lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=C(O)C(=O)O.c1ccc(CC2CCN(CC3CSC4(S3)c3ccccc3-c3ccccc34)CC2)cc1
InChIKey: ZPDGXPJTUJZHBL-UHFFFAOYSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: Displacement of [3H]-ditolylguanidine from human Sigma 2 receptor by radioligand displacement assay
Measurement: Ki = 71 nM (pChEMBL 7.150000095367432)
Descriptors: MW 443.68, ALogP 6.67, HBA 3, HBD 0, PSA 3.24, QED 0.44
Compound (SMILES): COc1cc(-c2cncc(-c3ccc(N4C[C@@H](C)N[C@@H](C)C4)cc3)c2C)cc(OC)c1OC
InChIKey: RPZNNVBZIMEQNF-HDICACEKSA-N
Target: TGF-beta receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P36897
Assay: Inhibition of human ALK5 using casein as substrate in presence of [gamma-33P]-ATP by radiometric hotspot assay
Measurement: IC50 = 1050 nM (pChEMBL 5.980000019073486)
Descriptors: MW 447.58, ALogP 4.94, HBA 6, HBD 1, PSA 55.85, QED 0.58
Compound (SMILES): Cc1cc(-c2ccnc3[nH]ncc23)cnc1OCC12CCC(N)(CC1)CC2
InChIKey: DWTASGLRYAARGP-UHFFFAOYSA-N
Target: Toll-like receptor 7 (SINGLE PROTEIN), Mus musculus
UniProt: P58681
Assay: Antagonist activity at TLR7 in mouse splenocytes assessed as inhibition of ssRNA40-induced IL6 production
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 363.47, ALogP 3.76, HBA 5, HBD 2, PSA 89.71, QED 0.74
Compound (SMILES): Oc1ccc2c3c1O[C@H]1c4ncc(-c5ccccc5)cc4C[C@@]4(OCCCCc5ccccc5)[C@@H](C2)N(CC2CC2)CC[C@]314
InChIKey: QCAAUOYUXPHLKT-QJMCPCMJSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Displacement of [3H]-diprenorphine from human delta opioid receptor expressed in CHO cell membranes incubated for 1 hr by competition radioligand binding assay
Measurement: Ki = 14.6 nM (pChEMBL 7.840000152587891)
Descriptors: MW 584.76, ALogP 7.2, HBA 5, HBD 1, PSA 54.82, QED 0.21
Compound (SMILES): COc1ccc([C@H]2O[C@@H](O)[C@H]3[C@@H]2C(=O)O[C@@H]3c2cc(OC)c3c(c2)OCO3)cc1OC
InChIKey: VBRSHBGIUDRWEJ-FEEZOJJESA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human erythrocyte acetylcholinesterase using acetylthiocholine as substrate by Ellman's method
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 430.41, ALogP 2.36, HBA 9, HBD 1, PSA 101.91, QED 0.72
Compound (SMILES): NC(=O)c1ccc(Nc2ncc(C(F)(F)F)c(N3CCCC3)n2)cc1
InChIKey: LPTLAGGCZBHKGC-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Lck (SINGLE PROTEIN), Homo sapiens
UniProt: P06239
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human Lck using TK-substrate-biotin as substrate incubated for 60 mins in presence of ATP by fluorescence method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 351.33, ALogP 2.94, HBA 5, HBD 2, PSA 84.14, QED 0.88
Compound (SMILES): O=C(NCC1CCOC1)c1n[nH]c2ccc(-c3cccc(F)c3F)cc12
InChIKey: QIJHQFDCIITVAM-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in CHOK1 cells assessed as reduction in tail current by measuring tail current amplitude measured after deploarization to +20 mV for 2s followed by 1s pulse to -40 mV by whole cell patch clamp assay
Measurement: IC50 = 4300 nM (pChEMBL 5.369999885559082)
Descriptors: MW 357.36, ALogP 3.27, HBA 3, HBD 2, PSA 67.01, QED 0.75
Compound (SMILES): O=C(CCc1ccccc1)CC(=O)NCc1ccccc1
InChIKey: WDDMVAJRPZWWHE-UHFFFAOYSA-N
Target: Phospholipase A and acyltransferase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P53816
Assay: Inhibition of full-length C-terminal FLAG-tagged human PLAAT3 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 281.36, ALogP 2.89, HBA 2, HBD 1, PSA 46.17, QED 0.79
Compound (SMILES): C=CC(=O)NCCOc1cc(Cc2c(OC)cccc2OC)cc2[nH]c(-c3n[nH]c4cc(C(F)F)ccc34)cc12
InChIKey: GYXOEVKWZVVSOG-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK (unknown origin) using TK as substrate incubated for 30 mins by HTRF assay
Measurement: IC50 = 331 nM (pChEMBL 6.480000019073486)
Descriptors: MW 546.57, ALogP 5.94, HBA 5, HBD 3, PSA 101.26, QED 0.14
Compound (SMILES): C[C@H]1[C@H]2Cc3ccc(O)cc3[C@]1(C)CCN2CCN(Cc1ccccc1)c1ccccc1
InChIKey: PRSHMYIURUILFQ-UNUDWIFVSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P33533
Assay: Displacement of [3H]DPDPE from DOR in rat brain membranes incubated for 45 mins by liquid scintillation counting
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 426.6, ALogP 5.62, HBA 3, HBD 1, PSA 26.71, QED 0.55
Compound (SMILES): COc1nn(-c2cncc(N(C)C)c2)cc1C(=O)Nc1cccc(-c2nncn2C(C)C)n1
InChIKey: KQBPDUUHJYKERD-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99683
Assay: Inhibition of V5 tagged human ASK1 expressed in HEK293T cells assessed as reduction in T848 autophosphorylation incubated for 1 hr by MSD assay
Measurement: IC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 447.5, ALogP 2.83, HBA 10, HBD 1, PSA 115.88, QED 0.46
Compound (SMILES): Cn1cc(-c2ccnc(-n3ncc4cc(C(C)(C)C)cc(F)c4c3=O)c2CO)cc(NC(=O)[C@@H]2C[C@@H]2F)c1=O
InChIKey: SEGFWFQHVPYNMS-QUCCMNQESA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK in human whole blood assessed as reduction in anti-IgM-stimulated CD69 expression preincubated for 1 hr followed by goat F(ab')2 anti-human IgM stimulation and measured after 18 hrs by FACS analysis
Measurement: IC50 = 78 nM (pChEMBL 7.110000133514404)
Descriptors: MW 535.55, ALogP 3.37, HBA 8, HBD 2, PSA 119.11, QED 0.4
Compound (SMILES): COc1ccc(OCC2c3sccc3CCN2C(=O)c2cccc(Cl)c2)cc1
InChIKey: PDFVJFUAZQBNAJ-UHFFFAOYSA-N
Target: Ionotropic glutamate receptor NMDA 1/2D (PROTEIN COMPLEX), Rattus norvegicus
UniProt: Q62645
Assay: Positive allosteric modulation of recombinant rat GluN1a/GluN2D receptor expressed in Xenopus laevis oocytes assessed as increase in glycine/L-glutamate-induced channel current by two-electrode voltage clamp method
Measurement: EC50 = 3981.07 nM (pChEMBL 5.400000095367432)
Descriptors: MW 413.93, ALogP 5.23, HBA 4, HBD 0, PSA 38.77, QED 0.57
Compound (SMILES): C=C(C(N)=O)[C@@H](NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@@H](CCCCNC(=N)N)NC(=O)[C@@H](N)Cc1ccc(O)cc1)c1ccco1
InChIKey: SAWCRWRDZHAHKP-RKDXIHMYSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P33535
Assay: Displacement of [3H]-DAMGO from Wistar rat mu opioid receptor incubated for 1 hr by liquid scintillation counting method
Measurement: Ki = 405 nM (pChEMBL 6.389999866485596)
Descriptors: MW 685.79, ALogP 1.1, HBA 8, HBD 10, PSA 267.47, QED 0.03
Compound (SMILES): Clc1cccc2c(-n3cnc4c(-c5nnc[nH]5)cc(-c5ccncc5)cc43)ccnc12
InChIKey: MASYQGOSXMDVNJ-UHFFFAOYSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P42336
Assay: Inhibition of human full length p110alpha/p85alpha using PIP2 as substrate after 30 mins in presence of ATP at 2xKm concentration by TR-FRET assay
Measurement: IC50 = 350 nM (pChEMBL 6.460000038146973)
Descriptors: MW 423.87, ALogP 5.07, HBA 6, HBD 1, PSA 85.17, QED 0.43
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O
InChIKey: BVVHATNAEODPPU-SKGSPYGFSA-N
Target: Neuropeptide Y receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P50391
Assay: Displacement of [3H]UR-KK200 from human Y4 receptor expressed in CHO cells co-expressing Gqi5-mtAEQ measured after 90 mins by scintillation counting analysis
Measurement: Ki = 29 nM (pChEMBL 7.539999961853027)
Descriptors: MW 1097.25
Compound (SMILES): O=C(Nc1ccc(-c2nc3ccc(Br)cc3[nH]2)cc1)c1ccc([N+](=O)[O-])cc1
InChIKey: JMGQZOUEAHSJGN-UHFFFAOYSA-N
Target: Neutrophil collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P22894
Assay: Inhibition of recombinant human MMP8 catalytic domain (Phe99 to Gln269 residues) expressed in Escherichia coli cells using Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2/TQ3-GABA-Pro-Cha-Abu-Smc-His-Ala-Dab(6'-TAMRA)-Ala-Lys-NH2 as fluorogenic substrate preincubated for 15 mins followed by substrate addition measured after 2 to 4 hrs by fluorometric assay
Measurement: IC50 = 7900 nM (pChEMBL 5.099999904632568)
Descriptors: MW 437.25, ALogP 5.15, HBA 4, HBD 2, PSA 100.92, QED 0.34
Compound (SMILES): CNC(=O)c1cc(C(=O)NCCC(C)C)cn(Cc2ccccc2)c1=O
InChIKey: JEQGAHKBIFRHMQ-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to 6His-Thr-BRD4 (1 to 477 residues) BD1 domain (unknown origin) incubated for 30 mins by TR-FRET assay
Measurement: IC50 = 31622.78 nM (pChEMBL 4.5)
Descriptors: MW 355.44, ALogP 2.03, HBA 4, HBD 2, PSA 80.2, QED 0.8
Compound (SMILES): CCNS(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(N3CCC(N4CCN(C)CC4)CC3)c(OC)c2)ncc1CCc1cc(OC)cc(OC)c1
InChIKey: WIMNUEGOKSDWHG-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of N-terminal GST-tagged human VEGFR2 cytoplasmic domain (790-1356 end amino acid residue) expressed in baculovirus expression system preincubated for 30 to 120 mins followed by incubation with substrate and ATP for 30 mins by off-chip mobility shift assay
Measurement: IC50 = 292 nM (pChEMBL 6.539999961853027)
Descriptors: MW 744.96, ALogP 5.29, HBA 12, HBD 3, PSA 133.42, QED 0.15
Compound (SMILES): CCN(C(=O)N1CCC(C(=O)c2ccc3cnn(C)c3c2)CC1)c1ccc(C(=O)O)cc1
InChIKey: XSSGDRWJVHTQAM-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase tankyrase-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H2K2
Assay: Inhibition of human GST-tagged tankyrase 2 autophosphorylation
Measurement: IC50 = 0.19 nM (pChEMBL 9.720000267028809)
Descriptors: MW 434.5, ALogP 3.81, HBA 5, HBD 1, PSA 95.74, QED 0.62
Compound (SMILES): COc1cc(/C=C2\CCCN3C2=NO[C@H](c2cc(F)c(F)c(F)c2)[C@@H]3C)ccc1-n1cnc(C)c1
InChIKey: WNLQYKOTLNFENJ-FGFGADHJSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of MK499 binding to human ERG
Measurement: IC50 = 1607 nM (pChEMBL 5.789999961853027)
Descriptors: MW 482.51, ALogP 5.56, HBA 6, HBD 0, PSA 51.88, QED 0.46
Compound (SMILES): CC(C)Nc1cc(Nc2nc3ccnn3cc2F)ncc1C(=O)NC[C@@H](F)C(C)(C)O
InChIKey: SNCZIVUNTWOQAF-OAHLLOKOSA-N
Target: Interleukin-1 receptor-associated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWZ3
Assay: Inhibition of IRAK4 in human PBMC assessed as inhibition of LTA-induced IL-6 production preincubated for 30 mins followed by LTA-stimulation and measured after 5 hrs by ELISA
Measurement: IC50 = 370 nM (pChEMBL 6.429999828338623)
Descriptors: MW 433.46, ALogP 2.67, HBA 8, HBD 4, PSA 116.47, QED 0.43
Compound (SMILES): O=C(CCCC(=O)NCCCN1c2ccccc2CCc2ccc(Cl)cc21)NO
InChIKey: GQWOSUWMYJKRHD-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of recombinant human C-terminal GST-tagged HDAC2 (1 to 488 residues) expressed in baculovirus infected sf21 cells using RHK-K(Ac)-AMC as substrate after 60 mins by fluorimetry assay
Measurement: IC50 = 5960 nM (pChEMBL 5.21999979019165)
Descriptors: MW 415.92, ALogP 3.76, HBA 4, HBD 3, PSA 81.67, QED 0.35
Compound (SMILES): C[C@@H]1CN(CCSC(c2ccc(F)cc2)c2ccc(F)cc2)C[C@H](C)N1
InChIKey: VWCPEARXGTWKHO-IYBDPMFKSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: P31652
Assay: Displacement of [3H]citalopram from SERT in Sprague-Dawley rat midbrain membranes incubated for 60 mins by microbeta scintillation counting method
Measurement: Ki = 13063 nM (pChEMBL 4.880000114440918)
Descriptors: MW 376.52, ALogP 4.47, HBA 3, HBD 1, PSA 15.27, QED 0.8
Compound (SMILES): O=C(N/N=C/c1ccc(OCc2cccc(F)c2)cc1)c1nc2ccccc2[nH]1
InChIKey: CJQSIZHZMVUJAB-ZMOGYAJESA-N
Target: Cocaine esterase (SINGLE PROTEIN), Homo sapiens
UniProt: O00748
Assay: Inhibition of CES2 (unknown origin)
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 388.4, ALogP 4.04, HBA 4, HBD 2, PSA 79.37, QED 0.39
Compound (SMILES): CC1CN2CCNCc3ccc(Cl)c1c32
InChIKey: PXYOIRBEMWJOGX-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Displacement of [125I]-1,4-Iodanyl-2,5-dimethoxyphenyl)propan-2amine from 5HT2C receptor (unknown origin)
Measurement: Ki = 0.8 nM (pChEMBL 9.100000381469727)
Descriptors: MW 222.72, ALogP 2.37, HBA 2, HBD 1, PSA 15.27, QED 0.73
Compound (SMILES): Nc1nc(N2CCC(N(CCc3ccc(Cl)cc3)Cc3cccc(O)c3)CC2)n[nH]1
InChIKey: IRENZKMIJSGHBF-UHFFFAOYSA-N
Target: Chitotriosidase-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13231
Assay: Inhibition of full length recombinant C-terminal His-taged human CHIT1 expressed in CHOK1 cells assessed as reduction in chitinolytic activity using 4-methylumbelliferyl-beta-D-N,N',N''-diacetylchitotrioside as substrate incubated for 60 mins under shaking condition by microplate fluorometry analysis
Measurement: IC50 = 79 nM (pChEMBL 7.099999904632568)
Descriptors: MW 426.95, ALogP 3.46, HBA 6, HBD 3, PSA 94.3, QED 0.54
Compound (SMILES): Cc1cc(-c2cnc3c(NCCC(F)(F)F)nc(Oc4ccccc4)cn23)ccc1C(=O)NC1CC1
InChIKey: FPYWIVXQQLAWEZ-UHFFFAOYSA-N
Target: Dual specificity protein kinase TTK (SINGLE PROTEIN), Homo sapiens
UniProt: P33981
Assay: Inhibition of GST-tagged recombinant human MPS1 expressed in baculovirus expression system using biotin-Ahx-PWDPDDADITEILG as substrate preincubated for 15 mins followed by substrate and 2 mM ATP addition and measured after 60 mins by TR-FRET assay
Measurement: IC50 = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 495.51, ALogP 5.75, HBA 6, HBD 2, PSA 80.55, QED 0.33
Compound (SMILES): N#Cc1ccccc1-c1cc(Oc2ccccc2)ccc1COC1CN(C#N)C1
InChIKey: CLMOBCVPJZABAT-UHFFFAOYSA-N
Target: N-acylethanolamine-hydrolyzing acid amidase (SINGLE PROTEIN), Homo sapiens
UniProt: Q02083
Assay: Inhibition Assay: In order to have an assay method more conducive to high-throughput screening than those published for measuring the NAE hydrolyzing activity of NAAA, we developed the fluorogenic PEA analog N-(4-methyl coumarin)palmitamide (PAMCA), which is hydrolyzed to fluorescent 7-amino-4-methyl coumarin (AMC) and palmitic acid. For three point concentration inhibition assays with hNAAA the following procedure is used. Purified activated NAAA (final concentration of 0.25 μg/mL) is incubated in assay buffer (100 mM citrate-phosphate buffer, pH 4.5, 3 mM DTT, 0.1% Triton X-100, 0.05% BSA, and 150 mM NaCl) made up to a total volume of 180 μL, followed by addition of the compound dissolved in 10 μL DMSO (along with DMSO neat for the control sample) with the final concentrations for each compound of 100, 10, and 1 μM, in triplicate on a 96 well plate. These samples are allowed to incubate for 15 min at room temperature and then 10 μL of a PAMCA stock solution in DMSO (final PAMCA concentration [5 μM]) was added. After 5 minutes of agitation on a shaking plate, the reaction is allowed to proceed at 37° C. for 120 minutes, with fluorescence readings taken every 10 minutes at a wavelength of 460 nm (using an excitation wavelength of 360 nm) on a Synergy HT Plate Reader using Gen5 software from Bio-Tek. The enzyme activity is calculated by converting the relative fluorescence units to AMC formed, using a standard curve of AMC. For compounds that inhibit hNAAA in range IC50 <1 μM full inhibition curves using eight different concentrations of inhibitor (8 point assay) are generated. The assay procedure used is the same as the three point assay. For ostensibly covalent compounds (as observed by a significant decrease in the slope of a plot of fluorescence vs. time in three point screen) samples are allowed to incubate for 2 hours at 37° C., instead of 15 minutes, before addition of 10 μL of a PAMCA stock solution in DMSO for a final PAMCA concentration of 5 μM. After 5 minutes of agitation on a shaking plate, the reaction is allowed to proceed at 37° C. for 120 minutes Inhibition constants are calculated using pro Fit software (Quantum Soft, Uetikon am See, Switzerland) and a Levenberg-Marquardt algorithm.
Measurement: IC50 = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 381.44, ALogP 4.7, HBA 5, HBD 0, PSA 69.28, QED 0.58
Compound (SMILES): O=C(O)C(=O)O.c1ccc(CC2CCN(CC3CSC4(CCCCCC4)S3)CC2)cc1
InChIKey: QMQBIFWCYRSMHI-UHFFFAOYSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: Displacement of [3H]-ditolylguanidine from human Sigma 2 receptor by radioligand displacement assay
Measurement: Ki = 8.1 nM (pChEMBL 8.09000015258789)
Descriptors: MW 375.65, ALogP 5.84, HBA 3, HBD 0, PSA 3.24, QED 0.65
Compound (SMILES): Cc1ccc(C(F)(F)F)cc1C(=O)N[C@@H](C(=O)N1CCC2(CC1)C(=O)N(C)C(=O)N2c1ccc2[nH]ncc2c1)C(C)C
InChIKey: DJIQHFHIIHEAKJ-HSZRJFAPSA-N
Target: Autotaxin (SINGLE PROTEIN), Homo sapiens
UniProt: Q13822
Assay: Autotaxin LPC Cascade Assay: The efficacy of the Examples described herein, as inhibitors of ATX are demonstrated and confirmed by pharmacological in vitro assays. The following assays and their respective methods are carried out with the compounds according to the present invention. Activity possessed by the compounds may be demonstrated in vivo. Those skilled in the art will appreciate that a variety of assay formats may be used to determine the activity of the compounds of this invention.Autotaxin LPC Cascade Assay:Assay Buffer:100 mM Tris-HCl, pH=9500 mM NaCl5 mM MgCl25 mM CaCl20.05% Triton X 100Reagents:Enzyme Source Stock conc Working conc. Final conc. Autotaxin X-Chem 4.6 μM 20 nM 5 nM LPC Sigma L5254 8 mM in assay buffer 400 μM 100 μM Choline Oxidase Sigma C5896 50 U/mL in water 0.8 U/mL 0.1 U/mL HRP Sigma P8375 1000 U/mL in water 8 U/mL 1 U/mL Ampliflu Red Sigma 90101 100 mM in DMSO 400 μM 50 μM.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 584.6, ALogP 4.1, HBA 5, HBD 2, PSA 118.71, QED 0.44
Compound (SMILES): N=c1oc2c(O)cccc2cc1C(=O)Nc1cccc(F)c1
InChIKey: SSZMTVBOJMKJFN-UHFFFAOYSA-N
Target: Aldo-keto reductase family 1 member C4 (SINGLE PROTEIN), Homo sapiens
UniProt: P17516
Assay: Inhibition of recombinant AKR1C4 (unknown origin) assessed as reduction in S-tetralol-induced dehydrogenase activity by measuring NADPH level
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 298.27, ALogP 3.01, HBA 4, HBD 3, PSA 86.32, QED 0.68
Compound (SMILES): Cc1cc(-c2nc(-c3ccc(F)cc3)c3c(n2)[C@]2(C)C=C(C#N)C(=O)[C@H](C)[C@H]2CC3)ccn1
InChIKey: VKHUYZPARSWSEB-KRLBWHOLSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at RORgammat in human CD4-positive T cells assessed as suppression of T cell differentiation to Th17 cells by reduction in measuring IL-17A secretion
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 438.51, ALogP 5.14, HBA 5, HBD 0, PSA 79.53, QED 0.55
Compound (SMILES): CC(C)Cn1cc(-c2ccncc2)c2ccncc21
InChIKey: DTGUVEZHIDDOLE-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of recombinant human His/GST-tagged GSK3beta (2 to 433 residues) expressed in baculovirus infected Sf9 cells using Ulight-glycogen synthase peptide as substrate incubated for 30 mins by TR-FRET LANCE method
Measurement: IC50 > 8300 nM (pChEMBL 5.080999851226807)
Descriptors: MW 251.33, ALogP 3.75, HBA 3, HBD 0, PSA 30.71, QED 0.71
Compound (SMILES): CNCCN1CCC(c2ccc3[nH]c(-c4ccccc4Cl)c(F)c3c2)CC1
InChIKey: FEHDCYJWQSIHJA-UHFFFAOYSA-N
Target: Toll-like receptor 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR96
Assay: Antagonist activity at human TLR9 overexpressed in HEK-Blue cells assessed as inhibition of ODN2006-induced NFkappaB and AP-1 activation preincubated for 30 mins followed by ODN2006 stimulation measured after 22 hrs by quanti-blue SEAP assay
Measurement: IC50 = 21700 nM (pChEMBL 4.659999847412109)
Descriptors: MW 385.91, ALogP 5.03, HBA 2, HBD 2, PSA 31.06, QED 0.65
Compound (SMILES): C[C@H](NS(=O)(=O)c1ccc(-c2sc(-c3noc(C(C)(C)O)n3)nc2C(=O)N2CCC(F)CC2)c(Cl)c1Cl)C(F)(F)F
InChIKey: INYSDJIZEVOPBK-JTQLQIEISA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Binding affinity to recombinant human RORgammat transfected in human HEK293T cells incubated for 24 hrs by dual-glo luciferase reporter gene assay
Measurement: IC50 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 660.5, ALogP 5.2, HBA 9, HBD 2, PSA 138.52, QED 0.33
Compound (SMILES): COc1cc(-c2cnc3cccc(-c4cc(F)c(CN5CCS(=O)(=O)CC5)c(F)c4)c3n2)ccc1OCCCN1CCOCC1
InChIKey: NVOIBHOEZNKMBT-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of JAK2 (unknown origin)
Measurement: IC50 = 0.2512 nM (pChEMBL 9.600000381469727)
Descriptors: MW 638.74, ALogP 4.58, HBA 9, HBD 0, PSA 94.09, QED 0.23
Compound (SMILES): CN1CCN(c2ccc(Nc3ncc(Cl)c(NCc4ccco4)n3)nc2)CC1
InChIKey: DADZAXRKSGGBOW-UHFFFAOYSA-N
Target: CDK9/Cyclin K (PROTEIN COMPLEX), Homo sapiens
UniProt: O75909
Assay: Inhibition of recombinant human full-length N-terminal GST-tagged CDK9/cyclinK expressed in baculovirus infected Sf9 insect cells using PDKtide as substrate measured after 120 mins by ADP-glo assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 399.89, ALogP 3.23, HBA 8, HBD 2, PSA 82.35, QED 0.65
Compound (SMILES): Cc1ccc2[nH]cc(C(=O)On3nnc4ccccc43)c2c1
InChIKey: BHLVBJANCKFRLU-UHFFFAOYSA-N
Target: NAD-dependent protein deacetylase sirtuin-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8IXJ6
Assay: Inhibition of SIRT2 deacetylation activity (unknown origin) using H3K9Ac ( 4 to 15 residues) as substrate by HPLC analysis
Measurement: IC50 = 74000 nM (pChEMBL 4.130000114440918)
Descriptors: MW 292.3, ALogP 2.49, HBA 5, HBD 1, PSA 72.8, QED 0.58
Compound (SMILES): NC(=O)CC1CCCCC1CNC(=O)[C@H](CC1CCCCC1)NC(=O)c1ccno1
InChIKey: HYTVWZSYYLWZPR-ABHNRTSZSA-N
Target: Proteinase-activated receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P55085
Assay: Agonist activity at human PAR2 expressed in HEK293T cells assessed as induction of Galphaq-stimulated IP1 formation incubated for 2 hrs by FRET assay
Measurement: EC50 = 640 nM (pChEMBL 6.190000057220459)
Descriptors: MW 418.54, ALogP 2.54, HBA 5, HBD 3, PSA 127.32, QED 0.57
Compound (SMILES): C=CC(=O)Nc1cccc(Oc2nc(Nc3ccc(OCCCN4CCOCC4)c(Cl)c3)nc3ccsc23)c1
InChIKey: BZFLKUGURVDIAB-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK (unknown origin) by ADP-Glo kinase assay
Measurement: IC50 >= 62.4 nM (pChEMBL 7.204999923706055)
Descriptors: MW 566.08, ALogP 6.11, HBA 9, HBD 2, PSA 97.84, QED 0.17
Compound (SMILES): Cc1cc(-c2cnc3c(NCCC(F)(F)F)cc(C4(c5cc(F)ccc5O)CC4)nn23)ccc1C(=O)NC1CC1
InChIKey: PRHOHAZWMXBOFO-UHFFFAOYSA-N
Target: Dual specificity protein kinase TTK (SINGLE PROTEIN), Homo sapiens
UniProt: P33981
Assay: Inhibition of GST-tagged recombinant human MPS1 expressed in baculovirus expression system using biotin-Ahx-PWDPDDADITEILG as substrate preincubated for 15 mins followed by substrate and 2 mM ATP addition and measured after 60 mins by TR-FRET assay
Measurement: IC50 = 0.9 nM (pChEMBL 9.050000190734863)
Descriptors: MW 553.56, ALogP 5.89, HBA 6, HBD 3, PSA 91.55, QED 0.24
Compound (SMILES): CCOC(=O)Cc1nn(CNC(=O)CCN2CCN(c3cccc(C(F)(F)F)c3)CC2)c(=O)c2ccccc12
InChIKey: XZKXBYWTTKNBBX-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Displacement of [3H]mesulergine from 5-HT2C receptor (unknown origin) by cell based radioligand competitive binding analysis
Measurement: IC50 = 3820 nM (pChEMBL 5.420000076293945)
Descriptors: MW 545.56, ALogP 2.81, HBA 8, HBD 1, PSA 96.77, QED 0.41
Compound (SMILES): Cc1ccc(Cn2c(=O)sn(Cc3ccccc3)c2=O)cc1
InChIKey: KXTNUKREBXHNDR-UHFFFAOYSA-N
Target: Sortase A (SINGLE PROTEIN), Staphylococcus aureus
UniProt: Q9S446
Assay: Inhibition of Staphylococcus aureus SrtA delta N24 mutant expressed in Escherichia coli BL21 (DE3) using Abz-LPATG-Dnp substrate incubated for 20 mins by FRET-based assay
Measurement: IC50 = 5100 nM (pChEMBL 5.289999961853027)
Descriptors: MW 312.39, ALogP 2.48, HBA 5, HBD 0, PSA 44, QED 0.74
Compound (SMILES): CC(C)CNc1ncc(-c2ccccc2)n2c(-c3ccc(C(=O)NC4CC4)cc3)cnc12
InChIKey: YWUXVVZOKRCHPL-UHFFFAOYSA-N
Target: Dual specificity protein kinase TTK (SINGLE PROTEIN), Homo sapiens
UniProt: P33981
Assay: Inhibition of GST-tagged recombinant human MPS1 expressed in baculovirus expression system using biotin-Ahx-PWDPDDADITEILG as substrate preincubated for 15 mins followed by substrate and 2 mM ATP addition and measured after 60 mins by TR-FRET assay
Measurement: IC50 = 726 nM (pChEMBL 6.139999866485596)
Descriptors: MW 425.54, ALogP 5.02, HBA 5, HBD 2, PSA 71.32, QED 0.44
Compound (SMILES): Cn1nccc1[C@H]1CCCC[C@@H]1Oc1cc(F)c(S(=O)(=O)Nc2cscn2)cc1F
InChIKey: JHSOBKSPKNURCU-WBMJQRKESA-N
Target: Sodium channel protein type 5 subunit alpha/beta-1/beta-2 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60939
Assay: Inhibition of human NaV1.5/beta1/beta2 expressed in HEK293A cells by Ionworks high-throughput electrophysiology method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 454.52, ALogP 4.06, HBA 7, HBD 1, PSA 86.11, QED 0.61
Compound (SMILES): O=C(/C=C/c1ccc(CNCCCN2c3ccccc3CCc3ccc(Cl)cc32)cc1)NO
InChIKey: TURBURJBILXASP-XNTDXEJSSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of recombinant human C-terminal GST-tagged HDAC2 (1 to 488 residues) expressed in baculovirus infected sf21 cells using RHK-K(Ac)-AMC as substrate after 60 mins by fluorimetry assay
Measurement: IC50 = 6620 nM (pChEMBL 5.179999828338623)
Descriptors: MW 461.99, ALogP 5.28, HBA 4, HBD 3, PSA 64.6, QED 0.18
Compound (SMILES): CC(C)c1onc(-c2ccccc2)c1COc1ccc(CCCCC(=O)O)cc1
InChIKey: NGLLVJZQEOJRRW-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor delta (SINGLE PROTEIN), Homo sapiens
UniProt: Q03181
Assay: Activation of human PPAR-delta LBD expressed in HEK293T cells assessed as induction of receptor activation incubated for 12 to 14 hrs by luciferase reporter gene assay
Measurement: EC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 393.48, ALogP 5.84, HBA 4, HBD 1, PSA 72.56, QED 0.44
Compound (SMILES): CCn1nnc2c(C)c([C@@H](CC(=O)O)c3cc(C)c4c(c3)CN(C(=O)c3ccccc3)CC4)ccc21
InChIKey: QQOWDADZZIZEDA-VWLOTQADSA-N
Target: Kelch-like ECH-associated protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14145
Assay: Binding affinity to Keap1 (unknown origin) by SPR assay
Measurement: Kd = 13.5 nM (pChEMBL 7.869999885559082)
Descriptors: MW 482.58, ALogP 4.87, HBA 5, HBD 1, PSA 88.32, QED 0.42
Compound (SMILES): CNC1CCN(Cc2c(C)cc(C)c3[nH]ccc23)C(c2ccccc2)C1
InChIKey: WHSFJJAVNLAHGJ-UHFFFAOYSA-N
Target: Complement factor B (SINGLE PROTEIN), Homo sapiens
UniProt: P00751
Assay: Human Complement Factor B TR-FRET Assay: CVF-Bb complex prepared from purified cobra venom factor (1 uM), recombinant human complement factor B (expressed in drosophila cells and purified using standard methods) and human complement factor D (expressed in E. Coli, refolded and purified using standard methods). CVF-Bb complex at 3 nM concentration was incubated with test compound at various concentrations for 1 hour at room temperature in PBS pH 7.4 containing 10 mM MgCl2 and 0.05% (w/v) CHAPS. Human complement C3 substrate purified from plasma was added to a final concentration of 1 uM. After 1 hour incubation at room temperature, the enzyme reaction was stopped by addition of a cocktail of concentrated pan-protease inhibitors. The product of the reaction, C3a, was quantified by means of an enzyme-linked-immunosorbent assay. IC50 values were calculated from percentage of inhibition of CVF-Bb activity as a function of test compound concentration.
Measurement: IC50 = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 347.51, ALogP 4.71, HBA 2, HBD 2, PSA 31.06, QED 0.72
Compound (SMILES): CNC(=O)c1cc(C(=O)NCCC[C@H]2OC[C@H](N)CO2)cc2c1O[C@H](CF)[C@H]2c1ccccc1
InChIKey: LIGIXEDRXVGJNJ-CIQXWFTPSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of Alexa Fluor 647 labelled ligand from His6-tagged BRD4 BD2 (1 to 477 residues)/BD1 Y97A mutant (unknown origin) after 30 mins by TR-FRET assay
Measurement: IC50 = 25.12 nM (pChEMBL 7.599999904632568)
Descriptors: MW 471.53, ALogP 2.12, HBA 6, HBD 3, PSA 111.91, QED 0.51
Compound (SMILES): CC[C@H](NS(=O)(=O)c1ccc(-c2sc(C(=O)NC3CC34CCOCC4)nc2C(=O)N2CCC(F)CC2)c(Cl)c1Cl)C(F)(F)F
InChIKey: LZTUHXJFHGTUKP-ZENAZSQFSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at human RORgammat LBD by M1H cell based assay
Measurement: IC50 = 5.1 nM (pChEMBL 8.289999961853027)
Descriptors: MW 701.59, ALogP 5.61, HBA 7, HBD 2, PSA 117.7, QED 0.35
Compound (SMILES): C=CC(=O)NCCOc1cc(Cc2cccc(OC)c2)cc2[nH]c(-c3n[nH]c4cc(C(F)F)ccc34)cc12
InChIKey: WSEIETFQEJLOPY-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK (unknown origin) using TK as substrate incubated for 30 mins by HTRF assay
Measurement: IC50 = 138 nM (pChEMBL 6.860000133514404)
Descriptors: MW 516.55, ALogP 5.93, HBA 4, HBD 3, PSA 92.03, QED 0.16
Compound (SMILES): O=[N+]([O-])c1ccc(-c2nc3ccc(Br)cc3[nH]2)cc1
InChIKey: AAKXXFVQNJXNTI-UHFFFAOYSA-N
Target: Neutrophil collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P22894
Assay: Inhibition of recombinant human MMP8 catalytic domain (Phe99 to Gln269 residues) expressed in Escherichia coli cells using Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2/TQ3-GABA-Pro-Cha-Abu-Smc-His-Ala-Dab(6'-TAMRA)-Ala-Lys-NH2 as fluorogenic substrate preincubated for 15 mins followed by substrate addition measured after 2 to 4 hrs by fluorometric assay
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 318.13, ALogP 3.9, HBA 3, HBD 1, PSA 71.82, QED 0.58
Compound (SMILES): CCOc1cc(Cl)c(-c2ccc(-c3nc4c(s3)CN(C(=O)CO)CC4)c(=O)[nH]2)cc1N1CCOCC1
InChIKey: LZRSMQARMRZWHQ-UHFFFAOYSA-N
Target: Growth hormone secretagogue receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92847
Assay: Displacement of [125I]-ghrelin from human GHS-R1a stably expressed in HEK cell membrane measured after 60 mins by gamma counter method
Measurement: IC50 = 1900 nM (pChEMBL 5.71999979019165)
Descriptors: MW 531.03, ALogP 2.93, HBA 8, HBD 2, PSA 107.99, QED 0.5
Compound (SMILES): CC(C)OC(=O)[C@H](C)N[P@](=O)(OC[C@H]1O[C@@H](n2ccc(=O)[nH]c2=O)[C@](Cl)(Br)[C@@H]1OC(=O)[C@@H](N)C(C)C)Oc1cccc2ccccc12
InChIKey: WORYNCYYTQIJJT-RZPXDGBLSA-N
Target: RNA-directed RNA polymerase (SINGLE PROTEIN), Hepacivirus hominis
UniProt: O39930
Assay: Inhibition of NS5B polymerase in HCV genotype 1b Con1 infected in human HuH7 replicon cells assessed as inhibition of viral replication after 3 days by luciferase reporter gene assay
Measurement: EC50 = 99 nM (pChEMBL 7)
Descriptors: MW 759.98, ALogP 3.95, HBA 12, HBD 3, PSA 190.27, QED 0.13
Compound (SMILES): CC[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)c1ccc(Br)cc1)C(=O)N[C@H](C(=O)N[C@@H](CCCC[N+](C)(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCCNC(=S)Nc1ccc(-c2c3ccc(=O)cc-3oc3cc(O)ccc23)c(C(=O)O)c1)C(N)=O)C1CCCC1
InChIKey: XSHXVWHTZPAYJC-TYYHSMTLSA-O
Target: Chromobox protein homolog 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14781
Assay: Binding affinity to CBX2 (unknown origin) assessed as dissociation constant by fluorescence polarization analysis
Measurement: Kd = 390 nM (pChEMBL 6.409999847412109)
Descriptors: MW 1462.51
Compound (SMILES): O=C(/C=C/CN1CCCC1)N1CCOc2cc3ncnc(Nc4ccc(OCc5cccc(F)c5)c(Cl)c4)c3cc21
InChIKey: ZZCPVBCYUULJEG-QPJJXVBHSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin) using FAM-labeled peptide as substrate preincubated for 10 mins followed by substrate addition measured after 40 mins in presence of ATP by caliper mobility shift assay
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 574.06, ALogP 6.12, HBA 7, HBD 1, PSA 79.82, QED 0.25
Compound (SMILES): CSc1cc(C)[nH]c(=O)c1CNC(=O)c1c(C)n([C@H](C)[C@H]2CC[C@H](N3CC(OC4CC4)C3)CC2)c2ncc(Cl)cc12
InChIKey: MPITVRQQHZHYDK-SYYKKAFVSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Inhibition of EZH2 in human HeLa cells assessed as inhibition of trimethylation of H3K27 after 72 hrs by AlphaLISA assay
Measurement: EC50 = 3.5 nM (pChEMBL 8.460000038146973)
Descriptors: MW 598.21, ALogP 5.63, HBA 7, HBD 2, PSA 92.25, QED 0.31
Compound (SMILES): C[C@@H]1[C@@H]2CN(c3nc(Nc4cnn(C)c4)ncc3F)C[C@]12NC(=O)[C@H]1CC1(F)F
InChIKey: VFTQZQGHFFDMQS-OFVQYIOZSA-N
Target: JAK1/TYK2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P29597
Assay: Inhibition of JAK1/TYK2 in human whole blood assessed as EPO signalling in CD34+ cells by flow cytometry
Measurement: IC50 = 18837 nM (pChEMBL 4.71999979019165)
Descriptors: MW 407.4, ALogP 1.69, HBA 7, HBD 2, PSA 87.97, QED 0.78
Compound (SMILES): CC1(C)CN2CCNCc3ccc(Cl)c1c32
InChIKey: HZQVOKXAHUWYNB-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Displacement of [125I]-1,4-Iodanyl-2,5-dimethoxyphenyl)propan-2amine from 5HT2C receptor (unknown origin)
Measurement: Ki = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 236.75, ALogP 2.54, HBA 2, HBD 1, PSA 15.27, QED 0.74
Compound (SMILES): C[C@@H]1COCCN1c1cc(C#Cc2cccnc2)c2ccnc(-c3ccn[nH]3)c2n1
InChIKey: RWXHVVLROWZSKK-MRXNPFEDSA-N
Target: Serine/threonine-protein kinase ATR (SINGLE PROTEIN), Homo sapiens
UniProt: Q13535
Assay: Inhibition of ATR in human HT-29 cells assessed as reduction in histone H2AX phosphorylation measured after 30 mins by immunofluorescence cytometric assay
Measurement: IC50 = 227 nM (pChEMBL 6.639999866485596)
Descriptors: MW 396.45, ALogP 3.04, HBA 6, HBD 1, PSA 79.82, QED 0.52
Compound (SMILES): NC(=O)c1ccc(Nc2ncc(C(F)(F)F)c(N3CC[C@H](O)C3)n2)cc1
InChIKey: ILQXDUWEGPNDGI-NSHDSACASA-N
Target: Tyrosine-protein kinase Lck (SINGLE PROTEIN), Homo sapiens
UniProt: P06239
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human Lck using TK-substrate-biotin as substrate incubated for 60 mins in presence of ATP by fluorescence method
Measurement: IC50 = 5900 nM (pChEMBL 5.230000019073486)
Descriptors: MW 367.33, ALogP 1.91, HBA 6, HBD 3, PSA 104.37, QED 0.76
Compound (SMILES): CCc1nc(-c2ccc(-c3ccc(CC[C@@](N)(CO)COP(=O)(O)O)cc3)cc2)co1
InChIKey: LWBXSTRPHHBOPE-JOCHJYFZSA-N
Target: Sphingosine 1-phosphate receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99500
Assay: Agonist activity at S1PR3 (unknown origin) by HTRF assay
Measurement: EC50 = 736 nM (pChEMBL 6.130000114440918)
Descriptors: MW 446.44, ALogP 3.3, HBA 6, HBD 4, PSA 139.04, QED 0.35
Compound (SMILES): O=S(=O)(NCc1cccc2ccccc12)c1cc(Cl)c(Oc2cccc(N3CCNCC3)c2)s1
InChIKey: YAAVQYDOVJQDFZ-UHFFFAOYSA-N
Target: Beta-glucuronidase (SINGLE PROTEIN), Homo sapiens
UniProt: P08236
Assay: β-Glucuronidase Activity Assay: The β-glucuronidase assay was performed by the addition of 0.5 μl of compound (or DMSO) to the well of a black 384-well plate followed by the addition of 30 μl of diluted β-glucuronidase enzyme. The enzyme was diluted in assay buffer (50 mM HEPES, pH 7.4) plus 0.0166% Triton X-100 for a final enzyme concentration of 50 pM and final detergent concentration of 0.01%. After a 15 minute incubation at room temperature (23° C.), 20 ul of substrate, 4-Methylumbelliferyl β-D-glucuronide hydrate (4MUG) diluted into assay buffer, was added to the reaction for a final concentration of 125 uM. β-glucuronidase hydrolyzes the non-fluorescent 4MUG resulting in a fluorescent product, 4-methylumbelliferyl. After a 30 minute incubation at room temperature, the reaction was stopped by the addition of 20 ul 1 M Na2CO3. The fluorescence (in relative fluorescence units, RFU) was measured using a 355 nm excitation filter and 460 nm emission filter using a Victor V (Perkin Elmer) plate reader. Minimum (min) controls were performed using reactions with no enzyme. Maximum (max) controls were performed using no compound. 1% DMSO was maintained in all reactions. Percent inhibition was calculated using RFU data by the following formula: [1−(assay readout-average of min)/(Average of Max-Average of Min)]×100
Measurement: IC50 = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 514.07, ALogP 5.24, HBA 6, HBD 2, PSA 70.67, QED 0.35
Compound (SMILES): CCN1CCN(c2ccc(Nc3ncc(Cl)c(Nc4ccccc4C)n3)nc2)CC1
InChIKey: QGXCAHQDBNSMDO-UHFFFAOYSA-N
Target: CDK9/Cyclin K (PROTEIN COMPLEX), Homo sapiens
UniProt: O75909
Assay: Inhibition of recombinant human full-length N-terminal GST-tagged CDK9/cyclinK expressed in baculovirus infected Sf9 insect cells using PDKtide as substrate measured after 120 mins by ADP-glo assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 423.95, ALogP 4.46, HBA 7, HBD 2, PSA 69.21, QED 0.61
Compound (SMILES): CCOc1cc(Cl)c(CNC(=O)Nc2nc3ccc(CN4CCN(C)CC4)cc3s2)cc1N1CCOCC1
InChIKey: KXJSTUSYZFHZMG-UHFFFAOYSA-N
Target: Growth hormone secretagogue receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92847
Assay: Displacement of [125I]-ghrelin from human GHS-R1a stably expressed in HEK cell membrane measured after 60 mins by gamma counter method
Measurement: IC50 > 4970 nM (pChEMBL 5.303999900817871)
Descriptors: MW 559.14, ALogP 4.25, HBA 8, HBD 2, PSA 82.2, QED 0.43
Compound (SMILES): N#Cc1ccccc1COc1ccc([C@H]2CC[C@@H](C(N)=O)N2)cc1
InChIKey: VVXOEXVYDZBBRP-MSOLQXFVSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 = 15848.93 nM (pChEMBL 4.800000190734863)
Descriptors: MW 321.38, ALogP 2.42, HBA 4, HBD 2, PSA 88.14, QED 0.88
Compound (SMILES): Cc1noc(C)c1-c1cc2ncc3c(c2cc1OCCCO)n(C(C)c1ccccn1)c(=O)n3C
InChIKey: UHCSXLDQYABTLW-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of Alexa Fluor 647 labelled I-BET762 from N-terminal His6-tagged human BRD4 BD1 (1 to 477 residues)/BD2 Y390A mutant expressed in Escherichia coli after 1 hr by TR-FRET assay
Measurement: IC50 = 501.19 nM (pChEMBL 6.300000190734863)
Descriptors: MW 473.53, ALogP 3.93, HBA 9, HBD 1, PSA 108.2, QED 0.36
Compound (SMILES): COc1nc2ccccc2cc1-c1cnc([C@@H](N)CCCCCC(=O)c2ncc[nH]2)[nH]1
InChIKey: QWCIDQYVYURRSR-KRWDZBQOSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of full length human recombinant FLAG-tagged HDAC2 expressed in baculovirus infected Sf9 cells using FLUOR DE LYS as substrate preincubated for 3 hrs followed by substrate addition and measured after 60 mins by fluorescence based assay
Measurement: IC50 = 4900 nM (pChEMBL 5.309999942779541)
Descriptors: MW 418.5, ALogP 4.19, HBA 6, HBD 3, PSA 122.57, QED 0.26
Compound (SMILES): CC(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CC(C)C)C(=O)[C@]1(C)CO1
InChIKey: QWEBSYDRFXZQMF-LFYAFONDSA-N
Target: Proteasome component C5 (SINGLE PROTEIN), Homo sapiens
UniProt: P20618
Assay: Inhibition of Beta1 subunit in human 20S proteasome using Ac-nLPnLD-AMC as substrate after 1 hr by fluorescence based microplate reader analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 514.62, ALogP 0.73, HBA 6, HBD 3, PSA 137.21, QED 0.35
Compound (SMILES): CNC(=O)c1cc(C(=O)NC2CC2)cn(Cc2ccccc2)c1=O
InChIKey: QZZCUOVXHPAQRQ-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to 6His-Thr-BRD4 (1 to 477 residues) BD1 domain (unknown origin) incubated for 30 mins by TR-FRET assay
Measurement: IC50 = 15848.93 nM (pChEMBL 4.800000190734863)
Descriptors: MW 325.37, ALogP 1.15, HBA 4, HBD 2, PSA 80.2, QED 0.87
Compound (SMILES): CCSSc1nc2ccccc2s1
InChIKey: JJOOBYVUSPDHJX-UHFFFAOYSA-N
Target: Fructose-1,6-bisphosphatase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09467
Assay: Inhibition of human liver FBPase C38S mutant expressed in Escherichia coli BL21 (DE3) using FBP as substrate incubated for 5 mins by malachite green dye based assay
Measurement: IC50 = 6600 nM (pChEMBL 5.179999828338623)
Descriptors: MW 227.38, ALogP 4.06, HBA 4, HBD 0, PSA 12.89, QED 0.73
Compound (SMILES): COc1cc(CN(C)C(=O)c2c(OCCCC3CCN(C(=O)OC(C)(C)C)CC3)c3cnccc3n(C)c2=O)cc(OC)c1
InChIKey: DXFXDYPGRZJZOG-UHFFFAOYSA-N
Target: Phosphatidylcholine:ceramide cholinephosphotransferase 2 (SINGLE PROTEIN), Mus musculus
UniProt: Q9D4B1
Assay: Inhibition of mouse recombinant C-terminal FLAG-tagged SMS2 expressed in mammalian expression system using C14-phosphatidylcholineD72 and C17-ceramide pre-incubated for 60 mins followed by incubation with substrate for 30 mins measured by RapidFire/MS assay
Measurement: IC50 = 340 nM (pChEMBL 6.46999979019165)
Descriptors: MW 608.74, ALogP 5.03, HBA 9, HBD 0, PSA 112.43, QED 0.29
Compound (SMILES): C[N+](C)(C)C[C@@H]1COC[C@H](c2ccc(-c3ccccc3)cc2)O1.[I-]
InChIKey: MUQJZAPXKBFEGH-GZJHNZOKSA-M
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]NMS from human recombinant muscarinic receptor M2 expressed in CHO-K1 cell membranes incubated for 2 hrs by scintillation counting method
Measurement: Ki = 8709.64 nM (pChEMBL 5.059999942779541)
Descriptors: MW 312.43, ALogP 3.52, HBA 2, HBD 0, PSA 18.46, QED 0.8
Compound (SMILES): NS(=O)(=O)Oc1ccc(NC(=O)C23CC4CC(CC(C4)C2)C3)cc1
InChIKey: GVPUYCLSISISPD-UHFFFAOYSA-N
Target: Steryl-sulfatase (SINGLE PROTEIN), Homo sapiens
UniProt: P08842
Assay: Inhibition of steroid sulfatase in human JEG3 cells using [3H] E1S as substrate incubated for 20 hrs by scintillation spectrometry analysis
Measurement: IC50 = 13.6 nM (pChEMBL 7.869999885559082)
Descriptors: MW 350.44, ALogP 2.42, HBA 4, HBD 2, PSA 98.49, QED 0.87
Compound (SMILES): C[C@H]1C[C@H](C(=O)O)CC[C@H]1C(=O)N1CC[C@@]2(S(=O)(=O)c3cccc(F)c3)c3ccc(C(F)(C(F)(F)F)C(F)(F)F)cc3CC[C@@H]12
InChIKey: YMYVBTYBEJRHKZ-QOTTZFGFSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at RORgammat in CD3 and CD28-stimulated human whole blood assessed as suppression of IL17 incubated for 1 hr before CD3 and CD28 stimulation for 20 hrs by AlphaLISA method
Measurement: EC50 = 38 nM (pChEMBL 7.420000076293945)
Descriptors: MW 667.61, ALogP 6.47, HBA 4, HBD 1, PSA 91.75, QED 0.37
Compound (SMILES): c1cn2cc(-c3ccc4nc[nH]c4c3)nc(Nc3ccc(N4CCN(C5COC5)CC4)cc3)c2n1
InChIKey: FRELFUBHIVXDTH-UHFFFAOYSA-N
Target: Tyrosine-protein kinase SYK (SINGLE PROTEIN), Homo sapiens
UniProt: P43405
Assay: Inhibition of SYK in human Ramos cells assessed as reduction in antihuman IgM F(ab)2-induced phosphorylation of BLNK at Y96 residue preincubated for 1 hr followed by antihuman IgM F(ab)2 stimulation for 5 mins by MSD high bind plate assay
Measurement: EC50 = 47 nM (pChEMBL 7.329999923706055)
Descriptors: MW 466.55, ALogP 3.54, HBA 8, HBD 2, PSA 86.61, QED 0.41
Compound (SMILES): Cc1cc(Cl)cc(-c2ccnc3cc(CN4C(=O)C5C(C4=O)C5(C)C)sc23)c1O[C@@H]1CCNC[C@@H]1C
InChIKey: LSPPODQSTNTKTE-AAORLSLPSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q93009
Assay: Inhibition of USP7 in human RKO cells transfected with p53 luciferase reporter vector assessed as increase in p53-dependent luciferase activity measured after 18 hrs by BrightGlo luciferase assay
Measurement: EC50 = 65 nM (pChEMBL 7.190000057220459)
Descriptors: MW 524.09, ALogP 5.44, HBA 6, HBD 1, PSA 71.53, QED 0.45
Compound (SMILES): CN(C)[C@H]1C[C@@]23CC[C@@]4(O2)C(=CC[C@]2(C)[C@@H](c5ccc6cnccc6c5)CC[C@H]24)C=C3[C@@H](O)[C@@H]1O
InChIKey: VTGCFFPYJCEAMB-DZBMUNJRSA-N
Target: Cyclin-dependent kinase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: P49336
Assay: Inhibition of biotinylated ligand binding to wild-type human partial length CDK8 (M1 to T360 residues) expressed in Escherichia coli BL21 measured after 1 hr by kinomescan assay
Measurement: Kd = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 472.63, ALogP 4.35, HBA 5, HBD 2, PSA 65.82, QED 0.68
Compound (SMILES): COc1ccccc1CCC(C)(C)NC[C@H](O)c1cc(O)cc2c1OCC(=O)N2.Cl
InChIKey: TYLKWSHZYCHATG-FERBBOLQSA-N
Target: Beta-1 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08588
Assay: Agonist activity at human beta1 adrenoreceptor overexpressed in human HEK293 cells assessed as cAMP accumulation incubated for 60 mins by HTRF assay
Measurement: EC50 = 1.413 nM (pChEMBL 8.850000381469727)
Descriptors: MW 400.48, ALogP 2.77, HBA 6, HBD 4, PSA 100.05, QED 0.54
Compound (SMILES): Cn1cc(-c2ncc(C#N)c(N3C[C@@H]4C[C@H]3CN4C(=O)C3CC3)n2)cn1
InChIKey: BAPNSRDKEKRQFX-GJZGRUSLSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3K delta in human whole blood assessed as inhibition of anti-IgE-stimulated CysLt release in basophils preincubated for 30 mins followed by anti-IgE stimulation and measured after 20 mins
Measurement: IC50 = 258 nM (pChEMBL 6.590000152587891)
Descriptors: MW 349.4, ALogP 0.95, HBA 7, HBD 0, PSA 90.94, QED 0.82
Compound (SMILES): COCCOc1cc(N)c2nc(O)n(Cc3ccc(C(=O)N[C@H]4[C@H](O)[C@H]5O[C@H]6[C@H](O)[C@@H](O)[C@@H](O[C@H]7[C@H](O)[C@@H](O)[C@@H](O[C@H]8[C@H](O)[C@@H](O)[C@@H](O[C@H]9[C@H](O)[C@@H](O)[C@@H](O[C@H]%10[C@H](O)[C@@H](O)[C@@H](O[C@H]%11[C@H](O)[C@@H](O)[C@@H](O[C@@H]4[C@@H](CO)O5)O[C@@H]%11CO)O[C@@H]%10CO)O[C@@H]9CO)O[C@@H]8CO)O[C@@H]7CO)O[C@@H]6CO)cc3)c2c1
InChIKey: FXJGFWWFNHGIBW-LDRYABBWSA-N
Target: Toll-like receptor 7 (SINGLE PROTEIN), Mus musculus
UniProt: P58681
Assay: Agonist activity at TLR7 in mouse BMDC cells assessed as immunostimulatory activity by measuring increase in IL6 secretion incubated for 18 hrs by ELISA
Measurement: EC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 1473.35
Compound (SMILES): COc1cc(N2CC(NC(=O)c3cn4c(C)c(C)nc4cn3)C2)c(Cl)cn1
InChIKey: KJXQSWPECRUGIT-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M4 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P08485
Assay: Positive allosteric modulation of rat muscarinic M4 receptor
Measurement: EC50 = 295 nM (pChEMBL 6.53000020980835)
Descriptors: MW 386.84, ALogP 2.02, HBA 7, HBD 1, PSA 84.65, QED 0.74
Compound (SMILES): O=C(O)C(=O)Nc1ccc(C#Cc2ccc3ccccc3c2)cc1
InChIKey: ICWIKZSSOKYBHJ-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: Inhibition of SHP2 (unknown origin) expressed in Escherichia coli BL21 using p-nitrophenyl phosphate as substrate measured after 30 mins by UV-vis spectrophotometric method
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 315.33, ALogP 3.26, HBA 2, HBD 2, PSA 66.4, QED 0.53