lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1ccc(-c2coc(-c3cc(Cl)ccc3-n3cncn3)n2)cc1OC
InChIKey: XWXQMMNNONAQSQ-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14831
Assay: Negative allosteric modulation of mGlu7 (unknown origin) in cells expressing G protein-regulated inwardly rectifying potassium channels (GIRKs) assessed as inhibition of L-AP4-induced response measured by thallium flux assay
Measurement: IC50 = 4400 nM (pChEMBL 5.360000133514404)
Descriptors: MW 382.81, ALogP 4.26, HBA 7, HBD 0, PSA 75.2, QED 0.51
Compound (SMILES): NS(=O)(=O)c1ccc(Nc2nc(N/N=C/c3cccc4ccccc34)nc(Nc3ccccc3)n2)cc1
InChIKey: PKVRLSWDFBFXCJ-OGLMXYFKSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human CA 12 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 32.2 nM (pChEMBL 7.489999771118164)
Descriptors: MW 510.58, ALogP 4.61, HBA 9, HBD 4, PSA 147.28, QED 0.17
Compound (SMILES): CCOc1ncc(-c2cccc(N(CC34CCC(c5noc(C(C)(C)C)n5)(CC3)CC4)C(=O)[C@H]3C[C@@](C)(O)C3)c2)cn1
InChIKey: VCCXEPWMFOKGSQ-BVLBHDCQSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of recombinant CYP2C19 (unknown origin) using fluorogenic substrate preincubated for 15 min followed by NADPH addition measured after 2 hrs by fluorescence method
Measurement: IC50 = 9000 nM (pChEMBL 5.050000190734863)
Descriptors: MW 573.74, ALogP 6.01, HBA 8, HBD 1, PSA 114.47, QED 0.35
Compound (SMILES): C[C@@H](C1CC1)N1Cc2cc(-c3ccn4nc(N)c(C(=O)NC5CC5)c4n3)cc(C(F)(F)F)c2C1=O
InChIKey: YISPEWWJGFBTMD-NSHDSACASA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta (unknown origin) using PIP2 as substrate preincubated for 1 hr followed by substrate addition and measured after 60 mins in presence of ATP by ADP-glo assay
Measurement: IC50 = 1950 nM (pChEMBL 5.710000038146973)
Descriptors: MW 484.48, ALogP 3.64, HBA 6, HBD 2, PSA 105.62, QED 0.58
Compound (SMILES): COc1cc2ncnc3c2cc1OCCOCCOc1ccc(Cl)c(c1)N3
InChIKey: XIAGGOHGBXOGNK-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin) L858R/T790M mutant preincubated with compound 30 mins followed ATP addition incubated for 30 mins by HTRF KinEASE TK assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 387.82, ALogP 3.82, HBA 7, HBD 1, PSA 74.73, QED 0.68
Compound (SMILES): COc1ccc2c(c1)c(CCNC(C)=O)cn2C(=O)OCc1ccccc1[N+](=O)[O-]
InChIKey: RHDQNEMKKDKLCX-UHFFFAOYSA-N
Target: Melatonin receptor type 1B (SINGLE PROTEIN), Homo sapiens
UniProt: P49286
Assay: Displacement of 2-[125I]iodomelatonin from human melatonin MT2 receptor stably expressing in human HEK293 cell membranes in presence of light-activated compounds by radioligand based competition binding assay
Measurement: Ki = 1.995 nM (pChEMBL 8.699999809265137)
Descriptors: MW 411.41, ALogP 3.42, HBA 7, HBD 1, PSA 112.7, QED 0.47
Compound (SMILES): CCS(=O)(=O)c1cc(-c2ccn3nc(N)c(C(=O)NC4CC4)c3n2)cc2c1C(=O)N([C@@H](C)C1CC1)C2
InChIKey: WSLSYHQEXCFTLS-ZDUSSCGKSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta (unknown origin) using PIP2 as substrate preincubated for 1 hr followed by substrate addition and measured after 60 mins in presence of ATP by ADP-glo assay
Measurement: IC50 = 835 nM (pChEMBL 6.079999923706055)
Descriptors: MW 508.6, ALogP 2.42, HBA 8, HBD 2, PSA 139.76, QED 0.5
Compound (SMILES): CCCC(CCC)c1nc2c(Nc3ccc(Cl)c(Cl)c3)nc3ccccc3c2[nH]1
InChIKey: XPBFTWFZESHABV-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Positive allosteric modulator activity in human wild type A3AR receptor stably expressed in human HEK293 cell membrane assessed as inhibition of radioligand [125I]-ABOPX orthosteric binding incubated for 18 hrs in presence of PSB603 by equilibrium radioligand binding assay
Measurement: Ki = 5400 nM (pChEMBL 5.269999980926514)
Descriptors: MW 427.38, ALogP 7.85, HBA 3, HBD 2, PSA 53.6, QED 0.32
Compound (SMILES): COC(=O)c1cc(O)c2cc(NC(=O)NCCCCNC(=N)NC/C=C/[C@H]3O[C@@H](n4cnc5c(N)ncnc54)[C@H](O)[C@@H]3O)ccc2c1
InChIKey: JYIRWTZMMGLPFI-HMZLUZKYSA-N
Target: Protein arginine N-methyltransferase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: O14744
Assay: Inhibition of human full length recombinant FLAG-tagged PRMT5 (2 to 637 residues) using histone H2A as substrate incubated for 20 mins in presence of [3H]-SAM by radioisotope-based filter assay
Measurement: IC50 = 1460 nM (pChEMBL 5.840000152587891)
Descriptors: MW 648.68, ALogP 0.95, HBA 13, HBD 9, PSA 254.88, QED 0.04
Compound (SMILES): CCOc1cc(F)ccc1-c1cnc2sc(N3CCC(O)(CN)CC3)nn12
InChIKey: SXLQWSOPHQGLLI-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: Kinase Biological Assay: Binding reactions were assembled by combining kinases, liganded affinity beads, and test compounds in 1× binding buffer (20% SeaBlock, 0.17×PBS, 0.05% Tween 20, 6 mM DTT). Test compounds were prepared as 111× stocks in 100% DMSO. Kds were determined using an 11-point 3-fold compound dilution series with three DMSO control points. All compounds for Kd measurements are distributed by acoustic transfer (non-contact dispensing) in 100% DMSO. The compounds were then diluted directly into the assays such that the final concentration of DMSO was 0.9%. All reactions performed in polypropylene 384-well plate. Each was a final volume of 0.02 ml. The assay plates were incubated at room temperature with shaking for 1 hour and the affinity beads were washed with wash buffer (1×PBS, 0.05% Tween 20). The beads were then re-suspended in elution buffer (1×PBS, 0.05% Tween 20, 0.5 μM non-biotinylated affinity ligand) and incubated at room temperature with shaking for 30 minutes. The kinase concentration in the eluates was measured by qPCR. Binding constants (Kds) were calculated with a standard dose-response curve using the Hill equation: Response=Background+(Signal−Background)/[1+(KdHill Slope/DoseHill Slope)]
Measurement: Kd > 100 nM (pChEMBL 7)
Descriptors: MW 391.47, ALogP 2.29, HBA 8, HBD 2, PSA 88.91, QED 0.69
Compound (SMILES): COc1ccc(CNC(=O)c2ccc(CNCc3cnc4nc(N)nc(N)c4n3)cc2)cc1OC
InChIKey: SIUIAKIEYVIHIL-UHFFFAOYSA-N
Target: Bifunctional dihydrofolate reductase-thymidylate synthase (SINGLE PROTEIN), Leishmania major
UniProt: P07382
Assay: Inhibition of recombinant Leishmania major DHFR-TS expressed in Escherichia coli BL21 (DE3) cells using dihydrofolate as substrate in presence of NADPH by spectrophotometric analysis
Measurement: IC50 = 100000 nM (pChEMBL 4)
Descriptors: MW 474.53, ALogP 1.82, HBA 10, HBD 4, PSA 163.19, QED 0.28
Compound (SMILES): CNc1nc(Nc2ccc(N3CCN(C)CC3)cc2)sc1C(=O)c1c(Cl)cccc1Cl
InChIKey: GQBMFAFMTZCQTB-UHFFFAOYSA-N
Target: CDK6/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24385
Assay: Inhibition of human recombinant full length GST-tagged CDK6/Cyclin D1 expressed in Baculovirus expression system by Adapta assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 476.43, ALogP 5.22, HBA 7, HBD 2, PSA 60.5, QED 0.48
Compound (SMILES): N#Cc1ccc(CSc2nc3ccccc3c(=O)n2CCc2ccc(S(N)(=O)=O)cc2)cc1
InChIKey: VQYOHNOWKLBJKQ-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Binding affinity to human CA12 assessed as inhibition constant by stopped-flow CO2 hydration assay
Measurement: Ki = 17.2 nM (pChEMBL 7.760000228881836)
Descriptors: MW 476.58, ALogP 3.45, HBA 7, HBD 1, PSA 118.84, QED 0.32
Compound (SMILES): FC(F)(F)Oc1cccc(CO[C@H]2CCCN(Cc3cn4ccccc4n3)C2)c1
InChIKey: PHIVTHZDRRRWRB-IBGZPJMESA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]N-methylspiperone from D4 receptor in HEK293 cell membrane
Measurement: Ki = 646 nM (pChEMBL 6.190000057220459)
Descriptors: MW 405.42, ALogP 4.41, HBA 5, HBD 0, PSA 39, QED 0.61
Compound (SMILES): CC(C)N(Cc1ccc(C(=O)NO)cc1)Cc1cc(F)c(F)c(F)c1F
InChIKey: VNNLYUYNDNJOFO-UHFFFAOYSA-N
Target: Histone deacetylase 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96DB2
Assay: Inhibition of full length human recombinant HDAC11 expressed in Sf9 baculovirus system using FAM-labeled acetylated peptide as substrate by measuring fluorescence intensity by EMSA method
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 370.35, ALogP 3.77, HBA 3, HBD 2, PSA 52.57, QED 0.27
Compound (SMILES): C=C(C(N)=O)[C@@H](NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@@H](C)N(C)C(=O)[C@@H](N)Cc1ccc(O)cc1)c1ccccc1
InChIKey: BVNIRYKOOCEIKH-DEUJINQISA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity at MOP (unknown origin) stably expressed in HEK293 cells assessed as forskolin stimulated cAMP accumulation incubated for 30 mins by radioactivity based scintillation counter analysis
Measurement: EC50 = 2.27 nM (pChEMBL 8.640000343322754)
Descriptors: MW 610.72, ALogP 2.22, HBA 6, HBD 6, PSA 183.64, QED 0.13
Compound (SMILES): N#Cc1ccc(Nc2ccc3[nH]nc(-c4ccncc4)c3c2)c(Cl)c1
InChIKey: NJYZVVCACZVMRL-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of pcDNA5FRT-TO-GFP fused - LRRK2 G2019S mutant (unknown origin) transfected in HEK293 cells incubated for 24 hrs by ELISA
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 345.79, ALogP 4.89, HBA 4, HBD 2, PSA 77.39, QED 0.55
Compound (SMILES): CC(C)C(=O)N1C[C@@H](C)N(c2ncc3[nH]nc(-c4ccc(N5CCN[C@H](C)C5)nc4)c3n2)[C@@H](C)C1
InChIKey: QXRCZGTZEWEMCZ-KURKYZTESA-N
Target: Activin receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q04771
Assay: HTRF Assay (100 uM ATP): ALK2 (aa 147-end) was obtained from BPS biosciences. The enzymatic assays were conducted in white 384-well polystyrene plates in a final volume of 8 μL. The inhibitors were serially diluted in DMSO and added to the plate wells prior to addition of the other reaction components. The assays were carried out at 25° C. in the assay buffer (50 mM HEPES, pH 7.1, 10% Glycerol, 0.01% Brij50, 10 mM MgCl2, 1 mM EGTA, 5 mM DTT, and 0.01% BSA), containing 50 nM LANCE Ultra ULight-DNA Topoisomerase 2-alpha peptide (Perkin Elmer TRF0130), and 100 uM ATP. The final concentration of DMSO in the assay was 1% and the enzyme concentration was 2.5 nM for ALK2. The reactions were allowed to proceed for 2-4 hr after which, the reaction was quenched by addition of EDTA at a final concentration of 20 mM along with 1.5 nM LANCE Ultra Europium-anti-phospho-DNA Topoisomerase 2-alpha (Thr1342) antibody (Perkin Elmer TRF0218). The reaction was read on a PHERAstar FS plate reader (BMG Labtech). IC50 determination was performed by fitting percent control activity versus the log of the inhibitor concentration using the IDBS XLFit and GraphPad Prism 5.0 software.
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 477.62, ALogP 2.29, HBA 8, HBD 2, PSA 106.17, QED 0.59
Compound (SMILES): O=C(O)/C=C/C(=O)NNC(=O)c1cnccc1Cc1ccccc1
InChIKey: OYQFTVWCICJGMS-VOTSOKGWSA-N
Target: Egl nine homolog 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9GZT9
Assay: Inhibition of recombinant N-terminal hexahistidine-tagged human PDH2 (181 to 426 residues) expressed in Escherichia coli BL21 (DE3) preincubated for 15 mins followed by substrate addition and measured after 15 mins using CODD peptide DLDLEMLAPYIPMDDDFQL as substrate by SPE-MS-based assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 325.32, ALogP 1.07, HBA 4, HBD 3, PSA 108.39, QED 0.56
Compound (SMILES): Fc1ccc(F)c(-c2ccc(NC[C@@H]3CC34CCN(CC3CCOCC3)CC4)nn2)c1
InChIKey: ZZBCCRRRODXGDA-SFHVURJKSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes using cocktail of isoform-specific probe substrate
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 428.53, ALogP 4.36, HBA 5, HBD 1, PSA 50.28, QED 0.74
Compound (SMILES): COc1cc(CCc2cc(-c3nc4ccc(N5C[C@@H](C)O[C@@H](C)C5)cc4[nH]3)n[nH]2)cc(OC)c1
InChIKey: QQZSRHQZWOITQR-CALCHBBNSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of recombinant N-terminal GST-tagged human KDR (790 to 1356 residues) expressed in baculovirus expression system using IGF-1Rtide peptide as substrate preincubated for 10 mins followed by substrate addition and measured after 1 hrs in the presence of ATP by ADP-Glo reagent based luminescence assay
Measurement: IC50 = 145.5 nM (pChEMBL 6.840000152587891)
Descriptors: MW 461.57, ALogP 4.37, HBA 6, HBD 2, PSA 88.29, QED 0.42
Compound (SMILES): COc1ccc(-c2ocnc2C(=O)NCCCn2cncn2)cc1Cl
InChIKey: RQFYFNAGNBUGFC-UHFFFAOYSA-N
Target: Microtubule-associated protein tau (SINGLE PROTEIN), Homo sapiens
UniProt: P10636
Assay: Inhibition of tau phosphorylation (unknown origin)
Measurement: IC50 = 466 nM (pChEMBL 6.329999923706055)
Descriptors: MW 361.79, ALogP 2.42, HBA 7, HBD 1, PSA 95.07, QED 0.65
Compound (SMILES): O=C(/C=C/C1CCN(Cc2cccc3ccccc23)CC1)NO
InChIKey: SRFTXZNZUQKTSF-CMDGGOBGSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant human HDAC8 using H2N-Arg- His-Lys(Ac)-Lys(Ac)-AMC as substrate incubated for 90 mins and measured after 20 mins by fluorescence assay
Measurement: IC50 = 420 nM (pChEMBL 6.380000114440918)
Descriptors: MW 310.4, ALogP 3.11, HBA 3, HBD 2, PSA 52.57, QED 0.52
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)CNC(=O)[C@@H](N)Cc1c[nH]cn1)[C@@H](C)O)C(C)C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(N)=O
InChIKey: RRALFQLGJKZGBF-ZAGFFSAWSA-N
Target: Glucagon-like peptide 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P43220
Assay: Agonist activity at human GLP-1R expressed in CHO cells coexpressing beta-arrestin-2 assessed as increase in beta arrestin-2 recruitment incubated for 1 hr by chemiluminescence based pathHunter assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 4067.52
Compound (SMILES): CCc1cc2ncc(CN3CC(Nc4ccc(C(=O)NC)nc4)C3)cc2[nH]c1=O
InChIKey: YEEMANFJIXWISV-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGN5
Assay: Inhibition of PARP-2 (unknown origin) binding to DNA assessed as DNA trapping activity
Measurement: IC50 = 12027 nM (pChEMBL 4.920000076293945)
Descriptors: MW 392.46, ALogP 1.54, HBA 6, HBD 3, PSA 103.01, QED 0.59
Compound (SMILES): N#Cc1ccc(COc2ccc3c(c2)SCC(=O)N3)cc1
InChIKey: LEAPEVPOKKKURT-UHFFFAOYSA-N
Target: D-amino-acid oxidase (SINGLE PROTEIN), Sus scrofa
UniProt: P00371
Assay: Inhibition of porcine kidney DAAO using D-serine as substrate assessed as H2O2 formation by amplex red and peroxidase-coupled continuous fluorescence spectrophotometric analysis
Measurement: IC50 = 47500 nM (pChEMBL 4.320000171661377)
Descriptors: MW 296.35, ALogP 3.18, HBA 4, HBD 1, PSA 62.12, QED 0.94
Compound (SMILES): N.N.Nc1nc2c(ncn2[C@@H]2O[C@@H]3COP(=O)(O)O[C@H]4[C@H](F)[C@H](n5cnc6c(N)ncnc65)O[C@@H]4COP(=O)(O)O[C@@H]2[C@@H]3F)c(=O)[nH]1
InChIKey: RCXGYDPPYKVDAP-SALLFFCHSA-N
Target: Stimulator of interferon genes protein (SINGLE PROTEIN), Mus musculus
UniProt: Q3TBT3
Assay: Agonist activity at STING HAQ variant in mouse BMDC cells assessed as increase in mouse INF-beta production incubated for 5 hrs by ELISA
Measurement: EC50 = 26800 nM (pChEMBL 4.570000171661377)
Descriptors: MW 678.4, ALogP -0.39, HBA 18, HBD 5, PSA 289.19, QED 0.17
Compound (SMILES): OC[C@H]1O[C@@H](n2cnc3c(N[C@@H]4CCC[C@H]4Oc4cccc(Br)c4)ncnc32)[C@H](O)[C@@H]1O
InChIKey: VENBOXOEVOUMJD-CPIJZORTSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P25099
Assay: Inhibition of CA200645 binding to NanoLuc-fused rat adenosine A1 receptor expressed in HEK293 cells measured for 10 mins by NanoBRET competition binding assay
Measurement: Ki = 114.82 nM (pChEMBL 6.940000057220459)
Descriptors: MW 506.36, ALogP 1.61, HBA 10, HBD 4, PSA 134.78, QED 0.39
Compound (SMILES): COc1cc(C)ccc1-c1cnc2sc(N3CCC(O)(CN)CC3)nn12
InChIKey: VTMHHYZIHFLGHQ-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11309
Assay: Kinase Biological Assay: Binding reactions were assembled by combining kinases, liganded affinity beads, and test compounds in 1× binding buffer (20% SeaBlock, 0.17×PBS, 0.05% Tween 20, 6 mM DTT). Test compounds were prepared as 111× stocks in 100% DMSO. Kds were determined using an 11-point 3-fold compound dilution series with three DMSO control points. All compounds for Kd measurements are distributed by acoustic transfer (non-contact dispensing) in 100% DMSO. The compounds were then diluted directly into the assays such that the final concentration of DMSO was 0.9%. All reactions performed in polypropylene 384-well plate. Each was a final volume of 0.02 ml. The assay plates were incubated at room temperature with shaking for 1 hour and the affinity beads were washed with wash buffer (1×PBS, 0.05% Tween 20). The beads were then re-suspended in elution buffer (1×PBS, 0.05% Tween 20, 0.5 μM non-biotinylated affinity ligand) and incubated at room temperature with shaking for 30 minutes. The kinase concentration in the eluates was measured by qPCR. Binding constants (Kds) were calculated with a standard dose-response curve using the Hill equation: Response=Background+(Signal−Background)/[1+(KdHill Slope/DoseHill Slope)]
Measurement: Kd > 100 nM (pChEMBL 7)
Descriptors: MW 373.48, ALogP 2.06, HBA 8, HBD 2, PSA 88.91, QED 0.73
Compound (SMILES): O=C(Nc1nc2cccc(C3=CC[C@H](NC(=O)[C@H]4CC4(F)F)CC3)n2n1)C1CC1
InChIKey: QRQOYUNGZSQNMP-UONOGXRCSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of recombinant human TYK2 using GGMEDIYFEFMGGKKK as substrate incubated for 40 mins in presence of Mg/ATP mixture by [gamma p33]-ATP based scintillation counting method
Measurement: IC50 = 71 nM (pChEMBL 7.150000095367432)
Descriptors: MW 401.42, ALogP 2.79, HBA 5, HBD 2, PSA 88.39, QED 0.81
Compound (SMILES): COc1ccccc1COc1ccc(C(N)=O)c(F)c1
InChIKey: AUATYPASZRYFMP-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGN5
Assay: Inhibition of human PARP2 using NAD+ as substrate incubated for 10 mins by fluorescence based analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 275.28, ALogP 2.51, HBA 3, HBD 1, PSA 61.55, QED 0.91
Compound (SMILES): O=C(NCc1cccs1)[C@@H]1CN(C(=O)c2cccnc2)CCN1c1ccc(Cl)c(Cl)c1
InChIKey: XEFYJHCPILXFKJ-FQEVSTJZSA-N
Target: Cathepsin F (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBX1
Assay: Inhibition of human Cathepsin F using Z-Phe-Arg-AMC as fluorogenic substrate incubated for 60 mins by FRET assay
Measurement: IC50 = 50000 nM (pChEMBL 4.300000190734863)
Descriptors: MW 475.4, ALogP 4.1, HBA 5, HBD 1, PSA 65.54, QED 0.6
Compound (SMILES): COc1ccc(C(=O)Nc2cccc([C@]3(C)O[C@H]4CO[C@@H]5N4[C@H]3O[C@@]5(C)c3cccc(NC(=O)c4ccc(OC)cc4)c3)c2)cc1
InChIKey: CEFZLJAZLPOVTE-WMUVQLMLSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Antagonist activity at OX1R (unknown origin)
Measurement: Ki = 5.23 nM (pChEMBL 8.279999732971191)
Descriptors: MW 621.69, ALogP 5.71, HBA 8, HBD 2, PSA 107.59, QED 0.26
Compound (SMILES): Cc1[nH]c2cc(Nc3ncc(Cl)c(Nc4ccccc4NS(C)(=O)=O)n3)ccc2c1C(=O)N1CCOCC1
InChIKey: SDVNXUSLFWQHQJ-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of N-terminal GST-tagged human ceritinib-resistant ALK G1202R mutant (1058 to 1620 residues) cytoplasmic domain expressed in baculovirus infected Sf21 cells incubated for 1 hrs in the presence of ATP by mobility shift assay
Measurement: IC50 = 5.9 nM (pChEMBL 8.229999542236328)
Descriptors: MW 556.05, ALogP 4.25, HBA 8, HBD 4, PSA 141.34, QED 0.27
Compound (SMILES): CC(C)c1cc(C(=O)N(C)Cc2ccc(C(=O)NO)cc2)c(O)cc1O
InChIKey: PDCLLGDACURYDE-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of HDAC1 (unknown origin) using fluorogenic substrate incubated for 30 mins by fluorescence plate reader
Measurement: IC50 = 654.5 nM (pChEMBL 6.179999828338623)
Descriptors: MW 358.39, ALogP 2.61, HBA 5, HBD 4, PSA 110.1, QED 0.49
Compound (SMILES): CCNNC(=O)c1ccc(CN2c3ccccc3Sc3ccccc32)cc1
InChIKey: AKGOFLVEVUSUIH-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombinant HDAC6 (unknown origin) using Boc-Lys(acetyl)-AMC as substrate preincubated for 1 hr followed by substrate addition and measured after 2 hrs by fluorescence based microplate reader analysis
Measurement: IC50 = 175 nM (pChEMBL 6.760000228881836)
Descriptors: MW 375.5, ALogP 4.74, HBA 4, HBD 2, PSA 44.37, QED 0.63
Compound (SMILES): O=C(CCCCC/C=C/c1csc(Br)n1)NO
InChIKey: WLRUIAIHXAKVSH-GQCTYLIASA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of full length C-terminal his6/FLAG-tagged human recombinant HDAC3 (1 to 2383 residues) expressed in Sf9 insect cells
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 319.22, ALogP 3.37, HBA 4, HBD 2, PSA 62.22, QED 0.46
Compound (SMILES): Cn1cc(S(N)(=O)=O)c2cc(NC(=O)c3ccnc(Br)c3)ccc21
InChIKey: XGVHTLPPMCXPGA-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human carbonic anhydrase 12 by stopped flow CO2 assay
Measurement: Ki = 62060 nM (pChEMBL 4.210000038146973)
Descriptors: MW 409.26, ALogP 2.24, HBA 5, HBD 2, PSA 107.08, QED 0.65
Compound (SMILES): Cc1cc(C(=O)NCc2ccc(CN)cc2)c(C)n1Cc1csc(-c2ccccc2)n1
InChIKey: SJVAITNWGSDKNM-UHFFFAOYSA-N
Target: Serine protease 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P07477
Assay: Plasma kallikrein assay: Plasma kallikrein inhibitory activity in vitro was determined using standard published methods (see e.g. Johansen et al., Int. J. Tiss. Reac. 1986, 8, 185; Shori et al., Biochem. Pharmacol., 1992, 43, 1209; Stürzebecher et al., Biol. Chem. Hoppe-Seyler, 1992, 373, 1025). Human plasma kallikrein (Protogen) was incubated at 37° C. with the fluorogenic substrate H-DPro-Phe-Arg-AFC and various concentrations of the test compound. Residual enzyme activity (initial rate of reaction) was determined by measuring the change in optical absorbance at 410 nm and the IC50 value for the test compound was determined.
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 430.58, ALogP 4.67, HBA 5, HBD 2, PSA 72.94, QED 0.45
Compound (SMILES): N.N.Nc1nc2c(ncn2[C@@H]2O[C@@H]3COP(=O)(O)O[C@H]4C[C@H](n5cnc6c(N)ncnc65)O[C@@H]4COP(=O)(O)O[C@@H]2[C@@H]3O)c(=O)[nH]1
InChIKey: QDFRLPNRNYUOHR-HNZKXKKDSA-N
Target: Stimulator of interferon genes protein (SINGLE PROTEIN), Mus musculus
UniProt: Q3TBT3
Assay: Agonist activity at STING HAQ variant in mouse BMDC cells assessed as increase in mouse INF-beta production incubated for 5 hrs by ELISA
Measurement: EC50 = 15300 nM (pChEMBL 4.820000171661377)
Descriptors: MW 658.42, ALogP -1.31, HBA 19, HBD 6, PSA 309.42, QED 0.14
Compound (SMILES): Cc1cc(-c2ccn3nc(N)c(C(=O)NC4CC4)c3n2)cc2c1C(=O)N([C@@H](C)C1CC1)C2
InChIKey: CVQCXZLBLLNPCB-ZDUSSCGKSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta (unknown origin) using PIP2 as substrate preincubated for 1 hr followed by substrate addition and measured after 60 mins in presence of ATP by ADP-glo assay
Measurement: IC50 = 1670 nM (pChEMBL 5.78000020980835)
Descriptors: MW 430.51, ALogP 2.93, HBA 6, HBD 2, PSA 105.62, QED 0.65
Compound (SMILES): CCc1c(-c2ccnc(C)c2)[nH]c2cc(F)c(C3CCNCC3)c(F)c12
InChIKey: AFETVRWREHOYTD-UHFFFAOYSA-N
Target: Toll-like receptor 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR97
Assay: Inhibition Reporter Assay: HEK-Blue-cells (Invivogen) overexpressing human TLR7, TLR8 or TLR9 receptors were used for screening inhibitors of these receptors using an inducible SEAP (secreted embryonic alkaline phosphatase) reporter gene under the control of the IFN-β minimal promoter fused to five NF-κB and AP-1-binding sites. Briefly, cells are seeded into Greiner 384 well plates (15000 cells per well for TLR7, 20,000 for TLR8 and 25,000 for TLR9) and then treated with test compounds in DMSO to yield a final dose response concentration range of 0.05 nM-50 μM. After a 30 minute compound pre-treatment at room temperature, the cells are then stimulated with a TLR7 ligand (gardiquimod at a final concentration of 7.5 μM), TLR8 ligand (R848 at a final concentration of 15.9 μM) or TLR9 ligand (ODN2006 at a final concentration of 5 nM) to activate NF-κB and AP-1 which induce the production of SEAP. After a 22 hour incubation at 37° C., 5% CO2, SEAP levels are determined with the addition of HEK-Blue Detection reagent (Invivogen), a cell culture medium that allows for detection of SEAP, according to manufacturer's specifications.
Measurement: IC50 = 3.6 nM (pChEMBL 8.4399995803833)
Descriptors: MW 355.43, ALogP 4.85, HBA 2, HBD 2, PSA 40.71, QED 0.71
Compound (SMILES): Clc1ccc(Nc2nc3ccccc3c3[nH]c([C@@H]4C[C@@H]5CCC[C@@H](C5)C4)nc23)cc1Cl
InChIKey: NGJLIUAVUBZXSF-MUJYYYPQSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Displacement of [3H]-DAMGO from human MOR receptor expressed in human HEK293 cell membrane incubated for 90 mins by radioligand binding assay
Measurement: Ki = 7220 nM (pChEMBL 5.139999866485596)
Descriptors: MW 451.4, ALogP 7.85, HBA 3, HBD 2, PSA 53.6, QED 0.33
Compound (SMILES): C=CC(=O)Nc1cc(Nc2ncc(Cl)c(O[C@@H]3CO[C@H]4[C@@H]3OC[C@H]4O)n2)ccc1N(C)CCN(C)C
InChIKey: PGIZGLPYTTWZCW-UGESXGAOSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of human TYK2 by FRET assay
Measurement: IC50 = 424 nM (pChEMBL 6.369999885559082)
Descriptors: MW 519, ALogP 1.9, HBA 10, HBD 3, PSA 121.31, QED 0.4
Compound (SMILES): COc1cc(N(C)CCN(C)C)c(NC(=O)c2ccncc2)cc1Nc1nccc(-c2cn(C)c3ccccc23)n1
InChIKey: TWTOVZQZCNMAGB-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of c-Met (unknown origin) by mobility shift assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 550.67, ALogP 5.03, HBA 9, HBD 2, PSA 100.44, QED 0.25
Compound (SMILES): Cc1ccc(C(=O)O)cc1-c1ccc2[nH]c(=O)c(=O)[nH]c2c1
InChIKey: USTBPBLWWNOSID-UHFFFAOYSA-N
Target: Glutamate receptor ionotropic, kainate 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13003
Assay: Binding affinity to GluK3 receptor (unknown origin)
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 296.28, ALogP 1.89, HBA 3, HBD 3, PSA 103.02, QED 0.63
Compound (SMILES): Nc1nc(C(=O)NCc2ccncc2)cn2c1nc1ccccc12
InChIKey: DBHBCVCCWMOUKI-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Antagonist activity at A2AAR in human T -cells assessed as increase in IL-2 production preincubated for 1 hr followed by CD3/CD28 monoclonal antibody addition and measured after 24 hrs in presence of NECA by ELISA
Measurement: EC50 = 1.56 nM (pChEMBL 8.8100004196167)
Descriptors: MW 318.34, ALogP 1.79, HBA 6, HBD 2, PSA 98.2, QED 0.6
Compound (SMILES): Cc1nc(N)sc1-c1cccc(N/C(N)=N/C(=O)NCCCCCCNC(=O)/N=C(\N)Nc2cccc(-c3sc(N)nc3C)c2)c1.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: XJYJHSHOVQOBFW-UHFFFAOYSA-N
Target: Histamine H2 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P25021
Assay: Displacement of [3H]UR-DE257 from human histamine H2 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing RG-Salpha S incubated for 60 mins by scintillation counting analysis
Measurement: Kd = 12.2 nM (pChEMBL 7.909999847412109)
Descriptors: MW 662.85, ALogP 4.85, HBA 8, HBD 8, PSA 236.84, QED 0.06
Compound (SMILES): CNC(=O)c1cc(F)c(F)c(-c2cnc3cc(-c4cnn(C)c4)c(O[C@H]4CCOC4)nn23)c1
InChIKey: NZHANKJSPAJGFW-AWEZNQCLSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of wild type partial length human FLT3 (V592 to Y969 residues) expressed in bacterial expression system using Ulight-p70S6K peptide substrate incubated for 90 mins in presence of ATP by HTRF assay
Measurement: IC50 = 155 nM (pChEMBL 6.809999942779541)
Descriptors: MW 454.44, ALogP 2.6, HBA 8, HBD 1, PSA 95.57, QED 0.5
Compound (SMILES): CNCc1ccccc1-c1csc([C@@H](C)Nc2nncc3cc(OC)c(OC)cc23)c1
InChIKey: VAGASTYGBBQOMO-OAHLLOKOSA-N
Target: Son of sevenless homolog 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07889
Assay: Inhibiting SOS1-Mediated GTP Nucleotide Exchange by Blocking Mant-GDP Exchange: Table 24: This Example illustrates that exemplary compounds of the present invention prevent KRas-mediated GTP nucleotide exchange mediated by SOS1 to inhibit KRas activity thereby inhibiting the generation of the downstream effector pERK. MKN1 cells (15,000/w) or H358 (30,000/w) were seeded in a black clear flat bottom 96-well cell culture plate (Corning, #3904) and incubated at 37° C. overnight. Assay day 1, cells were dosed with compounds of Formula (I) with a 10 μm starting concentration and serially diluted 3× for a total of 9 concentrations. The cells were incubated for approximately 0.5-1 hour with the compounds solubilized in DMSO at 37° C. Cells were immediately fixed by adding 50 μL of 4% formaldehyde to all wells in a fume hood and the plates were incubated for 20 minutes at room temperature. The formaldehyde was discarded from the plates and 150 μL of ice-cold methanol was added to permeabilize the cells for 10 minutes at −20° C. The methanol was discarded from each of the plates and any liquid remaining in the plate by tapping the plate against paper towels. Cells were then blocked with 150 μL of Odyssey blocking buffer (LI-COR Biosciences #927-50010) using 0.05% Tween for 1 hour at room temperature on a shaker. The blocking buffer was discarded and 50 μL of primary antibodies pERK (cell signaling Technology #9101L; Rabbit, 1:500) and GapDH (Millipore #MAB34; Mouse, 1:5000) diluted in Odyssey blocking buffer was added. The plates were incubated overnight at 4° C. on a shaker. On Assay Day 2, the primary antibody solution was removed. Each plate was washed 3× times with 150 μL of 1×PBST (PBS+0.1% Tween 20) and incubated with 50 μL of secondary antibodies: Anti-Rabbit (LI-COR Biosciences #926-32211) and Anti-Mouse (LI-COR Biosciences #68070) at 1:800 dilution in Odyssey blocking buffer with Tween at room temperature on a shaker for 2 hours (protected from light). The secondary antibody solution as removed and each plate was washed with PBST 3× times. Any liquid remaining was discarded and the plate was imaged using the Licor Odyssey machine according to the manufacturer's instruction, using a set focus length at 3 mm and both 800 nm and 700 nm filters. The GAPDH normalized scan values for each well were divided by the average of vehicle wells to get the % of pERK inhibition. The IC50 values were then calculated with the Graph pad Prism software.
Measurement: IC50 = 165 nM (pChEMBL 6.78000020980835)
Descriptors: MW 434.57, ALogP 5.27, HBA 7, HBD 2, PSA 68.3, QED 0.39
Compound (SMILES): Cl.Clc1ccc2[nH]c3c(c2c1)CCNC3c1ccc(Cl)s1
InChIKey: JFKYTYFNNSAHCH-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Agonist activity at human 5HT2C receptor stably expressed in Flp-In-T-REx-293 cells assessed as increase in Gq-mediated calcium flux by Fluo-4 direct dye based FLIPR Tetra assay
Measurement: EC50 = 43.65 nM (pChEMBL 7.360000133514404)
Descriptors: MW 323.25, ALogP 4.77, HBA 2, HBD 2, PSA 27.82, QED 0.66
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](COC)NC(=O)[C@H](COC)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](COC)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@@H](N)Cc1c[nH]cn1)[C@@H](C)OC)[C@@H](C)O)C(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(N)=O)C(C)C
InChIKey: GPZRXYYUFJICHR-PTZOYWKSSA-N
Target: Glucagon-like peptide 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P43220
Assay: Agonist activity at human GLP-1R assessed as increase in ERK1/2 phosphorylation at Thr202/Tyr204 residues incubated for 20 mins by AlphaLISA assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 3353.79
Compound (SMILES): Cc1ccc(CC(C)CNC(=O)/N=C(\N)Nc2ccc(-c3sc(N)nc3C)cc2)cc1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: SDMHKVKMURLVQH-UHFFFAOYSA-N
Target: Histamine H2 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P25021
Assay: Displacement of [3H]UR-DE257 from human histamine H2 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing RG-Salpha S incubated for 60 mins by scintillation counting analysis
Measurement: Kd = 12.2 nM (pChEMBL 7.909999847412109)
Descriptors: MW 436.59, ALogP 4.32, HBA 4, HBD 4, PSA 118.42, QED 0.34
Compound (SMILES): CCCCOc1c2cccc1Cc1cc(C(=O)P(=O)(O)O)cc(c1O)Cc1cccc(c1OCCCC)Cc1cc(C(=O)P(=O)(O)O)cc(c1O)C2
InChIKey: JDNMAGZNSICFGF-UHFFFAOYSA-N
Target: Glutathione S-transferase P (SINGLE PROTEIN), Homo sapiens
UniProt: P09211
Assay: Inhibition of recombinant human GSTP1-1 using GSH and CDNB as substrate preincubated for 2 mins followed by substrate addition and measured upto 6 mins in the presence of UV irradiation by spectrophotometric analysis
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 752.69, ALogP 6.77, HBA 8, HBD 6, PSA 208.12, QED 0.06
Compound (SMILES): O=C1NC(=O)/C(=C\c2ccc(OCC(=O)N3N=C(c4ccc(F)cc4)CC3c3ccco3)cc2)S1
InChIKey: KXAPDKXGXJJUQC-WSDLNYQXSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of recombinant human HDAC2 Boc-Lys(acetyl)-AMC as substrate incubated for 30 mins by fluorescence assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 491.5, ALogP 4.5, HBA 7, HBD 1, PSA 101.21, QED 0.51
Compound (SMILES): Cc1[nH]nc(-c2ccncc2)c1-c1ccc(-c2cccc(S(N)(=O)=O)c2)c(C2CC2)c1
InChIKey: SRXZEAZXVNKPBH-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Mus musculus
UniProt: Q5S006
Assay: Inhibition of mouse full-length wild type LRRK2 transfected in HEK293 cells using LRRKtide as substrate incubated for 1 hr in presence of ATP by TR-FRET based ADAPTA assay
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 430.53, ALogP 4.64, HBA 4, HBD 2, PSA 101.73, QED 0.48
Compound (SMILES): CCCC(=O)N(Cc1ccc(F)cc1)C1CCN(CCc2ccccc2)CC1
InChIKey: AXXWJGVWCSPDTD-UHFFFAOYSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: Binding affinity to sigma2 receptor (unknown origin) measured by radioligand binding assay
Measurement: Ki = 144.8 nM (pChEMBL 6.840000152587891)
Descriptors: MW 382.52, ALogP 4.66, HBA 2, HBD 0, PSA 23.55, QED 0.66
Compound (SMILES): CC1(C)C(=N)N[C@](C)(c2nc(NC(=O)c3ccc(C#N)cn3)ccc2F)CS1(=O)=O
InChIKey: LTYYZTCFGRCEBL-IBGZPJMESA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of MK499 from human ERG expressed in HEK membrane by radio ligand binding competition assay
Measurement: IC50 = 15890 nM (pChEMBL 4.800000190734863)
Descriptors: MW 430.47, ALogP 1.73, HBA 7, HBD 3, PSA 148.69, QED 0.67
Compound (SMILES): O=C1OC(Cc2ccc(F)c(F)c2)c2ccc(N3CC[C@@H](O)C3)cc21
InChIKey: YUPAFWDHCZWXIL-YJJYDOSJSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Rattus norvegicus
UniProt: P19643
Assay: Inhibition of Sprague-Dawley rat MAO-B
Measurement: IC50 = 320 nM (pChEMBL 6.5)
Descriptors: MW 345.35, ALogP 2.99, HBA 4, HBD 1, PSA 49.77, QED 0.87
Compound (SMILES): COc1ccc2nc(-c3ccccc3OC)cc(C(=O)Nc3ccc4c(c3)c(S(N)(=O)=O)cn4C)c2c1
InChIKey: DXOCRQAITAKLJO-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human carbonic anhydrase 12 by stopped flow CO2 assay
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 516.58, ALogP 4.31, HBA 7, HBD 2, PSA 125.54, QED 0.35
Compound (SMILES): CCNC(=O)[C@H]1O[C@@H](n2cnc3c(N[C@@H]4CCC[C@H]4Oc4cccc(Cl)c4)ncnc32)[C@H](O)[C@@H]1O
InChIKey: KDVVGWMFXLSEQE-SLHDEKGNSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Agonist activity at human adenosine A2B receptor expressed in CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation incubated for 30 mins by LANCE ultra assay
Measurement: EC50 = 977.24 nM (pChEMBL 6.010000228881836)
Descriptors: MW 502.96, ALogP 1.65, HBA 10, HBD 4, PSA 143.65, QED 0.38
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@@H](N)Cc1c[nH]cn1)[C@@H](C)O)C(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(N)=O)C(C)C
InChIKey: LGDDFUNEDXKVFM-MPAYVIJZSA-N
Target: Glucagon-like peptide 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P43220
Assay: Agonist activity at human GLP-1R expressed in CHO cells coexpressing beta-arrestin-2 assessed as increase in beta arrestin-2 recruitment incubated for 1 hr by chemiluminescence based pathHunter assay
Measurement: EC50 = 158.49 nM (pChEMBL 6.800000190734863)
Descriptors: MW 3251.66
Compound (SMILES): O=C(O)CC1CCC2(CC1)CCC(c1ccc(NC(=O)c3nnc(Nc4ccc(F)c(F)c4)o3)cc1)CC2
InChIKey: OQWPAKFHAYCXAX-UHFFFAOYSA-N
Target: Diacylglycerol O-acyltransferase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75907
Assay: Inhibition of human DGAT1 in serum starved HEK293 cells assessed as inhibition of triglyceride synthesis incubated for 20 mins followed by 13C-addition of 13C-oleic acid pre-complexed with BSA for 120 mins by LC-MS-based mass spectrophotometric analysis
Measurement: IC50 = 14.6 nM (pChEMBL 7.840000152587891)
Descriptors: MW 524.57, ALogP 6.65, HBA 6, HBD 3, PSA 117.35, QED 0.32
Compound (SMILES): CN[C@@H](C)C(=O)N[C@@H](CNC(=O)c1cc(S(=O)(=O)F)ccc1OC)C(=O)N1CCC[C@H]1C(=O)N[C@@H]1CCc2ccccc21
InChIKey: NUAUWPVMCPSATJ-JDGBCZCZSA-N
Target: Baculoviral IAP repeat-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13489
Assay: Antagonist activity at N-terminal His-tagged cIAP2-BIR3 domain (unknown origin) expressed in Escherichia coli BL21 using AVPIAQKSEK-biotinylated peptide as substrate incubated for 2 hrs by DELFIA assay
Measurement: IC50 = 59 nM (pChEMBL 7.230000019073486)
Descriptors: MW 617.7, ALogP 0.97, HBA 8, HBD 4, PSA 163.01, QED 0.27
Compound (SMILES): CCCCCCCCCSC[C@H](NC(=O)[C@H](CO)NC(=O)CN)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](Cc1c[nH]cn1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)O)C(C)C
InChIKey: IZNYDXUZSMWXNF-MAXOQOPMSA-N
Target: Appetite-regulating hormone (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBU3
Assay: Displacement of C-terminal Cys-tagged NanoLuc luciferase from C-terminal Cys-tagged human Ghrelin expressed in HEK293T cells by microplate reader based NanoBiT-binding assay
Measurement: EC50 = 1.58 nM (pChEMBL 8.800000190734863)
Descriptors: MW 3387.03
Compound (SMILES): C[N+]1(CCOc2ccc(/C=C/c3ccccc3)cc2)CCC1.[I-]
InChIKey: KRRAWALNDVAFCJ-HRNDJLQDSA-M
Target: Neuronal acetylcholine receptor subunit alpha-7 (SINGLE PROTEIN), Homo sapiens
UniProt: P36544
Assay: Antagonist activity at human alpha7 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response treated for 1 sec in presence of acetylcholine at holding potential of -70 mV by two electrode voltage-clamp assay
Measurement: IC50 = 2.45 nM (pChEMBL 8.609999656677246)
Descriptors: MW 294.42, ALogP 4.09, HBA 1, HBD 0, PSA 9.23, QED 0.58
Compound (SMILES): O=C(O)c1ccc(CNc2nc3ccc(-c4nc(N5CCOCC5)nc(N5CCOCC5)n4)cc3o2)cc1
InChIKey: AOSQGSGJTZNGRW-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3Kgamma (unknown origin) in presence of [33P]-ATP incubated for 2 hrs by hotspot kinase assay
Measurement: IC50 = 3487 nM (pChEMBL 5.460000038146973)
Descriptors: MW 517.55, ALogP 2.66, HBA 11, HBD 2, PSA 138.97, QED 0.37
Compound (SMILES): CCOC(=O)c1cnc2c(OC)cccc2c1-c1ccc(-c2cc(F)cnc2OC)nc1
InChIKey: NJHSEIYEXVXCPJ-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14831
Assay: Negative allosteric modulation of mGlu7 (unknown origin) in cells expressing G protein-regulated inwardly rectifying potassium channels (GIRKs) assessed as inhibition of L-AP4-induced response measured by thallium flux assay
Measurement: IC50 = 4570.88 nM (pChEMBL 5.340000152587891)
Descriptors: MW 433.44, ALogP 4.69, HBA 7, HBD 0, PSA 83.43, QED 0.41
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)CCC(=O)N[C@@H](CCCCNC(=O)[C@@H](CCCNC(=N)N)NC(=O)CCCCCCCC(=O)N1CCN(c2ncnc3[nH]ccc23)CC1)C(=O)N[C@H](CCCNC(=N)N)C(N)=O)C(=O)NCC(=O)CF
InChIKey: TZRLLCDNKOSPGK-BTRGJUCVSA-N
Target: cAMP-dependent protein kinase catalytic subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P17612
Assay: Covalent inhibition of human recombinant PKAC-alpha assessed as inhibition constant
Measurement: Ki = 0.63 nM (pChEMBL 9.199999809265137)
Descriptors: MW 1099.33
Compound (SMILES): Cc1ccc(Nc2ccc3[nH]nc(-c4ccncc4)c3c2)c(C#N)c1
InChIKey: AUJMMKVJUKYWCO-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of pcDNA5FRT-TO-GFP fused - LRRK2 G2019S mutant (unknown origin) transfected in HEK293 cells incubated for 24 hrs by ELISA
Measurement: EC50 = 530 nM (pChEMBL 6.28000020980835)
Descriptors: MW 325.38, ALogP 4.55, HBA 4, HBD 2, PSA 77.39, QED 0.58
Compound (SMILES): CS(=O)(=O)c1ccc(NC(=O)N/N=C\c2c(Cl)cccc2Cl)cc1
InChIKey: BHKDGLGFTAHYTQ-NVMNQCDNSA-N
Target: Monoglyceride lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q99685
Assay: Mixed inhibition MAGL (unknown origin) using 4-nitrophenyl acetate as substrate by Dixon plot analysis
Measurement: Ki = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 386.26, ALogP 3.55, HBA 4, HBD 2, PSA 87.63, QED 0.62
Compound (SMILES): CS(=O)(=O)N1CCc2cc(C3CC3NCC3CCNCC3)ccc21
InChIKey: DFOFKLSGYBTRDH-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human recombinant MAO-B expressed in baculovirus infected BTI insect cells using luminogenic MAO substrate incubated for 1 hr by luciferin-based luminescence assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 349.5, ALogP 1.45, HBA 4, HBD 2, PSA 61.44, QED 0.84
Compound (SMILES): Cn1nc(NC(=O)Nc2ccccc2)c2ccnc(NC3CCCCC3)c21
InChIKey: XXOSYNDAOHAYJW-UHFFFAOYSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30542
Assay: Antagonist activity at wild type A1R (unknown origin) expressed in CHO-K1 cells assessed as inhibition of NECA reduced forskolin stimulated cAMP accumulation incubated for 30 mins
Measurement: IC50 = 1.413 nM (pChEMBL 8.850000381469727)
Descriptors: MW 364.45, ALogP 4.36, HBA 5, HBD 3, PSA 83.87, QED 0.64
Compound (SMILES): COc1ccc(C2(C(=O)N3CCOCC(Cc4cccc5[nH]ncc45)C3)CCCC2)cc1
InChIKey: DUYFMLONWKDSAB-UHFFFAOYSA-N
Target: Histone acetyltransferase p300 (SINGLE PROTEIN), Homo sapiens
UniProt: Q09472
Assay: Inhibition of EP300 in human LK2 cells assessed as reduction in intracellular histone H3 acetylation at lysine 27 residue incubated for 3 hrs by chemiluminescence based ELISA
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 433.55, ALogP 4.1, HBA 4, HBD 1, PSA 67.45, QED 0.66
Compound (SMILES): CNC(=O)[C@@]12C[C@@H]1[C@@H](n1cnc3c(NCCc4ccc(OC)c(O)c4)nc(OCCCC4CCCCC4)nc31)[C@H](O)[C@@H]2O
InChIKey: VXZWWKSQYWINGU-VGGQNZTHSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Mus musculus
UniProt: Q61618
Assay: Displacement of [125I] N6-4-amino-3-iodobenzyl adenosine 5-N-methyluronamide from mouse A3A receptor stably expressed in HEK293 cell membrane by radioligand inhibition assay
Measurement: Ki = 6.42 nM (pChEMBL 8.1899995803833)
Descriptors: MW 594.71, ALogP 2.96, HBA 11, HBD 5, PSA 163.88, QED 0.2
Compound (SMILES): Cc1ccc(/C=N/Nc2nc(Nc3ccccc3)nc(Nc3ccc(S(N)(=O)=O)cc3)n2)cc1
InChIKey: ANFJDKCNBVZRHS-MFKUBSTISA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human CA 12 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 8.21 nM (pChEMBL 8.09000015258789)
Descriptors: MW 474.55, ALogP 3.76, HBA 9, HBD 4, PSA 147.28, QED 0.22
Compound (SMILES): CC(C)c1cnc(N2CC[C@@H]2C)c2cnc(Nc3ccnc(N4CC[C@@H](O)[C@@](C)(F)C4)n3)cc12
InChIKey: LUEQIDIGIGWGLR-ZCPGDWHISA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of wild type EGFR in human A-431 cells preincubated for 4 to 5 hrs followed by EGF stimulation for 10 mins by AlphaLISA method
Measurement: IC50 = 25000 nM (pChEMBL 4.599999904632568)
Descriptors: MW 465.58, ALogP 4.18, HBA 8, HBD 2, PSA 90.3, QED 0.58
Compound (SMILES): COc1ccccc1CCNc1nc(N)nc(NCCc2c[nH]c3ccccc23)n1
InChIKey: QKSQQPDOYVQCNJ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Displacement of [3H]-5-CT from human 5-HT7 receptor expressed in HEK293 cells incubated for 1 hr by microbeta plate reader analysis
Measurement: Ki = 196 nM (pChEMBL 6.710000038146973)
Descriptors: MW 403.49, ALogP 3.25, HBA 7, HBD 4, PSA 113.77, QED 0.34
Compound (SMILES): O=C(NC(=S)Nc1cc(Cl)c(O)c(Cl)c1)C12CC3CC(CC(C3)C1)C2
InChIKey: UEKJKZCGDQUUPW-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Antagonist activity at human P2X7 receptor expressed in human 1321N1 cells assessed as reduction in intracellular Ca2+ influx incubated for 30 mins by Fura-2 AM based fluorescence assay
Measurement: IC50 = 2453 nM (pChEMBL 5.610000133514404)
Descriptors: MW 399.34, ALogP 4.73, HBA 3, HBD 3, PSA 61.36, QED 0.5
Compound (SMILES): CCCC(=O)N1CCc2cc(C3CC3NCC3CCNCC3)ccc21
InChIKey: ZRQRSRLEWGEPTB-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human recombinant MAO-B expressed in baculovirus infected BTI insect cells using luminogenic MAO substrate incubated for 1 hr by luciferin-based luminescence assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 341.5, ALogP 2.82, HBA 3, HBD 2, PSA 44.37, QED 0.84
Compound (SMILES): C[C@H](N1Cc2cc(-c3ccn4nc(N)c(C(=O)NC5CC5)c4n3)cc(NS(C)(=O)=O)c2C1=O)C(F)(F)F
InChIKey: DVSVSACTSIIEOY-JTQLQIEISA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta (unknown origin) using PIP2 as substrate preincubated for 1 hr followed by substrate addition and measured after 60 mins in presence of ATP by ADP-glo assay
Measurement: IC50 = 68 nM (pChEMBL 7.170000076293945)
Descriptors: MW 537.52, ALogP 2.15, HBA 8, HBD 3, PSA 151.79, QED 0.44