED 0.29
Compound (SMILES): C[C@H](Cc1nncn1C)c1cccc(NC(=O)c2cc(C(=O)N3CC[C@H](O)C3)ccc2F)c1
InChIKey: AFACQWFXERQQKI-BEFAXECRSA-N
Target: E3 ubiquitin-protein ligase CBL-B (SINGLE PROTEIN), Homo sapiens
UniProt: Q13191
Assay: Binding affinity towards N-terminal biotinylated Avi-tagged human CBL-B (36 to 427 residues) measured by surface plasmon resonance assay
Measurement: Kd = 3001 nM (pChEMBL 5.519999980926514)
Descriptors: MW 451.5, ALogP 2.76, HBA 6, HBD 2, PSA 100.35, QED 0.6
Compound (SMILES): COc1ccc(C(=O)O[C@H]2C=C3[C@H]4CN(Cc5cc6c(cc54)OCO6)[C@H]3C[C@@H]2OC)cc1OC
InChIKey: ZDPZLTNELBAFQI-LSYVANFTSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human BuChE using butyrylthiocholine chloride as substrate by Ellman's method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 465.5, ALogP 3.28, HBA 8, HBD 0, PSA 75.69, QED 0.49
Compound (SMILES): O=c1[nH]nc2ccc(Sc3ccc(C(F)(F)F)cc3)nn12
InChIKey: CTEVAUWRCVUIGU-UHFFFAOYSA-N
Target: Palmitoleoyl-protein carboxylesterase NOTUM (SINGLE PROTEIN), Homo sapiens
UniProt: Q6P988
Assay: Inhibition of Notum (81 to 451 Cys330Ser) in HEK293T cells expressing TCF-LEF assessed as activation of Wnt signaling using WNT3A as substrate incubated for 16 to 20 mins by Steady-Glo luciferase assay
Measurement: EC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 312.28, ALogP 2.59, HBA 5, HBD 1, PSA 63.05, QED 0.79
Compound (SMILES): COc1ccc(N(C(=S)NCCCn2cncc2C)C2CCN(C)CC2)cc1OC
InChIKey: RGPGHWMCXHFPCU-UHFFFAOYSA-N
Target: Glutaminyl-peptide cyclotransferase (SINGLE PROTEIN), Homo sapiens
UniProt: Q16769
Assay: Inhibition of human recombinant glutaminyl cyclase using H-Gln-AMC hydrobromide as substrate measured after 15 mins by fluorimetry
Measurement: IC50 = 6.1 nM (pChEMBL 8.210000038146973)
Descriptors: MW 431.61, ALogP 3.07, HBA 6, HBD 1, PSA 54.79, QED 0.51
Compound (SMILES): C=CC(=O)Nc1cccc(-n2c(=O)c(-c3ccccc3)nc3cnc(Nc4ccc(OC)cc4)nc32)c1
InChIKey: MUHMCFYZMSUSBK-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ITK/TSK (SINGLE PROTEIN), Homo sapiens
UniProt: Q08881
Assay: Inhibition of human ITK using poly-Glu-Tyr (4:1) as substrate incubated for 1 hr by ELISA
Measurement: IC50 = 111.5 nM (pChEMBL 6.949999809265137)
Descriptors: MW 490.52, ALogP 4.72, HBA 8, HBD 2, PSA 111.03, QED 0.32
Compound (SMILES): NS(=O)(=O)c1ccc2c(c1)C(=O)C(=O)N2Cc1ccncc1
InChIKey: ZDWIPZFXMSDKLC-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of human CA1 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 212.1 nM (pChEMBL 6.670000076293945)
Descriptors: MW 317.33, ALogP 0.46, HBA 5, HBD 1, PSA 110.43, QED 0.83
Compound (SMILES): CCC1Cc2cc(C)ccc2C(NC(=O)c2ccc(C(F)(F)F)[nH]c2=O)C1
InChIKey: ZKEXEQBSJZTFOW-UHFFFAOYSA-N
Target: 17-beta-hydroxysteroid dehydrogenase type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P37059
Assay: Inhibition of HSD17B2 (unknown origin) using estradiol as substrate incubated for 45 mins and measured after 1 hr by NADH Glo luminescence assay
Measurement: IC50 = 25800 nM (pChEMBL 4.590000152587891)
Descriptors: MW 378.39, ALogP 4.15, HBA 2, HBD 2, PSA 61.96, QED 0.84
Compound (SMILES): CC(C)Oc1cc(NC(=O)N2CCCc3ccc(C=O)nc32)ncc1C#Cc1ccccn1
InChIKey: YCWJXKRCBZLEPZ-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of FGFR4 (unknown origin) using Tyr 04 peptide substrate measured after 2 hrs by FRET assay
Measurement: IC50 = 5.4 nM (pChEMBL 8.270000457763672)
Descriptors: MW 441.49, ALogP 3.86, HBA 6, HBD 1, PSA 97.31, QED 0.49