lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1ncc(-c2ccc(C(=O)O)cc2C)cc1-c1ccc(C(F)(F)F)cc1CN1C(=O)N[C@H](c2cc(C(F)(F)F)cc(C(F)(F)F)c2)[C@@H]1C
InChIKey: GJFJQKRNVJCTQC-HPGBDJQBSA-N
Target: Cholesteryl ester transfer protein (SINGLE PROTEIN), Homo sapiens
UniProt: P11597
Assay: Inhibition of recombinant CETP (unknown origin) assessed as inhibition of transfer of [3H] cholesteryl oleate or [3H] triolein between exogenous LDL and HDL in 2% human serum
Measurement: IC50 = 38 nM (pChEMBL 7.420000076293945)
Descriptors: MW 711.58, ALogP 9.14, HBA 4, HBD 2, PSA 91.76, QED 0.19
Compound (SMILES): CC(=O)N1CCN(c2ccc3c(c2)CCCN3S(=O)(=O)N(C)Cc2ccccc2C)CC1
InChIKey: KFHSPPPWAMYNOM-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at APC-labeled RORgammat LBD (unknown origin) assessed as inhibition of europium-labeled co-activator SRC1 recruitment incubated for 1 hr by FRET assay
Measurement: XC50 = 143 nM (pChEMBL 6.840000152587891)
Descriptors: MW 456.61, ALogP 2.79, HBA 4, HBD 0, PSA 64.17, QED 0.69
Compound (SMILES): COc1ccc(Cl)cc1NC[C@@H]1CC12CCN(S(N)(=O)=O)CC2
InChIKey: BSRNVKLQQHLHLE-NSHDSACASA-N
Target: Neuronal acetylcholine receptor subunit alpha-7 (SINGLE PROTEIN), Homo sapiens
UniProt: P36544
Assay: Positive allosteric modulation of recombinant human AChR alpha7 expressed in HEK cells co-expressing RIC-3 at -60 mV holding potential treated for 58 sec followed by acetylcholine applied for 1 sec measured potentiation effect by automated patch clamp electrophysiological method
Measurement: EC50 <= 100 nM (pChEMBL 7)
Descriptors: MW 359.88, ALogP 2.07, HBA 4, HBD 2, PSA 84.66, QED 0.84
Compound (SMILES): O=c1cc(-c2cccc3c2Sc2ccc(OCCN4CCCC45CCOC5)cc2C3)oc(N2CCOCC2)c1
InChIKey: GCTSASOEHREIQD-UHFFFAOYSA-N
Target: Serine-protein kinase ATM (SINGLE PROTEIN), Homo sapiens
UniProt: Q13315
Assay: Inhibition of recombinant full-length human FLAG-tagged ATM assessed as reduction in p53 S15 phosphorylation incubated for 30 mins by ELISA
Measurement: IC50 = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 546.69, ALogP 4.83, HBA 8, HBD 0, PSA 64.38, QED 0.34
Compound (SMILES): O=S1(=O)CCc2c(CN(CCO)Cc3ccccc3)nn(-c3ccccc3F)c2O1
InChIKey: BTOGWYRFXWZTSR-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE using butyrylthiocholine iodide as substrate preincubated with enzyme for 20 mins followed by addition of substrate and measured after 20 mins by DTNB reagent based Ellman's method
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 431.49, ALogP 2.27, HBA 7, HBD 1, PSA 84.66, QED 0.58
Compound (SMILES): COc1ccc(/C=C\c2cc(OC)c(OC)c(OC)c2)cc1OCc1ccc(CNCCN(C)C)cc1
InChIKey: YAJHJVVBPXBWIT-GHXNOFRVSA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NZQ7
Assay: Inhibition of PD1/PDL1 (unknown origin) protein-protein interaction measured after 15 mins by HTRF assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 506.64, ALogP 5.12, HBA 7, HBD 1, PSA 61.42, QED 0.24
Compound (SMILES): O=C(Nc1ccc(Br)cc1)N1CCc2c([nH]c3ccccc23)C1
InChIKey: ZJAHCVZROJUQCE-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NER1
Assay: Antagonist activity at human TRPV1 assessed as inhibition of capsaicin-induced channel activation
Measurement: IC50 = 212 nM (pChEMBL 6.670000076293945)
Descriptors: MW 370.25, ALogP 4.52, HBA 1, HBD 2, PSA 48.13, QED 0.65
Compound (SMILES): CCNC(=O)[C@H](CCC1CCCCC1)NC(=O)c1ccc(CNC(=O)c2cnn(-c3ccccc3)c2N)cc1
InChIKey: WJTJZDOMFKCYEA-SANMLTNESA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Inhibition of C-terminal NanoLuc-fused full length human MAPK14 expressed in HEK293T cells after 2 hrs by NanoBRET assay
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 530.67, ALogP 3.98, HBA 6, HBD 4, PSA 131.14, QED 0.3
Compound (SMILES): O=C(Nc1ccc(CN2CCCC2)cc1)c1n[nH]cc1/C=C/c1cccnc1
InChIKey: DRKMMTNMHQKWJS-VMPITWQZSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of recombinant DYRK1A (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 373.46, ALogP 3.82, HBA 4, HBD 2, PSA 73.91, QED 0.69
Compound (SMILES): Nc1cncc(-c2cnc3[nH]nc(-c4cc5c(-c6ccccc6F)ccnc5[nH]4)c3c2)c1
InChIKey: YCWGJOKZUMDVKO-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of recombinant DYRK1A (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 59 nM (pChEMBL 7.230000019073486)
Descriptors: MW 421.44, ALogP 4.95, HBA 5, HBD 3, PSA 109.16, QED 0.37
Compound (SMILES): CCNc1ncc2c(n1)N1CCC[C@H]1CN(c1cccc(OC(CCNC)c3ccccc3)c1)C2=O
InChIKey: QLIONHKEMUXUQB-XADRRFQNSA-N
Target: Voltage-dependent calcium channel subunit alpha-2/delta-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P54289
Assay: Displacement of [3H]-gabapentin from human Cav alpha2delta1 expressed in CHO-K1 cell membranes incubated for 60 mins by scintillation counting method
Measurement: Ki = 336 nM (pChEMBL 6.46999979019165)
Descriptors: MW 486.62, ALogP 4.27, HBA 7, HBD 2, PSA 82.62, QED 0.47
Compound (SMILES): N#Cc1cccc(/C=C/[N+](=O)[O-])c1
InChIKey: CDJHTQWXSZMZNZ-SNAWJCMRSA-N
Target: Fructose-1,6-bisphosphatase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09467
Assay: Inhibition of human wild type FBPase expressed in Escherichia coli BL12 (DE3) by malachite green method
Measurement: IC50 = 380 nM (pChEMBL 6.420000076293945)
Descriptors: MW 174.16, ALogP 1.81, HBA 3, HBD 0, PSA 66.93, QED 0.51
Compound (SMILES): CC(C)N1c2cc(Nc3nccc(-c4cccc5cnccc45)n3)ccc2N(C)C(=O)[C@H]1C
InChIKey: URJQRGYKGNGARR-QGZVFWFLSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of His6-tagged BRD4 bromodomain 1 (unknown origin) expressed in Escherichia coli Bl21(DE3) cells incubated for 4 hrs by FP assay
Measurement: IC50 = 75.9 nM (pChEMBL 7.119999885559082)
Descriptors: MW 438.54, ALogP 5.02, HBA 6, HBD 1, PSA 74.25, QED 0.48
Compound (SMILES): COc1cc(F)ccc1-c1cc(Nc2cc(CS(C)(=N)=O)ccn2)ncc1F
InChIKey: YZCUMZWULWOUMD-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9 (unknown origin)
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 404.44, ALogP 4.35, HBA 6, HBD 2, PSA 87.96, QED 0.64
Compound (SMILES): CC(C)(COP(=O)(O)OP(=O)(O)OC[C@@H]1O[C@H](n2cnc3c(N)ncnc32)[C@@H](O)[C@H]1OP(=O)(O)O)[C@H](O)C(=O)NCCC(=O)NCCS
InChIKey: RGJOEKWQDUBAIZ-FRSQKNERSA-N
Target: Aurora kinase A (SINGLE PROTEIN), Homo sapiens
UniProt: O14965
Assay: Inhibition of recombinant Aurora A (unknown origin) using myelin basic protein as substrate incubated for 30 mins in presence or absence of DTT by [gamma-33P]-ATP based radioactive filter binding assay
Measurement: IC50 = 5000 nM (pChEMBL 5.300000190734863)
Descriptors: MW 767.54, ALogP -1.67, HBA 18, HBD 10, PSA 346.56, QED 0.06
Compound (SMILES): COc1ccc(-c2cc(C(F)(F)F)n3nc(-c4cccs4)cc3n2)cc1OC
InChIKey: CLFOYJSEPPNFQZ-UHFFFAOYSA-N
Target: Far upstream element-binding protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96AE4
Assay: Inhibition of human full length FUBP1 expressed in Escherichia coli BL21 DE3 assessed as reduction in FUBP1 interaction with FUSE p21 oligonucleotide incubated for 21 hrs by Alphascreen assay
Measurement: IC50 = 23600 nM (pChEMBL 4.630000114440918)
Descriptors: MW 405.4, ALogP 5.16, HBA 6, HBD 0, PSA 48.65, QED 0.47
Compound (SMILES): C=CS(=O)(=O)Nc1ccccc1Nc1ccc2c(C(=O)c3cc(OC)cc(OC)c3)c[nH]c2n1
InChIKey: QHIAVSCMZIJUFF-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of human FGFR4 using poly (Glu, Tyr)4:1 as substrate incubated for 20 mins followed by [33P]-ATP addition and measured after 120 mins by radiometric hotspot assay
Measurement: IC50 = 223 nM (pChEMBL 6.650000095367432)
Descriptors: MW 478.53, ALogP 4.44, HBA 7, HBD 3, PSA 122.41, QED 0.3
Compound (SMILES): N#Cc1c(-c2ccccc2Cl)c2c(N/N=C3\C=CC(=O)c4ccccc43)n[nH]c2[nH]c1=O
InChIKey: LVPWFSJUVQIYQZ-WPWMEQJKSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: Inhibition of recombinant human GST-tagged PIM1 by ELISA
Measurement: IC50 = 95 nM (pChEMBL 7.019999980926514)
Descriptors: MW 440.85, ALogP 4.01, HBA 6, HBD 3, PSA 126.79, QED 0.41
Compound (SMILES): N=C(N)Nc1cccc(C(=O)NNC(=O)NC[C@H](NC(=O)[C@@H]2CCCN2S(=O)(=O)c2ccccc2)C(=O)O)c1
InChIKey: PDJSBAOCILQASK-ROUUACIJSA-N
Target: Integrin alpha-5/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P05556
Assay: Inhibition of alpha5beta1 integrin in human SW480 cells assessed as inhibition of cell adhesion to fibronectin incubated for 60 mins by crystal violet staining based analysis
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 560.59, ALogP -0.64, HBA 7, HBD 8, PSA 235.91, QED 0.11
Compound (SMILES): O=C(Nc1ccc(OC(F)(F)F)c(F)c1)NC1CCN(C(=O)C2(C(F)(F)F)CC2)CC1
InChIKey: VGDKHFMCPOLGSQ-UHFFFAOYSA-N
Target: Bifunctional epoxide hydrolase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34913
Assay: FRET-displacement assay: FRET assays to determine Ki for the compounds of Table I were carried out as described previously (Lee et al. Analytical Biochemistry 434 (2013) 259-268). In order to prevent leaching of fluorescence impurities from the plastic tube and non-specific binding to sEH inhibitors, the inhibitor stock solution (10 mM, DMSO) was stored in glass vials. In addition, sEH was diluted to desired concentration (20 nM) with sodium phosphate buffer (PB) (100 mM sodium phosphate, pH 7.4, 0.01% gelatin) to avoid loss of protein from non-specific binding to the cuvette surface. All buffer used in this assay was filtered by sterilized filtration unit (Millipore Durapore PVDF Membrane, pore size: 0.22 um).Measurement in 96-Well PlatesAll the measurement for FRET-based displacement assay in 96-well plate format were done in TECAN Infinite M1000 Pro 96 well fluorescence plate reader.Pre-Treatment of 96-Well PlateIn order to prevent non-specific binding of sEH or inhibitor on the 96-well plate, the 96 well plates were pre-incubated with PB with 0.1% gelatin overnight at rt. The gelatin coats the plate and prevents non-specific binding of sEH and sEH inhibitors to the plate. The buffer was discarded and the plate was dried before use.Assay ProcedureThe sEH stock was diluted to the desired concentration (20 nM) by PB (100 mM sodium phosphate, 0.1% gelatin, pH 7.4). ACPU (one equivalent to sEH, 10 mM, Ethanol) was added to the sEH solution and was incubated for 2 h at rt. The sEH-ACPU mixture (20 nM, 100 mM sodium phosphate, 0.1% gelatin, pH 7.4, 150 uL) was added to each well.The baseline fluorescence (F0) (λexcitation at 280 nm, λemission at 450 nm) of the samples was measured after the z-position and gain were optimized automatically by the fluorometers. The z and gain value was noted and will be used for the later fluorescent measurement. Because DMSO has been known to quench fluorescence. 1% DMSO in PB was served as a control (FDMSO). The desired concentration of inhibitors which is the concentration that 100% of sEH was bound to inhibitor, was added at the first well and was further diluted by 2-fold across the rest of the wells. Based on our study, 12 datum points which correspond to 12 different concentrations of the inhibitor, provide significant data to calculate the accurate Ki for the inhibitors. The samples were incubated at 30° C. for 1.5 h. Then, the fluorescence (λexcitation at 280 nm, λemission at 450 nm) of the samples was measured using the z-position and gain values that previously obtained.
Measurement: Ki < 0.05 nM (pChEMBL 10.300999641418457)
Descriptors: MW 457.35, ALogP 4.18, HBA 3, HBD 2, PSA 70.67, QED 0.67
Compound (SMILES): CC(=O)C1=C(O)C=C2Oc3c(-c4csc(N/N=C5/C[C@H]6CC[C@]5(C)C6(C)C)n4)c(O)c(C)c(O)c3[C@@]2(C)C1=O
InChIKey: TZQBHQHMFJQSHX-ICOCLAAVSA-N
Target: Tyrosyl-DNA phosphodiesterase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NUW8
Assay: Inhibition of recombinant TDP1 (unknown origin) expressed in Escherichia coli using 5'-FAM/3'-BHQ1 tagged oligonucleotide as substrate by fluorescence assay
Measurement: IC50 = 31 nM (pChEMBL 7.510000228881836)
Descriptors: MW 549.65, ALogP 5.66, HBA 10, HBD 4, PSA 141.34, QED 0.28
Compound (SMILES): COc1cccc(S(=O)(=O)n2cnc3c(N4CCNCC4)nccc32)c1
InChIKey: AYCFNZPRLOAXAZ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H]-LSD from human 5HT6R expressed in HEK293 cell membranes incubated for 1 hr by micro-beta plate reader based analysis
Measurement: Ki = 10 nM (pChEMBL 8)
Descriptors: MW 373.44, ALogP 1.09, HBA 8, HBD 1, PSA 89.35, QED 0.73
Compound (SMILES): Cc1ncc(C#Cc2cc(-c3nn(-c4nc(C(=O)O)cs4)c(CC4CC4)c3Cc3ccc(S(N)(=O)=O)c(F)c3)ccc2F)s1
InChIKey: LXVZZLVKUXDZRH-UHFFFAOYSA-N
Target: L-lactate dehydrogenase A chain (SINGLE PROTEIN), Homo sapiens
UniProt: P00338
Assay: Inhibition of recombinant human LDHA using sodium pyruvate as substrate preincubated for 5 mins followed by diaphorase/resazurin addition and measured after 20 mins by fluorescence based assay
Measurement: IC50 = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 651.74, ALogP 5.33, HBA 9, HBD 2, PSA 141.06, QED 0.22
Compound (SMILES): COc1cc(/C=C/C=C/C(=O)c2ccc(O)cc2)ccc1O
InChIKey: QAVLJFHJNQFAJN-ZUVMSYQZSA-N
Target: Calpain-1 catalytic subunit (SINGLE PROTEIN), Homo sapiens
UniProt: P07384
Assay: Inhibition of human erythrocytes mu-calpain using Pep1 as substrate incubated for 30 mins under shaking condition in presence of CaCl2 by fluorescence assay
Measurement: IC50 = 16810 nM (pChEMBL 4.769999980926514)
Descriptors: MW 296.32, ALogP 3.56, HBA 4, HBD 2, PSA 66.76, QED 0.5
Compound (SMILES): COc1ccc(NC(=O)NC2CCc3ccccc3C2)cc1Cl
InChIKey: NCJGYWDTLVHFJT-UHFFFAOYSA-N
Target: Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UDY8
Assay: Allosteric inhibition of human wild-type full-length MALT1 (329 to 824 residues) protease activity using Ac-Leu-Arg-Ser-Arg Rh110-dPro as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by fluorescence assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 330.81, ALogP 4.03, HBA 2, HBD 2, PSA 50.36, QED 0.89
Compound (SMILES): CNc1cc(C)nc(Nc2ccc(Cl)c(C3=CCNCCC3)c2)n1
InChIKey: MFOQRJHECLPWDG-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase EHMT2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96KQ7
Assay: Inhibition G9a (unknown origin)
Measurement: IC50 = 6.32 nM (pChEMBL 8.199999809265137)
Descriptors: MW 343.86, ALogP 3.99, HBA 5, HBD 3, PSA 61.87, QED 0.78
Compound (SMILES): CC(=O)C(C)(C)C1CC(=O)N(c2ccccc2)C1=O
InChIKey: FFQWGSBHIHMSPE-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 1 (SINGLE PROTEIN), Ovis aries
UniProt: P05979
Assay: Inhibition of sheep COX1 using arachidonic acid as substrate preincubated for 5 mins followed by substrate addition and measured after 5 mins by UV-visible spectrophotometric method
Measurement: IC50 = 39250 nM (pChEMBL 4.409999847412109)
Descriptors: MW 259.3, ALogP 2.18, HBA 3, HBD 0, PSA 54.45, QED 0.78
Compound (SMILES): N#Cc1cc(C(=O)N2CS(=O)(=O)c3ccccc32)cc(C(F)(F)F)c1O
InChIKey: MTHRZZFLSQRKKO-UHFFFAOYSA-N
Target: Solute carrier family 22 member 12 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96S37
Assay: Inhibition of URAT1 in human RPTEC assessed as inhibition of [14C]uric acid uptake preincubated for 15 mins followed by [14C]uric acid addition and incubated under shaking condition for 2 hrs by scintillation counter method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 382.32, ALogP 2.67, HBA 5, HBD 1, PSA 98.47, QED 0.82
Compound (SMILES): Nc1n[nH]c(=O)c2c1c(-c1ccc(Oc3ccccc3)cc1)nn2[C@@H]1CCCN(C(=O)/C=C/CN2CCOCC2)C1
InChIKey: KQOJNEYHROIYAN-FSNDINTDSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of recombinant human His-tagged full length BTK expressed in baculovirus expression system using TK1 as substrate incubated for 60 mins by HTRF assay
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 555.64, ALogP 3.21, HBA 9, HBD 2, PSA 131.6, QED 0.33
Compound (SMILES): COc1ccc(S(=O)(=O)NC(=O)c2cc3c(Nc4cccc(OC(F)F)c4)ccc([N+](=O)[O-])c3[nH]2)cc1
InChIKey: RPYZLUSSCXKLRE-UHFFFAOYSA-N
Target: Fructose-1,6-bisphosphatase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09467
Assay: Inhibition of human liver FBPase expressed in Escherichia coli BL21(DE3) using FBP as substrate in presence of PGI and G6PDH by spectrophotometric method
Measurement: IC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 532.48, ALogP 4.55, HBA 8, HBD 3, PSA 152.66, QED 0.21
Compound (SMILES): Clc1ccccc1SSc1nccs1
InChIKey: IWJOLPDDYBVLIB-UHFFFAOYSA-N
Target: Fructose-1,6-bisphosphatase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09467
Assay: Inhibition of wild-type full-length human liver FBPase expressed in Escherichia coli BL21 (DE3) using FBP as substrate by malachite green dye based assay
Measurement: IC50 = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 259.81, ALogP 4.6, HBA 4, HBD 0, PSA 12.89, QED 0.75
Compound (SMILES): COc1ncc(NC(=O)Nc2cnc3ccc(F)cc3c2N(C)C2CCCN(C)C2)cc1Cl
InChIKey: VVAWSCAKBGGGTH-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 = 9000 nM (pChEMBL 5.050000190734863)
Descriptors: MW 472.95, ALogP 4.61, HBA 6, HBD 2, PSA 82.62, QED 0.56
Compound (SMILES): CCc1cc(NC(=O)c2ccc(-c3nc([C@@H]4CCCN(C(=O)C5(C)COC5)C4)n4ccnc(N)c34)c(F)c2)ncn1
InChIKey: PREKNIIRSLFQDR-GOSISDBHSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Reversible inhibition of recombinant full length BTK (unknown origin) baculovirus infected Sf9 cells using biotinylated EQEDEPEGDYFEWLE-NH2 peptide as substrate preincubated for 60 mins followed by substrate addition and measured after 120 mins in presence of ATP by TR-FRET assay
Measurement: IC50 = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 558.62, ALogP 3.46, HBA 9, HBD 2, PSA 140.63, QED 0.37
Compound (SMILES): Cc1cc(-c2cnc3cc(-c4ccc(OC5CCN(C)CC5)nc4)ccn23)c2cc(F)ccc2n1
InChIKey: CWPFWCHASPMSDN-UHFFFAOYSA-N
Target: Activin receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q04771
Assay: Inhibition of human ALK2 using casein as substrate by [gamma-33P]-ATP assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 467.55, ALogP 5.53, HBA 6, HBD 0, PSA 55.55, QED 0.35
Compound (SMILES): CNC(=O)NC(=N)NCCC[C@H]1CN(C)[C@@H](Cc2ccccc2)C(=O)N[C@@H](C(=O)O)CCC(=O)N[C@@H](C(=O)O)CC(=O)N[C@H](C)C(=O)N1
InChIKey: DHHVTIQSEZUVAG-BLCKVISQSA-N
Target: Endochitinase B1 (SINGLE PROTEIN), Aspergillus fumigatus
UniProt: Q873X9
Assay: Inhibition of Aspergillus fumigatus chitinase B1 expressed in Escherichia coli using 4MU-GlcNAc2 as substrate by fluorescence method
Measurement: IC50 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 675.74, ALogP -1.92, HBA 9, HBD 10, PSA 271.25, QED 0.08
Compound (SMILES): COc1ccc(C(c2ccccn2)c2c[nH]c3ccccc23)cc1
InChIKey: GEVQBEHNBPSQEH-UHFFFAOYSA-N
Target: Aryl hydrocarbon receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35869
Assay: Agonist activity at AhR in human HepG2 cells co-transfected with pSELECT-zeo-Lucia and CYP1A1 assessed as induction of receptor transactivation incubated for 24 hrs by luciferase reporter gene assay
Measurement: EC50 = 21720 nM (pChEMBL 4.659999847412109)
Descriptors: MW 314.39, ALogP 4.75, HBA 2, HBD 1, PSA 37.91, QED 0.59
Compound (SMILES): C=CC(=O)NCC(=O)Nc1cccc(-c2cc(Nc3cnn(CCOC)c3)ncn2)c1
InChIKey: BUENNZLMRJPBKP-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of recombinant human GST-tagged JAK3 cytoplasmic domain (781 to 1124 residues) expressed in baculovirus expression system using TK-substrate-biotin preincubated for 5 mins followed by substrate addition and measured after 30 mins by HTRF assay
Measurement: IC50 = 66 nM (pChEMBL 7.179999828338623)
Descriptors: MW 421.46, ALogP 1.97, HBA 8, HBD 3, PSA 123.06, QED 0.43
Compound (SMILES): CN1CCN(c2cccc([C@H](CC(=O)O)C(=O)N3CC[C@@H](CCc4ccc5c(n4)NCCC5)C3)c2)CC1
InChIKey: QEDWYURCTRDSED-RLWLMLJZSA-N
Target: Integrin alpha-V/beta-3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P06756
Assay: Inhibition of integrin alphavbeta3 (unknown origin) by fluorescence polarization assay
Measurement: IC50 = 1258.93 nM (pChEMBL 5.900000095367432)
Descriptors: MW 505.66, ALogP 3.23, HBA 6, HBD 2, PSA 89.01, QED 0.57
Compound (SMILES): COc1cccc(/C=N\C2CCN(Cc3ccccc3)C2)c1OC
InChIKey: IPRATKIQYZCEHU-BKUYFWCQSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human AChE by Ellman's method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 324.42, ALogP 3.4, HBA 4, HBD 0, PSA 34.06, QED 0.76
Compound (SMILES): COc1ccc(F)cc1S(=O)(=O)Nc1ccc2c(c1)C(=C(C)C)C(=O)N2
InChIKey: SJHBWUUSQLTSKF-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of BRD4 BD1 (unknown origin) preincubated for 15 mins followed by peptide addition and measured after 60 mins by TR-FRET assay
Measurement: IC50 = 34 nM (pChEMBL 7.46999979019165)
Descriptors: MW 376.41, ALogP 3.38, HBA 4, HBD 2, PSA 84.5, QED 0.8
Compound (SMILES): Cc1cc2nc(N3CCC(Oc4ccc(F)cc4F)CC3)c(N[C@H]3CCOC3)nc2cn1
InChIKey: BPAIALIPDYXTFG-INIZCTEOSA-N
Target: G-protein coupled receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P46095
Assay: Modulation of GPR6 (unknown origin) expressed in CHO-K1 cells assessed as inhibition of constitutive cAMP activity by HTRF assay
Measurement: EC50 = 128 nM (pChEMBL 6.889999866485596)
Descriptors: MW 441.48, ALogP 3.86, HBA 7, HBD 1, PSA 72.4, QED 0.64
Compound (SMILES): Cn1cc(-c2cc3c(C(=O)Nc4ccc(OCCN5CCCC5)cc4)n[nH]c3cc2F)cn1
InChIKey: HBPHUHXCYJECEF-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Kinase Assay: GSK3β: Each compound is dissolved in DMSO as a 10 mM stock and used to prepare compound source plates. Serial dilution (1:3, 11-point dose-response curves from 10 M to 0.0003 M) and compound transfer was performed using the ECHO 550 (Labcyte, Sunnyvale, Calif.) into 1536-well black-walled round bottom plates (Corning).The GSK3β kinase assay is run using the Ser/Thr 09 peptide Z-lyte assay kit according to manufacturer's instructions (Life Technologiesa Division of Thermo-Fisher). This is a non-radioactive assay using fluorescence resonance energy transfer (FRET) between coumarin and fluorescein to detect kinase activity which is represented as ratio of coumarin emission/fluorescein emission.Briefly, recombinant GSK3β kinase, ATP and Ser/Thr peptide 09 are prepared in 1× Kinase buffer to final concentrations of 0.04 μg/mL, 46 μM, and 4 μM respectively. The mixture is allowed to incubate with the representative compounds for one hour at room temperature. All reactions were performed in duplicate. Unphosphorylated (0% Control) and phosphorylated (100% control) forms of Ser/Thr 18 serve as control reactions.After incubation, diluted Development Buffer is added to the reaction and allowed to further incubate for one hour at room temperature. The plate is read at Ex 400 Em 455 to detect the coumarin signal and Ex 400 Em 520 to measure the signal (EnVision Multilabel Plate Reader, PerkinElmer).
Measurement: EC50 = 38 nM (pChEMBL 7.420000076293945)
Descriptors: MW 448.5, ALogP 3.83, HBA 6, HBD 2, PSA 88.07, QED 0.45
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CS)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CS)NC(=O)[C@H](CS)NC(=O)CN)C(=O)N[C@@H](CS)C(N)=O
InChIKey: FIQKPIGOFVCVTG-PIJHVLQJSA-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 Ach-induced response at -80 mV holding potential preincubated for 5 mins followed by Ach stimulation by two electrode voltage-clamp assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 1811.04
Compound (SMILES): O=[N+]([O-])CC(c1ccc(-c2ccccc2)cc1)c1c(-c2ccccc2)[nH]c2ccccc12
InChIKey: PJFVPZZGRUKOHT-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Positive allosteric modulatory activity at human CB1 receptor expressed in CHO-K1 cells assessed as increase in CP55940-induced beta-arrestin recruitment preincubated 90 mins followed by CP55940 addition and measured after 60 mins by PathHunter assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 418.5, ALogP 6.91, HBA 2, HBD 1, PSA 58.93, QED 0.24
Compound (SMILES): C[C@@H](NC(=O)c1ccc2c(c1)OCc1cnccc1-2)c1ccccc1
InChIKey: JSBFPPNKJVBJKX-CQSZACIVSA-N
Target: Rho-associated protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75116
Assay: In Vitro Assay: The effectiveness of compounds of the present invention as ROCK inhibitors can be determined in a 30 μL assay containing 20 mM HEPES, pH 7.5, 20 mM MgCl2, 0.015% Brij-35, 4 mM DTT, 5 μM ATP and 1.5 μM peptide substrate (FITC-AHA-AKRRRLSSLRA-OH). Compounds were dissolved in DMSO so that the final concentration of DMSO was <2%, and the reaction was initiated with Rho kinase variants. After incubation, the reaction was terminated by the addition of EDTA and the phosphorylated and non-phosphorylated peptides separated using a LABCHIP® 3000 Reader (Caliper Life Sciences). Controls consisted of assays that did not contain compound, and backgrounds consisted of assays that contained enzyme and substrate but had EDTA from the beginning of the reaction to inhibit kinase activity. Compounds were tested in dose-response format, and the inhibition of kinase activity was calculated at each concentration of compound. The inhibition data were fit using a curve-fitting program to determine the IC50; i.e., the concentration of compound required to inhibit 50% of kinase activity.
Measurement: IC50 = 3.23 nM (pChEMBL 8.489999771118164)
Descriptors: MW 330.39, ALogP 4.13, HBA 3, HBD 1, PSA 51.22, QED 0.79
Compound (SMILES): CCCCCn1cc(-c2nc(C34CC5CC(CC(C5)C3)C4)no2)c(=O)c2cc(-c3ccco3)ccc21
InChIKey: WRSGHQPOWCAEEI-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Displacement of [3H]CP-55940 from human CB1 receptor expressed in HEK cells by competitive binding assay
Measurement: Ki = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 483.61, ALogP 6.97, HBA 6, HBD 0, PSA 74.06, QED 0.27
Compound (SMILES): Cc1ccc([C@@H](c2ccccc2)C2CCN(C(=O)N3CC[C@@H]4OCC(=O)N[C@@H]4C3)CC2)cc1
InChIKey: RHVCSUCYWRLPJI-RMTZWNOUSA-N
Target: Monoglyceride lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q99685
Assay: Inhibition of MAGL (unknown origin) using 2-AG as substrate incubated for 15 mins followed by substrate addition and measured after 30 mins by mass spectrophotometry
Measurement: IC50 = 0.1 nM (pChEMBL 10)
Descriptors: MW 447.58, ALogP 3.55, HBA 3, HBD 1, PSA 61.88, QED 0.78
Compound (SMILES): Cc1cc(C#Cc2sc(NC(=O)NC[C@H](C)OCC3CC3)nc2C)cnc1C
InChIKey: OZANXNDKKYVVMJ-AWEZNQCLSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3Kgamma (unknown origin) using PIP2 as substrate measured after 15 mins in presence of [33P]-ATP by liquid scintillation counting method
Measurement: Ki = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 398.53, ALogP 3.8, HBA 5, HBD 2, PSA 76.14, QED 0.73
Compound (SMILES): Clc1cccc(CCSc2ncnc3[nH]cnc23)c1
InChIKey: SCWWIAUMSPJKBG-UHFFFAOYSA-N
Target: CDC7/DBF4 (Cell division cycle 7-related protein kinase/Activator of S phase kinase) (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9UBU7
Assay: Inhibition of recombinant human CDC7/Dbf4 expressed in baculovirus infected Sf9 insect cells assessed as inhibition of fluorescein labelled substrate phosphorylation in presence of ATP measured after 60 mins by TR-FRET assay
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 290.78, ALogP 3.34, HBA 4, HBD 1, PSA 54.46, QED 0.59
Compound (SMILES): NS(=O)(=O)c1ccc(-c2nnc(SCC(=O)c3ccc([N+](=O)[O-])cc3)o2)cc1
InChIKey: HMAVCDJYLIPXAM-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of recombinant human carbonic anhydrase 1 incubated for 10 mins prior to testing measured for 5 to 10 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 70.7 nM (pChEMBL 7.150000095367432)
Descriptors: MW 420.43, ALogP 2.27, HBA 9, HBD 1, PSA 159.29, QED 0.26
Compound (SMILES): CCCCC(NCc1ccc(C(=O)NO)cc1)c1nnnn1Cc1ccccc1
InChIKey: VZPHVPHXVCVEGM-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of human recombinant HDAC1 using ZMAL (Z-Lys(Ac)-AMC) fluorogenic substrate incubated for 90 mins by fluorescence based assay
Measurement: IC50 = 2010 nM (pChEMBL 5.699999809265137)
Descriptors: MW 394.48, ALogP 2.86, HBA 7, HBD 3, PSA 104.96, QED 0.36
Compound (SMILES): C[C@@H](O)[C@@H](C)Oc1nc(Nc2ccc([S@@](=N)(=O)C3CC3)cc2)ncc1C(F)(F)F
InChIKey: UELYDGOOJPRWGF-CUWIOODTSA-N
Target: Cyclin-dependent kinase 1/cyclin B1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P06493
Assay: Inhibition of recombinant human GST-tagged CDK1/cyclin B expressed in Sf9 cells using histone 3S as substrate incubated for 10 mins in presence of ATP by scintillation counting method
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 430.45, ALogP 3.96, HBA 7, HBD 3, PSA 108.19, QED 0.61
Compound (SMILES): Cc1cccc(/C=N\C2CCN(Cc3ccccc3)C2)c1
InChIKey: KQYCJYRXJNDDRY-MOSHPQCFSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human AChE by Ellman's method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 278.4, ALogP 3.69, HBA 2, HBD 0, PSA 15.6, QED 0.78
Compound (SMILES): COc1cccc(Nc2ccc([N+](=O)[O-])c3[nH]c(C(=O)NS(=O)(=O)c4ccc(F)cc4)cc23)c1
InChIKey: BTSWWOKIVHIIEZ-UHFFFAOYSA-N
Target: Fructose-1,6-bisphosphatase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09467
Assay: Inhibition of human liver FBPase expressed in Escherichia coli BL21(DE3) using FBP as substrate in presence of PGI and G6PDH by spectrophotometric method
Measurement: IC50 = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 484.47, ALogP 4.09, HBA 7, HBD 3, PSA 143.43, QED 0.26
Compound (SMILES): COc1cc(C(=O)O)c(NC(=O)N[C@@H](C)c2ccccc2)cc1OCCCC(C)C
InChIKey: KNEYBDJYRHSGFC-INIZCTEOSA-N
Target: Complement C5 (SINGLE PROTEIN), Homo sapiens
UniProt: P01031
Assay: Inhibition of C5 complement protein in 2% human serum incubated for 15 mins
Measurement: IC50 = 620 nM (pChEMBL 6.210000038146973)
Descriptors: MW 414.5, ALogP 5.09, HBA 4, HBD 3, PSA 96.89, QED 0.47
Compound (SMILES): C[C@@H](C1CC1)N1Cc2cc(-c3cnc4[nH]cc(-c5cnn(C)c5)c4c3)cc(S(=O)(=O)N(C)C)c2C1=O
InChIKey: BPJMUVIAPYNYDV-HNNXBMFYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3K p120gamma (unknown origin) using phosphatidylinositol 4,5-bisphosphate as substrate in presence of ATP incubated for 60 mins by ADP-Glo assay
Measurement: IC50 = 2.6 nM (pChEMBL 8.59000015258789)
Descriptors: MW 504.62, ALogP 3.64, HBA 6, HBD 1, PSA 104.19, QED 0.43
Compound (SMILES): CN(C)CCNc1cc(F)cc(-c2cccc3[nH]c(-c4n[nH]c5ccc(-c6cncnc6)nc45)cc23)c1
InChIKey: ZZOINPXQYFFWRU-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of recombinant DYRK1A (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 75 nM (pChEMBL 7.119999885559082)
Descriptors: MW 492.56, ALogP 5.34, HBA 6, HBD 3, PSA 98.41, QED 0.28
Compound (SMILES): CN(Cc1ccccc1)c1cc(C(=O)NCC2CC2)nc(N(C)CCc2ccccc2)n1
InChIKey: OQNSNSGQOVWTFG-UHFFFAOYSA-N
Target: N-acyl-phosphatidylethanolamine-hydrolyzing phospholipase D (SINGLE PROTEIN), Homo sapiens
UniProt: Q6IQ20
Assay: Inhibition of full length human NAPE-PLD expressed in HEK293T cell lysate using PED6 as substrate preincubated for 30 mins followed by substrate addition and measured at 2 mins interval for 1 hr by tecan-plate reader analysis
Measurement: IC50 = 1096.48 nM (pChEMBL 5.960000038146973)
Descriptors: MW 429.57, ALogP 3.93, HBA 5, HBD 1, PSA 61.36, QED 0.53
Compound (SMILES): CCOC(=O)Nc1nc(=O)n(CCOCP(=O)(OC(C)C)OC(C)C)s1
InChIKey: OVEXNPRQIIQVGK-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of human recombinant GSK3beta using GSK3 peptide as substrate preincubated for 15 mins followed by ATP addition and measured after 90 mins by ADP-Glo kinase assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 411.42, ALogP 2.89, HBA 10, HBD 1, PSA 117.98, QED 0.44
Compound (SMILES): N#Cc1ncc(N2C(=O)C3(CCCC3)N(c3cnc4c(c3)COC4=O)C2=S)cc1C(F)(F)F
InChIKey: MESUTEVCZGNHMM-UHFFFAOYSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Antagonist activity at androgen receptor (unknown origin) expressed in HEK293 cells using DHT as substrate preincubated for 30 mins followed by substrate addition measured after 24 hrs by Steady-Glo luciferase assay
Measurement: IC50 = 2219 nM (pChEMBL 5.650000095367432)
Descriptors: MW 473.44, ALogP 3.49, HBA 7, HBD 0, PSA 99.42, QED 0.48
Compound (SMILES): CCCCCCCC(=O)OC[C@H](NC(=O)[C@H](CO)NC(=O)CN)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@H](CN)CC(C)C
InChIKey: UAXGTXSNMNEJTE-CQJMVLFOSA-N
Target: Membrane-bound ghrelin O-acyltransferase MBOAT4 (SINGLE PROTEIN), Mus musculus
UniProt: P0C7A3
Assay: Inhibition of N-terminal His10-tagged mouse GOAT expressed in baculovirus infected sf9 insect cell membrane using proghrelin-His8 and [3H]octanoyl CoA as substrate by scintillation counting method
Measurement: IC50 = 45000 nM (pChEMBL 4.349999904632568)
Descriptors: MW 620.79, ALogP 0.03, HBA 9, HBD 7, PSA 214.97, QED 0.07
Compound (SMILES): O=C(Nc1ccc(OC(F)(F)F)cc1)NC1CCN(C(=O)C2=COCC2)CC1
InChIKey: SMHPRXGGKKOZAK-UHFFFAOYSA-N
Target: Bifunctional epoxide hydrolase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34913
Assay: FRET-displacement assay: FRET assays to determine Ki for the compounds of Table I were carried out as described previously (Lee et al. Analytical Biochemistry 434 (2013) 259-268). In order to prevent leaching of fluorescence impurities from the plastic tube and non-specific binding to sEH inhibitors, the inhibitor stock solution (10 mM, DMSO) was stored in glass vials. In addition, sEH was diluted to desired concentration (20 nM) with sodium phosphate buffer (PB) (100 mM sodium phosphate, pH 7.4, 0.01% gelatin) to avoid loss of protein from non-specific binding to the cuvette surface. All buffer used in this assay was filtered by sterilized filtration unit (Millipore Durapore PVDF Membrane, pore size: 0.22 um).Measurement in 96-Well PlatesAll the measurement for FRET-based displacement assay in 96-well plate format were done in TECAN Infinite M1000 Pro 96 well fluorescence plate reader.Pre-Treatment of 96-Well PlateIn order to prevent non-specific binding of sEH or inhibitor on the 96-well plate, the 96 well plates were pre-incubated with PB with 0.1% gelatin overnight at rt. The gelatin coats the plate and prevents non-specific binding of sEH and sEH inhibitors to the plate. The buffer was discarded and the plate was dried before use.Assay ProcedureThe sEH stock was diluted to the desired concentration (20 nM) by PB (100 mM sodium phosphate, 0.1% gelatin, pH 7.4). ACPU (one equivalent to sEH, 10 mM, Ethanol) was added to the sEH solution and was incubated for 2 h at rt. The sEH-ACPU mixture (20 nM, 100 mM sodium phosphate, 0.1% gelatin, pH 7.4, 150 uL) was added to each well.The baseline fluorescence (F0) (λexcitation at 280 nm, λemission at 450 nm) of the samples was measured after the z-position and gain were optimized automatically by the fluorometers. The z and gain value was noted and will be used for the later fluorescent measurement. Because DMSO has been known to quench fluorescence. 1% DMSO in PB was served as a control (FDMSO). The desired concentration of inhibitors which is the concentration that 100% of sEH was bound to inhibitor, was added at the first well and was further diluted by 2-fold across the rest of the wells. Based on our study, 12 datum points which correspond to 12 different concentrations of the inhibitor, provide significant data to calculate the accurate Ki for the inhibitors. The samples were incubated at 30° C. for 1.5 h. Then, the fluorescence (λexcitation at 280 nm, λemission at 450 nm) of the samples was measured using the z-position and gain values that previously obtained.
Measurement: Ki = 0.77 nM (pChEMBL 9.109999656677246)
Descriptors: MW 399.37, ALogP 3, HBA 4, HBD 2, PSA 79.9, QED 0.82
Compound (SMILES): O=C(O)CCc1ccc(COc2cc(F)ccc2C(=O)O)cc1
InChIKey: IUEZHFSLUMISQG-UHFFFAOYSA-N
Target: Free fatty acid receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5NUL3
Assay: Agonist activity at human FFA4 receptor expressed in CHO-K1 cells assessed as increase in amplitude of dynamic mass redistribution response by DMR assay
Measurement: EC50 < 100000 nM (pChEMBL 4)
Descriptors: MW 318.3, ALogP 3.12, HBA 3, HBD 2, PSA 83.83, QED 0.82
Compound (SMILES): C=CC(=O)NCC(C)(C)C(=O)N1CCCC[C@H]1C(=O)O[C@H](CCc1ccc(OC)c(OC)c1)c1ccccc1
InChIKey: SSJVGSYCCVIXJC-LOSJGSFVSA-N
Target: Peptidyl-prolyl cis-trans isomerase FKBP1A (SINGLE PROTEIN), Homo sapiens
UniProt: P62942
Assay: Displacement of fluorescent probe SLFb-2PEG-TAMRA from N-terminal 6His-SUMO-tagged human full length FKBP12 expressed in Escherichia coli BL21 (DE3) cells measured after 1 hr by fluorescence polarisation assay
Measurement: IC50 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 536.67, ALogP 4.63, HBA 6, HBD 1, PSA 94.17, QED 0.31
Compound (SMILES): O=C(Nc1c2c(cc3c1CCC3)CCC2)NS(=O)(=O)/C=C/c1cncs1
InChIKey: AOORRWWNNGKYAH-BQYQJAHWSA-N
Target: NACHT, LRR and PYD domains-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96P20
Assay: Inhibition of NLRP3 in human THP1 cells assessed as inhibition of IL-1beta production
Measurement: IC50 = 126 nM (pChEMBL 6.900000095367432)
Descriptors: MW 389.5, ALogP 3.24, HBA 5, HBD 2, PSA 88.16, QED 0.84
Compound (SMILES): CN(C)CCCN1C(=O)c2ccccc2CCc2ccccc21
InChIKey: JNPCKUNFTKRCJC-UHFFFAOYSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P31645
Assay: Binding affinity to SERT (unknown origin)
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 308.43, ALogP 3.38, HBA 2, HBD 0, PSA 23.55, QED 0.86
Compound (SMILES): Cl.OCCC/C(=C(\c1ccc(O)cc1)c1ccc(OCCN2CCCC2)cc1)c1ccccc1
InChIKey: ZUTOLBYBBQFQMW-FJBFXRHMSA-N
Target: Estrogen-related receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P62508
Assay: Binding affinity to GST-tagged ERRgamma LBD (unknown origin) using fluorescein PGC1alpha as coactivator incubated for 1 hr by LanthaScreen TR-FRET co-regulator assay
Measurement: IC50 = 67 nM (pChEMBL 7.170000076293945)
Descriptors: MW 443.59, ALogP 5.6, HBA 4, HBD 2, PSA 52.93, QED 0.4
Compound (SMILES): COc1ccc2nccc(CC[C@H]3OC[C@H](NC(=O)c4ccc(C)cc4)CO3)c2c1
InChIKey: LTAIYJYCNFSYJU-UILWBTOOSA-N
Target: DNA gyrase (PROTEIN COMPLEX), Staphylococcus aureus
UniProt: P0A0K8
Assay: Inhibition of Staphylococcus aureus DNA gyrase using relaxed pBR322 as substrate by gel electrophoresis
Measurement: IC50 = 410 nM (pChEMBL 6.389999866485596)
Descriptors: MW 406.48, ALogP 3.66, HBA 5, HBD 1, PSA 69.68, QED 0.68
Compound (SMILES): O=c1nc(N2CCN(CC3CCCCC3)CC2)sc2nc(Cl)ncc12
InChIKey: SGLNSIBNJSRTBU-UHFFFAOYSA-N
Target: Decaprenylphosphoryl-beta-D-ribose oxidase (SINGLE PROTEIN), Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
UniProt: P9WJF1
Assay: Inhibition of Mycobacterium tuberculosis DprE1 expressed in Escherichia coli BL21 (DE3) cells assessed as formation of resorufin using FPR as substrate by Amplex Red hydrogen/peroxidase coupled assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 379.92, ALogP 2.8, HBA 7, HBD 0, PSA 62.22, QED 0.76
Compound (SMILES): Cc1ccc(C(=O)NCCCN2CCOCC2)cc1-c1ccc(F)c(C(=O)Nc2c[nH]nc2C(=O)Nc2ccc(F)cc2)c1F
InChIKey: IIBICTBSQKVFDN-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 1/cyclin B1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P06493
Assay: Inhibition of CDK1/cyclin B1 (unknown origin) using FAM-labeled peptide and ATP as substrate preincubated for 10 mins followed by substrate addition by mobility shift assay
Measurement: IC50 = 3689 nM (pChEMBL 5.429999828338623)
Descriptors: MW 620.63, ALogP 4.76, HBA 6, HBD 4, PSA 128.45, QED 0.19
Compound (SMILES): CCOC(=O)c1cccc(-c2ccc(CN3CCN(S(C)(=O)=O)CC3)o2)c1
InChIKey: ASJGWXCQBDDFAR-UHFFFAOYSA-N
Target: Patatin-like phospholipase domain-containing protein 2 (SINGLE PROTEIN), Mus musculus
UniProt: Q8BJ56
Assay: Inhibition of murine ATGL expressed in COS-7 cells
Measurement: IC50 = 100000 nM (pChEMBL 4)
Descriptors: MW 392.48, ALogP 2.2, HBA 6, HBD 0, PSA 80.06, QED 0.7
Compound (SMILES): N#CNC(COc1ccc(Oc2ccccc2)cc1)Cn1ncnn1
InChIKey: LBNLJDAYAKSRJW-UHFFFAOYSA-N
Target: Fatty-acid amide hydrolase 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P97612
Assay: Inhibition of FAAH in rat brain microsomes using N-(2-hydroxyethyl)-4-pyren-1-ylbutanamide as substrate incubated for 45 mins by reverse-phase HPLC-based fluorescence assay
Measurement: IC50 = 5300 nM (pChEMBL 5.28000020980835)
Descriptors: MW 336.36, ALogP 1.98, HBA 8, HBD 1, PSA 97.88, QED 0.5
Compound (SMILES): Cc1noc(C)c1-c1ccc2c(c1)C(c1ccccc1)N(Cc1cn(CCCCCCn3cc(CN4C(=O)Nc5ccc(-c6c(C)noc6C)cc5C4c4ccccc4)nn3)nn1)C(=O)N2
InChIKey: RWUOIBQXGQTLAF-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of BRD4 bromodomain1 (unknown origin) using peptide histone H4 (SGRGACKGGACKGLGAC-KGGAACKRHGSGSK-biotin) as substrate incubated for 15 mins followed by substrate addition measured after 1 hr by alphascreen assay
Measurement: IC50 < 2.1 nM (pChEMBL 8.678000450134277)
Descriptors: MW 883.03, ALogP 9.95, HBA 12, HBD 2, PSA 178.16, QED 0.09
Compound (SMILES): CC[C@](C)(O)c1nc([C@@H]2CC[C@@H](C)N(C(=O)c3cscc3-n3nccn3)C2)oc1C
InChIKey: QIFHYQSASFBJSW-VWLHBSKXSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Antagonist activity at human OX1R expressed in CHO cells assessed as inhibition of orexin A-induced intracellular Ca2+ release by FLIPR assay
Measurement: IC50 = 9770 nM (pChEMBL 5.010000228881836)
Descriptors: MW 429.55, ALogP 3.65, HBA 8, HBD 1, PSA 97.28, QED 0.66
Compound (SMILES): CC(C)COc1ccc2c(Oc3ccc(Nc4nccc5[nH]cc(-c6ccc(F)cc6)c(=O)c45)cc3F)ccnc2c1
InChIKey: VSZDQXYTNDPZOB-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of MET (unknown origin) using biotin as substrate preincubated for 5 mins followed by substrate addition and measured after 30 to 60 mins by HTRF assay
Measurement: IC50 = 27.8 nM (pChEMBL 7.559999942779541)
Descriptors: MW 564.59, ALogP 7.99, HBA 6, HBD 2, PSA 89.13, QED 0.19
Compound (SMILES): O=C(Nc1nc(-c2ccncc2)n[nH]1)C1CCCCC1
InChIKey: FHNMKTHKWQBUHT-UHFFFAOYSA-N
Target: Coagulation factor X (SINGLE PROTEIN), Homo sapiens
UniProt: P00742
Assay: Inhibition of human coagulation factor Xa using Boc-Ile-Glu-Gly-Arg-AMC as fluorogenic substrate measured at 1 min interval for 1 hr by fluorometric assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 271.32, ALogP 2.39, HBA 4, HBD 2, PSA 83.56, QED 0.9
Compound (SMILES): COc1cc2ncnc(Nc3ccc(NC(=O)c4cc(F)ccc4Br)cc3)c2cc1OC
InChIKey: PJKGPBSHZZQRHV-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR2 (unknown origin) by caliper mobility shift assay
Measurement: IC50 = 360 nM (pChEMBL 6.440000057220459)
Descriptors: MW 497.32, ALogP 5.54, HBA 6, HBD 2, PSA 85.37, QED 0.36
Compound (SMILES): Fc1ccc(Nc2ccc(F)c3[nH]ccc23)cc1Cl
InChIKey: KVNBHMGFSQZVIA-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of recombinant human IDO1 assessed as reduction in kynurenine formation using L-tryptophan as substrate incubated for 45 mins by microplate reader assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 278.69, ALogP 4.84, HBA 1, HBD 2, PSA 27.82, QED 0.69
Compound (SMILES): Cc1nc(N)ccc1-c1nc(Oc2ccc(C(=O)N(C)C)cc2)nc(N2CCOCC2)n1
InChIKey: RWSVVVRTFFBYDT-UHFFFAOYSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P42336
Assay: Inhibition of recombinant human full-length N-terminal His-tagged p110 alpha/p85 alpha expressed in baculovirus expression system using PIP2 as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by ADP HiLyte 647 tracer bound ADP2 antibody-Tb conjugate based HTRF assay
Measurement: IC50 = 3400 nM (pChEMBL 5.46999979019165)
Descriptors: MW 435.49, ALogP 2.15, HBA 9, HBD 1, PSA 119.59, QED 0.64
Compound (SMILES): COC(=O)c1cnc(Nc2cnc(C#N)cn2)cc1NC[C@H]1C[C@H]2CC[C@@H](C1)N2C
InChIKey: LCQNQQKHTBVCCY-RBVVOMGSSA-N
Target: Serine/threonine-protein kinase Chk1 (SINGLE PROTEIN), Homo sapiens
UniProt: O14757
Assay: Inhibition of CHK1 (unknown origin) using 5-FAM-KKKVSRSGLYRSPSMPENLNRPR-COOH peptide as substrate incubated for 1 hr in presence of ATP by caliper microfluidic assay
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 407.48, ALogP 2.56, HBA 9, HBD 2, PSA 116.06, QED 0.7
Compound (SMILES): CC(C)Nc1c(C(=O)NC[C@@H](F)C(C)(C)O)cnc2sc(-c3ccncc3)cc12
InChIKey: MJJCLSMARNVULZ-QGZVFWFLSA-N
Target: Interleukin-1 receptor-associated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWZ3
Assay: Inhibition of IRAK4 (unknown origin) using IPTSPITTTYFFFKKK peptide as substrate in presence of ATP measured after 60 mins by fluorescence assay
Measurement: IC50 = 4.8 nM (pChEMBL 8.319999694824219)
Descriptors: MW 416.52, ALogP 4.02, HBA 6, HBD 3, PSA 87.14, QED 0.54
Compound (SMILES): COc1ccc(CC(=O)NC(=N)N[C@H](CC2CCCCC2)C(=O)Nc2cc(S(=O)(=O)N3CCN(C)CC3)ccc2C)cc1OC.O=C(O)C(F)(F)F
InChIKey: YJJBPYJOVYTRIF-HZPIKELBSA-N
Target: Cathepsin D (SINGLE PROTEIN), Homo sapiens
UniProt: P07339
Assay: Inhibition of human liver Cathepsin D preincubated for 10 mins followed by substrate addition and further incubated for 2 hrs in dark by fluorimetric analysis
Measurement: IC50 = 86 nM (pChEMBL 7.070000171661377)
Descriptors: MW 642.82, ALogP 3.11, HBA 8, HBD 4, PSA 153.16, QED 0.22
Compound (SMILES): O=C(c1cnc(-c2ccccc2)s1)N1CCC[C@H]1c1ccncc1
InChIKey: HMKNOEAHTULQFA-INIZCTEOSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Displacement of [3H]-SB67404 from human orexin 1 receptor expressed in CHO cells incubated for 2 hrs by whole cell radioligand binding assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 335.43, ALogP 4.18, HBA 4, HBD 0, PSA 46.09, QED 0.72
Compound (SMILES): Clc1ccc(-c2nnc(N3CCN(c4ccccn4)CC3)o2)cc1
InChIKey: KBIVDYZJPVDUPZ-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of human BACE-1 using MOCA-SEV-NL-DAEFR-DNP-RR as substrate preincubated with substrate followed by enzyme addition by FRET assay
Measurement: IC50 = 1320 nM (pChEMBL 5.880000114440918)
Descriptors: MW 341.8, ALogP 3.11, HBA 6, HBD 0, PSA 58.29, QED 0.73
Compound (SMILES): O=C(NCc1cn(-c2ccc(O)cc2)nn1)c1cccs1
InChIKey: FRXCOZAODVHXTM-UHFFFAOYSA-N
Target: Macrophage migration inhibitory factor (SINGLE PROTEIN), Homo sapiens
UniProt: P14174
Assay: Inhibition of C-terminal His-tagged recombinant human MIF tautomerase activity expressed in Escherichia coli BL21 using 4-hydroxyphenyl pyruvic acid as substrate preincubated for 15 mins followed by substrate addition and measured for 10 mins in presence of 0.5 mM EDTA by UV absorbance analysis
Measurement: IC50 = 41000 nM (pChEMBL 4.389999866485596)
Descriptors: MW 300.34, ALogP 1.96, HBA 6, HBD 2, PSA 80.04, QED 0.77