lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): NCCc1cc(S(N)(=O)=O)ccc1Oc1ccc(F)c(Cl)c1
InChIKey: WDVWTPNEVTYLQC-UHFFFAOYSA-N
Target: Son of sevenless homolog 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07889
Assay: Agonist activity at His6-tagged-human SOS1 catalytic domain (564 to 1049 residues) expressed in Escherichia coli BL21-CodonPlus-RIPL cells assessed as increase in SOS1-mediated GDP/GTP nucleotide exchange upon K-Ras G12D mutant (1 to 169 residues) by BODIPY-GDP assay
Measurement: EC50 = 1320 nM (pChEMBL 5.880000114440918)
Descriptors: MW 344.8, ALogP 2.42, HBA 4, HBD 2, PSA 95.41, QED 0.87
Compound (SMILES): COc1ccc(-c2cnn3c(N)c(-c4nccs4)c(OC4CCN(C)CC4)nc23)cc1OC
InChIKey: OPRQSQDMYPVYOV-UHFFFAOYSA-N
Target: Kinesin-1 heavy chain/ Tyrosine-protein kinase receptor RET (CHIMERIC PROTEIN), Homo sapiens
UniProt: P07949
Assay: Inhibition of KIF5B-RET V804M mutant (unknown origin) transfected in mouse Ba/F3 cells assessed as reduction in cell viability incubated for 48 hrs by brightglo-luciferase reporter gene assay
Measurement: IC50 = 610 nM (pChEMBL 6.210000038146973)
Descriptors: MW 466.57, ALogP 3.59, HBA 10, HBD 1, PSA 100.03, QED 0.46
Compound (SMILES): CCCCc1nc(=O)cc(O)n1-c1ccccc1OC
InChIKey: FZZNDWZADHKAGJ-UHFFFAOYSA-N
Target: Apelin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35414
Assay: Agonist activity at human APJ expressed in HEK293 cells assessed as inhibition of forskolin-stimulated cAMP production
Measurement: EC50 = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 274.32, ALogP 2.29, HBA 5, HBD 1, PSA 64.35, QED 0.91
Compound (SMILES): CC(C)Cc1nc(-c2nnc(CC(C)(C)C(=O)O)o2)sc1-c1ccc(S(=O)(=O)N[C@@H](C)C(F)(F)F)c(F)c1C(F)F
InChIKey: CZZWOGGSAFJKEU-NSHDSACASA-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 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 628.62, ALogP 6.02, HBA 8, HBD 2, PSA 135.28, QED 0.25
Compound (SMILES): Br.CSc1nc2ccccc2n1-c1csc(=N)n1CC(=O)c1ccccc1
InChIKey: QXJFGBCXQWQNKE-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Inhibition of human recombinant COX2 using arachidonic acid as substrate preincubated for 10 mins followed by substrate addition and measured after 2 mins by EIA
Measurement: IC50 = 180 nM (pChEMBL 6.75)
Descriptors: MW 380.5, ALogP 3.97, HBA 7, HBD 1, PSA 63.67, QED 0.42
Compound (SMILES): c1cn2cc(-c3ccc4cn[nH]c4c3)nc(Nc3ccc(N4CC5COCC5C4)cc3)c2n1
InChIKey: HXAUKOJONYIXCH-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 = 187 nM (pChEMBL 6.730000019073486)
Descriptors: MW 437.51, ALogP 4.1, HBA 7, HBD 2, PSA 83.37, QED 0.44
Compound (SMILES): CS(=O)(=O)c1sc(-c2ccc(C#N)c(F)c2)c2c1[C@H](O)C(F)(F)C2
InChIKey: SOGLLVPAKXSELZ-ZDUSSCGKSA-N
Target: Endothelial PAS domain-containing protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99814
Assay: Inhibition of HIF2-alpha in human 786-0 cells cells harboring HRE-Luc2P reporter construct incubated for 48 hrs by ONE-Glo EX reagent based luminescence assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 373.38, ALogP 3.05, HBA 5, HBD 1, PSA 78.16, QED 0.88
Compound (SMILES): O=C(O)Cc1cc(Br)c(Oc2cc(I)c(O)c(I)c2)c(I)c1
InChIKey: KTERKZCXUGODHD-UHFFFAOYSA-N
Target: Thyroid hormone receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P10827
Assay: Agonist activity at THRalpha (unknown origin) incubated for 14 to 16 hrs by dual glo luciferase reporter gene assay
Measurement: EC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 700.83, ALogP 5.39, HBA 3, HBD 2, PSA 66.76, QED 0.42
Compound (SMILES): CC(C)c1cc(-c2ccc3c(c2)[C@H](N)CO3)cc([C@H](O)Cn2ccc3cccc(C(=O)O)c32)c1
InChIKey: GOERAAJVARXHDP-JWQCQUIFSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: Inhibition of N-terminal human plasma F11a catalytic domain expressed in Escherichia coli strain BL21(DE3) using D-Leu-Pro-Arg*Rh110-D-Pro as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by fluorescence assay
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 456.54, ALogP 5.26, HBA 5, HBD 3, PSA 97.71, QED 0.37
Compound (SMILES): COc1cccc(OC)c1-c1cc(C(=O)N[C@@H](CCc2ccccc2)CC(=O)O)nn1CC(C)C
InChIKey: PHWLRUWQFPDCSZ-FQEVSTJZSA-N
Target: Apelin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35414
Assay: Agonist activity at human APJ receptor stably expressed in CHOK1 cells assessed as induction of beta-arrestin 2 recruitment incubated for 90 mins by PathHunter assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 479.58, ALogP 4.43, HBA 6, HBD 2, PSA 102.68, QED 0.4
Compound (SMILES): CN1CCN(CCC(=O)Nc2ccc(-c3cn4c(=O)n(-c5ccccc5)nc4c(N)n3)cc2)CC1
InChIKey: XYSRFXJWVVBKGT-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Displacement of [3H]-NECA from human A2A receptor expressed in CHO cells
Measurement: Ki = 11.03 nM (pChEMBL 7.960000038146973)
Descriptors: MW 472.55, ALogP 1.71, HBA 9, HBD 2, PSA 113.79, QED 0.44
Compound (SMILES): CC(=O)N[C@@H]1CCCc2c1cncc2N1C(=O)c2ccc(Cl)cc2[C@H]1C
InChIKey: GELKDNJSUBLFHD-ADLMAVQZSA-N
Target: Cytochrome P450 11B1, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P15538
Assay: Inhibition of human CYP11B1 expressed in human renal leiomyoblastoma cells harboring FDXR/FDX using 1-deoxycortisol as substrate by HTRF assay
Measurement: IC50 = 5137 nM (pChEMBL 5.289999961853027)
Descriptors: MW 369.85, ALogP 3.97, HBA 3, HBD 1, PSA 62.3, QED 0.87
Compound (SMILES): CC(C)=CCCC1=CC[C@H](C(=O)Nc2ccc(O)cc2)[C@@H](c2ccccc2)C1
InChIKey: YHTHEHWLTPHYSR-BJKOFHAPSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Inhibition of Mcl-1 (unknown origin)/Bid interaction preincubated for 5 mins followed by fluorescein-labeled peptide addition and measured after 10 mins by fluorescein-labeled peptide displacement based fluorescence polarization assay
Measurement: Ki > 33000 nM (pChEMBL 4.480999946594238)
Descriptors: MW 375.51, ALogP 6.2, HBA 2, HBD 2, PSA 49.33, QED 0.47
Compound (SMILES): O=C(NCc1ccccc1)C(F)(F)C(O)CCc1ccccc1
InChIKey: INCSMEXWPSKUGX-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 319.35, ALogP 2.93, HBA 2, HBD 2, PSA 49.33, QED 0.82
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](C)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](Cc1ccccc1)NC(=O)CCNC(=S)Nc1ccc(-c2c3ccc(=O)cc-3oc3cc(O)ccc23)c(C(=O)O)c1)C(=O)N[C@@H](CCCC[N+](C)(C)C)C(=O)N[C@@H](CO)C(N)=O
InChIKey: DWHVELUHKZEMNM-CSSHXORXSA-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 = 3100 nM (pChEMBL 5.510000228881836)
Descriptors: MW 1214.43
Compound (SMILES): CC(C)=CCCC1=CC[C@@H](C(=O)O)[C@H](c2ccccc2)C1
InChIKey: GZLLWIUBFDJKDF-MSOLQXFVSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Inhibition of Mcl-1 (unknown origin)/Bid interaction preincubated for 5 mins followed by fluorescein-labeled peptide addition and measured after 10 mins by fluorescein-labeled peptide displacement based fluorescence polarization assay
Measurement: Ki = 8600 nM (pChEMBL 5.070000171661377)
Descriptors: MW 284.4, ALogP 4.94, HBA 1, HBD 1, PSA 37.3, QED 0.78
Compound (SMILES): N#CN1CC(OCc2ccc(-c3ccc4c(c3)OCO4)cc2)(c2ccccc2)C1
InChIKey: ZXODXOZCUBULBX-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 384.44, ALogP 4.29, HBA 5, HBD 0, PSA 54.72, QED 0.61
Compound (SMILES): NCCCN(CCc1ccccc1)CC(=O)N(CCc1ccc(S(N)(=O)=O)cc1)Cc1ccc(F)cc1
InChIKey: PTOFZDQATQXAPS-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human CA2 preincubated for 15 mins by stopped-flow CO2 hydration kinetic assay based Cheng-Prusoff equation analysis
Measurement: Ki = 30.4 nM (pChEMBL 7.519999980926514)
Descriptors: MW 526.68, ALogP 2.94, HBA 5, HBD 2, PSA 109.73, QED 0.34
Compound (SMILES): CCNS(=O)(=O)c1ccccc1Nc1ncnc(Nc2ccc(N3CCN(C)CC3)c(OCCN3CCN(C)CC3)c2)n1.Cl.Cl.Cl.Cl
InChIKey: PIKUZLCFIOUWGA-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 = 341 nM (pChEMBL 6.46999979019165)
Descriptors: MW 610.79, ALogP 2.04, HBA 12, HBD 3, PSA 131.09, QED 0.28
Compound (SMILES): CC/C(=C\c1ccccc1)[C@@H]1C[C@H]1NC1CCN(CCO)CC1
InChIKey: WMGGSTWZOXPKQC-KSRMRMEDSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Inhibition of recombinant N-terminal His-tagged LSD1 (unknown origin) expressed in Escherichia coli expression system using ART-K(Me1)-QTARKSTGGKAPRKQLAGGK(Biotin) as substrate incubated for 60 mins by TR-FRET assay
Measurement: IC50 < 2.6 nM (pChEMBL 8.585000038146973)
Descriptors: MW 314.47, ALogP 2.91, HBA 3, HBD 2, PSA 35.5, QED 0.81
Compound (SMILES): Cc1cccc(OCCNC(=O)COc2ccc(CC(=O)O)cc2)c1
InChIKey: RRIXASOOURNNQY-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor delta (SINGLE PROTEIN), Homo sapiens
UniProt: Q03181
Assay: Agonist activity at PPARdelta (unknown origin)
Measurement: EC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 343.38, ALogP 2.2, HBA 4, HBD 2, PSA 84.86, QED 0.68
Compound (SMILES): NC(=O)[C@@H]1CCC[C@H](c2ccc(OCc3cccc(F)c3)cc2)N1
InChIKey: QNXQSFGSRNYTGG-MSOLQXFVSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 = 31622.78 nM (pChEMBL 4.5)
Descriptors: MW 328.39, ALogP 3.07, HBA 3, HBD 2, PSA 64.35, QED 0.89
Compound (SMILES): CCCn1nc(C(=O)N[C@@H](CCC2CCCCC2)CC(=O)O)cc1-c1c(OC)cccc1OC
InChIKey: SRBJMCFCCIYEJA-IBGZPJMESA-N
Target: Apelin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35414
Assay: Agonist activity at human APJ receptor stably expressed in CHO cells co-expressing Galphaq16 assessed as increase in intracellular calcium mobilization measured at 1 sec intervals for 90 secs by calcium 5 dye based FLIPR assay
Measurement: EC50 = 416 nM (pChEMBL 6.380000114440918)
Descriptors: MW 471.6, ALogP 4.91, HBA 6, HBD 2, PSA 102.68, QED 0.46
Compound (SMILES): CCC(=O)CCCCCC(Oc1ccc2ccccc2c1)c1ncc(Cc2ccccc2)[nH]1
InChIKey: QAGAFOZDNIQYCO-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of human HDAC3
Measurement: IC50 = 4500 nM (pChEMBL 5.349999904632568)
Descriptors: MW 440.59, ALogP 7.2, HBA 3, HBD 1, PSA 54.98, QED 0.24
Compound (SMILES): COc1ccccc1CNc1nc(Nc2ccc(N3CCN(C)CC3)cn2)ncc1Cl
InChIKey: RRLQCJAXXYKHSZ-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 439.95, ALogP 3.64, HBA 8, HBD 2, PSA 78.44, QED 0.58
Compound (SMILES): C/C=C/C[C@@H]1NC(=O)[C@H](CC(C)C)N2C(=O)[C@H](C[C@](C)(O)[C@H]2O)N(C)C(=O)[C@H](C)NC(=O)[C@H](Cc2ccc(O)c([N+](=O)[O-])c2)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](Cc2cn(C(C)(C)[C@H]3CO3)c3ccccc23)NC1=O
InChIKey: LQUGKKZRMQHZBT-QSUUQULHSA-N
Target: ATP-dependent Clp protease ATP-binding subunit ClpC1 (SINGLE PROTEIN), Mycobacterium tuberculosis
UniProt: P9WPC9
Assay: Binding affinity to recombinant full length Mycobacterium tuberculosis H37Rv ClpC1 (1 to 842 residues) expressed in Escherichia coli BL21 cells by surface plasmon resonance analysis
Measurement: Kd = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 1058.24
Compound (SMILES): COC(=O)C1=C(N)Oc2cc(O)ccc2C1c1ccccc1
InChIKey: PIQPAUJUVOMPJC-UHFFFAOYSA-N
Target: Estrogen receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q92731
Assay: Displacement of fluorescent estrogen ligand from recombinant human full length untagged ERbeta expressed in baculovirus infected insect cells incubated in dark for 2 hrs by Beacon single-tube fluorescent polarization assay
Measurement: IC50 = 1590 nM (pChEMBL 5.800000190734863)
Descriptors: MW 297.31, ALogP 2.26, HBA 5, HBD 2, PSA 81.78, QED 0.83
Compound (SMILES): COc1cc(C(=O)N[C@@H]2C[C@H]3CCC[C@@H](C2)N3Cc2nc3c(C(F)(F)F)cccc3s2)cc(OC)c1OC
InChIKey: OZAGNFAFPKLYFB-NNZMDNLPSA-N
Target: C-X-C chemokine receptor type 6 (SINGLE PROTEIN), Homo sapiens
UniProt: O00574
Assay: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of forskolin-induced cAMP accumulation by DiscoveRx cell based assay
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 549.62, ALogP 5.66, HBA 7, HBD 1, PSA 72.92, QED 0.41
Compound (SMILES): CC(C)(C)c1cc(C(=O)Nc2ccc(C(=O)NO)cc2)cc(C(C)(C)C)c1
InChIKey: ARAJVEZEAQIYLH-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of C-terminal FLAG-tagged full length human HDAC6 expressed in baculovirus expression system using FAM-RHKK(Ac)-NH2 substrate incubated for 5 hrs by EMSA method
Measurement: IC50 = 190 nM (pChEMBL 6.71999979019165)
Descriptors: MW 368.48, ALogP 4.65, HBA 3, HBD 3, PSA 78.43, QED 0.54
Compound (SMILES): N#CN1CC(OCc2ccc(Oc3ccccc3)cc2-c2ccccc2)C1
InChIKey: BIFMPKUNYXQFNL-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 356.43, ALogP 4.83, HBA 4, HBD 0, PSA 45.49, QED 0.59
Compound (SMILES): CCC(CC)NC(=O)COc1cccc(-c2nc3c(c(Nc4ccc(-c5cn[nH]c5)cc4)n2)CNCC3)c1
InChIKey: PFLIRYZYQDPALI-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P11169
Assay: Inhibition of GLUT3 in SLC2A1-deficient human DLD1 cells assessed as reduction in ATP level measured after 90 mins by Celltiter-glo luminescent assay
Measurement: IC50 = 121 nM (pChEMBL 6.920000076293945)
Descriptors: MW 511.63, ALogP 4.61, HBA 7, HBD 4, PSA 116.85, QED 0.25
Compound (SMILES): Cc1cc(-c2cc(-c3nnc[nH]3)c3nc(C)n(-c4ccnc5c(F)ccc(F)c45)c3c2)ccn1
InChIKey: GPBJZHQBTXHZRQ-UHFFFAOYSA-N
Target: PI3K p110 beta/p85 alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of recombinant human full-length N-terminal His6-tagged p110beta/human recombinant full-length untagged p85alpha expressed in baculovirus infected Sf21 insect cells using PIP2 as substrate after 30 mins in presence of ATP at 2xKm concentration by TR-FRET assay
Measurement: IC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 453.46, ALogP 5.32, HBA 6, HBD 1, PSA 85.17, QED 0.39
Compound (SMILES): CNCCN1CCC(c2ccc3[nH]c(-c4ccc(OC)c(OC)c4)c(CC(F)(F)F)c3c2)CC1
InChIKey: VSVZAIJDVKEDBW-UHFFFAOYSA-N
Target: Toll-like receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYK1
Assay: Antagonist activity at human TLR7 overexpressed in HEK-Blue cells assessed as inhibition of gardiquimod-induced NFkappaB and AP-1 activation preincubated for 30 mins followed by gardiquimod stimulation measured after 22 hrs by quanti-blue SEAP assay
Measurement: IC50 = 70 nM (pChEMBL 7.159999847412109)
Descriptors: MW 475.56, ALogP 5.36, HBA 4, HBD 2, PSA 49.52, QED 0.46
Compound (SMILES): C[C@H](c1ccc(Cl)cc1Cl)n1nc(C#N)c2ncc(N3CC([C@H]4CCCN(CCO)C4)C3)nc21
InChIKey: PNCGVFJZWKHMCL-CVEARBPZSA-N
Target: C-C chemokine receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P51679
Assay: Antagonist activity at CCR4 in human CCRF-CEM cells assessed as inhibition of CCL22-mediated chemotaxis preincubated for 30 mins followed by CCL22 addition and measured after 60 mins in presence of 100% human serum by CellTiter-Glo assay
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 500.43, ALogP 3.75, HBA 8, HBD 1, PSA 94.1, QED 0.55
Compound (SMILES): CC[C@H](NS(=O)(=O)c1ccc(-c2sc(-c3nnc(CC(C)(C)C(=O)O)o3)nc2CC2CCCC2)c(C(F)F)c1F)C(F)(F)F
InChIKey: ILHSEFVQHFQLRM-KRWDZBQOSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at RORgammat in human whole blood assessed as reduction in IL-17a production
Measurement: IC50 = 1341 nM (pChEMBL 5.869999885559082)
Descriptors: MW 668.68, ALogP 6.94, HBA 8, HBD 2, PSA 135.28, QED 0.2
Compound (SMILES): COc1cc(OC)c2c(C3CCN(C(=O)OC(C)(C)C)CC3)nc3c(OC)cccc3c2c1
InChIKey: IFTPQBHWUQDJRS-UHFFFAOYSA-N
Target: Protein fosB/Transcription factor jun-D (PROTEIN COMPLEX), Homo sapiens
UniProt: P17535
Assay: Inhibition of recombinant Hi6-tagged deltaFOSB (unknown origin)/His6-tagged JUND (unknown origin) expressed in insect cells interaction with TAMRA labeled 5'-GTCGGTGACTCAAAACA-3' AP1 oligonucleotide measured after 15 mins by fluorescence polarization assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 452.55, ALogP 5.53, HBA 6, HBD 0, PSA 70.12, QED 0.49
Compound (SMILES): COc1ccc2nc(NC(=O)c3ccc(N)cc3)sc2c1
InChIKey: CACZFXNLHCSKAL-UHFFFAOYSA-N
Target: Stearoyl-CoA desaturase (SINGLE PROTEIN), Homo sapiens
UniProt: O00767
Assay: Inhibition of SCD in human H2009 cells non-expressing CYP4F11 assessed as reduction in cell viability incubated for 96 hrs by cell titer Glo reagent based assay
Measurement: IC50 = 22000 nM (pChEMBL 4.659999847412109)
Descriptors: MW 299.36, ALogP 3.14, HBA 5, HBD 2, PSA 77.24, QED 0.73
Compound (SMILES): O=C(Nc1ccc(F)cc1-c1cc(F)c(F)c(F)c1)OCC1CCNCC1
InChIKey: PXFVYJJBXFKROG-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]N-methylscopolamine from human muscarinic M2 receptor transiently expressed in HEK293T cell membranes incubated for 1 hr by scintillation counting method
Measurement: Ki = 520 nM (pChEMBL 6.28000020980835)
Descriptors: MW 382.36, ALogP 4.46, HBA 3, HBD 2, PSA 50.36, QED 0.61
Compound (SMILES): O=C(O)c1cc(-c2ccc(C34CCNCC3C4)cc2)cc(-n2cc(-c3ccc(C(F)(F)F)cc3)nn2)c1
InChIKey: DPNFGEIZRQGOMX-UHFFFAOYSA-N
Target: P2Y purinoceptor 14 (SINGLE PROTEIN), Mus musculus
UniProt: Q9ESG6
Assay: Inhibition of MRS4174 binding to mouse P2Y14R expressed in HEK293 cells pre-incubated for 30 mins before MRS4174 addition and further incubated for 30 mins by flow cytomtery based competitive fluorescence assay
Measurement: IC50 = 1160 nM (pChEMBL 5.940000057220459)
Descriptors: MW 504.51, ALogP 5.57, HBA 5, HBD 2, PSA 80.04, QED 0.37
Compound (SMILES): N#CC[C@H](C1CCCC1)n1cc(-c2ncnc3c2CCN3)cn1
InChIKey: UETFOWMIAKXOBV-OAHLLOKOSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of recombinant epitope-tagged JAK1 (837-1142 residues) (unknown origin) in presence of ATP by time resolved fluorescence assay
Measurement: IC50 = 5.9 nM (pChEMBL 8.229999542236328)
Descriptors: MW 308.39, ALogP 2.95, HBA 6, HBD 1, PSA 79.42, QED 0.94
Compound (SMILES): CCOC(=O)c1c(O)c2ccncc2[nH]c1=O
InChIKey: BFUDSGXVTFJZFS-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P29375
Assay: Inhibition of KDM5A (unknown origin ) by Alphalisa analysis
Measurement: IC50 = 15.1 nM (pChEMBL 7.820000171661377)
Descriptors: MW 234.21, ALogP 0.81, HBA 5, HBD 2, PSA 92.28, QED 0.75
Compound (SMILES): COc1ccc(CCNc2nc(Nc3ccc(N4CCN(C)CC4)cn3)ncc2Cl)cc1
InChIKey: WCMWVOBTIFCSKN-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 453.98, ALogP 3.68, HBA 8, HBD 2, PSA 78.44, QED 0.53
Compound (SMILES): Cc1cn(-c2cc(CCC(=O)O)cc(NC(=O)c3ccc(C)c(Nc4nccc(-c5ccccc5)n4)c3)c2)cn1
InChIKey: WAMCWDPKWNPMHS-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Inhibition of recombinant human N-terminal GST-tagged PDGFRbeta cytoplasmic domain (557 to 1106 residues) expressed in baculovirus expression system using FAM-labelled P22 peptide as substrate preincubated for 10 mins followed by substrate addition and measured after 1 hr in presence of ATP by fluorescence assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 532.6, ALogP 5.96, HBA 7, HBD 3, PSA 122.03, QED 0.21
Compound (SMILES): Cn1c(C(F)(F)F)nc2ccc(C(=O)NC3CN(c4cc(Cl)ncc4Cl)C3)cc21
InChIKey: UTEYRHVGCRGHDX-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M4 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P08485
Assay: Positive allosteric modulation of rat muscarinic M4 receptor
Measurement: EC50 = 378 nM (pChEMBL 6.420000076293945)
Descriptors: MW 444.24, ALogP 3.91, HBA 5, HBD 1, PSA 63.05, QED 0.62
Compound (SMILES): COc1ccccc1-c1cc(Oc2ccccc2)ccc1COC1CN(C#N)C1
InChIKey: AESXPEFWGXSXMN-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 386.45, ALogP 4.84, HBA 5, HBD 0, PSA 54.72, QED 0.54
Compound (SMILES): C[C@@]1(c2cc(NC(=O)c3cnc(OCF)cn3)ccc2F)CCC(F)(F)C(N)=N1
InChIKey: HMMWZIDNPYYZHM-KRWDZBQOSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of BACE1 (unknown origin) assessed as reduction in Abeta42 level by cell based assay
Measurement: IC50 = 16.2 nM (pChEMBL 7.789999961853027)
Descriptors: MW 411.36, ALogP 3.18, HBA 6, HBD 2, PSA 102.49, QED 0.74
Compound (SMILES): C[C@@H]1[C@@H]2CN(c3nc(Nc4cnn(CCO)c4)ncc3F)C[C@]12NC(=O)[C@H]1C[C@@H]1C#N
InChIKey: LFICXKJWMGNAQX-ZQQUVUGCSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of human recombinant JAK1 assessed as level of phosphorylation in presence of peptide substrate 5FAM-KKSRGDYMTMQUID and ATP by mobility shift assay
Measurement: IC50 = 41 nM (pChEMBL 7.389999866485596)
Descriptors: MW 426.46, ALogP 0.65, HBA 9, HBD 3, PSA 131.99, QED 0.59
Compound (SMILES): Cc1noc(C)c1-c1ccc2c(c1)C(c1ccccc1)NC(=O)N2C
InChIKey: XFBRDTMFVAACDR-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of BRD4 bromodomain1 (unknown origin) using peptide histone H4 (SGRGACKGGACKGLGAC-KGGAACKRHGSGSK-biotin) as substrate incubated for 15 mins followed by substrate addition measured after 1 hr by alphascreen assay
Measurement: IC50 = 32 nM (pChEMBL 7.5)
Descriptors: MW 333.39, ALogP 4.21, HBA 3, HBD 1, PSA 58.37, QED 0.76
Compound (SMILES): O=C(NCCCNC(=O)c1cc2ccccc2[nH]1)c1ccc(-c2ccccc2)cc1
InChIKey: LMBPXYBGEFGQEZ-UHFFFAOYSA-N
Target: Cysteine protease falcipain-3 (SINGLE PROTEIN), Plasmodium falciparum
UniProt: Q9NAW4
Assay: Inhibition of recombinant Plasmodium falciparum falcipain-3 expressed in bacterial expression system using ZFR-AMC as substrate measured for 30 mins by fluorimetric assay
Measurement: IC50 = 8560 nM (pChEMBL 5.070000171661377)
Descriptors: MW 397.48, ALogP 4.38, HBA 2, HBD 3, PSA 73.99, QED 0.4
Compound (SMILES): CCOC(=O)C1=C(C)Nc2nc3ccccc3n2C1c1cnoc1
InChIKey: IVYLBDIDLMJYKC-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) expressed in insect cell microsomes using dibenzylfluorescein substrate by fluorescence based assay
Measurement: IC50 = 4920 nM (pChEMBL 5.309999942779541)
Descriptors: MW 324.34, ALogP 2.88, HBA 7, HBD 1, PSA 82.18, QED 0.75
Compound (SMILES): CNC(=O)c1cc(C(=O)N[C@H]2[C@@H]3COC[C@@H]32)cc2c1O[C@H](CF)[C@H]2c1ccccc1
InChIKey: WZQLVEPIBAOOGF-RMMWZPCPSA-N
Target: Bromodomain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25440
Assay: BET mutant TR-FRET assay (BRD2 BD2)
Measurement: IC50 = 31.62 nM (pChEMBL 7.5)
Descriptors: MW 410.45, ALogP 2.28, HBA 4, HBD 2, PSA 76.66, QED 0.79
Compound (SMILES): C[C@@H]1CN(c2cnc(C#N)c(-c3cnn(C)c3)n2)CCN1C(=O)C1CC1
InChIKey: PKHDHJSKOLMIMB-GFCCVEGCSA-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 = 219 nM (pChEMBL 6.659999847412109)
Descriptors: MW 351.41, ALogP 1.2, HBA 7, HBD 0, PSA 90.94, QED 0.83
Compound (SMILES): CCn1cc(NC(=O)OCc2cccc(Cl)c2Cl)c2cc(-c3nc(CN4CCC[C@H]4CO)cs3)ccc21
InChIKey: VTIQYEUSJHKBGN-FQEVSTJZSA-N
Target: Autotaxin (SINGLE PROTEIN), Homo sapiens
UniProt: Q13822
Assay: Inhibition of human ATX pre-incubated for 45 mins before fluorogenic substrate-3 addition and measured every minute for 30 mins by fluorescence based assay
Measurement: IC50 = 127.3 nM (pChEMBL 6.889999866485596)
Descriptors: MW 559.52, ALogP 6.8, HBA 7, HBD 2, PSA 79.62, QED 0.25
Compound (SMILES): Cc1cc(C)c(-c2cn(C)cn2)cc1NC(=O)c1ccc(OCc2ccccn2)cc1
InChIKey: SMQVBAGSZVHCJP-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 = 21000 nM (pChEMBL 4.679999828338623)
Descriptors: MW 412.49, ALogP 4.93, HBA 5, HBD 1, PSA 69.04, QED 0.49
Compound (SMILES): CN(C1CCCCC1)C1CCNC(=O)C1
InChIKey: XUHAQJIIISMOCR-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 210.32, ALogP 1.53, HBA 2, HBD 1, PSA 32.34, QED 0.75
Compound (SMILES): O=C(NO)c1ccc(N(CC2CC2)C(=O)c2cccc(C(F)(F)F)c2)cc1
InChIKey: GNYGTGKQCARLNG-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of C-terminal FLAG-tagged full length human HDAC6 expressed in baculovirus expression system using FAM-RHKK(Ac)-NH2 substrate incubated for 5 hrs by EMSA method
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 378.35, ALogP 3.88, HBA 3, HBD 2, PSA 69.64, QED 0.61
Compound (SMILES): OCc1cc2c(s1)CCC(NCCCc1ccccc1)CC2
InChIKey: BHQKYFPBMUXBJD-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 membranes incubated for 120 mins by scintillation counting method
Measurement: Ki = 61 nM (pChEMBL 7.210000038146973)
Descriptors: MW 315.48, ALogP 3.71, HBA 3, HBD 2, PSA 32.26, QED 0.63
Compound (SMILES): CCN(CC)c1ccc(/C=C2\NC(=O)N(Cc3ccc(C)cc3)C2=O)cc1
InChIKey: OUSROLHKTUOLOF-ZHZULCJRSA-N
Target: NAD-dependent protein deacetylase sirtuin-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8IXJ6
Assay: Inhibition of recombinant human SIRT2 after 30 mins
Measurement: IC50 = 68700 nM (pChEMBL 4.159999847412109)
Descriptors: MW 363.46, ALogP 3.93, HBA 3, HBD 1, PSA 52.65, QED 0.62
Compound (SMILES): COc1ccc(C(=O)CSc2nccc(Nc3ccc(S(=O)(=O)Nc4ncccn4)cc3)n2)cc1
InChIKey: HIKLUBOHTJRULD-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human carbonic anhydrase 2 incubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red dye based stopped-flow CO2 hydration assay
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 508.59, ALogP 3.79, HBA 10, HBD 2, PSA 136.06, QED 0.18
Compound (SMILES): COc1cc2c3c(c1O)-c1cc(N)ccc1CC3N(C)CC2
InChIKey: LVGQSPSRQGIUSM-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Binding affinity to human D2 receptor
Measurement: Ki = 231 nM (pChEMBL 6.639999866485596)
Descriptors: MW 296.37, ALogP 2.74, HBA 4, HBD 2, PSA 58.72, QED 0.79
Compound (SMILES): CC(C)CNc1nc(-c2ccccc2)cc2c(-c3ccc(C(=O)NC4CC4)cc3)cnn12
InChIKey: ZBVXNQUDUXDUOZ-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 = 573 nM (pChEMBL 6.239999771118164)
Descriptors: MW 425.54, ALogP 5.02, HBA 5, HBD 2, PSA 71.32, QED 0.44
Compound (SMILES): Nc1nc(N2CCC(N(CCc3ccc(Cl)cc3)Cc3ccncc3Cl)CC2)n[nH]1
InChIKey: ANYIBKZROMWRSD-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 = 620 nM (pChEMBL 6.210000038146973)
Descriptors: MW 446.39, ALogP 3.8, HBA 6, HBD 2, PSA 86.96, QED 0.57
Compound (SMILES): CCc1ccc(Nc2nc(Nc3ccc(N4CCN(C)CC4)cn3)ncc2Cl)cc1
InChIKey: DCWNCWYHYUMEFR-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 = 6870 nM (pChEMBL 5.159999847412109)
Descriptors: MW 423.95, ALogP 4.33, HBA 7, HBD 2, PSA 69.21, QED 0.61
Compound (SMILES): CCc1c(-c2ccc(OC)c(OC)c2)[nH]c2ccc(C3CCN(CCNC)CC3)cc12
InChIKey: PKYFJFXBQWQBFJ-UHFFFAOYSA-N
Target: Toll-like receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYK1
Assay: Antagonist activity at human TLR7 overexpressed in HEK-Blue cells assessed as inhibition of gardiquimod-induced NFkappaB and AP-1 activation preincubated for 30 mins followed by gardiquimod stimulation measured after 22 hrs by quanti-blue SEAP assay
Measurement: IC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 421.59, ALogP 4.81, HBA 4, HBD 2, PSA 49.52, QED 0.55
Compound (SMILES): O=C(N[C@H]1CN(S(=O)(=O)c2ccccc2)C[C@@H]1C(=O)N[C@H]1CCCNC1)c1nnc(-c2ccc(F)cc2)s1
InChIKey: ABLSECMUBQGKAB-JBACZVJFSA-N
Target: Growth hormone secretagogue receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92847
Assay: Agonist activity at human GHSR expressed in HEK293 cells assessed as increase in IP1 accumulation measured after 90 mins in presence of LiCl by HTRF assay
Measurement: EC50 = 10.8 nM (pChEMBL 7.96999979019165)
Descriptors: MW 558.66, ALogP 1.63, HBA 8, HBD 3, PSA 133.39, QED 0.4
Compound (SMILES): CC(C)NC(=O)COc1cccc(-c2nc3c(c(Nc4ccc(-c5cn[nH]c5)cc4)n2)CNCC3)c1
InChIKey: GUJNVPQGUFMHQI-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P11169
Assay: Inhibition of GLUT3 in SLC2A1-deficient human DLD1 cells assessed as reduction in ATP level measured after 90 mins by Celltiter-glo luminescent assay
Measurement: IC50 = 365 nM (pChEMBL 6.440000057220459)
Descriptors: MW 483.58, ALogP 3.83, HBA 7, HBD 4, PSA 116.85, QED 0.3
Compound (SMILES): Cc1cccc(-n2ncc3c2CCCC3NC(=O)c2noc3c2CCCC3)c1C
InChIKey: KWESJWBFVAWPJT-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (quinone), mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q02127
Assay: Inhibition of recombinant human DHODH using dihydroorotic acid as substrate in presence of 2 nM of DHODH by DCIP assay
Measurement: IC50 = 2.7 nM (pChEMBL 8.569999694824219)
Descriptors: MW 390.49, ALogP 4.16, HBA 5, HBD 1, PSA 72.95, QED 0.73
Compound (SMILES): C#Cc1cccc(Nc2cccc3cc(OC)c(OCCCCCCC(=O)NO)cc23)c1
InChIKey: FUCZYDBKFNOERW-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of HDAC1 (unknown origin)
Measurement: IC50 = 4.4 nM (pChEMBL 8.359999656677246)
Descriptors: MW 432.52, ALogP 5.41, HBA 5, HBD 3, PSA 79.82, QED 0.16
Compound (SMILES): Cc1ccc2[nH]c(C(=O)N[C@H]3CN(S(=O)(=O)c4cnccn4)C[C@@H]3C(=O)NCCN(C)C)cc2c1
InChIKey: BRONYTUGNLAYCK-PXNSSMCTSA-N
Target: Growth hormone secretagogue receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92847
Assay: Displacement of [His[125I]]-ghrelin from GHS-R1a (unknown origin) expressed in HEK293 cell membranes measured after 1 hr by microbeta counting method
Measurement: IC50 = 29.3 nM (pChEMBL 7.53000020980835)
Descriptors: MW 499.6, ALogP 0.36, HBA 7, HBD 3, PSA 140.39, QED 0.41
Compound (SMILES): CCOC(=O)C1=C(C)Nc2nc3ccccc3n2C1c1cocn1
InChIKey: SCLOQWUULAWDOK-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) expressed in insect cell microsomes using dibenzylfluorescein substrate by fluorescence based assay
Measurement: IC50 = 6410 nM (pChEMBL 5.190000057220459)
Descriptors: MW 324.34, ALogP 2.88, HBA 7, HBD 1, PSA 82.18, QED 0.75
Compound (SMILES): NC(=O)c1ccc2[nH]c(-c3ccncc3)nc2c1
InChIKey: ZJKOBNREDNMDCN-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase N2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16513
Assay: Displacement of tracer from PKN2 (unknown origin) by TR-FRET assay
Measurement: Ki = 8110 nM (pChEMBL 5.090000152587891)
Descriptors: MW 238.25, ALogP 1.72, HBA 3, HBD 2, PSA 84.66, QED 0.71
Compound (SMILES): O=C1c2cccc3cccc(c23)N1CCCCCCN1CCN(c2nsc3ccccc23)CC1
InChIKey: HGMFNQHREUMSGP-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]8-OH-DPAT from human 5HT1A receptor expressed in HEK293 cell membranes measured after 1 hr by microbeta counting method
Measurement: Ki = 71 nM (pChEMBL 7.150000095367432)
Descriptors: MW 470.64, ALogP 5.79, HBA 5, HBD 0, PSA 39.68, QED 0.31
Compound (SMILES): CNC(=O)c1cc(C(=O)N[C@@H]2[C@@H]3COC[C@@H]32)cc2c1O[C@H](CF)[C@H]2c1ccccc1
InChIKey: WZQLVEPIBAOOGF-UJMXGEILSA-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 = 15.85 nM (pChEMBL 7.800000190734863)
Descriptors: MW 410.45, ALogP 2.28, HBA 4, HBD 2, PSA 76.66, QED 0.79
Compound (SMILES): CCOC(=O)c1cnc2cc(Cl)cc(Cl)c2c1Nc1cccc(S(=O)(=O)NC)c1
InChIKey: SWOMTHLQJFJUKX-UHFFFAOYSA-N
Target: Aurora kinase B (SINGLE PROTEIN), Homo sapiens
UniProt: Q96GD4
Assay: Inhibition of human Aurora B using [H-LRRASLG] as substrate in presence of [gamma-33P]-ATP incubated for 2 hrs by hotspot kinase assay
Measurement: IC50 = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 454.34, ALogP 4.37, HBA 6, HBD 2, PSA 97.39, QED 0.54
Compound (SMILES): O=C(O)Cc1ccccc1OCc1cccc(-c2ccc3c(c2)CNCC3)c1
InChIKey: PKSHGMOAJDEGBL-UHFFFAOYSA-N
Target: Complement factor D (SINGLE PROTEIN), Homo sapiens
UniProt: P00746
Assay: Inhibition of human complement FD by TR-FRET assay
Measurement: IC50 = 800 nM (pChEMBL 6.099999904632568)
Descriptors: MW 373.45, ALogP 4.21, HBA 3, HBD 2, PSA 58.56, QED 0.68
Compound (SMILES): CN1CCc2nc(-c3cccc(OCC(=O)NC4CCC4)c3)nc(Nc3ccc(-c4cn[nH]c4)cc3)c2C1
InChIKey: ACKYORBYCXXOKP-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P11169
Assay: Inhibition of GLUT3 in SLC2A1-deficient human DLD1 cells assessed as reduction in ATP level measured after 90 mins by Celltiter-glo luminescent assay
Measurement: IC50 = 566 nM (pChEMBL 6.25)
Descriptors: MW 509.61, ALogP 4.31, HBA 7, HBD 3, PSA 108.06, QED 0.32
Compound (SMILES): Cc1cccc(N(C)c2nccc(-c3cnn4ncccc34)n2)c1
InChIKey: XOBINHQHMGZFDI-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Binding affinity to DYRK1A (unknown origin) assessed as dissociation constant measured for 60 to 300 sec by SPR analysis
Measurement: Kd = 52 nM (pChEMBL 7.28000020980835)
Descriptors: MW 316.37, ALogP 3.26, HBA 6, HBD 0, PSA 59.21, QED 0.58
Compound (SMILES): c1cn2cc(-c3cnc4cn[nH]c4n3)nc(Nc3ccc(N4CCN(C5COC5)CC4)cc3)c2n1
InChIKey: MGRJMWYCHSGHRT-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 = 37 nM (pChEMBL 7.429999828338623)
Descriptors: MW 468.53, ALogP 2.33, HBA 10, HBD 2, PSA 112.39, QED 0.4
Compound (SMILES): Cc1ccc(-c2ncnc(Nc3cccc(C(=N)N)c3)c2O)cc1
InChIKey: YHDKEZHJEWCOPI-UHFFFAOYSA-N
Target: Coagulation factor X (SINGLE PROTEIN), Homo sapiens
UniProt: P00742
Assay: Inhibition of activated factor X (unknown origin) using CH3O-CO-D-CHG-Gly-Arg-pNA-AcOH as substrate by fluorescence based assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 319.37, ALogP 3.19, HBA 5, HBD 4, PSA 107.91, QED 0.44
Compound (SMILES): CC(C)Oc1cc(N2[C@H](C)COC[C@H]2C)nc2c(-c3ccn[nH]3)nccc12
InChIKey: XXIDXEBDJANSDE-ZIAGYGMSSA-N
Target: Serine/threonine-protein kinase ATR (SINGLE PROTEIN), Homo sapiens
UniProt: Q13535
Assay: Time-Resolved Fluorescence Energy Transfer (TR-FRET Tracer B): To determine of binding activity of the test compounds, full-length human ATR protein was expressed and purified together with ATRIP as described above. Furthermore, a fluorescently labelled compound (tracer B) was used as a tracer molecule. Detection of the binding event of the tracer was achieved by time-resolved fluorescence energy transfer (TR-FRET). We used an anti-GST-Terbium antibody (CisBio) that binds to the GST-tag at the N-terminus of ATR-kinase. Excitation of Terbium with 337 nm light results in emission of fluorescent light with 545 nm. In case a tetrameric complex has formed (antiGST-Tb+GST-ATR+Strp2-ATRIP+tracer), part of the energy will be transferred from the Terbium to the fluorophore that itself emits light of 570 nm. Displacement of the fluorescent tracer by a test compound leads to a reduction of the TR-FRET-signal.For the assay 50 nl of a 100-fold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (MTP, Greiner Bio-One, Frickenhausen, Germany). To prepare the ATR-working solution, ATR/ATRIP stock solution was diluted in assay buffer [50 mM HEPES (pH 7.0), 10 mM MgCl2, 1 mM DTT, 0.01% (w/v) Igepal, 0.01% (w/v) BSA] to 4.2 nM protein concentration (concentration may vary from lot to lot of protein preparation). AntiGST-Tb antibody was diluted to 4.2 nM. The ATR-working solution was incubated for 30 min at 22° C. prior to dispensing to pre-form the complex of antiGST-Tb+GST-ATR+ATRIP. Then, 3 μl of the ATR-working solution were added to the test compound and the mixture was incubated for 10 min at 22° C. to allow pre-binding of the test compounds to ATR/ATRIP. Then, 2 μl of a 100 nM solution of either tracer A or B in assay buffer were added to the ATR-working solution. The resulting mixture was incubated for 30 min at 22° C. The measurement of the TR-FRET signal was performed in a standard HTRF-compatible MTP reader instrument (e.g. BMG Pherastar) by recording the fluorescence emissions at 545 nm and 570 nm after excitation at 337-350 nm. The ratio between emission at 570 nm divided by emission at 545 nm was calculated to give the well ratio. The experimental data (well ratios) were normalised by the following way: positive control contained ATR-working solution plus either tracer A or B solution (=0% inhibition), the negative control contained all components except GST-ATR/ATRIP (=100% inhibition).
Measurement: IC50 = 1250 nM (pChEMBL 5.900000095367432)
Descriptors: MW 367.45, ALogP 3.42, HBA 6, HBD 1, PSA 76.16, QED 0.76
Compound (SMILES): C[C@H]1CN(c2c(Cl)c(=O)n(C)c3ccc(C#N)nc23)CCN1C(c1ccc(F)cc1)c1ccc(F)cc1
InChIKey: UFIZEEXQYAMFJQ-KRWDZBQOSA-N
Target: Diacylglycerol kinase zeta (SINGLE PROTEIN), Homo sapiens
UniProt: Q13574
Assay: Inhibition of full length C-terminal His6tagged TVMV-His-pFBgate fused human DGK-zeta expressed in baculovirus infected Sf9 insect cells using liposome as substrate preincubated for 10 mins followed by compound addition and measured after 1 hr in presence of ATP by LIPGLO luminescence based assay
Measurement: IC50 = 3300 nM (pChEMBL 5.480000019073486)
Descriptors: MW 519.98, ALogP 5.04, HBA 6, HBD 0, PSA 65.16, QED 0.38
Compound (SMILES): CCN(c1cc(-c2ccc(CN3CCN(C)CC3)cc2)cc(C(=O)NCc2c3c(c(C)[nH]c2=O)CCCC3)c1C)C1CCOCC1
InChIKey: KBQYYXDCPRZITN-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Inhibition of EZH2 A677G mutant (unknown origin) by AlphaLISA assay
Measurement: IC50 = 5.9 nM (pChEMBL 8.229999542236328)
Descriptors: MW 625.86, ALogP 5.22, HBA 6, HBD 2, PSA 80.91, QED 0.34