lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1cc(OC)c(F)c(N2Cc3cnc4[nH]ccc4c3N([C@@H]3CCC[C@H]3O)C2=O)c1F
InChIKey: ILNCSRUGKNZIBY-ZIAGYGMSSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Enzymatic Assay: The inhibitor potency of the exemplified compounds was measured in an enzyme assay that measures peptide phosphorylation using FRET measurements to detect product formation. Inhibitors were serially diluted in DMSO and a volume of 0.5 μL was transferred to the wells of a 384-well plate. For FGFR3, a 10 μL volume of FGFR3 enzyme (Millipore) diluted in assay buffer (50 mM HEPES, 10 mM MgCl2, 1 mM EGTA, 0.01% Tween-20, 5 mM DTT, pH 7.5) was added to the plate and pre-incubated for 5-10 minutes. Appropriate controls (enzyme blank and enzyme with no inhibitor) were included on the plate. The assay was initiated by the addition of a 10 μL solution containing biotinylated EQEDEPEGDYFEWLE peptide substrate (SEQ ID NO: 1) and ATP (final concentrations of 500 nM and 140 μM respectively) in assay buffer to the wells. The plate was incubated at 25° C. for 1 hr. The reactions were ended with the addition of 10 μL/well of quench solution (50 mM Tris, 150 mM NaCl, 0.5 mg/mL BSA, pH 7.8; 30 mM EDTA with Perkin Elmer Lance Reagents at 3.75 nM Eu-antibody PY20 and 180 nM APC-Streptavidin). The plate was allowed to equilibrate for 1 hr before scanning the wells on a PheraStar plate reader (BMG Labtech).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 444.44, ALogP 3.72, HBA 5, HBD 2, PSA 90.92, QED 0.64
Compound (SMILES): Fc1cc2[nH]ncc2c2c3c(c(-c4cn[nH]c4)nc12)CCCC3
InChIKey: QAWBPBLABQUSRL-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of human FLT3 ITD mutant using EAIYAAPFAKKK as substrate preincubated for 20 mins followed by 33P-ATP addition and measured after 2 hrs by filter binding method
Measurement: IC50 = 43 nM (pChEMBL 7.369999885559082)
Descriptors: MW 307.33, ALogP 3.52, HBA 3, HBD 2, PSA 70.25, QED 0.57
Compound (SMILES): CCC(NC(=O)c1ccc(Cl)cc1)[C@H]1[C@@H]2C[C@@H](n3cnc4c(F)cccc43)C[C@@H]21
InChIKey: OZPVWUDGSNMDJF-PXFYCIBDSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes using sulfaphenazole as substrate incubated for 10 mins in presence of NADPH by LCMS/MS analysis
Measurement: IC50 = 3900 nM (pChEMBL 5.409999847412109)
Descriptors: MW 411.91, ALogP 5.23, HBA 3, HBD 1, PSA 46.92, QED 0.62
Compound (SMILES): CCCCCCCC[C@]1(CO)NC[C@H](O)[C@@H](O)[C@@H]1O.Cl
InChIKey: YPDQPTJXUBBYFN-BHARVXRSSA-N
Target: Sucrase-isomaltase, intestinal (SINGLE PROTEIN), Rattus norvegicus
UniProt: P23739
Assay: Inhibition of rat intestinal isomaltase using p-nitrophenyl glycoside as substrate assessed as release of p-nitrophenol measured by spectrometric assay
Measurement: IC50 = 340 nM (pChEMBL 6.46999979019165)
Descriptors: MW 275.39, ALogP 0.15, HBA 5, HBD 5, PSA 92.95, QED 0.41
Compound (SMILES): CN1CCN(c2nc(-c3ccc(C(=O)NO)cc3)nc3cc(Cl)ccc23)CC1
InChIKey: DYZSQWJEPPEPAQ-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin)
Measurement: IC50 = 56 nM (pChEMBL 7.25)
Descriptors: MW 397.87, ALogP 2.82, HBA 6, HBD 2, PSA 81.59, QED 0.52
Compound (SMILES): CC1(C)[C@@H](Nc2nc(NCc3cnccc3C(F)(F)F)ncc2C#N)C[C@@H]1O
InChIKey: QHLWNCNFYOUHJB-KBPBESRZSA-N
Target: Protein kinase C delta type (SINGLE PROTEIN), Homo sapiens
UniProt: Q05655
Assay: Inhibition of PKA-delta (unknown origin) using Fam-labelled S6-derived peptide incubated for 2 hrs by TR-FRET assay
Measurement: IC50 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 392.39, ALogP 2.95, HBA 7, HBD 3, PSA 106.75, QED 0.72
Compound (SMILES): Cc1nc2c3cc(-c4ccc(NS(C)(=O)=O)cc4Cl)c(Cl)cc3[nH]c(=O)n2n1
InChIKey: FJHJGTCREGIOSM-UHFFFAOYSA-N
Target: Hepatitis A virus cellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TDQ0
Assay: Displacement of FITC-labelled SP2 probe from human TIM-3 IgV domain (residues 22 to 130) expressed in Escherichia coli BL21 (DE3) by FPA competition assay
Measurement: Ki = 204 nM (pChEMBL 6.690000057220459)
Descriptors: MW 438.3, ALogP 3.22, HBA 6, HBD 2, PSA 109.22, QED 0.51
Compound (SMILES): COc1cc([Te]CC(O)CSc2ccc(S(N)(=O)=O)cc2)cc(OC)c1OC
InChIKey: RDBLZYXAFPDYEH-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human CA2 pre-incubated for 15 mins measured by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 81.9 nM (pChEMBL 7.090000152587891)
Descriptors: MW 541.12
Compound (SMILES): O=C(O)c1ccccc1Nc1nc(Nc2ccc(OCC(=O)N3CCOCC3)cc2)ncc1Cl
InChIKey: NFCJTJDNKRXDRB-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of wild type EGFR (unknown origin) measured after 60 mins by ADP-Glo kinase based luminescence assay
Measurement: IC50 = 81.4 nM (pChEMBL 7.090000152587891)
Descriptors: MW 483.91, ALogP 3.55, HBA 8, HBD 3, PSA 125.91, QED 0.44
Compound (SMILES): O=C(O)CCc1nc(-c2ccccc2)c(-c2cccc(Cl)c2Cl)o1
InChIKey: LLKOESCDAUXPJB-UHFFFAOYSA-N
Target: Retinoic acid receptor RXR-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P19793
Assay: Agonist activity at human RXRalpha transfected in human HEK293T cells co-expressing pFR/pRL-Luc incubated for 14 to 16 hrs by hybrid reporter gene assay
Measurement: EC50 = 1200 nM (pChEMBL 5.920000076293945)
Descriptors: MW 362.21, ALogP 5.33, HBA 3, HBD 1, PSA 63.33, QED 0.67
Compound (SMILES): S=C=N[C@H]1C[C@H](OCc2ccc(-c3ccccc3)cc2)C1
InChIKey: HWBJOLGBXMIBHP-IYARVYRRSA-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 > 1000 nM (pChEMBL 6)
Descriptors: MW 295.41, ALogP 4.5, HBA 3, HBD 0, PSA 21.59, QED 0.6
Compound (SMILES): C#CCN1CC(C(N)=O)Oc2ccccc21
InChIKey: MLYFLGGMOAMHEG-UHFFFAOYSA-N
Target: NAD-dependent protein deacetylase sirtuin-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8IXJ6
Assay: Inhibition of His6-tagged/TEV fused SIRT2 (unknown origin) expressed in Escherichia coli BL21 (DE3) preincubated for 15 mins followed by NAD+ addition and measured after 30 mins by FLucK529Ac based luminescence assay
Measurement: IC50 > 60000 nM (pChEMBL 4.2220001220703125)
Descriptors: MW 216.24, ALogP 0.37, HBA 3, HBD 1, PSA 55.56, QED 0.73
Compound (SMILES): CCn1c(-c2cnc(C)nc2)nc2c(O[C@H]3CCN(C(=O)C4CCC4)C3)ncnc21
InChIKey: AATSAMRSGNEIGC-INIZCTEOSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta in human Ramos cells assessed as reduction in anti-IgM-antibody-induced phosphorylation of AKT at Ser473 residue preincubated for 20 mins followed by anti-IgM antibody stimulation and measured after 30 mins by alphascreen assay
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 407.48, ALogP 2.39, HBA 8, HBD 0, PSA 98.92, QED 0.64
Compound (SMILES): O=C(O)CCNC(=S)NCC/C=C/c1cc(NCc2ccccc2)ccc1[N+](=O)[O-]
InChIKey: GABLGPDRBURDQZ-XBXARRHUSA-N
Target: NAD-dependent protein deacylase sirtuin-5, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NXA8
Assay: Inhibition of human recombinant SIRT5 (34 to 269 residues) using Ac-Leu-Gly-Ser-Lys(Su)-AMC as substrate in presence of NAD+ by fluorescence based analysis
Measurement: IC50 = 82224.26 nM (pChEMBL 4.079999923706055)
Descriptors: MW 428.51, ALogP 3.55, HBA 5, HBD 4, PSA 116.53, QED 0.19
Compound (SMILES): CCC(=O)CCCCC[C@H]1NC(=O)[C@H]2CCCCN2C(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H](Cc2cn(OC)c3ccccc23)NC1=O
InChIKey: JWOGUUIOCYMBPV-SGTPJKRGSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of recombinant human C-terminal FLAG-tagged HDAC2 expressed in human HEK293F cells using Fluor-de-lys substrate as substrate incubated for 3 hrs followed by substrate addition and measured after 60 mins by fluorescence based assay
Measurement: IC50 = 9 nM (pChEMBL 8.050000190734863)
Descriptors: MW 623.8, ALogP 3.07, HBA 7, HBD 3, PSA 138.84, QED 0.31
Compound (SMILES): CC#CCn1c(N2CCC[C@@H](N)C2)cc(=O)n(Cc2cc(C(=O)O)ccc2Br)c1=O
InChIKey: RUFVCBKABZGJLK-MRXNPFEDSA-N
Target: Dipeptidyl peptidase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6V1X1
Assay: Inhibition of human recombinant DPP8 using Gly-Pro-AMC as substrate preincubated for 15 mins followed by substrate addition and measured for 20 mins by fluorescence based microplate reader assay
Measurement: IC50 > 100 nM (pChEMBL 7)
Descriptors: MW 475.34, ALogP 1.47, HBA 7, HBD 2, PSA 110.56, QED 0.63
Compound (SMILES): O=C(N[C@@H](Cc1ccc(O)c(Cl)c1)C(=O)O)c1cc2c(F)cccc2[nH]1
InChIKey: XWUDWLQZXNWPPA-HNNXBMFYSA-N
Target: Albumin (SINGLE PROTEIN), Homo sapiens
UniProt: P02768
Assay: Binding affinity to human serum albumin by fluorescence polarization assay
Measurement: Kd = 580 nM (pChEMBL 6.239999771118164)
Descriptors: MW 376.77, ALogP 3.09, HBA 3, HBD 4, PSA 102.42, QED 0.55
Compound (SMILES): CC(C)c1ccc(CC(=O)N(CC(=O)NCc2ccccc2)Cc2ccc(C(=O)NO)cc2)cc1
InChIKey: BOQOVYAIEYDBSI-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of N-terminal GST-tagged full length human recombinant HDAC6 expressed in baculovirus infected Sf9 cells using ZMAL (Z-Lys(Ac)-AMC) fluorogenic substrate incubated for 90 mins by fluorescence based assay
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 473.57, ALogP 3.82, HBA 4, HBD 3, PSA 98.74, QED 0.31
Compound (SMILES): CN1CCN(c2cccc(Nc3nccc(-c4c[nH]c5cccnc45)n3)c2)CC1
InChIKey: IPFHPUNNVNIMJV-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 ITD mutant (unknown origin) using Glu/Tyr peptide substrate incubated for 120 mins measured after 40 mins incubation under dark by ADP-glo based luminescence assay
Measurement: Ki = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 385.48, ALogP 3.52, HBA 6, HBD 2, PSA 72.97, QED 0.56
Compound (SMILES): CCOCc1nc(O)c(-c2nnc(Cc3ccc(Cl)cn3)o2)c(O)c1-c1c(OC)cccc1OC
InChIKey: AGZKELPIAJYRDT-UHFFFAOYSA-N
Target: Apelin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35414
Assay: Intracellular cAMP Accumulation Assay: HEK293 cells stably expressing human APJ receptor were used to assess the activity of compounds. Cultured cells were detached and resuspended in the cAMP Homogeneous Time-Resolved Fluorescence (HTRF) assay buffer (Cisbio cat; #62AM4PEJ). The assay was performed in 384-well assay plates (Perkin-Elmer; cat #6008289) according to assay protocol provided by the manufacturer. Serial dilutions of a compound together with assay buffer containing 0.2 nM IBMX and 2 μM forskolin were added to each well containing 5,000 cells and incubated for 30 minutes at room temperature. Subsequently, cAMP D2 reagent was added in the lysis buffer followed by the EuK antibody (Cisbio; cat #62AM4PEJ) and incubated for 60 min. The fluorescence emission ratio was measured using fluorometer. The intracellular cAMP concentrations (compound-stimulated inhibition of forskolin-mediated cAMP production) were calculated by extrapolation from a standard curve using known cAMP concentrations. The EC50 values were obtained by fitting the data to a sigmoidal concentration-response curve with variable slope. The maximal achievable inhibition of forskolin-induced cAMP levels (Ymax) for each compound was expressed as relative percentage of inhibition attained using pyroglutamated apelin-13 ((Pyr1)apelin-13) peptide, which was set to 100%.The examples disclosed below were tested in the APJ in vitro assays described above and were found having human APJ cyclic AMP (hcAMP) activity. The EC50 value of each compound is presented at the end of the example description.
Measurement: EC50 = 5.5 nM (pChEMBL 8.260000228881836)
Descriptors: MW 498.92, ALogP 4.4, HBA 10, HBD 2, PSA 132.85, QED 0.34
Compound (SMILES): CN(CCC=C1c2ccccc2CCc2ccccc21)C(CCN)C(=O)NCc1ccc(Cl)cc1
InChIKey: MEYQZEAPWOENKX-UHFFFAOYSA-N
Target: GABA transporter 2 (SINGLE PROTEIN), Mus musculus
UniProt: P31651
Assay: Inhibition of mouse GAT2 expressed in human HEK293 cell line assessed as inhibition of [3H]GABA uptake measured after 40 mins by LC-ESI-MS/MS analysis
Measurement: IC50 = 10964.78 nM (pChEMBL 4.960000038146973)
Descriptors: MW 488.08, ALogP 5.23, HBA 3, HBD 2, PSA 58.36, QED 0.43
Compound (SMILES): NS(=O)(=O)c1ccc(Cc2c(-c3ccc(F)c(Oc4[nH]nnc4C(=O)O)c3)nn(-c3nc(C(=O)O)cs3)c2CC2CC2)cc1F
InChIKey: DBJCYAKNWIURTJ-UHFFFAOYSA-N
Target: L-lactate dehydrogenase A chain (SINGLE PROTEIN), Homo sapiens
UniProt: P00338
Assay: Inhibition of recombinant human LDHA expressed in BL21 gold (DE3) using sodium pyruvate as substrate preincubated for 10 mins followed by sodium pyruvate and NADPH addition
Measurement: IC50 = 0.4 nM (pChEMBL 9.399999618530273)
Descriptors: MW 657.64, ALogP 3.77, HBA 11, HBD 4, PSA 216.27, QED 0.16
Compound (SMILES): NS(=O)(=O)c1ccc(NC2CCN(c3ccccc3)C2=O)cc1
InChIKey: GMEWFLAMITTXEF-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human CA2 pre-incubated for 15 mins prior to testing by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 36.9 nM (pChEMBL 7.429999828338623)
Descriptors: MW 331.4, ALogP 1.55, HBA 4, HBD 2, PSA 92.5, QED 0.89
Compound (SMILES): Cc1ccc(C2=C(c3nnn[nH]3)C(=O)N[C@@](c3ccc(OCCCCCC(F)(F)F)c(F)c3)(C(F)(F)F)C2)cc1
InChIKey: IINAPCCFQTUIHN-DEOSSOPVSA-N
Target: Alpha-1,6-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase (SINGLE PROTEIN), Mus musculus
UniProt: Q921V5
Assay: Inhibition of mouse recombinant MGAT2 expressed in Sf9 cell membrane using 2-oleoylglycerol and oleoyl-CoA as substrates incubated for 10 mins by LCMS assay
Measurement: IC50 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 571.5, ALogP 6.04, HBA 5, HBD 2, PSA 92.79, QED 0.24
Compound (SMILES): CCCNNC(=O)N[C@H]1CC(C(=O)O)=C[C@@H](OC(CC)CC)[C@@H]1NC(C)=O
InChIKey: GDCXEZBHTKSNCZ-ARFHVFGLSA-N
Target: Neuraminidase (SINGLE PROTEIN), Influenza A virus
UniProt: Q2LFS1
Assay: Inhibition of Influenza A virus (A/Anhui/1/2005(H5N1) Neuraminidase H274Y mutant using MUNANA as substrate preincubated for 5 to 15 mins followed by substrate addition and measured after 30 mins by fluorescence spectrophotometric method
Measurement: IC50 = 259 nM (pChEMBL 6.590000152587891)
Descriptors: MW 384.48, ALogP 1.06, HBA 5, HBD 5, PSA 128.79, QED 0.28
Compound (SMILES): CCC(NC(=O)c1ccc(Cl)cc1)[C@@H]1[C@@H]2C[C@H](Oc3ccnc4cccnc34)C[C@@H]21
InChIKey: QWHNGHDNBOPCLG-STJUPPKHSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using midazolam as substrate incubated for 5 mins in presence of NADPH by LCMS/MS analysis
Measurement: IC50 = 13000 nM (pChEMBL 4.889999866485596)
Descriptors: MW 421.93, ALogP 4.9, HBA 4, HBD 1, PSA 64.11, QED 0.61
Compound (SMILES): Cc1ccc(COC2CN(C(=O)[C@H]3C[C@]4(COC(=O)N4)C3)C2)cc1Cl
InChIKey: AKBHYCHPWZPGAH-QGGXVJLZSA-N
Target: Fatty-acid amide hydrolase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O00519
Assay: Inhibition of human recombinant FAAH
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 364.83, ALogP 2.26, HBA 4, HBD 1, PSA 67.87, QED 0.89
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)[C@@H](N)CCCNC(=N)N)C(C)C)C(=O)N1Cc2cc(O)ccc2C[C@H]1C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1ccccc1)C(=O)O
InChIKey: KJMSMRFIBSPTDL-MUVJKTISSA-N
Target: Type-2 angiotensin II receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P50052
Assay: Displacement of [125-I]-[Sar1, Ile8] from recombinant human AT2R transfected in human HEK293 cells incubated for 2 hrs by liquid scintillation counter analysis
Measurement: IC50 = 118.8 nM (pChEMBL 6.920000076293945)
Descriptors: MW 969.15, ALogP 1.14, HBA 11, HBD 11, PSA 322.7, QED 0.04
Compound (SMILES): COc1cc2c(cc1OC)C1CC(O)(CO)C(CC(C)C)CN1CC2
InChIKey: YAUAQNZUGKKMFP-UHFFFAOYSA-N
Target: Synaptic vesicular amine transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q01827
Assay: Inhibition of [3H]DA uptake at VMAT2 in rat striatal synaptosome incubated for 10 mins followed by [3H]DA addition and measured after 20 mins by TopCount scintillation counting method
Measurement: IC50 = 5.14 nM (pChEMBL 8.289999961853027)
Descriptors: MW 349.47, ALogP 2.39, HBA 5, HBD 2, PSA 62.16, QED 0.85
Compound (SMILES): COc1nc2ccc3c(c2n1CCNC(C)=O)CCO3
InChIKey: HIZPNVPXLSHAHA-UHFFFAOYSA-N
Target: Melatonin receptor type 1B (SINGLE PROTEIN), Homo sapiens
UniProt: P49286
Assay: Displacement of 2-[1251]-iodomelatonin from human MT2 receptor expressed in CHO cells incubated for 120 mins by scintillation counting analysis
Measurement: Ki = 0.38 nM (pChEMBL 9.420000076293945)
Descriptors: MW 275.31, ALogP 1.12, HBA 5, HBD 1, PSA 65.38, QED 0.91
Compound (SMILES): O=C(c1cccc(C#Cc2ccccc2Nc2ncnc3ccc(Cl)nc23)c1)N1CCOCC1
InChIKey: KGMVXDYNLGLTES-UHFFFAOYSA-N
Target: MAP kinase-interacting serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HBH9
Assay: Inhibition of MKN2 (unknown origin) in presence of ATP by HTRF assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 469.93, ALogP 4.29, HBA 6, HBD 1, PSA 80.24, QED 0.36
Compound (SMILES): COc1cc(OC)c(F)c(N2Cc3cnc4[nH]c(C(=O)N5CCN(C)CC5)cc4c3N(C)C2=O)c1F
InChIKey: XNSPFEJRLDJPIA-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Enzymatic Assay: The inhibitor potency of the exemplified compounds was measured in an enzyme assay that measures peptide phosphorylation using FRET measurements to detect product formation. Inhibitors were serially diluted in DMSO and a volume of 0.5 μL was transferred to the wells of a 384-well plate. For FGFR3, a 10 μL volume of FGFR3 enzyme (Millipore) diluted in assay buffer (50 mM HEPES, 10 mM MgCl2, 1 mM EGTA, 0.01% Tween-20, 5 mM DTT, pH 7.5) was added to the plate and pre-incubated for 5-10 minutes. Appropriate controls (enzyme blank and enzyme with no inhibitor) were included on the plate. The assay was initiated by the addition of a 10 μL solution containing biotinylated EQEDEPEGDYFEWLE peptide substrate (SEQ ID NO: 1) and ATP (final concentrations of 500 nM and 140 μM respectively) in assay buffer to the wells. The plate was incubated at 25° C. for 1 hr. The reactions were ended with the addition of 10 μL/well of quench solution (50 mM Tris, 150 mM NaCl, 0.5 mg/mL BSA, pH 7.8; 30 mM EDTA with Perkin Elmer Lance Reagents at 3.75 nM Eu-antibody PY20 and 180 nM APC-Streptavidin). The plate was allowed to equilibrate for 1 hr before scanning the wells on a PheraStar plate reader (BMG Labtech).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 500.51, ALogP 2.82, HBA 6, HBD 1, PSA 94.24, QED 0.59
Compound (SMILES): Cc1c(O)ccc2c(O)c(NC(=O)c3ccc(O)c(CCC(C)C)c3)c(=O)oc12
InChIKey: JJEYPKKXPKNPIS-UHFFFAOYSA-N
Target: Microtubule-associated protein 1 light chain 3 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H492
Assay: Binding affinity to human LC3A expressed in Escherichia coli BL21-(DE3) by isothermal titration calorimetry
Measurement: Kd = 14200 nM (pChEMBL 4.849999904632568)
Descriptors: MW 397.43, ALogP 4.06, HBA 6, HBD 4, PSA 120, QED 0.48
Compound (SMILES): Cc1cnc(Nc2ccc3c(c2)CCN3S(=O)(=O)c2ccc(C(F)(F)F)cc2)nc1-c1cnn(CCC#N)c1
InChIKey: BNXOIVMMIFOVPX-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of recombinant human TYK2 (875 to end residues) using GGMEDIYFEFMGG as substrate incubated for 40 mins in presence of [gamma33P]ATP by scintillation counting based radiometry assay
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 553.57, ALogP 5.08, HBA 8, HBD 1, PSA 116.8, QED 0.34
Compound (SMILES): COc1ccc(C)cc1-c1ncc(S(=O)(=O)c2ccc(C(C)(C)C)cc2)[nH]1
InChIKey: GTMOGLDGMYWKBV-UHFFFAOYSA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Agonist activity at human PXR expressed in HepG2 cells co-expressing luciferase gene under control of CYP3A4 promoter incubated for 24 hrs by luciferase reporter assay
Measurement: EC50 = 700 nM (pChEMBL 6.159999847412109)
Descriptors: MW 384.5, ALogP 4.52, HBA 4, HBD 1, PSA 72.05, QED 0.72
Compound (SMILES): O=C(NC[C@H]1[C@H]2C[C@@H](Oc3ccnc4ccc(F)cc34)C[C@@H]12)c1ccc(Cl)cc1
InChIKey: YNQNZOOVNCLJBO-LAGDQHSMSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using midazolam as substrate incubated for 5 mins in presence of NADPH by LCMS/MS analysis
Measurement: IC50 = 6700 nM (pChEMBL 5.170000076293945)
Descriptors: MW 410.88, ALogP 4.86, HBA 3, HBD 1, PSA 51.22, QED 0.65
Compound (SMILES): COc1ccc(N(C)c2nc(C)nc3ccccc23)cc1OC(C)C(=O)NO
InChIKey: RLOIBTKMGJXCEY-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin) using Ac-peptide-AMC as substrate incubated for 1 hr by fluorescence method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 382.42, ALogP 2.99, HBA 7, HBD 2, PSA 96.81, QED 0.5
Compound (SMILES): CNC(=O)N[C@@H]1CC[C@@]2(S(=O)(=O)c3ccc(F)cc3)c3ccc(C(F)(C(F)(F)F)C(F)(F)F)cc3CC[C@@H]12
InChIKey: PKHDPGAMOUIIJK-QKNQBKEWSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at RORgammat in CD3 and CD28-stimulated human whole blood assessed as suppression of IL17 preincubated for 1 hr followed by CD3 and CD28 stimulation measured after 20 hrs by AlphaLISA method
Measurement: EC50 = 101 nM (pChEMBL 7)
Descriptors: MW 570.5, ALogP 5.44, HBA 3, HBD 2, PSA 75.27, QED 0.38
Compound (SMILES): Cc1[nH]c(C(=O)Nc2nc3ccc(C(=O)O)cc3s2)c(Cl)c1Cl
InChIKey: GEZPDKBNSBNCLH-UHFFFAOYSA-N
Target: DNA gyrase (PROTEIN COMPLEX), Escherichia coli
UniProt: P0AES4
Assay: Inhibition of Escherichia coli DNA gyrase incubated for 30 mins by fluorescence based assay
Measurement: IC50 = 3.3 nM (pChEMBL 8.479999542236328)
Descriptors: MW 370.22, ALogP 4.19, HBA 4, HBD 3, PSA 95.08, QED 0.64
Compound (SMILES): CCCCCc1cc(OC)c2cc(Cc3ccncc3)c(=O)oc2c1
InChIKey: ISCAIPJNPCMLMO-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]-CP55940 from human recombinant CB2 receptor expressed in CHO-K1 cell membrane measured after 3 hrs by scintillation spectrometry
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 337.42, ALogP 4.52, HBA 4, HBD 0, PSA 52.33, QED 0.47
Compound (SMILES): CN1C(=O)CSC[C@@H](C(N)=O)NC(=O)[C@H](Cc2ccc(C(N)=O)cc2)NC(=O)[C@@H]2Cc3ccccc3CN2C(=O)[C@@H]2CCCN2C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@@H]2CCCN2C(=O)[C@@H]1Cc1ccccc1
InChIKey: XRWFACNHHWSYMQ-XJIZABAQSA-N
Target: Nicotinamide N-methyltransferase (SINGLE PROTEIN), Mus musculus
UniProt: O55239
Assay: Inhibition of mouse recombinant NNMT using nicotinamide and SAM as substrate assessed as reduction in 1-methyl-nicotinamide formation incubated for 22 to 24 hrs by RapidFire Mass spectroscopy
Measurement: IC50 = 253 nM (pChEMBL 6.599999904632568)
Descriptors: MW 1168.39
Compound (SMILES): COc1ccc(C)cc1-n1nnc(S(=O)(=O)c2ccc(C(C)(C)C)cc2)c1N
InChIKey: PIUANHUFEHCJIG-UHFFFAOYSA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Agonist activity at human PXR expressed in HepG2 cells co-expressing luciferase gene under control of CYP3A4 promoter incubated for 24 hrs by luciferase reporter assay
Measurement: EC50 = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 400.5, ALogP 3.3, HBA 7, HBD 1, PSA 100.1, QED 0.72
Compound (SMILES): Cc1ccnc(C(C)C)c1-n1c(=O)nc(N2CCN(C(=O)[C@@H]3O[C@H]3CO)C[C@@H]2C)c2cc(Cl)c(-c3ccccc3F)nc21
InChIKey: UPNPGIBFJWOTFY-IKKGAQDJSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Inhibition of GDP-bound KRAS G12C mutant (1 to 169 residues) (unknown origin) assessed as inhibition of SOS-mediated nucleotide exchange pretreated with KRAS for 20 hrs followed by incubation with SOS (564 to 1049 residues) and GTP for 30 mins and later incubated with GST-tagged cRAF (1 to 149 residues) for 10 mins by AlphaLISA assay
Measurement: IC50 = 64 nM (pChEMBL 7.190000057220459)
Descriptors: MW 607.09, ALogP 3.86, HBA 9, HBD 1, PSA 116.98, QED 0.33
Compound (SMILES): NS(=O)(=O)OC[C@H]1C[C@@H](Nc2ncncc2C(=O)c2cc(C3NCCc4ccc(Cl)cc43)c(Cl)s2)C[C@@H]1O
InChIKey: WJVMLOURSYSAQY-BNSLVSHRSA-N
Target: NEDD8 activating enzyme (PROTEIN COMPLEX), Homo sapiens
UniProt: Q13564
Assay: Inhibition of recombinant NAE (unknown origin) in presence of ATP at Km concentration by HTRF assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 598.53, ALogP 3.08, HBA 10, HBD 4, PSA 156.53, QED 0.29
Compound (SMILES): CC(C)n1cc(C(=O)Nc2ccc(Oc3ccnc(NC(=O)CN(C)C)c3)cc2)c(=O)n(-c2ccc(F)cc2)c1=O
InChIKey: NCYONVSVKQVALR-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Mer (SINGLE PROTEIN), Homo sapiens
UniProt: Q12866
Assay: Inhibition of recombinant human GST-tagged Mer using biotinylated peptide as substrate incubated for 1 hr by TR-FRET analysis
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 560.59, ALogP 3.66, HBA 9, HBD 2, PSA 127.56, QED 0.32
Compound (SMILES): Cc1ncsc1-c1ccc(CNC(=O)N2C[C@H](O)CC2C(=O)[C@H](NC(=O)C2(F)CC2)C(C)(C)C)c(OCCOCc2cn(CCOc3ccc(Cn4c(-c5ccc(O)cc5)c(C)c5cc(O)ccc54)cc3)nn2)c1
InChIKey: VYYKTWKDERPACN-FFDUFJBXSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Binding affinity to ERalpha Y537S mutant (unknown origin) expressed in Escherichia coli preincubated for 15 mins followed by ligand addition and measured after 1 hr by fluorescent polarization assay
Measurement: IC50 = 52 nM (pChEMBL 7.28000020980835)
Descriptors: MW 1029.2
Compound (SMILES): Cc1c(COc2cc(OCc3cncc(C#N)c3)c(CN(CCCN(C)C)CCS(=O)(=O)O)cc2Cl)cccc1-c1ccc2c(c1)OCCO2
InChIKey: QJSJWFVBDAPNAE-UHFFFAOYSA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NZQ7
Assay: Inhibition of PD-1/His-tagged PD-L1 (unknown origin) protein-protein interaction incubated for 90 mins by AlphaLISA
Measurement: IC50 = 23.49 nM (pChEMBL 7.630000114440918)
Descriptors: MW 721.28, ALogP 6.15, HBA 10, HBD 1, PSA 134.45, QED 0.13
Compound (SMILES): CCOc1cccnc1Oc1cncc(-c2ncc(C(=O)N[C@@H]3CNCC(F)(F)C3)cn2)c1
InChIKey: STEOFTXCZZHZJZ-INIZCTEOSA-N
Target: Diacylglycerol O-acyltransferase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96PD7
Assay: In Vitro Assay: For determination of IC50 values, the reactions were carried out in 384-well white polypropylene plates (Nunc) in a total volume of 20 μL. To 1 μL of compounds dissolved in 100% DMSO and spotted at the bottom of each well, 5 μL of 0.04% bovine serum albumin (BSA) (fatty acid free, Sigma Aldrich) was added and the mixture was incubated at room temperature for 15 minutes. hDGAT2 membrane fractions were diluted in 100 mM Hepes-NaOH, pH 7.4, 20 mM MgCl2 containing 200 nM methyl arachidonyl fluorophosphonate (Cayman Chemical, dried from ethyl acetate stock solution under argon gas and dissolved in DMSO as 5 mM stock). 10 μL of this enzyme working solution was added to the plates and incubation continued for 2 hours at room temperature. DGAT2 reactions were initiated by the addition of 4 μL of substrates containing 30 μM [1-14C]decanoyl-CoA (custom-synthesized by Perkin Elmer, 50 mCi/mmol) and 125 μM 1,2-didecanoyl-sn-glycerol (Avanti Polar Lipids) dissolved in 12.5% acetone. The reaction mixtures were incubated at room temperature for 40 min and the reactions were stopped by addition of 5 μL of 1% H3PO4. After the addition of 45 μL MicroScint-E (Perkin-Elmer), plates were sealed with Top Seal-A covers (Perkin-Elmer) and phase partitioning of substrates and products was achieved using a HT-91100 microplate orbital shaker (Big Bear Automation, Santa Clara, Calif.). Plates were centrifuged at 2,000×g for 1 minute in an Allegra 6R Centrifuge (Beckman Coulter) and then were sealed again with fresh covers before reading in a 1450 Microbeta Wallac Trilux Scintillation Counter (Perkin Elmer). DGAT2 activity was measured by quantifying the generated product [14C]tridecanoylglycerol in the upper organic phase.
Measurement: IC50 = 140 nM (pChEMBL 6.849999904632568)
Descriptors: MW 456.45, ALogP 2.85, HBA 8, HBD 2, PSA 111.15, QED 0.56
Compound (SMILES): CCc1cnc(NC(=O)c2cc3c(nc2OC)nc(C(O)(c2ccccc2)c2ccccc2)n3CC)o1
InChIKey: HSHKHTIZIQXZAX-UHFFFAOYSA-N
Target: Acetyl-coenzyme A synthetase, cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR19
Assay: Inhibition of ACSS2 in human HCT-15 cells assessed as inhibition of 14C acetate incorporation into fatty acids by microbeta scintillation counting analysis
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 497.56, ALogP 4.55, HBA 8, HBD 2, PSA 115.3, QED 0.32
Compound (SMILES): Cc1cc(NNC(=O)Nc2cc(Cl)nc(Cl)c2)nc(C(=O)NC2CC2)c1
InChIKey: WZDWGFOENNUCKD-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O95136
Assay: Antagonist activity at human S1P2 receptor expressed in CHO cells assessed as EC80 S1P-induced calcium flux measured for 3 mins by fluorescence assay
Measurement: IC50 = 4500 nM (pChEMBL 5.349999904632568)
Descriptors: MW 395.25, ALogP 3.13, HBA 5, HBD 4, PSA 108.04, QED 0.46
Compound (SMILES): CC(C)c1ccc(CC(=O)N(CC(=O)NC2CCCCC2)Cc2ccc(C(=O)NO)cc2)cc1
InChIKey: KTRGONFVDLXQSG-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of N-terminal GST-tagged full length human recombinant HDAC6 expressed in baculovirus infected Sf9 cells using ZMAL (Z-Lys(Ac)-AMC) fluorogenic substrate incubated for 90 mins by fluorescence based assay
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 465.59, ALogP 3.95, HBA 4, HBD 3, PSA 98.74, QED 0.39
Compound (SMILES): CC(=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(=N)N)NCCN1CCN(C(=O)CCCC2CCN(CC(=O)N3c4ccccc4NC(=O)c4ccccc43)CC2)CC1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: ODEXJVNPPCASDJ-PHRONXMNSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]-NMS from human muscarinic M2 receptor expressed in CHO cell membranes assessed as inhibition constant by radioligand competition analysis
Measurement: Ki = 17.78 nM (pChEMBL 7.75)
Descriptors: MW 859.09, ALogP 1.44, HBA 11, HBD 8, PSA 251.42, QED 0.05
Compound (SMILES): c1ccc2c(-c3ccc4nnn(CC5CCCO5)c4c3)c[nH]c2c1
InChIKey: KYTMIFWYXYDFJY-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of human TDO2 expressed in mouse P815B cells assessed as kynurenine concentration formation using L-tryptophan as substrate incubated for 7 hrs by UPLC analysis
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 318.38, ALogP 3.76, HBA 4, HBD 1, PSA 55.73, QED 0.63
Compound (SMILES): C#CC(=O)N1CCC(c2cnn3c(C(N)=O)c(-c4ccc(Oc5ccccc5OC)cc4)[nH]c23)C1
InChIKey: BAYUMEAMGPZXKA-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of N-terminal DYKDDDD-tagged EGFR (669 to 1210 residues) (unknown origin) expressed in Sf21 insect cells using NH2-ETVYSEVRK-biotin as substrate preincubated for 1 hr followed by ATP addition and measured after 2 hrs by ELISA
Measurement: IC50 = 104 nM (pChEMBL 6.980000019073486)
Descriptors: MW 469.5, ALogP 3.18, HBA 6, HBD 2, PSA 114.95, QED 0.42
Compound (SMILES): CNC(=O)c1cc(C(=O)N[C@H]2[C@@H]3C[C@@H](O)C[C@@H]32)cc(Cc2ccccc2)n1
InChIKey: IDTVWUPTEXWHRV-RDHRVNKHSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of Alexa Fluor 647 labelled ligand from 6His-Thr tagged BRD4 BD2/BD1 Y97A mutant (1 to 477 residue) (unknown origin) measured after 30 mins by TR-FRET assay
Measurement: IC50 = 50.12 nM (pChEMBL 7.300000190734863)
Descriptors: MW 365.43, ALogP 1.53, HBA 4, HBD 3, PSA 91.32, QED 0.75
Compound (SMILES): O=C([O-])c1ccc2c(c1)cc(Cl)c1ccncc12.[Na+]
InChIKey: KSVMFLWJXJVKFG-UHFFFAOYSA-M
Target: Casein kinase II subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P68400
Assay: Inhibition of CSNK2A1(unknown origin) using Ser/Thr 11 as substrate incubated for 60 mins in presence of ATP by Z'-LYTE assay
Measurement: IC50 < 300 nM (pChEMBL 6.5229997634887695)
Descriptors: MW 257.68, ALogP 3.74, HBA 2, HBD 1, PSA 50.19, QED 0.68
Compound (SMILES): CC(=O)NCCC1CCc2ccn3nc(C)cc3c21
InChIKey: LNOYRKHBFXIKQK-UHFFFAOYSA-N
Target: Melatonin receptor type 1B (SINGLE PROTEIN), Homo sapiens
UniProt: P49286
Assay: Displacement of 2-[125l]-lodomelatonin from human MT2 expressed in CHO cell membrane incubated for 150 mins by radioligand binding assay
Measurement: Ki = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 257.34, ALogP 2.2, HBA 3, HBD 1, PSA 46.4, QED 0.92
Compound (SMILES): COc1ccc(F)cc1C1CC1CNCCCOc1ccc2ccc(=O)[nH]c2c1
InChIKey: GZSCSKUGXORHGO-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-N-methylspiperone from D2 receptor (unknown origin) expressed in HEK293T cell membranes measured after 2 hrs by microbeta scintillation counting method
Measurement: Ki = 25.7 nM (pChEMBL 7.590000152587891)
Descriptors: MW 396.46, ALogP 3.84, HBA 4, HBD 2, PSA 63.35, QED 0.54
Compound (SMILES): CC(C)c1ccccc1-c1ccc(S(=O)(=O)Nc2ccc(F)c(C(=O)O)c2)c2ccccc12
InChIKey: PUCVVZGGGGDPMN-UHFFFAOYSA-N
Target: Fatty acid-binding protein 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q01469
Assay: Displacement of 1,8-ANS from FABP5 (unknown origin) incubated for 3 mins by fluorescence based analysis
Measurement: IC50 = 16840 nM (pChEMBL 4.769999980926514)
Descriptors: MW 463.53, ALogP 6.27, HBA 3, HBD 2, PSA 83.47, QED 0.35
Compound (SMILES): COc1ccncc1-n1c2c(cc(-c3nc(-c4ccc(Cl)cc4)cs3)c1=O)C(=O)CC(C)(C)C2
InChIKey: FOPUJAYZVAFJTK-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132C mutant (unknown origin) assessed as reduction in NADPH consumption using alpha-KG as substrate incubated for 5 mins by diaphorase/resazurin-coupled system
Measurement: IC50 > 38000 nM (pChEMBL 4.420000076293945)
Descriptors: MW 492, ALogP 5.84, HBA 7, HBD 0, PSA 74.08, QED 0.36
Compound (SMILES): CCN(CC)CCOc1ccc(Nc2ncc3cc(-c4c(Cl)cccc4Cl)c(=O)n(Cc4ccc(S(C)(=O)=O)cc4)c3n2)cc1
InChIKey: VNJSERLEIJDSJV-UHFFFAOYSA-N
Target: Nucleotide-binding oligomerization domain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HC29
Assay: Inhibition of human NOD2 expressed in HEK-blue cells coexpressing NFkappaB-SEAP reporter assessed as reduction in L18-MDP-induced NF-kappaB activation preincubated for 15 mins followed by L18-MDP stimulation and further incubated for 8 hrs by SEAP reporter gene assay
Measurement: IC50 = 94 nM (pChEMBL 7.03000020980835)
Descriptors: MW 666.63, ALogP 6.68, HBA 9, HBD 1, PSA 106.42, QED 0.16
Compound (SMILES): C[C@@H](C[C@@]1(C2CC2)NC(=O)NC1=O)C(=O)N1CCN(c2ccc(F)c(F)c2)[C@@H](C)C1
InChIKey: RKYYWBHSYPIJKC-BYVOGVQKSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using midazolam as substrate
Measurement: IC50 = 7800 nM (pChEMBL 5.110000133514404)
Descriptors: MW 420.46, ALogP 2.02, HBA 4, HBD 2, PSA 81.75, QED 0.71
Compound (SMILES): Cc1c(CN2CCN(C(=O)c3cc4cccc(C(N)=O)c4o3)CC2)sc2c(N3CCOCC3)nc(-c3ccc4cn[nH]c4c3)nc12
InChIKey: GRIJQLQVZRHMRU-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of PI3Kalpha (unknown origin) using PIP2 as substrate measured after 40 mins by ADP-glo plus luminescence assay
Measurement: IC50 = 3806 nM (pChEMBL 5.420000076293945)
Descriptors: MW 636.74, ALogP 4.18, HBA 10, HBD 2, PSA 146.71, QED 0.27
Compound (SMILES): COc1ccc(C23CC(C(=O)N[C@H]4C[C@@H](N=C=S)C4)(C2)C3)cc1
InChIKey: OALVNXHNYKJXTH-MWABVPJASA-N
Target: N-acylethanolamine-hydrolyzing acid amidase (SINGLE PROTEIN), Homo sapiens
UniProt: Q02083
Assay: Inhibition of human NAAA using N-(4-methyl coumarin)-palmitamide as fluorogenic substrate preincubated for 90 mins followed by substrate addition by fluorescence assay
Measurement: IC50 = 127.8 nM (pChEMBL 6.889999866485596)
Descriptors: MW 328.44, ALogP 2.87, HBA 4, HBD 1, PSA 50.69, QED 0.67
Compound (SMILES): CNC(=O)c1ccc(Nc2ncc(C(F)(F)F)c(Nc3ccccc3OC)n2)cc1
InChIKey: MZKCTWNUCVKGCB-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR-2 (unknown origin) incubated for 40 mins by HTRF assay
Measurement: IC50 = 291.8 nM (pChEMBL 6.539999961853027)
Descriptors: MW 417.39, ALogP 4.35, HBA 6, HBD 3, PSA 88.17, QED 0.55
Compound (SMILES): CN(CCC=C1c2ccccc2-c2ccccc21)C(CCO)C(=O)NCc1ccccc1Cl
InChIKey: QAJPGPJUFIXPGH-UHFFFAOYSA-N
Target: GABA transporter 2 (SINGLE PROTEIN), Mus musculus
UniProt: P31651
Assay: Inhibition of mouse GAT2 expressed in human HEK293 cell line assessed as inhibition of [3H]GABA uptake measured after 40 mins by LC-ESI-MS/MS analysis
Measurement: IC50 = 25703.96 nM (pChEMBL 4.590000152587891)
Descriptors: MW 461.01, ALogP 5.14, HBA 3, HBD 2, PSA 52.57, QED 0.36
Compound (SMILES): CC(C)CNC(=O)CCCC(=O)NC(C)C12CC3CC(CC(C3)C1)C2
InChIKey: XJDUVHOVMDVTBE-UHFFFAOYSA-N
Target: Bifunctional epoxide hydrolase 2 (SINGLE PROTEIN), Mus musculus
UniProt: P34914
Assay: Inhibition of mouse recombinant sEH using PHOME as substrate measured after 10 mins by fluorescent based assay
Measurement: IC50 = 693.7 nM (pChEMBL 6.159999847412109)
Descriptors: MW 348.53, ALogP 3.65, HBA 2, HBD 2, PSA 58.2, QED 0.7
Compound (SMILES): CCCCCCCCCCCCCCOCC(CNC(=O)[C@H](CCCCN)NC(C)=O)OCCCCCCCCCCCCCC.Cl
InChIKey: LXNYLOWTXJFIKY-NSWCCMNESA-N
Target: Toll-like receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60603
Assay: Antagonist activity at human TLR2 expressed in HEK-Blue cells assessed as inhibition of Pam2CSK4-induced TLR2/TLR6 activation by measuring decrease in NFkappaB activation pretreated for 2 hrs followed by incubation with agonist for 18 hrs by SEAP assay
Measurement: IC50 = 17000 nM (pChEMBL 4.769999980926514)
Descriptors: MW 654.08, ALogP 9.54, HBA 5, HBD 3, PSA 102.68, QED 0.06
Compound (SMILES): COc1ccc2c3c1O[C@H]1[C@@]4(OC)CC[C@@]5(C[C@@H]4c4cccc(NCc6ccc(O)cc6)c4)[C@@H](C2)N(CC2CC2)CC[C@]315
InChIKey: CGKGFXLBGZLTOO-BNZUBNTLSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P33533
Assay: Displacement of [3H]DPDPE from rat delta opioid receptor expressed in CHO cell membrane measured after 30 mins by liquid scintillation counting method
Measurement: Ki = 1105 nM (pChEMBL 5.960000038146973)
Descriptors: MW 578.75, ALogP 6.41, HBA 6, HBD 2, PSA 63.19, QED 0.32
Compound (SMILES): O=C(CCCN1CCN(c2ccccn2)CC1)c1ccc2c(c1)CCC2
InChIKey: OJFGNESHNMETMU-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]N-methylspiperone from human dopamine D2 receptor incubated for 1 hr by liquid scintillation counting method
Measurement: Ki = 691.83 nM (pChEMBL 6.159999847412109)
Descriptors: MW 349.48, ALogP 3.36, HBA 4, HBD 0, PSA 36.44, QED 0.75
Compound (SMILES): COc1ccc(C)cc1-n1nnc(S(=O)(=O)c2ccc(C(C)(C)C)cc2)c1C
InChIKey: XQAAHNAFJONDOV-UHFFFAOYSA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Antagonist activity at human PXR expressed in HepG2 cells co-expressing luciferase gene under control of CYP3A4 promoter incubated for 24 hrs in presence of 5 uM rifampicin by luciferase reporter assay
Measurement: IC50 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 399.52, ALogP 4.02, HBA 6, HBD 0, PSA 74.08, QED 0.66
Compound (SMILES): COc1cccc2cc(S(N)(=O)=O)c(=O)oc12
InChIKey: FAYOQNPFCPWXBX-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human carbonic anhydrase 2 assessed as inhibition constant incubated for 15 mins prior to testing by phenol red based stopped-flow CO2 hydration assay
Measurement: Ki = 85.4 nM (pChEMBL 7.070000171661377)
Descriptors: MW 255.25, ALogP 0.45, HBA 5, HBD 1, PSA 99.6, QED 0.79
Compound (SMILES): Cc1ccc(C2=NOC(C)(C)C2=O)cc1-c1ccc(NC(=O)c2c(F)cccc2F)nc1
InChIKey: BBFUAFQFQUCONY-UHFFFAOYSA-N
Target: Interleukin-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P60568
Assay: Inhibition of PHA-stimulated IL2 secretion in human Jurkat T cells preincubated for 10 mins followed by PHA addition and measured after 20 to 24 hrs by ELISA
Measurement: IC50 = 178 nM (pChEMBL 6.75)
Descriptors: MW 435.43, ALogP 4.67, HBA 5, HBD 1, PSA 80.65, QED 0.65
Compound (SMILES): CC(C)C(NC(=O)Cn1cccc(NC(=O)Oc2ccccc2)c1=O)P(=O)(Oc1ccccc1)Oc1ccccc1
InChIKey: QCRLFRZMKZDITK-UHFFFAOYSA-N
Target: Neutrophil elastase (SINGLE PROTEIN), Homo sapiens
UniProt: P08246
Assay: Inhibition of human neutrophil elastase using methoxysuccinyl-Ala-Ala-Pro-Val-pNA as substrate incubated for 15 min
Measurement: IC50 = 12810 nM (pChEMBL 4.889999866485596)
Descriptors: MW 575.56, ALogP 5.91, HBA 8, HBD 2, PSA 124.96, QED 0.21
Compound (SMILES): COc1cc(OC)c(F)c(N2Cc3cnc4[nH]cnc4c3N(C)C2=O)c1F
InChIKey: TZMMPGOEQVZVGB-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Enzymatic Assay: The inhibitor potency of the exemplified compounds was measured in an enzyme assay that measures peptide phosphorylation using FRET measurements to detect product formation. Inhibitors were serially diluted in DMSO and a volume of 0.5 μL was transferred to the wells of a 384-well plate. For FGFR3, a 10 μL volume of FGFR3 enzyme (Millipore) diluted in assay buffer (50 mM HEPES, 10 mM MgCl2, 1 mM EGTA, 0.01% Tween-20, 5 mM DTT, pH 7.5) was added to the plate and pre-incubated for 5-10 minutes. Appropriate controls (enzyme blank and enzyme with no inhibitor) were included on the plate. The assay was initiated by the addition of a 10 μL solution containing biotinylated EQEDEPEGDYFEWLE peptide substrate (SEQ ID NO: 1) and ATP (final concentrations of 500 nM and 140 μM respectively) in assay buffer to the wells. The plate was incubated at 25° C. for 1 hr. The reactions were ended with the addition of 10 μL/well of quench solution (50 mM Tris, 150 mM NaCl, 0.5 mg/mL BSA, pH 7.8; 30 mM EDTA with Perkin Elmer Lance Reagents at 3.75 nM Eu-antibody PY20 and 180 nM APC-Streptavidin). The plate was allowed to equilibrate for 1 hr before scanning the wells on a PheraStar plate reader (BMG Labtech).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 375.34, ALogP 2.83, HBA 5, HBD 1, PSA 83.58, QED 0.76
Compound (SMILES): CCCCc1nc(=O)c(C(=O)N2CCC(c3ccccn3)C2)c(O)n1-c1c(OC)cccc1OC
InChIKey: ATBDLSRTTBGEPS-UHFFFAOYSA-N
Target: Apelin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35414
Assay: Agonist activity at human APJ receptor expressed in HEK293T cells assessed as compound stimulated inhibition of forskolin stimulated cAMP production incubated for 30 mins by HTRF assay
Measurement: EC50 = 0.12 nM (pChEMBL 9.920000076293945)
Descriptors: MW 478.55, ALogP 3.32, HBA 8, HBD 1, PSA 106.78, QED 0.53
Compound (SMILES): Nc1nc(Cl)c2c(n1)N(Cc1ccc(C(F)(F)F)cc1)C(=O)C2
InChIKey: RFNSMFOUHVZBMK-UHFFFAOYSA-N
Target: Heat shock protein HSP 90-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P07900
Assay: Inhibition of PU-H71-FITC3 binding to recombinant N-terminal HSP90alpha (unknown origin) incubated for 2 hrs by fluorescence polarization assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 342.71, ALogP 2.82, HBA 4, HBD 1, PSA 72.11, QED 0.85
Compound (SMILES): C[n+]1ccc2c(c1)c1cc(F)ccc1n2CCC(=O)N1c2ccccc2Sc2ccccc21.[I-]
InChIKey: UFUNJAXKRQLFJP-UHFFFAOYSA-M
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of recombinant human AChE expressed in HEK293 cells by Ellman's method
Measurement: IC50 = 2600 nM (pChEMBL 5.579999923706055)
Descriptors: MW 454.55, ALogP 5.98, HBA 3, HBD 0, PSA 29.12, QED 0.31
Compound (SMILES): NS(=O)(=O)c1ccc(N/N=C(/CS(=O)(=O)c2ccccc2)c2ccc(Br)cc2)cc1
InChIKey: KQXLDCJHTCXEGO-GFMRDNFCSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human carbonic anhydrase 2 by stopped-flow CO2 hydration assay
Measurement: Ki = 794.2 nM (pChEMBL 6.099999904632568)
Descriptors: MW 508.42, ALogP 3.39, HBA 6, HBD 2, PSA 118.69, QED 0.37
Compound (SMILES): COc1ccccc1C1CC1CNCC[C@H]1CC[C@H](NC(=O)N2CCCC2)CC1
InChIKey: LFZXCNYEMUTWJM-JUWDIMJDSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-N-methylspiperone from D2 receptor (unknown origin) expressed in HEK293T cell membranes measured after 2 hrs by microbeta scintillation counting method
Measurement: Ki = 2187.76 nM (pChEMBL 5.659999847412109)
Descriptors: MW 399.58, ALogP 4.14, HBA 3, HBD 2, PSA 53.6, QED 0.65
Compound (SMILES): CNC(=O)c1cc(-n2ncc3cc(Nc4ccccc4Cl)c(F)cc32)cs1
InChIKey: XMMMCYBZGARUKP-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: P45983
Assay: Inhibition of JNK1 (unknown origin) using biotinylated FL-ATF-2 as substrate measured after 22 mins by homogeneous time-resolved fluorescence analysis
Measurement: IC50 = 619 nM (pChEMBL 6.210000038146973)
Descriptors: MW 400.87, ALogP 4.98, HBA 5, HBD 2, PSA 58.95, QED 0.51