lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1ccc(OC(=O)CC(=O)O[C@H]2[C@@H](O)[C@@H](CO)O[C@@H](OC)[C@@H]2O)cc1
InChIKey: OOVCCQDADMNHJY-GNXUOLQESA-N
Target: Galectin-8 (SINGLE PROTEIN), Homo sapiens
UniProt: O00214
Assay: Binding affinity to N-terminal domain of human galectin-8 (8-154 residues) by ITC assay
Measurement: Kd = 9470 nM (pChEMBL 5.019999980926514)
Descriptors: MW 386.35, ALogP -1.01, HBA 10, HBD 3, PSA 140.98, QED 0.3
Compound (SMILES): O=C(CCCCC1CCSS1)OC1CCN(Cc2ccc(F)cc2)CC1
InChIKey: DUNPPMPHSGLFIA-UHFFFAOYSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Cavia porcellus
UniProt: Q60492
Assay: Displacement of [3H]-(+)-pentazocine from sigma1 receptor in guinea pig brain membrane incubated for 150 mins by liquid scintillation counting method
Measurement: Ki = 4.1 nM (pChEMBL 8.390000343322754)
Descriptors: MW 397.58, ALogP 5.05, HBA 5, HBD 0, PSA 29.54, QED 0.35
Compound (SMILES): CC1(Oc2ccc3[nH]nc(-c4cc(N5CCN(C(=O)CCOCCOCCNc6cccc7c6C(=O)N(C6CCC(=O)NC6=O)C7)CC5)ncn4)c3c2)CC1
InChIKey: SOIJLRBEKLCOTC-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of recombinant human GST-tagged LRRK2 (970 to 2527 residues) expressed in insect cells using LRRKtide as substrate measured after 1 hr by Adapta TR-FRET assay
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 751.85, ALogP 2.9, HBA 12, HBD 3, PSA 184.21, QED 0.12
Compound (SMILES): CN1CCc2ccc(OCCCN3CCN(c4ccc(Cl)cc4)CC3)cc2C1=O
InChIKey: OFNWXXGHORGIMJ-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P61169
Assay: Displacement of [3H]spiperone from D2 receptor in rat striatum measured after 15 mins by liquid scintillation counting method
Measurement: Ki = 268.3 nM (pChEMBL 6.570000171661377)
Descriptors: MW 413.95, ALogP 3.56, HBA 4, HBD 0, PSA 36.02, QED 0.68
Compound (SMILES): O=C1NCc2cc(N(Cc3ccc(C4CCCCC4)cn3)C(=O)[C@H]3CCN3S(=O)(=O)c3c(F)c(F)c(F)c(F)c3F)ccc21
InChIKey: GMWIWXLYVRJLPF-JOCHJYFZSA-N
Target: Signal transducer and activator of transcription 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P40763
Assay: Inhibition of oligonucleotide [32P]-labelled 5'-AGCITCATTTCCCGTAAATCCCTA probe binding to STAT3 SH2 domain (unknown origin) preincubated for 30 mins followed by hSIE probe addition by EMSA analysis
Measurement: IC50 = 640 nM (pChEMBL 6.190000057220459)
Descriptors: MW 634.63, ALogP 5.06, HBA 5, HBD 1, PSA 99.68, QED 0.22
Compound (SMILES): Nc1nccn2c([C@@H]3CC[C@H]4COC(=O)N4C3)nc(-c3ccc(C(=O)Nc4cc(C(F)(F)F)ccn4)cc3)c12
InChIKey: CDISOBGWDHAHGF-AEFFLSMTSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of recombinant full length BTK (unknown origin) expressed in baculovirus infected Sf9 cells using Biotin-EQEDEPEGDYFEWLE-NH2 peptide as substrate incubated for 60 mins followed by further incubation with substrate and ATP for 120 mins by TR-FRET assay
Measurement: IC50 = 0.083 nM (pChEMBL 10.079999923706055)
Descriptors: MW 537.5, ALogP 4.34, HBA 8, HBD 2, PSA 127.74, QED 0.4
Compound (SMILES): CC(C)C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1c[nH]cn1)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N1[C@H](C(=O)N[C@@H](Cc2ccc(I)cc2)C(=O)N2CCC[C@H]2C(=O)N[C@H](Cc2ccc(-c3ccccc3)cc2)C(=O)O)C[C@@H]2CCCC[C@@H]21)N(C)C(=O)[C@@H](CCCNC(=N)N)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCCNC(=N)N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](CCCNC(=N)N)NC(=O)[C@H](CCCCNC(=N)N)NC(=O)COCCOCCNC(=O)COCCOCCNC(=O)CC[C@H](NC(=O)CCCCCCC(=O)O)C(=O)O
InChIKey: AQYIHVPCLRNABA-MUZFVGERSA-N
Target: Apelin receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9JHG3
Assay: Agonist activity at rat APJ receptor stably expressed in CHO cell membranes in presence of [35S]GTPgammaS by scintillation proximity assay
Measurement: EC50 = 2.61 nM (pChEMBL 8.579999923706055)
Descriptors: MW 2752.99
Compound (SMILES): COC(=O)N(CC(C)(C)N)C1(c2ccc(F)c(C(F)(F)F)c2)CC1
InChIKey: WIAUIJHTIFNYNU-UHFFFAOYSA-N
Target: Intermediate conductance calcium-activated potassium channel protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O15554
Assay: Inhibition of Kca3.1 in human erythrocytes
Measurement: IC50 = 8.6 nM (pChEMBL 8.069999694824219)
Descriptors: MW 348.34, ALogP 3.64, HBA 3, HBD 1, PSA 55.56, QED 0.85
Compound (SMILES): CC(=O)N1CCC[C@@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](Cc1ccccc1)B(O)O
InChIKey: UQRLJTJWBLQQJM-MAZHCROVSA-N
Target: Proteasome component C5 (SINGLE PROTEIN), Homo sapiens
UniProt: P20618
Assay: Inhibition of human 20S constitutive proteasome beta 1 subunit caspase-like activity using fluorogenic peptide Ac-nLPnLD-AMC as substrate in presence of PA28alpha incubated for 1 to 2 hrs by fluorescence microplate reader assay
Measurement: IC50 = 3400 nM (pChEMBL 5.46999979019165)
Descriptors: MW 375.23
Compound (SMILES): O=C(c1nn(-c2ccccc2)c2c1CC(NCCc1ncc[nH]1)CC2)N1CCCCC1
InChIKey: YZVOURSTUXWJQT-UHFFFAOYSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99720
Assay: Binding affinity to sigma 1 receptor (unknown origin)
Measurement: Ki = 1000 nM (pChEMBL 6)
Descriptors: MW 418.55, ALogP 2.91, HBA 5, HBD 2, PSA 78.84, QED 0.65
Compound (SMILES): CCS(=O)(=O)c1ccc(CNc2nc3cnc(-c4cncnc4C(C)C)nc3n(C(C)C)c2=O)nc1
InChIKey: SOJVINDXUAZELV-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Antagonist activity at RORgamma in human whole blood derived CD4-positive T cells assessed as inhibition of IL-17 secretion from differentiated Th17 cells preincubated for 1 hr and measured after 48 hrs
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 508.61, ALogP 3.15, HBA 11, HBD 1, PSA 145.51, QED 0.38
Compound (SMILES): N#Cc1cnc2c(OC3CCC3)cccc2c1N1CCN(c2ccccc2F)CC1
InChIKey: WEJWXNRDXFQKDR-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P35400
Assay: Positive allosteric modulation of rat mGlu7 receptor expressed in HEK293 cells co-expressing Gai5 assessed as potentiation of L-AP4-induced calcium mobilization preincubated for 140 secs and treated with EC20 L-AP4 for 125 secs and followed by subsequent addition of EC80 L-AP4 by Fluo-4-AM dye based fluorescence assay
Measurement: EC50 = 1800 nM (pChEMBL 5.75)
Descriptors: MW 402.47, ALogP 4.5, HBA 5, HBD 0, PSA 52.39, QED 0.64
Compound (SMILES): COc1cc(-c2cnn3cc(OC)c([C@@H]4COC(C)(C)C4)nc23)ccn1
InChIKey: PETJVBHONPBYQW-ZDUSSCGKSA-N
Target: TGF-beta receptor type-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P37173
Assay: Inhibition of TGFbeta receptor 2 (unknown origin) using biotin-labelled TTLKDLIYDMTTSGSGSGLPLLVQRTIARTsubstrate in presence of [gamma33P] ATP measured after 50 min
Measurement: IC50 = 3.6 nM (pChEMBL 8.4399995803833)
Descriptors: MW 354.41, ALogP 3.09, HBA 7, HBD 0, PSA 70.77, QED 0.72
Compound (SMILES): CN(C)CCNCc1cc(-c2cc3c(N[C@H](CO)c4ccccc4)ncnc3[nH]2)ccc1F
InChIKey: LSKMQVVNBHCIOJ-HSZRJFAPSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of human EGFR using poly[Glu:Tyr] (4:1) as substrate in presence of [gamma33P]ATP by radiometric HotSpot assay
Measurement: IC50 = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 448.55, ALogP 3.56, HBA 6, HBD 4, PSA 89.1, QED 0.28
Compound (SMILES): CCCCCn1c(-c2ccco2)nc2c(NCc3ccccc3)nccc21
InChIKey: AIQFHNQYZNRWNO-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4B (SINGLE PROTEIN), Homo sapiens
UniProt: Q07343
Assay: Inhibition of human recombinant PDE4B using cAMP as substrate incubated for 20 mins measured by Kinase Glo reagent based microplate reader assay
Measurement: IC50 = 8340 nM (pChEMBL 5.079999923706055)
Descriptors: MW 360.46, ALogP 5.49, HBA 5, HBD 1, PSA 55.88, QED 0.42
Compound (SMILES): CNC(=O)c1cnc2ccccc2c1Nc1ccc(Cl)cc1F
InChIKey: LGOWINSNBQYCTH-UHFFFAOYSA-N
Target: Oxidized purine nucleoside triphosphate hydrolase (SINGLE PROTEIN), Homo sapiens
UniProt: P36639
Assay: Inhibition of MTH1 (unknown origin) using 8-oxo-dGTP as substrate preincubated for 15 mins followed by substrate addition and measured after 20 mins by PPiLight detection reagent based luminescence assay
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 329.76, ALogP 4.13, HBA 3, HBD 2, PSA 54.02, QED 0.76
Compound (SMILES): CC[C@@H]1c2nncn2-c2cnc(Nc3ccc(C(=O)NC4CCN(C)CC4)cc3OC)nc2N1Cc1cccc(Br)c1
InChIKey: FBMMHPFJCKVOQE-XMMPIXPASA-N
Target: Serine/threonine-protein kinase PLK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53350
Assay: Inhibition of full length human PLK1 using casein as substrate incubated for 40 mins in presence of [gamma-33P]-ATP by radiometric assay
Measurement: IC50 = 2764 nM (pChEMBL 5.559999942779541)
Descriptors: MW 632.57, ALogP 4.87, HBA 10, HBD 2, PSA 113.33, QED 0.28
Compound (SMILES): C#Cc1cc(C(=O)N2CS(=O)(=O)c3ccccc32)cc(C#N)c1O
InChIKey: OGCQMWGDTFSQEL-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 = 3200 nM (pChEMBL 5.5)
Descriptors: MW 338.34, ALogP 1.64, HBA 5, HBD 1, PSA 98.47, QED 0.8
Compound (SMILES): COc1cc2c(cc1O)CCC(C)(CC(=O)NCCCCCCNc1c3c(nc4ccccc14)CCCC3)O2
InChIKey: LXSUQNNLNNUDLZ-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of recombinant human AChE expressed in HEK293 cells using acetylthiocholine iodide as substrate preincubated for 15 mins followed by substrate addition by Ellman's method
Measurement: IC50 = 275 nM (pChEMBL 6.559999942779541)
Descriptors: MW 531.7, ALogP 6.09, HBA 6, HBD 3, PSA 92.71, QED 0.26
Compound (SMILES): Nc1ncc(-c2ccc(C(=O)O)cc2)cc1-c1ccccc1Cl
InChIKey: VOBHPWNSDZXBME-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O95819
Assay: Inhibition of recombinant human GST-tagged MAP4K4 catalytic domain (1 to 328 residues) expressed in baculovirus expression system pre-incubated for 30 mins before Ser/Thr 07 peptide substrate and 10 uM ATP addition and further incubated for 90 mins by Z'-lyte assay
Measurement: IC50 = 62 nM (pChEMBL 7.210000038146973)
Descriptors: MW 324.77, ALogP 4.35, HBA 3, HBD 2, PSA 76.21, QED 0.75
Compound (SMILES): O=C(Nc1ccc(C(F)(F)F)cc1)NC1CCN(C(=O)c2cc[nH]c2)CC1
InChIKey: GKESASBPGZTTKO-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 = 0.5 nM (pChEMBL 9.300000190734863)
Descriptors: MW 380.37, ALogP 3.46, HBA 2, HBD 3, PSA 77.23, QED 0.76
Compound (SMILES): CC(C)(C)c1ccc(Oc2cccc(CN3C[C@@H]4CN(C(=O)Nc5noc6ccccc56)C[C@@H]4C3)c2)cc1
InChIKey: CCBPOOBJSFOZSY-ZRZAMGCNSA-N
Target: Fatty-acid amide hydrolase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O00519
Assay: Inhibition of human FAAH1 incubated for 60 mins
Measurement: IC50 = 6000 nM (pChEMBL 5.21999979019165)
Descriptors: MW 510.64, ALogP 6.51, HBA 5, HBD 1, PSA 70.84, QED 0.33
Compound (SMILES): CCCNC(=O)/C(Cc1ccc(O)c(Br)c1)=N/O
InChIKey: IEQGHCGFXBYYRQ-XNTDXEJSSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombinant full length C-terminal FLAG-tagged human HDAC6 expressed in baculovirus infected Sf9 cells using Boc-Lys(Ac)-AMC as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by fluorescence based assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 315.17, ALogP 2.05, HBA 4, HBD 3, PSA 81.92, QED 0.44
Compound (SMILES): Nc1c(C(=O)NCc2ccc(C(=O)N[C@@H](CCC3CCCCC3)C(=O)NC3CCCCC3)cc2)cnn1-c1ccccc1
InChIKey: PKDCKOQKRFFVGE-PMERELPUSA-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 = 47 nM (pChEMBL 7.329999923706055)
Descriptors: MW 584.77, ALogP 5.29, HBA 6, HBD 4, PSA 131.14, QED 0.24
Compound (SMILES): O=C(N[C@@H]1Cc2ccc3[nH]ncc3c2CN(CCc2ccncc2)C1=O)N1CCC(N2Cc3ccccc3NC2=O)CC1
InChIKey: LKAJWQGUTMRDRV-GDLZYMKVSA-N
Target: Calcitonin gene-related peptide type 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16602
Assay: Antagonist activity at human CGRP receptor
Measurement: Ki = 7.1 nM (pChEMBL 8.149999618530273)
Descriptors: MW 578.68, ALogP 3.68, HBA 5, HBD 3, PSA 126.56, QED 0.33
Compound (SMILES): O=[N+]([O-])c1ccccc1Nc1cc(N2CCNCC2)nc2ccnn12
InChIKey: NVTRFTNYSREHBG-UHFFFAOYSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Inhibition of DPP4 in human Caco-2 cells using AP-AFC as substrate preincubated with enzyme for 10 mins followed by substrate addition and measured after 10 mins by fluorescence based analysis
Measurement: IC50 = 3500 nM (pChEMBL 5.460000038146973)
Descriptors: MW 339.36, ALogP 1.79, HBA 8, HBD 2, PSA 100.63, QED 0.55
Compound (SMILES): O=C1NN=C2CN(C(=O)[C@@H]3CCCN3)Cc3[nH]c4cc(F)cc1c4c32
InChIKey: VGJWFKZVPZAJAX-JTQLQIEISA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Inhibition of PARP-1 in human HeLa cells incubated for 18 hrs in presence of H2O2
Measurement: EC50 = 11.7 nM (pChEMBL 7.929999828338623)
Descriptors: MW 341.35, ALogP 0.85, HBA 4, HBD 3, PSA 89.59, QED 0.72
Compound (SMILES): Cc1cccc(C(=O)n2cc(C#N)c3ccncc32)c1
InChIKey: GKEQKZSOHBBKEV-UHFFFAOYSA-N
Target: Neutrophil elastase (SINGLE PROTEIN), Homo sapiens
UniProt: P08246
Assay: Inhibition of human neutrophil elastase using N-methylsuccinyl-Ala-Ala-Pro-Val-7-amino-4-methylcoumarin as substrate measured for every 30 sec for 10 mins by fluorescence based assay
Measurement: IC50 = 194 nM (pChEMBL 6.710000038146973)
Descriptors: MW 261.28, ALogP 2.9, HBA 4, HBD 0, PSA 58.68, QED 0.68
Compound (SMILES): Cc1ccc(NC(=O)c2ccc(F)cc2)cc1-n1cc(-c2cnc3ccnn3c2)cn1
InChIKey: YPEBEBBSFDWQHW-UHFFFAOYSA-N
Target: Bcr/Abl fusion protein (CHIMERIC PROTEIN), Homo sapiens
UniProt: P11274
Assay: Inhibition of BCR (unknown origin)/recombinant human N-terminal His-tagged ABL1 (27 to end residues) expressed in baculovirus infected Sf9 cells using ABLtide as substrate preincubated for 30 mins followed by substrate addition and measured after 1 hr in presence of ATP by kinase-Glo luminescence assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 412.43, ALogP 4.28, HBA 6, HBD 1, PSA 77.11, QED 0.48
Compound (SMILES): CC(C)C(=O)N1CCC(NC(=O)Nc2ccc(C(F)(F)F)c(F)c2)CC1
InChIKey: MUXBEWJOYODXBO-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 = 0.49 nM (pChEMBL 9.3100004196167)
Descriptors: MW 375.37, ALogP 3.61, HBA 2, HBD 2, PSA 61.44, QED 0.79
Compound (SMILES): Cc1cc(/C=C2\SC(=O)NC2=O)c(C)n1-c1ccc(C(C)(C)C)cc1
InChIKey: FOONSDURONQDMT-BOPFTXTBSA-N
Target: Bile acid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RI1
Assay: Agonist activity at human FXR-LBD transfected in human HEK293T cells co-expressing pFR-Luc/pRL incubated for 14 to 16 hrs by hybrid reporter gene assay
Measurement: EC50 = 2600 nM (pChEMBL 5.579999923706055)
Descriptors: MW 354.48, ALogP 4.72, HBA 4, HBD 1, PSA 51.1, QED 0.79
Compound (SMILES): Cc1cccc(-c2ccc(-c3coc(C)n3)cc2)c1
InChIKey: ZNEOGDARPLRNJL-UHFFFAOYSA-N
Target: Ectonucleotide pyrophosphatase/phosphodiesterase family member 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O14638
Assay: Inhibition of human recombinant NPP3 expressed in COS-7 cell membrane at 100 uM using p-nitrophenyl thymidine monophosphate substrate incubated for 35 mins by spectrophotometric analysis
Measurement: IC50 = 1700 nM (pChEMBL 5.769999980926514)
Descriptors: MW 249.31, ALogP 4.63, HBA 2, HBD 0, PSA 26.03, QED 0.66
Compound (SMILES): CC[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(=N)N)NC(C)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(N)=O)[C@@H](C)O
InChIKey: RXQXHVWOHBMNRY-OFWPZXCBSA-N
Target: Furin (SINGLE PROTEIN), Homo sapiens
UniProt: P09958
Assay: Inhibition of recombinant soluble human furin using pyroGlu-Arg-Thr-Lys-Arg-methyl-coumaryl-7-amide as substrate measured after 1 hr
Measurement: Ki = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 1197.46
Compound (SMILES): N=C(N)Nc1cc(NC(=O)CCNC(=O)C23CC4CC(CC(C4)C2)C3)cc(C(=O)NCC(=O)NC[C@H](NC(=O)[C@@H]2CCCN2S(=O)(=O)c2ccccc2)C(=O)O)c1
InChIKey: SAFQBUKUEAMDGO-GAQHEQIDSA-N
Target: Integrin alpha-5/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P05556
Assay: Inhibition of alpha5beta1 integrin (unknown origin) by solid phase binding assay
Measurement: IC50 = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 807.93, ALogP 0.92, HBA 9, HBD 9, PSA 282.08, QED 0.08
Compound (SMILES): C[C@@H](OCc1ccccc1)[C@@H](C#N)NC(=O)[C@H](Cc1cccc(Br)c1)NC(=O)c1ccc(-c2cccnc2)cc1
InChIKey: FSMMLXYBGWEIQQ-ZDERHKTGSA-N
Target: Cathepsin B (SINGLE PROTEIN), Homo sapiens
UniProt: P07858
Assay: Inhibition of human cathepsin B using Z-Phe-Arg-AMC fluorogenic peptide as substrate preincubated for 2 mins followed by substrate addition and measured for 5 mins by fluorescence assay
Measurement: Ki = 12.59 nM (pChEMBL 7.900000095367432)
Descriptors: MW 597.51, ALogP 5.47, HBA 5, HBD 2, PSA 104.11, QED 0.24
Compound (SMILES): CCc1ccnc(NC(=O)Cc2ccc3ccccc3c2)c1
InChIKey: GPAGARLGXJGAMW-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase RIO2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BVS4
Assay: Displacement of tracer K5 from N-terminal nanoluciferase-tagged RIOK2 (unknown origin) expressed in HEK293 cells measured after 2 hrs by NanoBRET assay
Measurement: IC50 = 14500 nM (pChEMBL 4.840000152587891)
Descriptors: MW 290.37, ALogP 3.98, HBA 2, HBD 1, PSA 41.99, QED 0.79
Compound (SMILES): CC#CCn1c(N2CCC[C@@H](N)C2)nc2c1c(=O)n(CCCN1CCN(c3ncc(F)cn3)CC1)c(=O)n2C
InChIKey: WSFJNADMSLWRJC-HXUWFJFHSA-N
Target: Dipeptidyl peptidase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P27487
Assay: Inhibition of DPP4 (unknown origin) using Gly-Pro-p-nitroanilide as substrate incubated for 1 hr
Measurement: IC50 = 350 nM (pChEMBL 6.460000038146973)
Descriptors: MW 538.63, ALogP -0.01, HBA 12, HBD 1, PSA 123.34, QED 0.41
Compound (SMILES): COc1ccc(OC)c2c1c(OC)cc1c(=O)cc(-c3ccc(F)cn3)oc12
InChIKey: XSYRPTQXBMWIDY-UHFFFAOYSA-N
Target: Cytochrome P450 1B1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16678
Assay: Inhibition of recombinant human CYP1B1 using 7-ethoxyresorufin as substrate after 35 mins in presence of NADP+ by EROD assay
Measurement: IC50 = 0.07 nM (pChEMBL 10.149999618530273)
Descriptors: MW 381.36, ALogP 4.17, HBA 6, HBD 0, PSA 70.79, QED 0.49
Compound (SMILES): CN(CCc1ccccc1)c1nc(C(=O)NCC2CC2)cc(N2CCC(c3ccccc3)C2)n1
InChIKey: SPEQXVXIKZIVMW-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 = 1412.54 nM (pChEMBL 5.849999904632568)
Descriptors: MW 455.61, ALogP 4.29, HBA 5, HBD 1, PSA 61.36, QED 0.52
Compound (SMILES): Cc1cccc(Cc2nc3cc(O[C@H]4CC[C@@H](c5nnn[nH]5)CC4)ccc3n2C)c1
InChIKey: CIRKBUPKWHTTOT-HDICACEKSA-N
Target: Long-chain-fatty-acid--CoA ligase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P41216
Assay: Inhibition of recombinant mouse ACSL1 assessed as reduction in acetyl-coA prodution incubated for 90 mins in presence of Coenzyme A, ATP and MgCl2 by MALDI-TOF MS analysis
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 402.5, ALogP 4.09, HBA 6, HBD 1, PSA 81.51, QED 0.54
Compound (SMILES): COc1ccc(CCNC(=O)[C@@H]2CCCN2C(=O)NCc2cccc3ccccc23)cc1
InChIKey: HMNBKWNEJGMBRQ-DEOSSOPVSA-N
Target: Complement factor D (SINGLE PROTEIN), Homo sapiens
UniProt: P00746
Assay: Inhibition of recombinant human CFD catalytic domain (G24 to A253 residues) expressed in Escherichia coli (Rosetta) using Z-Lys-thiobenzyl and 2,4-dinitrobenzenesulfonyl-2,7-desmethyl-fluorecein as substrate preincubated for 1 hr followed by substrate addition by spectrofluorimetric method
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 431.54, ALogP 3.88, HBA 3, HBD 2, PSA 70.67, QED 0.6
Compound (SMILES): Nc1ncc(-c2nc(N3CCOCC3)nc(N3[C@@H]4CC[C@H]3COC4)n2)c(C(F)F)n1
InChIKey: YMPHJTSPBGJDAR-PHIMTYICSA-N
Target: mTORC2 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9BPZ7
Assay: Inhibition of mTORC2 in human A2058 cells assessed as reduction in PKB phosphorylation at S473 residue incubated for 1 hr by Western blot analysis
Measurement: IC50 = 73 nM (pChEMBL 7.139999866485596)
Descriptors: MW 420.42, ALogP 1.05, HBA 10, HBD 1, PSA 115.41, QED 0.77
Compound (SMILES): Nc1ncc(-c2cnc(C3CCNCC3)s2)cc1OCc1ccncc1
InChIKey: HSEGDFMLRPWOHH-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8IVH8
Assay: Inhibition of GLK in human T cells assessed as reduction in PKCtheta phosphorylation by Western blot analysis
Measurement: IC50 = 434 nM (pChEMBL 6.360000133514404)
Descriptors: MW 367.48, ALogP 3.23, HBA 7, HBD 2, PSA 85.95, QED 0.72
Compound (SMILES): CCn1cc(C(=O)O)c2ccc(N3CCC(F)(COCc4c(-c5ccccc5OC(F)(F)F)noc4C4CC4)CC3)cc21
InChIKey: QKDNZMUZQVJEEZ-UHFFFAOYSA-N
Target: Bile acid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RI1
Assay: Agonist activity at GST-tagged human FXR LBD assessed as induction of biotinylated coactivator SRC-1 peptide recruitment measured after 2 hrs by streptavidin-conjugated AlphaScreen assay
Measurement: EC50 = 1110 nM (pChEMBL 5.960000038146973)
Descriptors: MW 601.6, ALogP 7.32, HBA 7, HBD 1, PSA 89.96, QED 0.19
Compound (SMILES): Cc1n[nH]c2ccc(-c3cncc(OC[C@@H]4Cc5ccccc5CN4)n3)cc12
InChIKey: PHFMDTXEQGTCLR-SFHVURJKSA-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 = 56 nM (pChEMBL 7.25)
Descriptors: MW 371.44, ALogP 3.42, HBA 5, HBD 2, PSA 75.72, QED 0.57
Compound (SMILES): O=C(c1ccccc1)N(CCCN1CCC(c2noc3cc(F)ccc23)CC1)C1COC1
InChIKey: OZGHVKYGFAYUBW-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Antagonist activity at human D2 receptor expressed in HEK293 cells incubated for 60 mins by Eu-cAMP tracer based LANCE ultra cAMP assay
Measurement: IC50 = 156 nM (pChEMBL 6.809999942779541)
Descriptors: MW 437.52, ALogP 4.08, HBA 5, HBD 0, PSA 58.81, QED 0.56
Compound (SMILES): O=C(NO)c1ccc(CCCN2CCC(CN[C@H]3C[C@@H]3c3ccccc3)CC2)cc1
InChIKey: HACUHRDPZRXYSI-RPWUZVMVSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Inhibition of LSD1 (unknown origin)
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 407.56, ALogP 3.6, HBA 4, HBD 3, PSA 64.6, QED 0.44
Compound (SMILES): Nc1nc(-c2ccccn2)nn1C(=O)c1ccc(NC(=O)C(F)(F)F)cc1
InChIKey: AOFAPBZPGRSCAZ-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 376.3, ALogP 2.11, HBA 7, HBD 2, PSA 115.79, QED 0.72
Compound (SMILES): Cc1ccc(Oc2cc(C)c3nc(COc4cccc(C(=O)O)c4)n(C)c3c2)c(C)n1
InChIKey: UILRJZSMSDGETI-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q07869
Assay: Agonist activity at human Gal4 fused PPARalpha LBD (unknown origin) expressed in COS-7 cells incubated for 24 hrs by firefly luciferase assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 417.47, ALogP 4.96, HBA 6, HBD 1, PSA 86.47, QED 0.48
Compound (SMILES): COC[C@]12C[C@H]1[C@@](CF)(c1cc(/C=C(/F)c3ccc(Cl)cn3)ccc1F)N=C(N)S2
InChIKey: DGFXDPYXKFNNAW-VDTLHJFLSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: In Vitro Enzymatic BACE1 and BACE2 FRET (Fluorescence Resonance Energy Transfer) Assays: The cDNAs for both human recombinant BACE1 and 2 with C-terminal 6-His Tags were cloned into transient protein expression vectors, which were subsequently transfected into mammalian cell lines. These recombinant proteins were further purified using Ni-NTA affinity chromatography (Qiagen). The assay buffer used in these screens was 0.05M acetate, pH 4.5, 8% DMSO final, 100 uM genapol (which is a nonionic detergent, below its Critical Micelle Concentration). The Beta Secretase enzyme (0.02 nM for BACE1 and 0.64 nM for BACE2) is pre-incubated for one hour with inhibitors, typically in about 1 uL of DMSO according to a serial dilution, are added thereto. This assay is effectively started by the addition of FRET substrate (50 nM) and the combination is incubated for one hour. The FRET assay is terminated by addition of Tris buffer, which raises the pH to neutrality, and the fluorescence is determined. The FRET substrate is a peptide with commercially available fluorophore and quencher, on opposite sides of the BACE cleavage site. Proteolytic cleavage of the FRET substrate releases quenching of fluorescence (excitation 488 nm and emission 590 nm).
Measurement: IC50 = 303 nM (pChEMBL 6.519999980926514)
Descriptors: MW 453.92, ALogP 4.97, HBA 5, HBD 1, PSA 60.5, QED 0.67
Compound (SMILES): CC(C)c1cc(Oc2c(Cl)cc(NC(=O)Cc3cccnc3)cc2Cl)ccc1F
InChIKey: YMBZMCCODMVJQN-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Agonist activity at Gal4-fused RORgammat (unknown origin) expressed in Jurkat cells by reporter assay
Measurement: EC50 = 212 nM (pChEMBL 6.670000076293945)
Descriptors: MW 433.31, ALogP 6.62, HBA 3, HBD 1, PSA 51.22, QED 0.48
Compound (SMILES): COc1cc(OC)cc(Sc2c[nH]c3ccc(Cl)cc23)c1
InChIKey: HJNFDKXNCYNJAV-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of human IDO1 incubated for 60 mins in presence of L-tryptophan by HPLC analysis
Measurement: IC50 = 7000 nM (pChEMBL 5.159999847412109)
Descriptors: MW 319.81, ALogP 4.99, HBA 3, HBD 1, PSA 34.25, QED 0.74
Compound (SMILES): CCC(CC)O[C@@H]1C=C(C(=O)O)C[C@H](NCc2ccc(Oc3cccc(C)c3)cc2)[C@H]1NC(C)=O
InChIKey: DMNZXNCLBMPOCA-OYUWMTPXSA-N
Target: Neuraminidase (SINGLE PROTEIN), Influenza A virus
UniProt: Q2LFS1
Assay: Inhibition of Influenza A virus (A/Anhui/1/2005(H5N1)) neuraminidase H274Y mutant using 4-MU-NANA as substrate preincubated for 5 mins followed by substrate addition and measured after 30 to 60 mins by fluorescence assay
Measurement: IC50 = 3560 nM (pChEMBL 5.449999809265137)
Descriptors: MW 480.61, ALogP 4.74, HBA 5, HBD 3, PSA 96.89, QED 0.43
Compound (SMILES): CC(C)(C)c1cc(NC(=O)Nc2ccc3c(c2)sc2nc(-c4ccc(OCCN5CCOCC5)cc4)cn23)on1
InChIKey: HZGCJNAPGVXKIZ-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 ITD mutant (unknown origin)
Measurement: IC50 = 6.83 nM (pChEMBL 8.170000076293945)
Descriptors: MW 560.68, ALogP 5.86, HBA 9, HBD 2, PSA 106.16, QED 0.26
Compound (SMILES): COc1cc(N2CCC(N3CCN(C)CC3)CC2)ccc1Nc1ncc2c(n1)N(C)c1sc(C)nc1C(=O)N2
InChIKey: BLCXBPBZTTWEPM-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: Inhibition of Focal adhesion kinase (unknown origin) using Tyr 07 peptide substrate incubated for 60 mins at room temperature followed by 60 mins development reaction measured fluorescence by Z-LYTE assay
Measurement: IC50 = 62.2 nM (pChEMBL 7.210000038146973)
Descriptors: MW 549.71, ALogP 3.54, HBA 11, HBD 2, PSA 101.99, QED 0.49
Compound (SMILES): COc1cc2nccc(Oc3ccc(NC(=O)C(OC(=O)c4ccccc4)C4CCCCC4)cc3F)c2cc1OC
InChIKey: ZJRPGBQJANNIEO-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of c-MET (unknown origin) using poly (Glu, Tyr) 4:1 as substrate measured after 30 mins by HTRF assay
Measurement: IC50 = 30.38 nM (pChEMBL 7.519999980926514)
Descriptors: MW 558.61, ALogP 6.93, HBA 7, HBD 1, PSA 95.98, QED 0.22
Compound (SMILES): O=C(N1CCN(Cc2nc3cc(F)ccc3n3cccc23)CC1)n1cncn1
InChIKey: LALNVBRCBCNEMZ-UHFFFAOYSA-N
Target: Fatty-acid amide hydrolase 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P97612
Assay: Inhibition of FAAH in rat brain homogenate using 2-arachidonoyl-[3H]-glycerol as substrate by scintillation counting method
Measurement: IC50 = 20.7 nM (pChEMBL 7.679999828338623)
Descriptors: MW 379.4, ALogP 2, HBA 7, HBD 0, PSA 71.56, QED 0.53
Compound (SMILES): CCN(CCNC)Cc1c(-c2cc(C)cc(C)c2)cnc2ncn(-c3cccc(O)c3)c(=O)c12
InChIKey: OVIFVLVJLJPJEZ-UHFFFAOYSA-N
Target: Somatostatin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P30874
Assay: Agonist activity at human SST2 expressed in CHOK1 cells assessed as inhibition of NKH477-stimulated intracellular cAMP levels
Measurement: EC50 = 39.81 nM (pChEMBL 7.400000095367432)
Descriptors: MW 457.58, ALogP 3.81, HBA 7, HBD 2, PSA 83.28, QED 0.42
Compound (SMILES): CCCOc1ccc([C@H](CO)NC(=O)[C@@H](C)c2ccccc2)cc1
InChIKey: WPBXYXMULDUMHW-KXBFYZLASA-N
Target: G protein-coupled receptor 88 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9GZN0
Assay: Agonist activity at GPR88 (unknown origin) expressed in CHO cells assessed as inhibition of forskolin-induced cAMP production by TR-FRET assay
Measurement: EC50 = 562.34 nM (pChEMBL 6.25)
Descriptors: MW 327.42, ALogP 3.43, HBA 3, HBD 2, PSA 58.56, QED 0.78
Compound (SMILES): CC(=O)N[C@@H]1CCC[C@H](C(=O)Nc2cc(-c3cnc4n3CC(C)(C)C4)c(Cl)cn2)C1
InChIKey: AKHNSDCQWFJNJI-LSDHHAIUSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of recombinant full length human N-terminal GST-fused CDK9 (1 to 372 residues)/His-tagged CyclinT1 (1 to 726 residues) expressed in baculovirus infected insect cells using FITC-X-GSRTPMY-NH2 as substrate preincubated for 10 mins followed by MgCl2 addition and measured after 90 mins in presence of 5 mM ATP by mobility shift assay
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 429.95, ALogP 3.81, HBA 5, HBD 2, PSA 88.91, QED 0.77
Compound (SMILES): O=C(c1ccc(Cl)cc1)C1CCN(C(=O)c2ccc(OC(F)(F)F)cc2)CC1
InChIKey: KTBBACKZIQKOQD-UHFFFAOYSA-N
Target: Monoglyceride lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q99685
Assay: Inhibition of human recombinant MAGL using 4-NPA substrate incubated for 30 mins
Measurement: IC50 = 26600 nM (pChEMBL 4.579999923706055)
Descriptors: MW 411.81, ALogP 4.97, HBA 3, HBD 0, PSA 46.61, QED 0.67
Compound (SMILES): Nc1cccc(F)c1C(=O)NCCCC[C@H](NC(=O)c1cncs1)c1ncc(-c2ccc3ccccc3c2)[nH]1
InChIKey: ZCJZGAMBGOPNSV-QHCPKHFHSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of human recombinant full length FLAG-tagged HDAC1 expressed in HEK293F cells using BML-KI104 as substrate in presence of SAHA as inhibitor preincubated for 3 hrs followed by addition of substrate measured after 30 mins by fluorescence based assay
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 542.64, ALogP 5.48, HBA 6, HBD 4, PSA 125.79, QED 0.14
Compound (SMILES): CC(O)(C#Cc1ccc2nccc(-c3cn[nH]c3)c2c1)c1ccccn1
InChIKey: YZVSHCLCVXHXOP-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99558
Assay: Inhibition of recombinant N-terminal GST-fused human NIK (319 to 947 residues) expressed in baculovirus expression system incubated for 120 mins in presence of ATP by ADP-glo based luminescence assay
Measurement: IC50 = 590.9 nM (pChEMBL 6.230000019073486)
Descriptors: MW 340.39, ALogP 3.28, HBA 4, HBD 2, PSA 74.69, QED 0.55
Compound (SMILES): Cc1ccc(C2NCCc3c2[nH]c2ccc(Cl)cc32)cc1.Cl
InChIKey: GOAHQIOTMBQKKQ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Agonist activity at human 5HT2A receptor stably expressed in Flp-In-T-REx-293 cells assessed as increase in Gq-mediated calcium flux by Fluo-4 direct dye based FLIPR Tetra assay
Measurement: EC50 = 303 nM (pChEMBL 6.519999980926514)
Descriptors: MW 296.8, ALogP 4.36, HBA 1, HBD 2, PSA 27.82, QED 0.69
Compound (SMILES): COc1cc(C(=O)N2CCc3c(-c4ccccc4)cccc32)ccc1CN1CCC[C@H]1CO
InChIKey: VFHNNTWNEQTPGV-QHCPKHFHSA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NZQ7
Assay: Inhibition of PD-1/PDL1 interaction (unknown origin) by HTRF assay
Measurement: IC50 = 619.9 nM (pChEMBL 6.210000038146973)
Descriptors: MW 442.56, ALogP 4.52, HBA 4, HBD 1, PSA 53.01, QED 0.61
Compound (SMILES): CCN1c2nc(Nc3ccc(N4CCC(N5CCN(C)CC5)CC4)cc3OC)ncc2N(C)C(=O)c2nc(C)sc21
InChIKey: GBCMBDNJISPETG-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: Inhibition of Focal adhesion kinase (unknown origin) using Tyr 07 peptide substrate incubated for 60 mins at room temperature followed by 60 mins development reaction measured fluorescence by Z-LYTE assay
Measurement: IC50 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 577.76, ALogP 3.96, HBA 11, HBD 1, PSA 93.2, QED 0.46
Compound (SMILES): CNC(=O)C1CN(S(=O)(=O)c2ccc(-c3ccccc3)cc2)CCN1S(=O)(=O)c1cccc(-c2cccnc2OC)c1
InChIKey: STLURACFLXLIHL-UHFFFAOYSA-N
Target: Falcilysin (SINGLE PROTEIN), Plasmodium falciparum (isolate 3D7)
UniProt: Q76NL8
Assay: Inhibition of Plasmodium falciparum FLN
Measurement: Ki = 4000 nM (pChEMBL 5.400000095367432)
Descriptors: MW 606.73, ALogP 3.23, HBA 7, HBD 1, PSA 125.98, QED 0.33
Compound (SMILES): N#Cc1c(N)nc(N)nc1N1CC2(CC2)C[C@H]1c1nc2cccc(Cl)c2c(=O)n1-c1ccccc1
InChIKey: DEQCFSACIVEXND-SFHVURJKSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: O00329
Assay: Inhibition of human full-length recombinant His-tagged PI3K p110delta/p85alpha expressed in baculovirus expression system using PIP2 as substrate measured after 2 hrs by ADP-Glo luminescence assay
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 484.95, ALogP 3.6, HBA 9, HBD 2, PSA 139.74, QED 0.45
Compound (SMILES): CNC(=O)c1sc(-c2ccnc(NC(=O)C3CC3)c2)nc1OCCCCCCCCn1cc(COc2cccc3c2C(=O)N(C2CCC(=O)NC2=O)C3=O)nn1
InChIKey: RKLZXLGYRQMLHE-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of N-terminal His6-tagged recombinant human GSK3beta H350L mutant expressed in baculovirus infected Sf21 cells using GSM as substrate incubated for 30 mins in presence of ATP by Kinase-Glo luminescent assay
Measurement: IC50 = 83.1 nM (pChEMBL 7.079999923706055)
Descriptors: MW 783.87, ALogP 3.9, HBA 14, HBD 3, PSA 216.7, QED 0.1
Compound (SMILES): COc1cc(CN2CCN([C@H]3CC[C@@H](C(C)(C)C)CC3)CC2)ccc1O
InChIKey: QVHBVDBXNHUCSR-KDURUIRLSA-N
Target: Transient receptor potential cation channel subfamily V member 6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H1D0
Assay: Inhibition of human TRPV6 expressed in HEK293 cells assessed as reduction in Cd2+ influx by calcium-5 fluorescence dye-based FLIPR assay
Measurement: IC50 = 2400 nM (pChEMBL 5.619999885559082)
Descriptors: MW 360.54, ALogP 4.12, HBA 4, HBD 1, PSA 35.94, QED 0.88
Compound (SMILES): CC1(C)CC(Oc2nc(N3CCC[C@@H](CC(=O)O)C3)ccc2C(=O)NC2CCCCC2)C1
InChIKey: CFKJCZKABFJIBO-KRWDZBQOSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132H mutant (unknown origin) using alpha-ketoglutarate and NADPH incubated for 30 mins by fluorescence based assay
Measurement: IC50 = 7200 nM (pChEMBL 5.139999866485596)
Descriptors: MW 443.59, ALogP 4.4, HBA 5, HBD 2, PSA 91.76, QED 0.65
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)Cc1ccc(O)cc1)B(O)O
InChIKey: RSBWUUOKMMINBY-PMACEKPBSA-N
Target: Proteasome component C5 (SINGLE PROTEIN), Homo sapiens
UniProt: P20618
Assay: Inhibition of human 20S constitutive proteasome beta 1 subunit caspase-like activity using fluorogenic peptide Ac-nLPnLD-AMC as substrate in presence of PA28alpha incubated for 1 to 2 hrs by fluorescence microplate reader assay
Measurement: IC50 = 52 nM (pChEMBL 7.28000020980835)
Descriptors: MW 412.3
Compound (SMILES): Cc1cc(/C=N/O)c(O)c(CN2CCN(c3ccncc3)CC2)c1
InChIKey: YTRWDALSIVPPCW-UDWIEESQSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Reactivation of VX-inhibited human AChE assessed as dissociation constant incubated for 30 mins by Ellman's method
Measurement: Kd = 17300 nM (pChEMBL 4.760000228881836)
Descriptors: MW 326.4, ALogP 2.23, HBA 6, HBD 2, PSA 72.19, QED 0.51
Compound (SMILES): CNc1ncnc2c1c(-c1ccc3ccccc3c1)nn2C(C)(C)C
InChIKey: YWMRNOUYLNCRCH-UHFFFAOYSA-N
Target: Transitional endoplasmic reticulum ATPase (SINGLE PROTEIN), Homo sapiens
UniProt: P55072
Assay: Inhibition of His6-tagged p97 (unknown origin) expressed in Escherichia coli BL21 (DE3) assessed as reduction in ATPase activity measured after 60 mins by biomol green reagent based assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 331.42, ALogP 4.44, HBA 5, HBD 1, PSA 55.63, QED 0.59
Compound (SMILES): CN(CCCCc1ccccc1)c1nc(C(=O)NCC2CC2)cc(N2CCOCC2)n1
InChIKey: BCCACEQJKTZQNI-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 = 10000 nM (pChEMBL 5)
Descriptors: MW 423.56, ALogP 2.91, HBA 6, HBD 1, PSA 70.59, QED 0.59
Compound (SMILES): CCN1CCN(C(=O)CS(=O)(=O)c2ccc(Nc3ncc(Cl)c(Nc4ccccc4S(=O)(=O)C(C)C)n3)c(OC)c2)CC1
InChIKey: MAKLQLGGXQPLRV-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase ROS (SINGLE PROTEIN), Homo sapiens
UniProt: P08922
Assay: Inhibition of ROS1 (unknown origin) using peptide substrate incubated for 60 mins in presence of ATP by HTRF assay
Measurement: IC50 = 1.9 nM (pChEMBL 8.720000267028809)
Descriptors: MW 651.21, ALogP 3.75, HBA 11, HBD 2, PSA 150.9, QED 0.31
Compound (SMILES): O=C(Nc1nc(-c2ccncc2)c(CN2CCOCC2)s1)c1cccnc1
InChIKey: DBZOHTJBAVLXLU-UHFFFAOYSA-N
Target: Rho-associated protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75116
Assay: Inhibition of ROCK2 (unknown origin) using C-terminus recombinant MBS (654-880 residues) as substrate incubated for 30 mins in presence of ATP by ELISA
Measurement: IC50 = 9120 nM (pChEMBL 5.039999961853027)
Descriptors: MW 381.46, ALogP 2.68, HBA 7, HBD 1, PSA 80.24, QED 0.73
Compound (SMILES): O=c1[nH]cc(C2CCCCC2)c2nc(I)c(I)n12
InChIKey: QIQALKWJJOMICU-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24864
Assay: Inhibition of CDK2/cyclin E (unknown origin) using peptide substrate in presence of [gamma33P]ATP by image analyser
Measurement: IC50 = 4600 nM (pChEMBL 5.340000152587891)
Descriptors: MW 469.06, ALogP 3.28, HBA 3, HBD 1, PSA 50.16, QED 0.65
Compound (SMILES): CC1(C)CCN(c2ccc(C(=O)S)cc2)CC1
InChIKey: BRLGSTBRNBGLCH-UHFFFAOYSA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07817
Assay: Inhibition of FITC-labeled Bak BH3 peptide binding to His6-tagged GST-fused Bcl-xL (unknown origin) expressed in Escherichia coli BL21 preincubated for 10 mins followed by Bak BH3 peptide addition and measured after 30 mins by fluorescence polarization-based competitive binding assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 249.38, ALogP 3.38, HBA 2, HBD 1, PSA 20.31, QED 0.81
Compound (SMILES): COc1ccc(-c2noc(CC(=O)NCCCCNC(=O)Cc3onc(-c4ccc(OC)cc4)c3-c3ccc(OC)cc3)c2-c2ccc(OC)cc2)cc1
InChIKey: PMFYIRQUBJSCJR-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 1 (SINGLE PROTEIN), Ovis aries
UniProt: P05979
Assay: Inhibition of ovine COX-1 assessed as peroxidase activity using arachidonic acid as substrate by colorimetric method
Measurement: IC50 = 9000 nM (pChEMBL 5.050000190734863)
Descriptors: MW 730.82, ALogP 7.16, HBA 10, HBD 2, PSA 147.18, QED 0.09
Compound (SMILES): CN1CCN(c2nccc3[nH]c(-c4n[nH]c5ccc(-c6cncc(NC(=O)CC7CCNCC7)c6)cc45)cc23)CC1
InChIKey: PULNHRRGQQQAGZ-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 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 549.68, ALogP 4.25, HBA 7, HBD 4, PSA 117.86, QED 0.25
Compound (SMILES): COc1ccc2ncc(=O)n(CCCCN3CCN(c4cccc5sccc45)CC3)c2c1
InChIKey: SGBPCRMSBHXSHV-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Antagonist activity at D2 receptor (unknown origin) preincubated for 60 mins followed by addition of Eu-cAMP and measured after 60 mins by plate reader method
Measurement: IC50 = 77.62 nM (pChEMBL 7.110000133514404)
Descriptors: MW 448.59, ALogP 4.22, HBA 7, HBD 0, PSA 50.6, QED 0.4
Compound (SMILES): C/C(=N\NC(=S)NCCCCCC(=O)NO)c1ccc(F)cc1
InChIKey: MEZNEOSGOHNEJC-WOJGMQOQSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of recombinant human HDAC1 using Boc-Lys(Ac)-AMC as substrate incubated for 60 mins by fluorimetric assay
Measurement: IC50 = 69.25 nM (pChEMBL 7.159999847412109)
Descriptors: MW 340.42, ALogP 2.08, HBA 4, HBD 4, PSA 85.75, QED 0.19
Compound (SMILES): Cn1cc2c(nc(NC(=O)Nc3ccc(CC(=O)OCCCOCCOCCOCCCN)cc3)n3nc(-c4ccco4)nc23)n1.O=C(O)C(F)(F)F
InChIKey: ZXTWHYBZUKETDM-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Displacement of [3H]CGS21680 from recombinant human A2AAR expressed in HEK293 cell membranes
Measurement: Ki = 328 nM (pChEMBL 6.480000019073486)
Descriptors: MW 635.68, ALogP 2.79, HBA 14, HBD 3, PSA 195.18, QED 0.09
Compound (SMILES): O=C1C(Cl)=C(NCCN2CCNCC2)C(=O)c2ccccc21
InChIKey: NSSMXCNEKHURJO-UHFFFAOYSA-N
Target: Cystathionine gamma-lyase (SINGLE PROTEIN), Homo sapiens
UniProt: P32929
Assay: Inhibition of human CSE using L-Cys as the substrate by tandem well based HTS assay
Measurement: IC50 < 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 319.79, ALogP 1.01, HBA 5, HBD 2, PSA 61.44, QED 0.87
Compound (SMILES): C#CCCCCc1cn(-c2ccc(O)cc2)nn1
InChIKey: WGDYOSQQFDVMOT-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 = 9500 nM (pChEMBL 5.019999980926514)
Descriptors: MW 241.29, ALogP 2.32, HBA 4, HBD 1, PSA 50.94, QED 0.65
Compound (SMILES): CNC(=O)Cn1cc(-c2nc(N3CCOC[C@@H]3c3ccccc3)c3cc(-c4c(C)noc4C)ccc3n2)cn1
InChIKey: HUCGPHRBJJVBKJ-RUZDIDTESA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Competitive binding affinity to human partial length BRD4 (BD1,2) (N44 to E460 residues) expressed in bacterial expression system by BROMOscan assay
Measurement: Kd = 85 nM (pChEMBL 7.070000171661377)
Descriptors: MW 523.6, ALogP 4.09, HBA 9, HBD 1, PSA 111.2, QED 0.35