lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC[C@H](NS(=O)(=O)c1ccc(-c2sc(-c3nnc(CC(C)(C)O)o3)nc2C(=O)N2CCC(F)CC2)c(Cl)c1Cl)C(F)(F)F
InChIKey: VWOLTHFSWIIFKC-HNNXBMFYSA-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 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 688.55, ALogP 5.67, HBA 9, HBD 2, PSA 138.52, QED 0.27
Compound (SMILES): CCCCNCCc1c[nH]c2c1C(=O)C(c1cccnc1)=CC2=O
InChIKey: PTALNTOMYQXLAG-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IFNgamma-stimulated IDO1 in human HeLa cells
Measurement: EC50 = 2720 nM (pChEMBL 5.570000171661377)
Descriptors: MW 323.4, ALogP 2.8, HBA 4, HBD 2, PSA 74.85, QED 0.77
Compound (SMILES): CC(C)c1onc(-c2c(Cl)cccc2Cl)c1COc1ccc(-c2nc3ccc(C(=O)O)cc3n2CC2CC2)cc1
InChIKey: JFANKCLDOFXHRQ-UHFFFAOYSA-N
Target: Bile acid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RI1
Assay: Agonist activity at human FXR expressed in human HuH7 cells by luciferase reporter gene assay
Measurement: EC50 = 19.4 nM (pChEMBL 7.710000038146973)
Descriptors: MW 576.48, ALogP 8.48, HBA 6, HBD 1, PSA 90.38, QED 0.19
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O
InChIKey: JCRVCNMDDFQPJX-IRGGMKSGSA-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 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 803.97, ALogP -3.3, HBA 10, HBD 16, PSA 394.52, QED 0.02
Compound (SMILES): c1ccc2c(NCCCN3CCCCC3)cc(-c3ccc4c(c3)OCO4)nc2c1
InChIKey: PFEMKWMYFFJDAG-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of electric eel AChE using acetylthiocholine chloride as substrate preincubated for 15 mins followed by substrate addition by Ellman's method
Measurement: IC50 = 4780 nM (pChEMBL 5.320000171661377)
Descriptors: MW 389.5, ALogP 4.92, HBA 5, HBD 1, PSA 46.62, QED 0.61
Compound (SMILES): COc1c(OCCOCCOCCOc2ccc(C3CCN(c4ccn5c(CC6CC6)nnc5c4Cl)CC3)cc2)cccc1C(=O)C1CCN(CCc2ccc(F)cc2)CC1
InChIKey: SLBQKYUURZKYBP-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A/Metabotropic glutamate receptor 2 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q14416
Assay: Antagonist activity at human 5HT2A/mGlu2 receptor expressed in HEK293 cells co-expressing Gqo5 assessed as inhibition of glutamate-induced intracellular Ca2+ mobilization incubated for 1 hr by Fluo-4 dye based fluorescence assay 5HT2A_HUMAN/GRM2_HUMAN P28223/Q14416
Measurement: IC50 = 5248.07 nM (pChEMBL 5.28000020980835)
Descriptors: MW 854.46, ALogP 8.5, HBA 11, HBD 0, PSA 99.89, QED 0.05
Compound (SMILES): Clc1ccc2c3c1CCN3CCNC2
InChIKey: WMEVNRBPSZDLCJ-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 = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 208.69, ALogP 1.81, HBA 2, HBD 1, PSA 15.27, QED 0.7
Compound (SMILES): CC(C)(C(N)=O)c1cc(COc2ccccc2CC(=O)O)cc(-c2ccc3c(c2)[C@H](N)CO3)c1
InChIKey: YYZIUIZQIMNJMB-JOCHJYFZSA-N
Target: Complement factor D (SINGLE PROTEIN), Homo sapiens
UniProt: P00746
Assay: Inhibition of human complement FD by TR-FRET assay
Measurement: IC50 = 320 nM (pChEMBL 6.5)
Descriptors: MW 460.53, ALogP 3.71, HBA 5, HBD 3, PSA 124.87, QED 0.47
Compound (SMILES): COc1ccccc1CCC(C)(C)NCC(O)c1cc(O)cc2c1OCC(=O)N2.Cl
InChIKey: TYLKWSHZYCHATG-UHFFFAOYSA-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 = 3.89 nM (pChEMBL 8.40999984741211)
Descriptors: MW 400.48, ALogP 2.77, HBA 6, HBD 4, PSA 100.05, QED 0.54
Compound (SMILES): CCC(=O)N[C@@H]1CCCc2c1cncc2N1Cc2cc(Cl)ccc2C1=O
InChIKey: OUSFXXZFDQOXDO-QGZVFWFLSA-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 = 5208 nM (pChEMBL 5.28000020980835)
Descriptors: MW 369.85, ALogP 3.8, HBA 3, HBD 1, PSA 62.3, QED 0.89
Compound (SMILES): COC(=O)c1ccc(-c2cccn3cc(-c4ccccc4)nc23)cc1
InChIKey: BWTFPMWBBQNGJF-UHFFFAOYSA-N
Target: Retinaldehyde dehydrogenase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P47895
Assay: Competitive inhibition of human recombinant ALDH1A3 pre-incubated for 5 mins before acetaldehyde addition by continuous spectrometric assay relative to control
Measurement: Ki = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 328.37, ALogP 4.45, HBA 4, HBD 0, PSA 43.6, QED 0.52
Compound (SMILES): COc1cccc(-c2ccc(COC3CN(C#N)C3)c(F)c2)c1
InChIKey: BIQIEYTVFJJQNU-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 312.34, ALogP 3.18, HBA 4, HBD 0, PSA 45.49, QED 0.8
Compound (SMILES): O=C(CCCc1ccccc1)C(=O)NCCc1ccccc1Cl
InChIKey: AMGNVNMVMJJETR-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 = 1258.93 nM (pChEMBL 5.900000095367432)
Descriptors: MW 329.83, ALogP 3.59, HBA 2, HBD 1, PSA 46.17, QED 0.75
Compound (SMILES): CNS(=O)(=O)c1cccc(-c2ccc3nc(Nc4ccccc4C#N)nn3c2)c1
InChIKey: UZXHORICGCDFBC-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 = 1800 nM (pChEMBL 5.75)
Descriptors: MW 404.46, ALogP 2.92, HBA 7, HBD 2, PSA 112.18, QED 0.53
Compound (SMILES): COc1cc2c(cc1O)C(c1ccccc1)CNCC2
InChIKey: KJTCMLYTSGLTBF-UHFFFAOYSA-N
Target: D(1B) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21918
Assay: Displacement of [3H]SCH23390 from dopamine D5 receptor (unknown origin)
Measurement: Ki = 309.9 nM (pChEMBL 6.510000228881836)
Descriptors: MW 269.34, ALogP 2.68, HBA 3, HBD 2, PSA 41.49, QED 0.88
Compound (SMILES): CC(C)NC(=O)COc1cccc(-c2nc3c(c(Nc4ccc(-c5cn[nH]c5)cc4)n2)CN(C2CCC2)CC3)c1
InChIKey: IGRMNQVNHGGSFN-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 = 238 nM (pChEMBL 6.619999885559082)
Descriptors: MW 537.67, ALogP 5.09, HBA 7, HBD 3, PSA 108.06, QED 0.27
Compound (SMILES): CC(=O)N[C@@H]1CCCc2c1cncc2N1Cc2cc(Cl)ccc2C1=O
InChIKey: UEOYRTWNORFJAG-QGZVFWFLSA-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 = 2332 nM (pChEMBL 5.630000114440918)
Descriptors: MW 355.83, ALogP 3.41, HBA 3, HBD 1, PSA 62.3, QED 0.9
Compound (SMILES): CC(C)N(C(=O)c1cc(C(F)(F)F)cc(C(F)(F)F)c1)c1ccc(C(=O)NO)cc1
InChIKey: JVCQXJCACOCTST-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 434.34, ALogP 4.9, HBA 3, HBD 2, PSA 69.64, QED 0.41
Compound (SMILES): CC#CC(=O)N[C@H]1CCCN(c2ccc(C(N)=O)c3[nH]c(C)c(C)c23)C1
InChIKey: FINWLFMFLDVOFY-AWEZNQCLSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Btk Enzyme Assay: To V-bottom 384-well plates were added test compounds, human recombinant Btk (1 nM, Invitrogen Corporation), fluoresceinated peptide (1.5 μM), ATP (20 μM), and assay buffer (20 mM HEPES pH 7.4, 10 mM MgCl2, 0.015% Brij 35 surfactant and 4 mM DTT in 1.6% DMSO), with a final volume of 30 μL. After incubating at room temperature for 60 min., the reaction was terminated by adding 45 μL of 35 mM EDTA to each sample. The reaction mixture was analyzed on the Caliper LABCHIP® 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison to control reactions with no enzyme (for 100% inhibition) and controls with no inhibitor (for 0% inhibition). Dose response curves were generated to determine the concentration required for inhibiting 50% of Btk activity (IC50). Compounds were dissolved at 10 mM in DMSO and evaluated at eleven concentrations.
Measurement: IC50 = 0.52 nM (pChEMBL 9.279999732971191)
Descriptors: MW 352.44, ALogP 1.99, HBA 3, HBD 3, PSA 91.22, QED 0.74
Compound (SMILES): C[C@H]1C(=O)C(C#N)=C[C@@]2(C)c3nc(-c4ccnc(C5CC5)c4)nc(-c4ccccc4F)c3C[C@H]12
InChIKey: KFZMMZGJJTWWCC-WCADHIDISA-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 = 117 nM (pChEMBL 6.929999828338623)
Descriptors: MW 450.52, ALogP 5.32, HBA 5, HBD 0, PSA 79.53, QED 0.54
Compound (SMILES): Cc1ccccc1Nc1nc(NCCc2cccnc2)ncc1Cl
InChIKey: AEIDYKFCSCDMJC-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 339.83, ALogP 4.23, HBA 5, HBD 2, PSA 62.73, QED 0.7
Compound (SMILES): CCOC(=O)Cc1nn(CNC(=O)CCN2CCN(c3c(C)cccc3C)CC2)c(=O)c2ccccc12
InChIKey: XWSQBZPYGQJAPE-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 = 4590 nM (pChEMBL 5.340000152587891)
Descriptors: MW 505.62, ALogP 2.4, HBA 8, HBD 1, PSA 96.77, QED 0.45
Compound (SMILES): C=C1CC(CI)(c2ccccc2)OC1=O
InChIKey: LRFQOHDLAVEYSZ-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of wild type EGFR (unknown origin)
Measurement: IC50 = 47000 nM (pChEMBL 4.329999923706055)
Descriptors: MW 314.12, ALogP 2.82, HBA 2, HBD 0, PSA 26.3, QED 0.36
Compound (SMILES): CC(C)c1cc(-c2ccc3c(c2)[C@H](N)CO3)cc([C@@H]2CNc3cccc(CC(=O)O)c3O2)c1
InChIKey: HECONMODEBIAKY-RDGATRHJSA-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 444.53, ALogP 5.04, HBA 5, HBD 3, PSA 93.81, QED 0.51
Compound (SMILES): CC(=O)C1CCC(Cn2c(-c3ccc(OCc4c(-c5c(Cl)cccc5Cl)noc4C(C)C)cc3)nc3ccc(C(=O)O)cc32)CC1
InChIKey: KKYWWJQQQXHEMS-UHFFFAOYSA-N
Target: Vitamin D3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P11473
Assay: Antagonist activity at human VDR transfected in HEK293T cells measured after 24 hrs by luciferase reporter gene assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 660.6, ALogP 9.46, HBA 7, HBD 1, PSA 107.45, QED 0.16
Compound (SMILES): N#CCC(=O)N1CCC2CN(c3ncnc4[nH]ccc34)CC21
InChIKey: QMRYMBDPVADAEF-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 296.33, ALogP 0.91, HBA 5, HBD 1, PSA 88.91, QED 0.89
Compound (SMILES): Cc1ccc2[nH]c(C(=O)N[C@H]3CN(S(=O)(=O)c4ccccc4)CC[C@H]3C(=O)NCCN(C)C)cc2c1
InChIKey: PVSRCYUGLXXTCX-QPPBQGQZSA-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 = 1220 nM (pChEMBL 5.909999847412109)
Descriptors: MW 511.65, ALogP 1.96, HBA 5, HBD 3, PSA 114.61, QED 0.43
Compound (SMILES): Cc1cc(Cl)cc(-c2ccnc3cc(CN4C(=O)C5C(C4=O)C5(C)C)sc23)c1OC1CCCNC1
InChIKey: MHUASFFQYUOBDL-UHFFFAOYSA-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 = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 510.06, ALogP 5.2, HBA 6, HBD 1, PSA 71.53, QED 0.48
Compound (SMILES): Cl.Fc1ccc(OC[C@@H]2C[C@H]3C[C@H]3N2)cn1
InChIKey: NCBVQDKXLNOBSE-ANYFZDTESA-N
Target: Neuronal acetylcholine receptor; alpha3/beta4 (PROTEIN COMPLEX), Homo sapiens
UniProt: P32297
Assay: Displacement of [3H]epibatidine from human alpha3beta4 nAChR expressed in IMR32 cell membrane by microbeta scintillation counting method
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 208.24, ALogP 1.35, HBA 3, HBD 1, PSA 34.15, QED 0.76
Compound (SMILES): CSCC[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCNC(C)=S)NC(=O)[C@@H]1Cc2ccc(cc2)OCCCCCCCCCCC(=O)N[C@@H](Cc2c[nH]cn2)C(=O)N1)C(N)=O
InChIKey: WPDHBTFCFWMTHA-MQDBWYGVSA-N
Target: NAD-dependent protein deacetylase sirtuin-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8IXJ6
Assay: Inhibition of His6-tagged human SIRT2 deacetylation activity using SIRT1 acetyl-lysine as substrate in presence of beta-NAD+ after 12 mins by reversed-phase HPLC analysis
Measurement: IC50 = 4310 nM (pChEMBL 5.369999885559082)
Descriptors: MW 914.25, ALogP 3.91, HBA 10, HBD 8, PSA 238.53, QED 0.07
Compound (SMILES): N=C(N)NCCC[C@@H]1NC(=O)C2(CCCCC2)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](CC(=O)O)NC(=O)CNC1=O.O=C(O)C(F)(F)F
InChIKey: OMJMFGNEULHCIP-NJBQKBHSSA-N
Target: Integrin alpha-V/beta-5 (PROTEIN COMPLEX), Homo sapiens
UniProt: P18084
Assay: Inhibition of vitronectin binding to recombinant human integrin alphaV (Phe31 to Val992 residues) beta5 (Gly24 to Asn719 residues) expressed in CHO cells by ELISA based solid phase binding assay
Measurement: IC50 = 63 nM (pChEMBL 7.199999809265137)
Descriptors: MW 600.68, ALogP -1.63, HBA 7, HBD 9, PSA 244.7, QED 0.09
Compound (SMILES): O=C(NO)c1ccc(NC(=O)C2(c3ccc4ccccc4c3)CCOCC2)cc1
InChIKey: VNRCXPZNHIIBGH-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of human recombinant HDAC2 pre-incubated for 30 mins before Ac-Leu- Gly-Lys(Ac)-AMC substrate addition and measured after 90 mins by fluorescence based assay
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 390.44, ALogP 3.65, HBA 4, HBD 3, PSA 87.66, QED 0.47
Compound (SMILES): CN(CCc1ccccc1)C1CCc2cc(CO)sc2CC1
InChIKey: KXEOTKSBFLAVBI-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 = 56 nM (pChEMBL 7.25)
Descriptors: MW 315.48, ALogP 3.66, HBA 3, HBD 1, PSA 23.47, QED 0.85
Compound (SMILES): CCCCCC(=O)N[C@@H](C(=O)NCc1ccc(CN)cc1)c1ccc(OCc2ccc(Cl)c(Cl)c2)cc1.O=C(O)C(F)(F)F
InChIKey: YXONDJBKEKNMHT-LNLSOMNWSA-N
Target: Genome polyprotein (SINGLE PROTEIN), West Nile virus
UniProt: P06935
Assay: Inhibition of West Nile virus NS2B-NS3 protease expressed in Escherichia coli BL21 lambda (DE3) cells using Abz-Gly-Leu-Lys-Arg-Gly-Gly-3-(NO2)Tyr as substrate preincubated for 15 mins followed by substrate addition measured for 15 mins by fluorimetric analysis
Measurement: IC50 = 11000 nM (pChEMBL 4.960000038146973)
Descriptors: MW 542.51, ALogP 6.09, HBA 4, HBD 3, PSA 93.45, QED 0.23
Compound (SMILES): C=CCc1c(NCc2ccccc2N2CCN(C)CC2)cnn(C)c1=O
InChIKey: VIOFJJIXYZYAFW-UHFFFAOYSA-N
Target: Peregrin (SINGLE PROTEIN), Homo sapiens
UniProt: P55201
Assay: Binding affinity to human partial length BRPF1 (E627 to G740 residues) expressed in bacterial expression system by BROMOscan assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 353.47, ALogP 1.87, HBA 6, HBD 1, PSA 53.4, QED 0.8
Compound (SMILES): Cc1cn([C@H]2C[C@H](n3cc(CN(CCc4ccc(S(N)(=O)=O)cc4)Cc4cn([C@H]5C[C@H](n6cc(C)c(=O)[nH]c6=O)O[C@@H]5CO)nn4)nn3)[C@@H](CO)O2)c(=O)[nH]c1=O
InChIKey: VSBFRYBQVSVEQT-RWJWSVIKSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human CA2 pre-incubated for 15 mins by stopped flow CO2 hydrase assay
Measurement: Ki = 70.7 nM (pChEMBL 7.150000095367432)
Descriptors: MW 810.85, ALogP -1.88, HBA 19, HBD 5, PSA 293.46, QED 0.08
Compound (SMILES): N#CN1CC(OCc2ccc(-c3ccccc3)cc2)C1
InChIKey: ZSTZNGPOKKKVCT-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 264.33, ALogP 3.04, HBA 3, HBD 0, PSA 36.26, QED 0.8
Compound (SMILES): Cn1cc(-c2ccc(NC(=O)[C@H](NCCc3ccc(C#N)cc3)c3ccccc3)nn2)cn1
InChIKey: CDYZSDIRBQXFGC-XMMPIXPASA-N
Target: Histone acetyltransferase p300 (SINGLE PROTEIN), Homo sapiens
UniProt: Q09472
Assay: Biochemical Assay: The full length p300 SPA assay was run following the same protocol as p300 HAT SPA assay, but used 6 nM purified full length p300 (purchased from Active Motif) in place of the purified p300-HAT domain.Select compounds were also evaluated in a H3K18Ac MSD cellular assay that measures the ability of compounds to inhibit the the acetylation of chromatin at H3K18, a process catalyzed by p300 and CBP. In a typical experiment the p300 HAT inhibitory activity inside cells of the compounds described herein was determined in accordance with the following experimental method. 20 k HCT-116 cells per well are plated in 75 μL RPMI+10% FBS media the night before treatment. Compounds plated in DMSO at 4× final concentration are resuspended in 30 μL RPMI+10% FBS, then 25 μL is combined with corresponding wells containing cells. Treated cells are incubated for 2 hr at 37° C., then lysed in 500 μL final volume and frozen at −80° C. MSD plates (Meso Scale Discovery) are coated overnight at 4° C. with 60 μL 1:500 α-total histone antibody (Millipore MAB3422) in PBS. Plates are then blocked with 5% BSA in TBST shaking at RT for 1 hr, washed, and 30 μL lysate added to each well for 2 hr shaking at RT. Plates are washed and 25 μL 1:216 α-H3K18ac antibody (CST 9675) in PBS added, then incubated for 1 hr shaking at RT. Plates are washed again, then 25 μL 1:1000 Sulfo-Tag goat α-rabbit antibody (Meso Scale Discovery R32Ab-1) in PBS is added for 1 hr shaking at RT. Plates are washed once more, then 150 μL 1× Read Buffer (MSD #R92TD-3) is added to all wells and read on MSD SECTOR Imager 2400 using the conventional read setup.
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 437.51, ALogP 3.26, HBA 7, HBD 2, PSA 108.52, QED 0.44
Compound (SMILES): O=C(NCCN1CCOCC1)c1ccc2c(c1)C(=O)c1ccc(Nc3ccc(F)c(/C=N/NC(=O)c4ccc[se]4)c3)cc1CC2
InChIKey: VWGFPXWBIHPPFF-FDALDRLYSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Inhibition of NanoBRET kinase tracer K4 binding to full-length human C-terminal NanoLuc-tagged p38alpha MAPK expressed in HEK293T cells incubated for 2 hrs by NanoBRET NanoGlo substrate based NanoBRET assay
Measurement: IC50 = 30.4 nM (pChEMBL 7.519999980926514)
Descriptors: MW 672.62
Compound (SMILES): NS(=O)(=O)c1ccc(-c2ccc(C(=O)c3cccc(C(=O)O)c3)cc2)cc1
InChIKey: OYOIAWKBJGRLED-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human carbonic anhydrase 2 preincubated with enzyme for 10 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 0.94 nM (pChEMBL 9.029999732971191)
Descriptors: MW 381.41, ALogP 2.93, HBA 4, HBD 2, PSA 114.53, QED 0.66
Compound (SMILES): COC(=O)c1ccc2c(c1)NC(=O)/C2=C(\Nc1ccc(-n2cccc2CN(C)C)c(C)c1)c1ccccc1
InChIKey: QZVJOWZERRROFN-ZIADKAODSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Inhibition of N-terminal GST-fused human PDGFRbeta cytoplasmic domain (557 to 1106 (end) residues) expressed in baculovirus expression system using FAM-labeled peptide and ATP as substrate preincubated for 10 mins followed by substrate addition measured after 1 hr by mobility shift assay
Measurement: IC50 = 31 nM (pChEMBL 7.510000228881836)
Descriptors: MW 506.61, ALogP 5.57, HBA 6, HBD 2, PSA 75.6, QED 0.25
Compound (SMILES): O=C(NCc1ccc(Cl)cc1Cl)[C@@H]1CCC(=O)N1c1cccs1
InChIKey: PCHSDJRKGJKOAG-ZDUSSCGKSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Inhibition of human P2X7 expressed in human HEK293 cells assessed as reduction in BzATP-stimulated TO-PRO-3 incorporation preincubated with compound and TO-PRO-3 for 15 mins prior to BzATP addition and measured after 1 hr by Fluo-3AM dye based flow cytometry
Measurement: IC50 = 229 nM (pChEMBL 6.639999866485596)
Descriptors: MW 369.27, ALogP 3.87, HBA 3, HBD 1, PSA 49.41, QED 0.89
Compound (SMILES): CCn1sc(=O)n(Cc2ccc(C)cc2)c1=O
InChIKey: KGCPMYZRLUSJRN-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 = 16700 nM (pChEMBL 4.78000020980835)
Descriptors: MW 250.32, ALogP 1.45, HBA 5, HBD 0, PSA 44, QED 0.83
Compound (SMILES): NC(=O)[C@@H]1CC[C@H](c2ccc(OCc3ccc(F)cc3)cc2)N1
InChIKey: AQOBMGIKHTWQEH-SJORKVTESA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 = 7943.28 nM (pChEMBL 5.099999904632568)
Descriptors: MW 314.36, ALogP 2.68, HBA 3, HBD 2, PSA 64.35, QED 0.89
Compound (SMILES): Fc1ccc2c3c1CCN3CCNC2
InChIKey: OAWPQISEPYCCKX-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Agonist activity at 5HT2B receptor (unknown origin)
Measurement: EC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 192.24, ALogP 1.29, HBA 2, HBD 1, PSA 15.27, QED 0.67
Compound (SMILES): Cn1nccc1[C@H]1CCCCC[C@@H]1Oc1cc(F)c(S(=O)(=O)Nc2ccncn2)c(F)c1
InChIKey: NEBBLFXFQXPNBT-BEFAXECRSA-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 = 96000 nM (pChEMBL 4.019999980926514)
Descriptors: MW 463.51, ALogP 3.78, HBA 7, HBD 1, PSA 99, QED 0.56
Compound (SMILES): O=C(CCC(=O)N1CCN(Cc2ccc(NC(=O)c3n[nH]cc3Nc3ncnc4[nH]ccc34)cc2)CC1)NCCNc1cccc2c1C(=O)N(C1CCC(=O)NC1=O)C2=O
InChIKey: BRYMZSSAIDEFEM-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of tracer K10 binding to NanoLuc-CDK9/Cyclin T1 (unknown origin) expressed in human HEK293 cells after 1 hr in presence of ATP by NanoBRET assay
Measurement: IC50 = 14.5 nM (pChEMBL 7.840000152587891)
Descriptors: MW 815.85, ALogP 1.73, HBA 13, HBD 7, PSA 259.61, QED 0.06
Compound (SMILES): Cc1cccc(CNc2cnn(C)c(=O)c2Cl)c1
InChIKey: RTUHMTDAYSJHQE-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to BRD4 (1) (unknown origin) N-terminal bromodomain by TR-FRET assay
Measurement: IC50 = 19952.62 nM (pChEMBL 4.699999809265137)
Descriptors: MW 263.73, ALogP 2.35, HBA 4, HBD 1, PSA 46.92, QED 0.92
Compound (SMILES): C[C@H](C(=O)Nc1ccc(Cl)cc1)C12CC(NC(=O)c3cccc(Cl)c3)(C1)C2
InChIKey: BNRLLFCJYSXTKN-ZJDGCUJOSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in human whole blood stimulated with IFNgamma/LPS using L-tryptophan/kynurenine as substrate incubated for 15 mins prior to IFNgamma/LPS stimulation and further incubated for 18 hrs followed by isotope labeled L-tryptophan/kynurenine addition on day 2 by LC/MS-MS analysis
Measurement: IC50 = 137 nM (pChEMBL 6.860000133514404)
Descriptors: MW 403.31, ALogP 4.92, HBA 2, HBD 2, PSA 58.2, QED 0.74
Compound (SMILES): O=C(Nc1nc2ccc(OCCBr)cc2s1)c1ccc(C(=O)c2ccccc2)cc1
InChIKey: MYXGDDQVVISPPH-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 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 481.37, ALogP 5.55, HBA 5, HBD 1, PSA 68.29, QED 0.28
Compound (SMILES): CC1CC1C(=O)N1CCN(c2nc(-c3cnn(C)c3)ncc2C#N)C[C@H]1C
InChIKey: ZXXHAWWIMOPNIX-MFOWVQHXSA-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 = 557 nM (pChEMBL 6.25)
Descriptors: MW 365.44, ALogP 1.44, HBA 7, HBD 0, PSA 90.94, QED 0.82
Compound (SMILES): COCC(C)OC(=O)[C@H](C)NP(=O)(OC[C@H]1O[C@@H](n2ccc(=O)[nH]c2=O)[C@](Cl)(Br)[C@@H]1O)Oc1ccccc1
InChIKey: TZQHRVVWTLCDGG-WEMGFATFSA-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 = 387 nM (pChEMBL 6.409999847412109)
Descriptors: MW 640.81, ALogP 1.88, HBA 11, HBD 3, PSA 167.41, QED 0.18
Compound (SMILES): Brc1ccc2c3c1CCCCN3CCNC2
InChIKey: MFRUSLSKSYHARP-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Agonist activity at 5HT2B receptor (unknown origin)
Measurement: EC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 281.2, ALogP 2.7, HBA 2, HBD 1, PSA 15.27, QED 0.79
Compound (SMILES): COc1ccccc1C1C([N+](=O)[O-])C(Cc2c[nH]cn2)NC12c1ccccc1-c1nc3ccccc3nc12
InChIKey: SLXSPHAYNAQJBQ-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of BChE (unknown origin)
Measurement: IC50 = 14220 nM (pChEMBL 4.849999904632568)
Descriptors: MW 504.55, ALogP 4.23, HBA 7, HBD 2, PSA 118.86, QED 0.27
Compound (SMILES): O=C(CC1c2ccccc2N=C(SCCCCCN2CCCC2)N1c1ccc(-c2ccc(F)cc2)cc1)NCc1ccccc1
InChIKey: BFFIZNMTHIORQW-UHFFFAOYSA-N
Target: Voltage-dependent T-type calcium channel subunit alpha-1H (SINGLE PROTEIN), Homo sapiens
UniProt: O95180
Assay: Inhibition of human Cav3.2 expressed in tsA-201 cells by patch clamp electrophysiology
Measurement: IC50 = 260 nM (pChEMBL 6.579999923706055)
Descriptors: MW 620.84, ALogP 8.75, HBA 5, HBD 1, PSA 47.94, QED 0.16
Compound (SMILES): O=c1n(CCCCCCN2CCN(c3nsc4ccccc34)CC2)c2cccc3c2n1CCC3
InChIKey: LXNQXNYRRQSMER-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 = 44 nM (pChEMBL 7.360000133514404)
Descriptors: MW 475.66, ALogP 4.74, HBA 7, HBD 0, PSA 46.3, QED 0.35
Compound (SMILES): COc1cccc(-c2nn(-c3ccccc3)cc2-c2ccnc(NCCCNC(=O)Nc3ccc(Cl)c(Cl)c3)c2)c1
InChIKey: NLBSIZDYPZEHPY-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of B-RAF V600E mutant (unknown origin) using magnesium acetate as substrate incubated for 40 mins in presence of [gamma33P]ATP by scintillation counting based hotspot kinase assay
Measurement: IC50 = 770 nM (pChEMBL 6.110000133514404)
Descriptors: MW 587.51, ALogP 7.54, HBA 6, HBD 3, PSA 93.1, QED 0.15
Compound (SMILES): CCOC(=O)c1cc(-c2cn(Cc3ccc(F)cc3)cc2-c2ccccc2)n[nH]1
InChIKey: WVCJMZNNLMBJRX-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 integrase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q7ZJM1
Assay: Inhibition of wild type HIV1 subtype B NL4-3 6xHis-tagged integrase expressed in Escherichia coli BL21 (DE3) assessed as inhibition of 3'-processing and strand-transfer reactions using DNA as substrate preincubated with enzyme for 1 hr followed by addition of recombinant 6xHis-tagged LEDGF/p75 expressed in Escherichia coli BL21 (DE3), DNA donor substrate and DNA acceptor substrate and further incubated for 90 mins by HTRF assay
Measurement: IC50 = 75000 nM (pChEMBL 4.119999885559082)
Descriptors: MW 389.43, ALogP 4.91, HBA 4, HBD 1, PSA 59.91, QED 0.48
Compound (SMILES): OCCCCNc1cc(-c2ccccc2)nc2ccccc12
InChIKey: KIDVGKQSENQBSJ-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of electric eel AChE using acetylthiocholine chloride as substrate preincubated for 15 mins followed by substrate addition by Ellman's method
Measurement: IC50 = 9850 nM (pChEMBL 5.010000228881836)
Descriptors: MW 292.38, ALogP 4.09, HBA 3, HBD 2, PSA 45.15, QED 0.67
Compound (SMILES): CN1C[C@H](Cc2ccc(Cl)cc2)N(C2CCN(c3n[nH]c(N)n3)CC2)Cc2cc(Cl)ccc21
InChIKey: LTOBNYIXGDLZAY-NRFANRHFSA-N
Target: Acidic mammalian chitinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BZP6
Assay: Inhibition of full length recombinant C-terminal His-tagged human acidic mammalian chitinase expressed in CHOK1 cells assessed as reduction in chitinolytic activity using 4-methylumbelliferyl-beta-D-N,N-diacetylchitobioside hydrate as substrate incubated for 60 mins under shaking condition by microplate fluorometry analysis
Measurement: IC50 = 0.7 nM (pChEMBL 9.149999618530273)
Descriptors: MW 486.45, ALogP 4.23, HBA 6, HBD 2, PSA 77.31, QED 0.58
Compound (SMILES): CC[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](Cc1ccccc1)NC(C)=O)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: KNTVOGGZZGGXNN-JSWZDDDHSA-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 = 10000 nM (pChEMBL 5)
Descriptors: MW 1468.72
Compound (SMILES): CC(C)C[C@@H](NC1CCC1)C(=O)N1CCC[C@H]1C(=O)NCc1ccc2c(N)nccc2c1
InChIKey: OMOBVXHXXRZRHF-YADHBBJMSA-N
Target: Prothrombin (SINGLE PROTEIN), Homo sapiens
UniProt: P00734
Assay: Inhibition of thrombin (unknown origin)
Measurement: IC50 = 44 nM (pChEMBL 7.360000133514404)
Descriptors: MW 437.59, ALogP 2.98, HBA 5, HBD 3, PSA 100.35, QED 0.59
Compound (SMILES): O=Cc1ccc2nc3n(c(=O)c2c1)-c1ccc(F)cc1C3=O
InChIKey: NVTGCQBQEMBYCC-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in human HeLa cells
Measurement: IC50 = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 294.24, ALogP 1.88, HBA 5, HBD 0, PSA 69.03, QED 0.5
Compound (SMILES): CC(C)c1onc(-c2c(Cl)cccc2Cl)c1COc1ccc(-c2nc3ccc(C(=O)O)cc3n2C)cc1
InChIKey: MFHKIRWEZYBPJQ-UHFFFAOYSA-N
Target: Bile acid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RI1
Assay: Agonist activity at human FXR expressed in human HuH7 cells by luciferase reporter gene assay
Measurement: EC50 = 32 nM (pChEMBL 7.5)
Descriptors: MW 536.42, ALogP 7.6, HBA 6, HBD 1, PSA 90.38, QED 0.23
Compound (SMILES): O=S(=O)(CCNc1nonc1/C(=N/O)Nc1ccc(F)c(Br)c1)NCC(F)(F)F
InChIKey: CVNDPCARSHUGKC-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in IFN-gamma stimulated human HeLa cells assessed as reduction in kynurenine formation using L-tryptophan as substrate incubated for 24 hrs by UV-spectrophotometry
Measurement: EC50 = 268 nM (pChEMBL 6.570000171661377)
Descriptors: MW 505.25, ALogP 2.11, HBA 8, HBD 4, PSA 141.74, QED 0.14
Compound (SMILES): COc1ccc(CC2(CCCCCCCC(F)CF)C(=O)NC(=O)NC2=O)cc1
InChIKey: FITYZYBFZVGBBP-UHFFFAOYSA-N
Target: Neutrophil collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P22894
Assay: Inhibition of human active MMP8 using (7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-(3-(2,4-dinitrophenyl)-L-2,3-diamino-propionyl)Ala-Arg-NH2 as substrate preincubated for 30 mins followed by substrate addition and measured for 10 mins by fluorescence assay
Measurement: IC50 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 410.46, ALogP 3.63, HBA 4, HBD 2, PSA 84.5, QED 0.41
Compound (SMILES): CC1(C)O[C@H]2[C@H](O)CN(CCCCCCn3cc(CNc4ccc(S(N)(=O)=O)cc4)nn3)C[C@H]2O1
InChIKey: PNQLYJMCGFDUPZ-VSKRKVRLSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human carbonic anhydrase 2 preincubated with enzyme for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 80.3 nM (pChEMBL 7.090000152587891)
Descriptors: MW 508.65, ALogP 1.29, HBA 10, HBD 3, PSA 144.83, QED 0.38
Compound (SMILES): C=CC(=O)Nc1cccc(C(=O)Nc2ncc(SCc3ncc(C(C)(C)C)o3)s2)c1
InChIKey: HMAJGFYNRRZUJX-UHFFFAOYSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51948
Assay: Inhibition of recombinant human full-length His-tagged CDK7/Cyclin H/MNAT1 expressed in baculovirus infection system using Cdk7/9tide as substrate measured after 1 hr by Alexa Fluor 647 ADP Tracer-based Adapta assay
Measurement: IC50 = 1140 nM (pChEMBL 5.940000057220459)
Descriptors: MW 442.57, ALogP 5.1, HBA 7, HBD 2, PSA 97.12, QED 0.39
Compound (SMILES): CC(C)=CCCC1=CC[C@@H](C(N)=O)[C@H](c2ccccc2)C1
InChIKey: BMSQWEZBWQWFAU-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 > 33000 nM (pChEMBL 4.480999946594238)
Descriptors: MW 283.42, ALogP 4.34, HBA 1, HBD 1, PSA 43.09, QED 0.8
Compound (SMILES): CN1CCN(c2cc(-c3ccncc3)c(-c3ccc4c(F)cccc4c3)nn2)CC1
InChIKey: ADPDKBUFJALLBQ-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15759
Assay: Inhibition of human p38beta
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 399.47, ALogP 4.25, HBA 5, HBD 0, PSA 45.15, QED 0.52
Compound (SMILES): Cc1[nH]nc2[nH]c(=O)cc([C@H]3C[C@H]4C[C@@H]3C[C@@H]4CC#N)c12
InChIKey: KGKZRAAHCZTDQA-USZNOCQGSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of N-terminal His-tagged human JAK2 catalytic domain incubated for 20 mins in presence of TK substrate-biotin by TR-FRET assay
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 282.35, ALogP 2.6, HBA 3, HBD 2, PSA 85.33, QED 0.89
Compound (SMILES): COc1cc2c(cc1O)C(c1ccccc1Cl)CN(C)CC2
InChIKey: PTYGLGJZOJASIH-UHFFFAOYSA-N
Target: D(1B) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21918
Assay: Displacement of [3H]SCH23390 from dopamine D5 receptor (unknown origin)
Measurement: Ki = 46.4 nM (pChEMBL 7.329999923706055)
Descriptors: MW 317.82, ALogP 3.67, HBA 3, HBD 1, PSA 32.7, QED 0.92
Compound (SMILES): C[C@H]1COc2c(N3CCN(C)CC3)c(F)cc3c(=O)c(C(=O)OCc4cn(CCCCCCC(=O)NO)nn4)cn1c23
InChIKey: ZJSJZYZFLWCJCG-SFHVURJKSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of human HDAC2 incubated for 30 mins by SpectraMax M2 microplate reader analysis
Measurement: IC50 = 82 nM (pChEMBL 7.090000152587891)
Descriptors: MW 585.64, ALogP 2.25, HBA 12, HBD 2, PSA 144.05, QED 0.15
Compound (SMILES): CCCCN1CC(C(=O)O)=C(NC(=O)CCc2ccc3c(Cl)c(O)ccc3c2)C1=O
InChIKey: FKUOGFZBLYAXKM-UHFFFAOYSA-N
Target: Hydroxycarboxylic acid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TDS4
Assay: Agonist activity at GPR109A receptor (unknown origin) expressed in HEK293T cell membranes after 30 mins by [35S]GTPgammaS binding based microbeta scintillation counting analysis
Measurement: EC50 = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 430.89, ALogP 3.23, HBA 4, HBD 3, PSA 106.94, QED 0.6
Compound (SMILES): N#CN1CC(OCc2ccc(-c3ccc4c(c3)OCCO4)cc2)(c2ccccc2)C1
InChIKey: DFOHFZNZQQZKIH-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 398.46, ALogP 4.33, HBA 5, HBD 0, PSA 54.72, QED 0.6
Compound (SMILES): C[C@@H](NS(=O)(=O)c1ccc(-c2sc(C(=O)NCC(C)(C)O)nc2C(=O)N2CCC(F)CC2)c(Cl)c1Cl)C(F)(F)F
InChIKey: VZRCTKJCGGBKBW-LLVKDONJSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Binding affinity to human RORgamma LBD by thermofluor thermal shift assay
Measurement: Kd = 121 nM (pChEMBL 6.920000076293945)
Descriptors: MW 649.52, ALogP 4.42, HBA 7, HBD 3, PSA 128.7, QED 0.36
Compound (SMILES): COc1ccc(-c2[nH]c3ccc(C4CCN(C5CNC5)CC4)cc3c2C)cc1OC
InChIKey: GKHRYAQSYJDANG-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 = 1720 nM (pChEMBL 5.760000228881836)
Descriptors: MW 405.54, ALogP 4.31, HBA 4, HBD 2, PSA 49.52, QED 0.66
Compound (SMILES): O=C(N/N=C/c1cccc(Cl)c1Cl)c1cc2c(s1)CCCC2
InChIKey: KFAROEDAIDJVQW-DJKKODMXSA-N
Target: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q15118
Assay: Binding affinity to PDK1 (unknown origin) assessed as dissociation constant by surface plasmon resonance assay
Measurement: Kd = 15000 nM (pChEMBL 4.820000171661377)
Descriptors: MW 353.27, ALogP 4.7, HBA 3, HBD 1, PSA 41.46, QED 0.63
Compound (SMILES): CCCCCCC(C)(C)c1cc(OC)cc(OCCCCCCCCCCC(=O)NC2CC2)c1
InChIKey: CRMRXGKJSTWDOQ-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]-CP55940 from human recombinant CB2 receptor expressed in HEK cell membrane
Measurement: Ki = 26.1 nM (pChEMBL 7.579999923706055)
Descriptors: MW 473.74, ALogP 8.11, HBA 3, HBD 1, PSA 47.56, QED 0.19
Compound (SMILES): O=C(CCCc1ccccc1)C(=O)NCCc1ccc(Cl)cc1Cl
InChIKey: KYNFWFZZNSOMKQ-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 = 251.19 nM (pChEMBL 6.599999904632568)
Descriptors: MW 364.27, ALogP 4.24, HBA 2, HBD 1, PSA 46.17, QED 0.71
Compound (SMILES): O=c1sn(CCc2ccccc2)c(=O)n1C1CCCCC1
InChIKey: LRKZAGMQOOEWMC-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) assessed as reduction in IsdA (64 to 323 residues) transpeptidation incubated for 20 mins by SDS-PAGE analysis
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 304.42, ALogP 2.82, HBA 5, HBD 0, PSA 44, QED 0.87
Compound (SMILES): O=C(NCCN1CCC(Cc2ccccc2)CC1)c1ccc(CO[N+](=O)[O-])cc1
InChIKey: DTSRZCMUDCPMBA-UHFFFAOYSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: Displacement of [3H]-di-o-tolylguanidine from sigma2 receptor (unknown origin) incubated for 1 hr in presence of (+)SKF10047 by liquid scintillation counting method
Measurement: Ki = 2673 nM (pChEMBL 5.570000171661377)
Descriptors: MW 397.48, ALogP 3.08, HBA 5, HBD 1, PSA 84.71, QED 0.52
Compound (SMILES): COc1cc(/C=C2\CCCN3C2=NO[C@H](c2cc(F)cc(F)c2)[C@@H]3C)ccc1-n1cnc(C)c1
InChIKey: UXDBRWRDVOSHLO-OPHOUFSOSA-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 = 2007 nM (pChEMBL 5.699999809265137)
Descriptors: MW 464.52, ALogP 5.42, HBA 6, HBD 0, PSA 51.88, QED 0.52