lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CCc1cc2c(cc1N1CCC(N3CCN(C(=O)CNc4cccc5c4CN(C4CCC(=O)NC4=O)C5=O)CC3)CC1)C(C)(C)c1[nH]c3cc(C#N)ccc3c1C2=O
InChIKey: BWJIJVUAQRLZRJ-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of ALK G1202R mutant (unknown origin)
Measurement: IC50 = 90500 nM (pChEMBL 4.039999961853027)
Descriptors: MW 780.93, ALogP 4.46, HBA 9, HBD 3, PSA 161.95, QED 0.23
Compound (SMILES): C=CCn1c(SCCCCCC(=O)O)nnc1-c1ccncc1
InChIKey: DOJJJXMQCCVQAB-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of human full-length recombinant HDAC2 preincubated for 5 mins followed by HDAC substrate addition and further incubated for 45 mins by fluorescence microplate reader assay
Measurement: IC50 = 10120 nM (pChEMBL 5)
Descriptors: MW 332.43, ALogP 3.26, HBA 6, HBD 1, PSA 80.9, QED 0.41
Compound (SMILES): Cn1cc(-c2nc3c(-c4ccc(CNC(=O)c5noc(C(C)(C)C)n5)c(F)c4)ccnc3[nH]2)cn1
InChIKey: FQFRYNVWFJCZOA-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK in human PBMC
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 474.5, ALogP 3.78, HBA 8, HBD 2, PSA 127.41, QED 0.4
Compound (SMILES): COc1ccc(-c2ccccc2)c2c1CCN(Cc1ccc(C(=O)NO)cc1)CC2
InChIKey: DHYRDICZCDYLIV-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of human HDAC1 preincubated for 15 mins followed by substrate addition by fluorescence-based assay
Measurement: IC50 = 826 nM (pChEMBL 6.079999923706055)
Descriptors: MW 402.49, ALogP 4.08, HBA 4, HBD 2, PSA 61.8, QED 0.5
Compound (SMILES): NS(=O)(=O)c1ccc(C(=O)N[C@@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)cc1
InChIKey: XNOMSXYPJLBWKR-BZNQNGANSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human CA2 by stopped-flow assay
Measurement: IC50 = 270 nM (pChEMBL 6.570000171661377)
Descriptors: MW 362.36, ALogP -3.14, HBA 8, HBD 6, PSA 179.41, QED 0.33
Compound (SMILES): COc1cc(/C=C/c2coc3ccccc3c2=O)cc(OC)c1OC
InChIKey: ZXFCFJGJSFBFQA-CMDGGOBGSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of human recombinant MAO-A using pargyline as incubated for 20 mins measuring increase in emission signal at 310 nm multimode plate reader assay
Measurement: IC50 = 67000 nM (pChEMBL 4.170000076293945)
Descriptors: MW 338.36, ALogP 3.99, HBA 5, HBD 0, PSA 57.9, QED 0.7
Compound (SMILES): CN1CCN(c2nc(N)nc(CCCOc3cc(Cl)ccc3Cl)n2)CC1
InChIKey: OAYFFKDPUNMJMP-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H]-Ketanserin from human 5-HT2A receptor expressed in CHO-K1 cells incubated for 1 hr by microbeta counting method
Measurement: Ki = 1457 nM (pChEMBL 5.840000152587891)
Descriptors: MW 397.31, ALogP 2.52, HBA 7, HBD 1, PSA 80.4, QED 0.75
Compound (SMILES): C[C@H](CCC(=O)O[C@@H]1CC[C@@]2(C)[C@@H](C1)C[C@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)CCC(=O)NCCS(=O)(=O)O)CC[C@@H]12)[C@H]1CC[C@H]2[C@@H]3[C@@H](O)C[C@@H]4C[C@H](O)CC[C@]4(C)[C@H]3CC[C@]12C
InChIKey: OMOQUAVLSFNQGI-PBQTULMZSA-N
Target: Hepatic sodium/bile acid cotransporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q14973
Assay: Inhibition of human NTCP-mediated [3H]-TCA uptake expressed in human HepG2 cells pretreated for 2 hrs followed by [3H]-TCA addition in absence of FBS
Measurement: IC50 = 36.2 nM (pChEMBL 7.440000057220459)
Descriptors: MW 874.28, ALogP 8.36, HBA 8, HBD 5, PSA 170.46, QED 0.1
Compound (SMILES): O=C(CN(Cc1ccc(C(=O)NO)cc1)C(=O)Cc1ccccc1)NC1CCCCC1
InChIKey: IUWIVEROLJCNHO-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 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 423.51, ALogP 2.83, HBA 4, HBD 3, PSA 98.74, QED 0.45
Compound (SMILES): CCc1cc(Nc2nc(N[C@@H](C)c3ccc(C#N)cn3)nc3cccc(F)c23)n[nH]1
InChIKey: NYHGUPGYNIRFGO-LBPRGKRZSA-N
Target: Aurora kinase A (SINGLE PROTEIN), Homo sapiens
UniProt: O14965
Assay: Inhibition of recombinant full length human Aurora A using LRRASLG as substrate incubated for 40 mins in presence of [gamma-33ATP] by radiometric scintillation counting method
Measurement: IC50 = 220 nM (pChEMBL 6.659999847412109)
Descriptors: MW 402.44, ALogP 4.24, HBA 7, HBD 3, PSA 115.2, QED 0.44
Compound (SMILES): COC(=O)c1ccc2c(c1)[nH]c1c(NC(=O)C3CC3)nccc12
InChIKey: ACRYPFBNYMEDTL-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BChE using butyrylthiocholine iodide as substrate preincubated with enzyme for 20 mins followed by substrate addition and measured after 20 mins by Ellman's method
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 309.33, ALogP 2.85, HBA 4, HBD 2, PSA 84.08, QED 0.73
Compound (SMILES): CNc1nc(C)c(-c2nc(Nc3cccc(N4CCN(C)CC4)c3)ncc2C)s1
InChIKey: TZUWFXHCJVWHSH-UHFFFAOYSA-N
Target: CDK2/Cyclin A2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P20248
Assay: Inhibition of recombinant human full length CDK2/Cyclin A using histone H1 as substrate incubated for 40 mins in presence of [gamma-33P]-ATP by scintillation counting method
Measurement: Ki = 586 nM (pChEMBL 6.230000019073486)
Descriptors: MW 409.56, ALogP 3.75, HBA 8, HBD 2, PSA 69.21, QED 0.66
Compound (SMILES): Cc1scnc1-c1ccc2nc(NC(=O)[C@@H]3C[C@@H]3F)sc2c1
InChIKey: QOPWKBHJNJRYEG-ZJUUUORDSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: c-abl Kinase Assay: ADP-Glo assay kit was purchased from Promega. Magnesium chloride (MgCl2), bovine serum albumin (BSA), ethylene glycol-bis(β-aminoethyl ether)-N,N′,N′-tetraacetic acid (EGTA), tween-20, 1,4-dithiothreitol (DTT) and dimethyl sulfoxide (DMSO) were purchased from Sigma-Aldrich. HEPES buffer was purchased from Gibco. ABL1 kinase and Abltide were purchased from Signalchem.c-abl kinase activity was measured by Promega's ADP-Glo Assay. In this assay, His-tagged recombinant human ABL1 (0.25 ng/μl) is incubated with 5 μL of compounds (0.5% DMSO), 5 μL of Abltide (0.01 μg/μl) and 5 μL of ATP (25 μM) in buffer (50 mM HEPES, 7.5; 10 mM MgCl2; 1 mM EGTA; 0.05% BSA; 0.01% Tween-20; 2 mM DTT). The assay was started by incubating the reaction mixture in a 96-well plate at 30° C. for 30-min. After the incubation, 25 μL ADP-Glo reagent was added and the reaction was incubated at room temperature for 40-min to stop the reaction and degrade residual ATP. The ADP product was then converted to ATP by adding 50 μL per well of detection reagent. Luminescence was detected after 30-min room temperature incubation with the Molecular device I3X plate reader. The IC50 values were calculated from a series of percent inhibition values determined at a range of inhibitor concentration using software routines as implemented in the GraphPad Prism 7 software or SigmaPlot 13.0.
Measurement: IC50 = 40.4 nM (pChEMBL 7.389999866485596)
Descriptors: MW 333.41, ALogP 4.02, HBA 5, HBD 1, PSA 54.88, QED 0.79
Compound (SMILES): COc1ccn2c(-c3cc(NCc4ccc(-c5cnn(C)c5)cc4)ncn3)cnc2c1
InChIKey: REODFJPJFIFZBL-UHFFFAOYSA-N
Target: Mast/stem cell growth factor receptor Kit (SINGLE PROTEIN), Homo sapiens
UniProt: P10721
Assay: Inhibition of KIT (delta 560 to 576 residues) deletion/V654A double mutant autophosphorylation at Y703 in human GIST-430/654 harboring KIT (delta560 to 576 residues) deletion mutation and V654A point mutation incubated for 45 mins by Luminex-based bead assay
Measurement: IC50 = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 411.47, ALogP 3.81, HBA 8, HBD 1, PSA 82.16, QED 0.46
Compound (SMILES): CNC(=O)c1cc(C(=O)NC2CC2)cc(Cc2cccc3c2CCN3)n1.Cl
InChIKey: IHDOOUNKCRLZBK-UHFFFAOYSA-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 = 79.43 nM (pChEMBL 7.099999904632568)
Descriptors: MW 350.42, ALogP 1.89, HBA 4, HBD 3, PSA 83.12, QED 0.77
Compound (SMILES): CC#CC(=O)N1CCCC[C@H]1c1nc(-c2ccc(C(=O)Nc3cc(-c4ccccc4)ccn3)cc2)c(C(N)=O)n1N
InChIKey: KDYQGXDLDYYRDX-DEOSSOPVSA-N
Target: Cytoplasmic tyrosine-protein kinase BMX (SINGLE PROTEIN), Homo sapiens
UniProt: P51813
Assay: Inhibition of full-length N-terminal GST-tagged BMX (1 to 675 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 = 903 nM (pChEMBL 6.039999961853027)
Descriptors: MW 547.62, ALogP 3.75, HBA 7, HBD 3, PSA 149.23, QED 0.25
Compound (SMILES): CCc1cccc(C)c1-n1c2c(cc(-c3nc(-c4ccc(Cl)cc4)cs3)c1=O)C(=O)CC(C)(C)C2
InChIKey: QZCKJZIDFGDGNQ-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 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 503.07, ALogP 7.31, HBA 5, HBD 0, PSA 51.96, QED 0.29
Compound (SMILES): Cn1cc(-c2ccc(-c3cnc4cc(-c5ccc(S(C)(=O)=O)cc5)ccn34)s2)cn1
InChIKey: OAUINKGXYDIKQG-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase Nek2 (SINGLE PROTEIN), Homo sapiens
UniProt: P51955
Assay: Inhibition of NEK2 (unknown origin) using 5' FAM-KKLNRTLSVA-COOH peptide as a substrate in the presence of ATP incubated for 60 mins by microfluidics assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 434.55, ALogP 4.53, HBA 7, HBD 0, PSA 69.26, QED 0.42
Compound (SMILES): O/N=C(/NCc1cccc(Cl)c1)c1ccc2oc3ccccc3c2c1
InChIKey: YJYONDXFCQLGNI-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in IFNgamma-stimulated human HeLa cells assessed as reduction in kynurenine formation using L-tryptophan as substrate by absorbance based analysis
Measurement: IC50 = 29600 nM (pChEMBL 4.53000020980835)
Descriptors: MW 350.81, ALogP 5.17, HBA 3, HBD 2, PSA 57.76, QED 0.23
Compound (SMILES): C[n+]1ccc2[nH]c3ccc(F)cc3c2c1.[I-]
InChIKey: DSHSZSVVNRGDOH-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of recombinant equine BChE by Ellman's method
Measurement: IC50 = 2700 nM (pChEMBL 5.570000171661377)
Descriptors: MW 201.22, ALogP 2.28, HBA 0, HBD 1, PSA 19.67, QED 0.54
Compound (SMILES): O=C(O)CCNC(=S)NCCCNc1nc(CCc2ccccc2)ncc1C(=O)O
InChIKey: KSGXIVSHTKBIDV-UHFFFAOYSA-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 = 22803.42 nM (pChEMBL 4.639999866485596)
Descriptors: MW 431.52, ALogP 1.7, HBA 6, HBD 5, PSA 136.47, QED 0.25
Compound (SMILES): Fc1ccc(Nc2ncc(Cl)c(Nc3cccc(C(F)(F)F)c3)n2)cc1
InChIKey: UGBDWDUEHMHBDO-UHFFFAOYSA-N
Target: Dipeptidyl peptidase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53634
Assay: Inhibition of human Cathepsin C in human THP-1 cells using H-Gly-Phe-AFC as substrate pretreated for 60 mins followed by substrate addition incubated for 60 mins
Measurement: IC50 = 992 nM (pChEMBL 6)
Descriptors: MW 382.75, ALogP 5.78, HBA 4, HBD 2, PSA 49.84, QED 0.56
Compound (SMILES): Cc1cc2nc3n(c(=O)c2cc1NCc1ccccc1O)CCC3
InChIKey: BGHPQGWCHCMYRN-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BChE using butyrylthiocholine iodide as substrate preincubated for 10 mins followed by addition of substrate and measured after 15 mins by Ellman's method
Measurement: IC50 = 18470 nM (pChEMBL 4.730000019073486)
Descriptors: MW 321.38, ALogP 2.97, HBA 5, HBD 2, PSA 67.15, QED 0.78
Compound (SMILES): Cn1cc(-c2nc3ccc4[nH]ncc4c3c3c2CCCC3)c(C2CC2)n1
InChIKey: NAQCTGFUBGSCAM-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 = 3660 nM (pChEMBL 5.440000057220459)
Descriptors: MW 343.43, ALogP 4.27, HBA 4, HBD 1, PSA 59.39, QED 0.59
Compound (SMILES): CCS(=O)(=O)c1ccc(C(NC(=O)CC2CC2)C(=O)Nc2ccc(C(O)(C(F)(F)F)C(F)(F)F)cc2)nc1
InChIKey: QYYWIBMHOMQEDF-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 = 34000 nM (pChEMBL 4.46999979019165)
Descriptors: MW 567.51, ALogP 3.78, HBA 6, HBD 3, PSA 125.46, QED 0.4
Compound (SMILES): CC(C)[C@H]1NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@@H]2CCCCNC(=O)c3cc(cc(c3)C(=O)N[C@H](Cc3ccc4ccccc4c3)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](Cc3ccc4ccccc4c3)C(=O)N[C@@H](c3ccccc3)C(=O)N2)C(=O)NC[C@@H](C(N)=O)NC(=O)[C@H](CCCNC(=N)N)NC1=O
InChIKey: SQULGOCJFQHCRQ-GFWZJIFDSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Binding affinity to GppNHp-bound K-Ras G12V mutant (1 to 185 residues) (unknown origin) expressed in Escherichia coli BL21 cells incubated for 2.5 hrs by fluorescence anisotropy
Measurement: Kd = 1600 nM (pChEMBL 5.800000190734863)
Descriptors: MW 1688.92
Compound (SMILES): COC(=O)N1c2ccc(C3(NC(=O)c4ccc(F)cc4)CC3)cc2[C@H]2CC[C@H]21
InChIKey: ULNIHFOLHILCPG-SJLPKXTDSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of human IDO1 by human whole blood assay
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 380.42, ALogP 4.08, HBA 3, HBD 1, PSA 58.64, QED 0.87
Compound (SMILES): O=S(=O)(N[C@H]1CCCC[C@@H]1N1CCN(c2ccccc2)CC1)c1ccccc1
InChIKey: CQKGBMYHUARKBL-VXKWHMMOSA-N
Target: Mucolipin-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8IZK6
Assay: Activation of human TRPML2-YFP expressed in HEK293 cells incubated for 10 mins by Fluo-4 dye calcium imaging based FLIPR analysis
Measurement: EC50 = 3600 nM (pChEMBL 5.440000057220459)
Descriptors: MW 399.56, ALogP 3.1, HBA 4, HBD 1, PSA 52.65, QED 0.84
Compound (SMILES): Cn1cnc2ncn(Cc3nc([C@@H]4CO[C@@H](c5ccc(Cl)cc5)C4)no3)c(=O)c21
InChIKey: UGLQOTZNBCEHHB-GXTWGEPZSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 412.84, ALogP 2.46, HBA 9, HBD 0, PSA 100.86, QED 0.51
Compound (SMILES): Cc1ccc(-c2cc3cnc4[nH]ccc4c3n2-c2cnn(CCC#N)c2)o1
InChIKey: MZINQMQWRJFSFA-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of recombinant human N-terminal His-tagged JAK2 (826 to 1132 residues) expressed in baculovirus expression system
Measurement: IC50 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 356.39, ALogP 4.19, HBA 6, HBD 1, PSA 88.36, QED 0.52
Compound (SMILES): O=C(CN1CCOCC1)Nc1ccc(Nc2ncc(Cl)c(Nc3ccccc3C(=O)NO)n2)cc1
InChIKey: MLNHYVUEDYMASN-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 = 126 nM (pChEMBL 6.900000095367432)
Descriptors: MW 497.94, ALogP 3.01, HBA 9, HBD 5, PSA 140.74, QED 0.23
Compound (SMILES): Cn1cc(-c2ccc3nc(-c4cnn(CC(C)(C)O)c4)nc(N4CCOC[C@@H]4c4ccc(F)cc4)c3c2)c2cc[nH]c2c1=O
InChIKey: NWBXSSAAUAOJIK-MUUNZHRXSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of binding of N-terminal His-tagged human full length recombinant BRD4 (2 to 1362 residues) expressed in baculovirus-infected Sf9 cells with acetylated histone H4 peptide (1 to 21) preincubated for 30 mins followed by H4 ligand addition and measured after 30 mins AlphaScreen assay
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 593.66, ALogP 4.83, HBA 9, HBD 2, PSA 114.09, QED 0.28
Compound (SMILES): CCC[C@@H]1CN([C@H](Cc2ccccc2)N2CCC[C@H]2CN2C(=N)NC[C@H]2C(C)C)C(=N)N1CCCC(C)C
InChIKey: GUFZIAOEZHMXKI-GIFPIDKJSA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Mus musculus
UniProt: P33033
Assay: Antagonist activity at mouse melanocortin receptor 3 expressed in HEK293 cells assessed as inhibition of NDP-MSH-induced intracellular cAMP accumulation incubated for 24 hrs by beta-galactosidase reporter gene assay
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 523.81, ALogP 5.04, HBA 3, HBD 3, PSA 72.69, QED 0.34
Compound (SMILES): NS(=O)(=O)c1ccc([Se]CC(O)CSc2ccccc2)cc1
InChIKey: MMVOFFDQNAVGDE-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 = 3.1 nM (pChEMBL 8.510000228881836)
Descriptors: MW 402.4
Compound (SMILES): CC(=O)OC[C@]12[C@H](OC(C)=O)C(=O)[C@@H]3[C@@H](OC(C)=O)[C@]1(OC3(C)C)[C@H](C)C[C@H](O)[C@@H]2OC(C)=O
InChIKey: ZFNDZHVNJCYSEW-KYJRXYQZSA-N
Target: ATP-dependent translocase ABCB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08183
Assay: Reversal of P-gp-mediated multidrug resistance in human KB/VCR cells assessed as potentiation of vincristine-induced antiproliferative activity by measuring vincristine IC50 at 2 uM measured after 72 hrs by CCK8 assay (Rvb = 0.51 uM)
Measurement: IC50 = 480 nM (pChEMBL 6.320000171661377)
Descriptors: MW 484.5, ALogP 0.48, HBA 11, HBD 1, PSA 151.73, QED 0.43
Compound (SMILES): Nc1cc(Oc2ccc(NC(=O)Nc3cccc(C(F)(F)F)c3)cc2)ncn1
InChIKey: AVKRLFMBOPHBOL-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase TNNI3K (SINGLE PROTEIN), Homo sapiens
UniProt: Q59H18
Assay: Inhibition of human myc-TNNI3K expressed in HEK-MSR2 cells assessed as reduction in TNNI3K autophosphorylation preincubated for 30 mins followed by pervanadate addition and measured after 20 mins by DELFIA
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 389.34, ALogP 4.51, HBA 5, HBD 3, PSA 102.16, QED 0.61
Compound (SMILES): O=C1Cc2cccc(c2)OCC/C=C/CCOc2cccc(c2)CC(=O)Nc2nnc(s2)CCCCc2ccc(nn2)N1
InChIKey: IFQQSJCIINHYQE-OWOJBTEDSA-N
Target: Glutaminase kidney isoform, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: O94925
Assay: Binding affinity to human GLS1 expressed in Escherichia coli strain BL21 (DE3) assessed as dissociation constant by surface plasmon resonance analysis
Measurement: Kd = 24.19 nM (pChEMBL 7.619999885559082)
Descriptors: MW 598.73, ALogP 5.36, HBA 9, HBD 2, PSA 128.22, QED 0.26
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@@H]1COCCCCCC(=O)N2CCCC[C@H]2C(=O)N1)C(=O)[C@@]1(C)CO1
InChIKey: KEARFWHDBPWDLV-GSRZOBFVSA-N
Target: Proteasome subunit beta type-8 (SINGLE PROTEIN), Homo sapiens
UniProt: P28062
Assay: Inhibition of human 20S proteasome LMP7 using Ac-ANW-AMC as fluorogenic substrate measured every minute for 1 hr by fluorescence assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 465.59, ALogP 1.33, HBA 6, HBD 2, PSA 117.34, QED 0.57
Compound (SMILES): CCOC(=O)/C(=N\Nc1ccc(C)cc1)C(=O)C(F)(F)F
InChIKey: MXVXMWJOHZMDDT-ZDLGFXPLSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human erythrocyte AChE using acetylthiocholine iodide as substrate preincubated for 10 mins followed by substrate addition by Ellman's method
Measurement: IC50 = 7320 nM (pChEMBL 5.130000114440918)
Descriptors: MW 302.25, ALogP 2.46, HBA 5, HBD 1, PSA 67.76, QED 0.39
Compound (SMILES): NS(=O)(=O)c1ccc(CNC(=O)CNc2ccc(F)cc2)cc1
InChIKey: YICHSKQGZLZABH-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 stopped flow CO2 hydration assay
Measurement: Ki = 139.5 nM (pChEMBL 6.860000133514404)
Descriptors: MW 337.38, ALogP 1.2, HBA 4, HBD 3, PSA 101.29, QED 0.74
Compound (SMILES): CC[C@H](C)[C@H]1C(=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)C[C@@H](c2cccc3ccccc23)NC(=O)N[C@H]2CSSC[C@H](NC(=O)C[C@@H](c3cccc4ccccc34)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]3CCCN3C(=O)[C@@H]3CCCN13)C(=O)N[C@@H](Cc1ccccc1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(=O)O)C(=O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](Cc1ccccc1)NC2=O
InChIKey: QUBBKFWMXILQNG-KKHAWTMVSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: Binding affinity to HER2 domain IV (unknown origin) by SPR analysis
Measurement: Kd = 346 nM (pChEMBL 6.460000038146973)
Descriptors: MW 1883.19
Compound (SMILES): CCC(=O)N1CC[C@H](Nc2ncnc3c2nc(-c2cnn(CC)c2C)n3CC)C1
InChIKey: YRHMXJOWXZBWSP-AWEZNQCLSA-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 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 396.5, ALogP 2.46, HBA 8, HBD 1, PSA 93.76, QED 0.69
Compound (SMILES): O=C(c1ccccn1)N1CCN(Cc2c(O)cc(O)c3c(=O)cc(-c4ccc(O)cc4)oc23)CC1
InChIKey: YBFDJRDCTPQNDP-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGN5
Assay: Inhibition of recombinant human full-length PARP-2 using biotinylated substrate
Measurement: IC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 473.49, ALogP 2.93, HBA 8, HBD 3, PSA 127.34, QED 0.41
Compound (SMILES): Fc1ccc2c(c1)C(C1=CCNCC1)=Nc1cc(Cl)ccc1N2
InChIKey: VMCOQPDINSDQFU-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Agonist activity at muscarinic M2 receptor (unknown origin) expressed in CHO cells
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 327.79, ALogP 4.58, HBA 3, HBD 2, PSA 36.42, QED 0.8
Compound (SMILES): NS(=O)(=O)c1ccc(C(=O)N[C@@H]2O[C@H](CO)[C@@H](O)[C@H]2O)cc1
InChIKey: QSRVQCMYJZKFHJ-DNRKLUKYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human CA2 by stopped-flow assay
Measurement: IC50 = 80 nM (pChEMBL 7.099999904632568)
Descriptors: MW 332.33, ALogP -2.5, HBA 7, HBD 5, PSA 159.18, QED 0.41
Compound (SMILES): CCCCC1(c2cc(O)c3cc(C)c(=O)oc3c2)CCCCC1
InChIKey: OXGIDMVFIFMGAK-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 = 104.71 nM (pChEMBL 6.980000019073486)
Descriptors: MW 314.43, ALogP 5.2, HBA 3, HBD 1, PSA 50.44, QED 0.79
Compound (SMILES): CCCN(C[C@@H](O)[C@H](Cc1ccccc1)NC(=O)CCc1cc(OC)c(O)cc1OC)S(=O)(=O)c1ccc(OC)cc1
InChIKey: QXXQWIDOJKUBHN-XTEPFMGCSA-N
Target: Human immunodeficiency virus type 1 protease (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72874
Assay: Inhibition of wild type HIV1 protease expressed in Escherichia coli using Arg-Glu (EDANS)-Ser-Gln-Asn-Tyr-Pro-Ile-Val-Gln-Lys(DABCYL)-Arg as substrate preincubated for 20 to 30 mins followed by substrate addition and measured for 10 mins by FRET assay
Measurement: IC50 = 86.44 nM (pChEMBL 7.059999942779541)
Descriptors: MW 600.73, ALogP 3.54, HBA 8, HBD 3, PSA 134.63, QED 0.23
Compound (SMILES): CCCCC1(c2cc(O)c3cc(-c4ccccc4O)c(=O)oc3c2)CCCC1
InChIKey: YZFLRYDYOSBGGE-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 378.47, ALogP 5.87, HBA 4, HBD 2, PSA 70.67, QED 0.54
Compound (SMILES): C[C@@H](NC(=O)c1ccc(Cl)cc1)[C@H]1[C@@H]2C[C@@H](n3cnc4cc(F)c(F)cc43)C[C@@H]21
InChIKey: CAPFNEJTKCIVRA-IDJJVQAESA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of Tracer Red from human ERG measured after 4 hrs by fluorescence polarization assay
Measurement: IC50 = 520 nM (pChEMBL 6.28000020980835)
Descriptors: MW 415.87, ALogP 4.98, HBA 3, HBD 1, PSA 46.92, QED 0.65
Compound (SMILES): COc1ccc2[nH]cc(CCNC(=O)CCCCn3cc(CCCCN4CC[C@@]56C=C[C@H](O)C[C@@H]5Oc5c(OC)ccc(c56)C4)nn3)c2c1
InChIKey: GRGRSPYUJIFMHC-AEOVLEPASA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human serum BuChe using butyrylthiocholine iodide as substrate incubated for 25 mins by DTNB reagent based Ellman's method
Measurement: IC50 = 963 nM (pChEMBL 6.019999980926514)
Descriptors: MW 668.84, ALogP 4.85, HBA 9, HBD 3, PSA 126.76, QED 0.12
Compound (SMILES): CC1(C)C[C@@H](Nc2cc(NCc3cnccc3C(F)(F)F)ncc2C#N)CC[C@H]1O
InChIKey: VDRCTDRTPPONJY-MAUKXSAKSA-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 = 2400 nM (pChEMBL 5.619999885559082)
Descriptors: MW 419.45, ALogP 4.33, HBA 6, HBD 3, PSA 93.86, QED 0.67
Compound (SMILES): O=c1[nH]c2c(OCCNCc3ccccc3)cccc2n1Cc1ccccc1
InChIKey: ANHGJPIQEGVWNM-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE using BTC as substrate preincubated with enzyme for 5 mins followed by substrate addition for 5 mins by Ellman's method
Measurement: IC50 = 1844 nM (pChEMBL 5.730000019073486)
Descriptors: MW 373.46, ALogP 3.55, HBA 4, HBD 2, PSA 59.05, QED 0.46
Compound (SMILES): COC(=O)/C(=N\Nc1ccccc1)C(=O)C(F)(F)F
InChIKey: WWZILGNFFPBJFT-PXNMLYILSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human erythrocyte AChE using acetylthiocholine iodide as substrate preincubated for 10 mins followed by substrate addition by Ellman's method
Measurement: IC50 = 20100 nM (pChEMBL 4.699999809265137)
Descriptors: MW 274.2, ALogP 1.76, HBA 5, HBD 1, PSA 67.76, QED 0.39
Compound (SMILES): O=C(NO)c1ccc(CN2CCCc3cc(Cl)ccc32)c(F)c1
InChIKey: YWGJBRYPUNDFFF-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: HDAC Enzyme Activity Inhibition Assay (In Vitro): The effectiveness, or potency, of a present HDACI with respect to inhibiting the activity of an HDAC is measured by an IC50 value. The quantitative IC50 value indicates the concentration of a particular compound that is needed to inhibit the activity of an enzyme by 50% in vitro. Stated alternatively, the IC50 value is the half maximal (50%) inhibitory concentration of a compound tested using a specific enzyme, e.g., HDAC, of interest. The smaller the IC50 value, the more potent the inhibiting action of the compound because a lower concentration of the compound is needed to inhibit enzyme activity by 50%.In preferred embodiments, a present HDACI inhibits HDAC enzymatic activity by about at least 50%, preferably at least about 75%, at least 90%, at least 95%, or at least 99%.Compounds of the present invention were tested for IC50 values against both HDAC6 and HDAC1. In some embodiments, a present compound also was tested against HDAC1, 2, 3, 4, 5, 8, 10, and 11. The tested compounds showed a range of IC50 values vs. HDAC6 of about 1 nm to greater than 30 μm, and a range of IC50 values vs. HDAC1 of about 91 nm to greater than 30 μm. Therefore, in some embodiments, a present HDACI is a selective HDAC6 inhibitor which, because of a low affinity for other HDAC isozymes, e.g., HDAC1, give rise to fewer side effects than compounds that are non-selective HDAC inhibitors.In some embodiments, the present HDACIs interact with and reduce the activity of all histone deacetylases in a cell. In some preferred embodiments, the present HDACIs interact with and reduce the activity of fewer than all histone deacetylases in the cell. In certain preferred embodiments, the present HDACIs interact with and reduce the activity of one histone deacetylase (e.g., HDAC-6), but do not substantially interact with or reduce the activities of other histone deacetylases (e.g., HDAC-1, HDAC-2, HDAC-3, HDAC-4, HDAC-5, HDAC-7, HDAC-8, HDAC-9, HDAC-10, and HDAC-11).
Measurement: IC50 = 12.4 nM (pChEMBL 7.909999847412109)
Descriptors: MW 334.78, ALogP 3.55, HBA 3, HBD 2, PSA 52.57, QED 0.67
Compound (SMILES): Cc1cc(-c2ccnc3[nH]c(-c4cnn(C)c4)nc23)ccc1CNC(=O)c1ccc(C(C)(C)C)cc1
InChIKey: GMMDLUVGCVNIFG-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Microfluidic Off-Chip Mobility Shift Assay Protocol for Potency Assessment Against BTK C481S Enzyme: The protocol below describes a microfluidic, off-chip mobility shift kinase assay to measure inherent potency of compounds against BTK C481S enzyme. The mechanics of the assay platform are described by the vendor (PerkinElmer, Hopkinton, Mass.) on their website at the following URL: http://caliperls.com.Briefly, 2.5× stocks of His-TEV-hsBTK(328-659)(C481S) from the Merck Serono Protein Purification Laboratory in Darmstadt, Germany (PCS, Q27/234), 1.6×ATP and appropriate KinKDR peptide substrate (FITC-AHA-EEPLYWSFPAKKK-NH2; Tufts University Core Facility custom synthesis) were prepared in kinase reaction buffer consisting of 25 mM MgCl2, 0.015% Brij-35 (30%), 100 mM HEPES, pH 7.5, and 10 mM DTT.5 uL of enzyme buffer and 7.5 uL of ATP/KinKDR peptide substrate mix were added to Matrix (#4315) 384-well, sterile, flat-bottom polypropylene plates (Thermo Fisher Scientific, Hudson, N.H.) with 125 nL of serially diluted compounds prepared in 100% DMSO, and incubated for 90 min. at 25° C. Following the incubation period, reactions were terminated by adding 65 uL quench buffer consisting of 100 mM HEPES, pH 7.5, 0.015% Brij-35 (30%), 0.277% Coating Reagent #3 (PerkinElmer, Mountain View, Calif.), 5% DMSO. Terminated reactions were monitored at −2 PSI, −3000 V/−700 Volts in a LabChip 3000 plate reader from Caliper Life Sciences, a PerkinElmer Company (Hopkinton, Mass.), and the activity was quantified by laser-induced fluorescence measuring the charge/mass difference between substrate and product resulting from peptide phosphorylation. IC50 and efficacy were determined by plotting log [Inhibitor] vs. % Activity in GeneData Screener (Basel, Switzerland).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 478.6, ALogP 5.56, HBA 5, HBD 2, PSA 88.49, QED 0.35
Compound (SMILES): COc1ccc(-c2cnc(C(=O)N[C@H]3C[C@@H](N=C=S)C3)cn2)cc1
InChIKey: UZIRQHSFYNCKNL-BETUJISGSA-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 = 853.2 nM (pChEMBL 6.070000171661377)
Descriptors: MW 340.41, ALogP 2.52, HBA 6, HBD 1, PSA 76.47, QED 0.67
Compound (SMILES): Cc1cnc(Nc2ccc3c(c2)CCN3S(=O)(=O)C2CC2)nc1-c1cnn(C(C)C)c1
InChIKey: WMCFPFONXNCULT-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 = 2.69 nM (pChEMBL 8.569999694824219)
Descriptors: MW 438.56, ALogP 3.83, HBA 7, HBD 1, PSA 93.01, QED 0.63
Compound (SMILES): CC(C)c1cnn2c(NCc3ccccc3)nc(OC3CCN(C)CC3)nc12
InChIKey: BWJDMRPMFRWAOP-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P24941
Assay: Inhibition of CDK2 (unknown origin) using ULight 4EBP1 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: IC50 = 2006 nM (pChEMBL 5.699999809265137)
Descriptors: MW 380.5, ALogP 3.33, HBA 7, HBD 1, PSA 67.58, QED 0.71
Compound (SMILES): CCCCCOc1ccc(-c2nnn(C[C@H](N)CC(=O)O)n2)cc1
InChIKey: UBJBMJVCOROOEO-CYBMUJFWSA-N
Target: Leukotriene A-4 hydrolase (SINGLE PROTEIN), Homo sapiens
UniProt: P09960
Assay: Inhibition of LTA4H in human whole blood assessed as reduction of calcium ionophore A23187-stimulated LTB4 generation preincubated for 15 mins followed by ionophore stimulation and measured after 15 hrs by EIA assay
Measurement: IC50 = 156 nM (pChEMBL 6.809999942779541)
Descriptors: MW 333.39, ALogP 1.71, HBA 7, HBD 2, PSA 116.15, QED 0.64
Compound (SMILES): Cc1cccc(CNCCOc2cccc3c2ccn3S(=O)(=O)c2ccccc2)c1
InChIKey: KPULSQQTOLRHKW-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE using BTC as substrate preincubated with enzyme for 5 mins followed by substrate addition for 5 mins by Ellman's method
Measurement: IC50 = 401.3 nM (pChEMBL 6.400000095367432)
Descriptors: MW 420.53, ALogP 4.36, HBA 5, HBD 1, PSA 60.33, QED 0.43
Compound (SMILES): CCCCCCCC(=O)NCC(=O)Nc1ccc2c(c1)[C@@]13CCN4CC5=CCO[C@H]6CC(=O)N2[C@H]1[C@H]6[C@H]5C[C@H]43
InChIKey: WAPQUQFEOPBULC-YOMUDNKVSA-N
Target: Glycine receptor subunit alpha-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23415
Assay: Antagonist activity at human glycine receptor subunit alpha-1 expressed in human tsA201 cells assessed as reduction in glycine-induced response incubated for 30 mins by fluorescence-based FLIPR membrane potential blue assay
Measurement: IC50 = 776.25 nM (pChEMBL 6.110000133514404)
Descriptors: MW 532.69, ALogP 3.51, HBA 5, HBD 2, PSA 90.98, QED 0.38
Compound (SMILES): COc1ccn(-c2ccc(N3CCN(CCCCCc4c[nH]c5ccc(C#N)cc45)CC3)cc2)c(=O)c1
InChIKey: WKFGRPZNHZHBDB-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P19327
Assay: Rat Synaptosome Binding Assay: The synaptosomes (150 μg) prepared from a rat brain were incubated at 37° C. for 15 minutes with 0.1 μCi [3H]5-HT in the absence or presence of the test compound or the reference compound in a buffer solution containing 106.2 mM NaCl, 4.5 mM KCl, 2.25 mM MgSO4, 1.08 mM NaH2PO4, 22.5 mM NaHCO3, 9.9 mM glucose, 9 μM EGTA and 45 μM ascorbic acid (pH 7.4).The basal control activity was determined by incubating the same mixture at 4° C. for 15 minutes in the presence of 10 μM imipramine to block the uptake of 5-HT, which was taken as the standard reference compound and tested in each experiment at several concentrations to obtain an inhibition curve.Following the incubation, the samples were filtered rapidly under vacuum through glass fiber filters (GF/B, Packard) and rinsed twice with an ice-cold incubation buffer using a 96-sample cell harvester (Unifilter, Packard) to eliminate free [3H]5-HT. The filters were dried and the retained radioactivity was measured in a scintillation counter (Topcount, Packard) using a scintillation cocktail (Microscint 0, Packard). The experimental results were expressed as a percent inhibition of the control uptake of [3H]5-HT.Data AnalysisInhibition of serotonin transporter in rat synaptosome was measured by the concentrations of [3H]5-HT. The test compounds were required to be tested at least twice in the case of the concentration thereof being greater than 6 log, and the obtained data were subjected to a nonlinear regression analysis via a curve of Hill equation, to obtain IC50 value.
Measurement: IC50 = 5.5 nM (pChEMBL 8.260000228881836)
Descriptors: MW 495.63, ALogP 4.73, HBA 6, HBD 1, PSA 77.29, QED 0.34
Compound (SMILES): N#Cc1cccc(C(=O)NCc2ccccc2CN2CCc3cc(O)c(O)cc3C2)c1
InChIKey: WRUNDYWPHKJEIH-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]-methylspiperone from dopamine D3 receptor (unknown origin)
Measurement: Ki = 370 nM (pChEMBL 6.429999828338623)
Descriptors: MW 413.48, ALogP 3.46, HBA 5, HBD 3, PSA 96.59, QED 0.56
Compound (SMILES): CCN(c1ccccc1)S(=O)(=O)C1CC2OC1C(c1ccc(NC(=O)CCCCCCC(=O)O)cc1)=C2c1ccc(O)cc1
InChIKey: QEJNJIFNEZVYAP-UHFFFAOYSA-N
Target: Estrogen receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q92731
Assay: Binding affinity to human ERbeta LBD assessed as inhibition constant measured after 2 hrs by microplate reader
Measurement: Ki = 346.94 nM (pChEMBL 6.460000038146973)
Descriptors: MW 618.75, ALogP 6.06, HBA 6, HBD 3, PSA 133.24, QED 0.19
Compound (SMILES): CC(C)C(/C=C1\CCNC1=O)c1ccc(-c2ccc3cccc(F)c3c2)[nH]c1=O
InChIKey: SYAXGJOJMZPSRW-GHRIWEEISA-N
Target: Prostaglandin E2 receptor EP3 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P43115
Assay: Antagonist activity at human EP3 receptor expressed in CHO cells by cell based cAMP functional assay
Measurement: IC50 = 8.7 nM (pChEMBL 8.0600004196167)
Descriptors: MW 390.46, ALogP 4.52, HBA 2, HBD 2, PSA 61.96, QED 0.64
Compound (SMILES): CN1CCN(c2ccc(C(=O)Nc3n[nH]c4c3CN(Cc3cc(F)cc(F)c3)C4(C)C)cc2)CC1
InChIKey: XHKNPVMZBCKSLF-UHFFFAOYSA-N
Target: BDNF/NT-3 growth factors receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16620
Assay: Inhibition of human intracellular domain of TRKB expressed in Sf9 cells incubated for 1 hr by HTRF method
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 480.56, ALogP 3.94, HBA 5, HBD 2, PSA 67.5, QED 0.58
Compound (SMILES): CC1(C)[C@@H](O)C[C@H]1Nc1nc(NCc2cncnc2OCC(F)F)ncc1C#N
InChIKey: RRGJUOHIDUNWCQ-OLZOCXBDSA-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 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 405.41, ALogP 1.97, HBA 9, HBD 3, PSA 128.87, QED 0.6
Compound (SMILES): CCn1ncc2c(F)cc(-c3ccc(C(CC)(CC)c4nncn4C)c(=O)[nH]3)cc21
InChIKey: ORDJBPXXNPFJIB-UHFFFAOYSA-N
Target: Prostaglandin E2 receptor EP3 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P43115
Assay: Antagonist activity at human EP3 receptor expressed in CHO cells by cell based cAMP functional assay
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 408.48, ALogP 3.79, HBA 6, HBD 1, PSA 81.39, QED 0.53
Compound (SMILES): Cn1nc(Cc2nnc(SCC(=O)Nc3ccc(Cl)cc3Cl)n2CCCO)c2ccccc2c1=O
InChIKey: CNUYNTXJWXSAFC-UHFFFAOYSA-N
Target: Interleukin-15 (SINGLE PROTEIN), Mus musculus
UniProt: P48346
Assay: Inhibition of IL-15 in mouse 32Dbeta cells assessed as decrease in cell growth in presence of IL2 incubated for 30 mins followed by IL2 addition and measured after 2.5 days by alamar blue assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 533.44, ALogP 3.54, HBA 9, HBD 2, PSA 114.93, QED 0.32
Compound (SMILES): CC(C)(C)c1ccc(-c2ccc3cc(C(=O)NCC4CCNCC4)[nH]c3c2)cc1
InChIKey: LTFNBFZRZBRYTM-UHFFFAOYSA-N
Target: Genome polyprotein (SINGLE PROTEIN), dengue virus type 2
UniProt: P29990
Assay: Inhibition of Dengue virus 2 NS2B (50 to 95 residues)/NS3 (1 to 182 residues) protease expressed in Escherichia coli BL21 using Bz-Nle-Lys-Lys-Arg-AMC as substrate preincubated for 10 mins by fluorescence-based biochemical assay
Measurement: IC50 = 15000 nM (pChEMBL 4.820000171661377)
Descriptors: MW 389.54, ALogP 4.86, HBA 2, HBD 3, PSA 56.92, QED 0.6
Compound (SMILES): CC(C)C(c1ncco1)c1ccc(-c2ccc3cccc(F)c3c2)[nH]c1=O
InChIKey: QXJPSMHEPDTSJG-UHFFFAOYSA-N
Target: Prostaglandin E2 receptor EP3 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P43115
Assay: Antagonist activity at human EP3 receptor expressed in CHO cells by cell based cAMP functional assay
Measurement: IC50 = 64 nM (pChEMBL 7.190000057220459)
Descriptors: MW 362.4, ALogP 5.11, HBA 3, HBD 1, PSA 58.89, QED 0.55
Compound (SMILES): CNC(=O)CN(Cc1ccc(C(=O)NO)cc1)C(=O)c1ccc(C(C)C)cc1
InChIKey: OVTMYGNGUMISIX-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 = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 383.45, ALogP 2.32, HBA 4, HBD 3, PSA 98.74, QED 0.5
Compound (SMILES): CCc1cc(-c2nc3c(Cl)cc(OC)cc3s2)c2ncn(C)c(=O)c2c1
InChIKey: DUWRZIFULVNPGV-UHFFFAOYSA-N
Target: Proteinase-activated receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RI0
Assay: Antagonist activity at PAR4 in human platelet-rich plasma assessed as inhibition of PAR4 AP AYPGKF-NH2-induced platelet aggregation by photo-turbidimetry assay
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 385.88, ALogP 4.43, HBA 6, HBD 0, PSA 57.01, QED 0.52
Compound (SMILES): N#Cc1ncc(N2C(=O)C3(CCC3)N(c3ccc(OC4CCNCC4)nc3)C2=S)cc1Cl
InChIKey: ZXSHKSIAPKOCNB-UHFFFAOYSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Antagonist activity at AR wild-type (unknown origin) transfected in human LNCAP cells cotransfected with ARE-LUC incubated for 20 to 24 hrs in presence of AR agonist R1881 by steady-glo luciferase reporter gene assay
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 468.97, ALogP 3.19, HBA 7, HBD 1, PSA 94.38, QED 0.68
Compound (SMILES): CNC(=O)c1cc(C(=O)N[C@H]2C[C@@H]2C)cc(Cc2ccccc2)n1
InChIKey: QEPZFLZVHFIDCF-LRDDRELGSA-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 = 39.81 nM (pChEMBL 7.400000095367432)
Descriptors: MW 323.4, ALogP 2.17, HBA 3, HBD 2, PSA 71.09, QED 0.89
Compound (SMILES): COc1cc(/C=C/c2ccc(NC(=O)C3CC3)cc2)c(/C=C/[N+](=O)[O-])c(OC)c1
InChIKey: RGZUNRLNIINAOD-NMHALSJOSA-N
Target: NACHT, LRR and PYD domains-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96P20
Assay: Binding affinity to His-GFP fused tagged NLRP3 (unknown origin) expressed in HEK293T incubated for 30 mins by microscale thermophoresis assay
Measurement: Kd = 263 nM (pChEMBL 6.579999923706055)
Descriptors: MW 394.43, ALogP 4.47, HBA 5, HBD 1, PSA 90.7, QED 0.41
Compound (SMILES): O=C1c2ccccc2S(=O)(=O)N1CCCN1CCN(c2cccc(C(F)(F)F)c2)CC1
InChIKey: NXFJDIPRFJANKK-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]-ketanserin from human 5-HT2AR expressed in CHO cells
Measurement: Ki = 700 nM (pChEMBL 6.159999847412109)
Descriptors: MW 453.49, ALogP 3.06, HBA 5, HBD 0, PSA 60.93, QED 0.7
Compound (SMILES): CC(Sc1nc2nn(C3COC3)cc2c(=O)n1-c1ccccc1)c1ccccn1
InChIKey: WNWQYZJEBKIGQP-UHFFFAOYSA-N
Target: Retinal dehydrogenase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O94788
Assay: Inhibition of human ALDH1A2 assessed as NADH formation using propionaldehyde as substrate by spectrophotometery
Measurement: IC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 405.48, ALogP 3.4, HBA 8, HBD 0, PSA 74.83, QED 0.37
Compound (SMILES): O=C(NO)c1ccc(Cl)c(NC(=O)c2ccc(-c3ccccc3)cc2Cl)c1
InChIKey: IXVQMXXRQZSYJR-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of human recombinant HDAC8 using H2N-Arg-His-Lys(Ac)-Lys(Ac)-AMC as substrate after 90 mins by fluorescence based micro plate assay
Measurement: IC50 = 780 nM (pChEMBL 6.110000133514404)
Descriptors: MW 401.25, ALogP 5.03, HBA 3, HBD 3, PSA 78.43, QED 0.42
Compound (SMILES): COC(=O)/C(=N\Nc1ccc(OC)cc1)C(=O)C(F)(F)C(F)(F)C(F)(F)F
InChIKey: IHRHACRFXNFJBN-AQHIEDMUSA-N
Target: Liver carboxylesterase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23141
Assay: Inhibition of human recombinant CES1 expressed in baculovirus infected BTI insect cells using 4-NPA as substrate by spectrophotometric analysis
Measurement: IC50 = 111.28 nM (pChEMBL 6.949999809265137)
Descriptors: MW 404.24, ALogP 3.04, HBA 6, HBD 1, PSA 76.99, QED 0.25
Compound (SMILES): CC(C)S(=O)(=O)c1ccccc1Nc1nc(Nc2ccc(C(=O)NCCCCCCC(=O)NO)cc2)ncc1Cl
InChIKey: RBYNLDMNBXNZMS-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of HDAC2 (unknown origin)
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 589.12, ALogP 4.99, HBA 9, HBD 5, PSA 162.41, QED 0.1
Compound (SMILES): CC(C)(C)c1ccc(C(=O)N2CCc3cc(Nc4ncc(F)c(-c5cnn(CCC#N)c5)n4)ccc32)cc1
InChIKey: YPCHIACHOJRUKS-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 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 509.59, ALogP 5.64, HBA 7, HBD 1, PSA 99.73, QED 0.36
Compound (SMILES): Nc1ccccc1-c1nnc(S)[nH]1
InChIKey: ZDDFXJUKACZJTP-UHFFFAOYSA-N
Target: DCN1-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96GG9
Assay: Inhibition of recombinant human His-tagged DCN1 (58 to 259 residues) expressed in Escherichia coli BL21 (DE3) using MIKLFSLKQQKKEEESAGGTK-biotin as substrate incubated for 30 mins by HTRF assay
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 192.25, ALogP 1.34, HBA 4, HBD 3, PSA 67.59, QED 0.47
Compound (SMILES): Cc1cc(=O)oc2cc(OC(C)c3ccccc3)ccc12
InChIKey: KHLSXVLGCMGZRA-UHFFFAOYSA-N
Target: Immunoglobulin lambda variable 6-57 (SINGLE PROTEIN), Homo sapiens
UniProt: P01721
Assay: Stabilization of AL patient derived full length fluorescein-labeled IGLV6-57 expressed in Escherichia coli BL21 (DE3) measured after 24 hrs by proteolysis coupled-fluorescence polarization assay
Measurement: EC50 = 1960 nM (pChEMBL 5.710000038146973)
Descriptors: MW 280.32, ALogP 4.24, HBA 3, HBD 0, PSA 39.44, QED 0.67
Compound (SMILES): O=C(c1cccc(Cl)c1)N1CCCC2CC(C3(C(=O)Nc4ccc(F)cc4)CCC3)CCC21
InChIKey: WNGYCURBOWVNHW-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in human HeLa cells assessed as production of N-formylkynurenine using tryptophan as substrate in presence of inactivated fetal bovine serum
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 469, ALogP 6.31, HBA 2, HBD 1, PSA 49.41, QED 0.57
Compound (SMILES): CC(Sc1nc2c(cnn2C)c(=O)n1-c1ccccc1)c1cncnc1
InChIKey: BOHYGHCQWOSGHW-UHFFFAOYSA-N
Target: Retinal dehydrogenase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O94788
Assay: Inhibition of human ALDH1A2 assessed as NADH formation using propionaldehyde as substrate by spectrophotometery
Measurement: IC50 = 380 nM (pChEMBL 6.420000076293945)
Descriptors: MW 364.43, ALogP 2.76, HBA 8, HBD 0, PSA 78.49, QED 0.41
Compound (SMILES): CC(C)C[C@@H]1CNC(=N)N1C[C@@H]1CCCN1[C@@H](CC1CCCCC1)N1C[C@@H](C(C)C)N(CC23CC4CC(CC(C4)C2)C3)C1=N
InChIKey: JXJIXMLEXKCZPP-WGFPFELBSA-N
Target: Melanocortin receptor 5 (SINGLE PROTEIN), Mus musculus
UniProt: P41149
Assay: Agonist activity at mouse melanocortin receptor 5 expressed in HEK293 cells assessed as stimulation of intracellular cAMP accumulation incubated for 24 hrs by beta-galactosidase reporter gene assay
Measurement: EC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 607.98, ALogP 6.8, HBA 3, HBD 3, PSA 72.69, QED 0.24
Compound (SMILES): CSCC[C@H](NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CS)NC(C)=O)[C@@H](C)O)C(=O)N[C@@H](CC(=O)O)C(=O)NCC(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(N)=O
InChIKey: LBSJIZBYRZVTNK-OVPJFHAQSA-N
Target: Frizzled-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UP38
Assay: Antagonist activity at Wnt3a-stimulated frizzled-1 (unknown origin) expressed in human HEK293superTOP flash cells incubated for 24 hrs by luciferase reporter gene assay
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 1427.6