lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): [2H]C([2H])([2H])NC(=O)c1nnc(NC(=O)C2CC2)cc1Nc1cccc(-c2ccc(C(=O)N(C)C)cn2)c1OC
InChIKey: QWYHQNIOFBKVSH-FIBGUPNXSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of TYK2 in IFN-alpha stimulated human Kit225 T cells by luciferase reporter gene assay
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 489.54, ALogP 2.7, HBA 8, HBD 3, PSA 138.44, QED 0.44
Compound (SMILES): O=C(Nc1c[nH]nc1C(=O)Nc1ccc(N2CCC(F)(F)C2)nc1)c1cncc(OC2CCNCC2)c1
InChIKey: QHSLNROXYOMVCC-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49760
Assay: Inhibition of recombinant CLK2 (unknown origin) using Ser/Thr 6 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 512.52, ALogP 2.68, HBA 8, HBD 4, PSA 137.16, QED 0.38
Compound (SMILES): COc1ccccc1N1CCN(CCCCCn2cc(CCCC(=O)O)c3ccccc32)CC1
InChIKey: COCNNTPCKDDPMD-UHFFFAOYSA-N
Target: Alpha-1B adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35368
Assay: Antagonist activity at human alpha1B receptor transfected in HEK293 cells co-transfected with Galpha16 assessed as reduction in intracellular calcium release incubated for 40 mins by Fluo-4AM dye based fluorescence assay
Measurement: IC50 = 9.8 nM (pChEMBL 8.010000228881836)
Descriptors: MW 463.62, ALogP 5.05, HBA 5, HBD 1, PSA 57.94, QED 0.38
Compound (SMILES): CCN1CCN(Cc2ccc(Nc3nc(Oc4ccc5ccc(=O)[nH]c5c4)c4sccc4n3)cc2)CC1
InChIKey: MUHAICPFWNLXSQ-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of N-terminal GST-fused human wild type EGFR cytoplasmic domain (669 to 1210 residues) expressed in baculovirus expression system using 5-FAM-EEPLYWSFPAKKK-CONH2 as substrate incubated for 20 mins by Mobility shift assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 512.64, ALogP 5.21, HBA 8, HBD 2, PSA 86.38, QED 0.31
Compound (SMILES): C[C@H](CCC(=O)OCCN=[N+]=[N-])[C@H]1CC[C@H]2[C@@H]3CC[C@@H]4C[C@H](OC(=O)[C@H](CC(=O)O)Nc5ccc([N+](=O)[O-])c6nonc56)CC[C@]4(C)[C@H]3CC[C@]12C
InChIKey: PEAYJMZIZUBTMO-WNRPKZJSSA-N
Target: Beta-galactoside alpha-2,6-sialyltransferase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P15907
Assay: Inhibition of human alpha-2,6-ST6GAL1 assessed as reduction in sialylated-product formation using Gal-beta1-4GlcNac and CMP-NeuSAc incubated for 15 mins by reverse-phase HPLC analysis
Measurement: IC50 = 4200 nM (pChEMBL 5.380000114440918)
Descriptors: MW 723.83, ALogP 7.23, HBA 12, HBD 2, PSA 232.75, QED 0.04
Compound (SMILES): Cc1c(C(C)C)nnc2sc(C(=O)NC3CN(c4ncc(C(F)(F)F)cn4)C3)c(N)c12
InChIKey: XYYIKXAMUKBPEK-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Positive allosteric modulation of human M2 receptor/Gqi5 in presence of EC20 glutamate by calcium mobilization assay
Measurement: EC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 451.48, ALogP 3.13, HBA 8, HBD 2, PSA 109.92, QED 0.63
Compound (SMILES): CC1CCN(Cc2cncc(-c3ccc4[nH]nc(C(=O)Nc5cccnc5)c4c3)c2)CC1
InChIKey: OLUJPDZZXTUOGS-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: DYRK1A activity assay: SH-SY5Y cells are cultured in DMEM/F-12 medium supplemented with 15% FBS, Non-essential Amino Acid and Penicillin/Streptamycin. Two days before treatment, cells are seeded onto 96 well plates at 20e5 cells/well.DMSO-resuspended compounds are dispensed to 8 wells as a serial titration from 10 μM to 4.6 nM final and cells are exposed overnight (16-18 h) before harvest. Wells are visualized checked for cell death or change in morphology and supernatants are tested for cytotoxicity by measurement of lactate dehydrogenase release (LDH, CytoToxOne kit, Progema) if necessary. As controls, commercially available DYRK1A inhibitors, Harmine and Indy were shown to have good DYRK1A inhibition in the kinase assay with no CDK1 activity (EC50 18 and 53n M respectively, 6 μM for CDK1) but weak EC50 in the Tau assay: about 10 μM for Harmine and 30 μM for Indy.Cells are lyzed with RIPA buffer complemented with phosphatase and protease inhibitors (Thermo Scientific) then lysates are sonicated and spun down at 12,000 g for 10 min to remove any cellular debris. Lysates are then either directly tested for pSer396 by ELISA (Life Technology, Kit KHB7031) or loaded on NuPage Bis-Tris gels for western blot analysis. Colorimetric detection of ELISA signal is performed by Cytation3 plate reader (Biotek) and the chemoluminecence signal for HRP-linked antibodies used in western blotting is detected using a Carestream Image Station. The same pSer396 antibody is used for detection of pTau in both assays.Blot densitometry for pSer396 and beta-actin are analyzed using ImageJ (NIH) and pSer396/Total Tau ELISA signal was used to plot, draw the curve fitting, and determine each compounds EC50 in Prism (GraphPad).
Measurement: EC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 426.52, ALogP 4.5, HBA 5, HBD 2, PSA 86.8, QED 0.49
Compound (SMILES): CNC(=O)c1sc(-c2ccnc(NC(=O)C3CC3)c2)nc1OCC1CCN(Cc2cccc(Br)c2)CC1
InChIKey: UQTYKFVTMYTFSQ-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human BChE using butyrylthiocholineiodide as substrate incubated for 10 mins by Ellman's method
Measurement: IC50 = 15000 nM (pChEMBL 4.820000171661377)
Descriptors: MW 584.54, ALogP 4.97, HBA 7, HBD 2, PSA 96.45, QED 0.37
Compound (SMILES): Fc1cccc(-c2ccnc3[nH]c(-c4n[nH]c5ncc(-c6cn[nH]c6)cc45)nc23)c1
InChIKey: OVALWWJIGLEHJA-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P49760
Assay: Inhibition of recombinant CLK2 (unknown origin) using Ser/Thr 6 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 396.39, ALogP 4.09, HBA 5, HBD 3, PSA 111.82, QED 0.42
Compound (SMILES): Cn1nc(-c2ccc(OC[C@H]3CC[C@H](N)CC3)c(F)c2)c2cnc(N)nc21
InChIKey: MYTYKOZIRPDGSI-AULYBMBSSA-N
Target: Toll-like receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYK1
Assay: Antagonist activity at TLR7 in human PBMC assessed as inhibition of ssRNA40-induced IFNalpha production
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 370.43, ALogP 2.65, HBA 7, HBD 2, PSA 104.87, QED 0.73
Compound (SMILES): COc1ccc(C(NC(=O)c2cnc(-c3cccnn3)nc2O)c2ccc(OC)cc2)cc1
InChIKey: WXLPERVDMILVIF-UHFFFAOYSA-N
Target: Prolyl hydroxylase EGLN2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96KS0
Assay: Inhibition of FLAG-tagged full-length HIF-PHD1 (unknown origin) expressed in baculovirus infected Sf9 cells using 2-oxoglutarate and HIF1alpha biotinyl-DLDLEMLAPYIPMDDDFQL as peptide substrates preincubated for 30 mins followed by substrate addition and measured after 2 hrs by LANCE assay
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 443.46, ALogP 3.18, HBA 8, HBD 2, PSA 119.35, QED 0.45
Compound (SMILES): O=C(c1nc2cccnc2n1-c1ccc(Cl)c(Cl)c1)N1CC(F)(F)C1
InChIKey: KQDYNRPFUNNOAV-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Inhibition of 5HT2C (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 383.19, ALogP 3.82, HBA 4, HBD 0, PSA 51.02, QED 0.68
Compound (SMILES): COc1ccc2[nH]cc(/C=C/c3n[nH]c(=O)o3)c2c1
InChIKey: MBWWTUVCPDXVML-GORDUTHDSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of human MAO-A using p-tyramine as substrate by Amplex Red reagent based fluorescence analysis
Measurement: IC50 = 53000 nM (pChEMBL 4.28000020980835)
Descriptors: MW 257.25, ALogP 2.02, HBA 4, HBD 2, PSA 83.91, QED 0.75
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)Cc1ccc(O)cc1)C(=O)N[C@@H](Cc1ccccc1)C(N)=O
InChIKey: RIAMNAXKRHKRFB-YKPIBRNVSA-N
Target: Neuropeptide FF receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X5
Assay: Agonist activity at NPFFR2 (unknown origin) expressed in HEK-293A cells assessed as inhibition of forskolin-induced cAMP accumulation preincubated for 30 mins followed by [3H] cAMP addition measured after 2 hrs by scintillation counting method
Measurement: EC50 = 25.3 nM (pChEMBL 7.599999904632568)
Descriptors: MW 1228.42
Compound (SMILES): OC[C@@H]1N[C@@H](c2ccc(O)cc2)[C@H](O)[C@H]1O
InChIKey: BRPXIQPSCKPBLH-NAKRPEOUSA-N
Target: Alpha-mannosidase (SINGLE PROTEIN), Canavalia ensiformis
UniProt: C0HJB3
Assay: Inhibition of jack bean alpha-mannosidase using PNPG as substrate incubated for 10 mins by spectrophotometric method
Measurement: IC50 = 28000 nM (pChEMBL 4.550000190734863)
Descriptors: MW 225.24, ALogP -0.88, HBA 5, HBD 5, PSA 92.95, QED 0.45
Compound (SMILES): Cc1cc(Cl)cc(N2C=Nc3cc(C)c(-c4cccc(F)c4O)cc3C2C(=O)N(C)CC2CCCN2)c1
InChIKey: FGVUWBKWBAZBPK-UHFFFAOYSA-N
Target: Somatostatin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P30874
Assay: Agonist activity at human SST2 expressed in CHO-K1 cells assessed as reduction in NKH477-induced intracellular cAMP accumulation
Measurement: EC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 521.04, ALogP 5.9, HBA 5, HBD 2, PSA 68.17, QED 0.44
Compound (SMILES): COc1ccccc1-c1cc2c(N[C@H](CO)c3ccccc3)ncnc2[nH]1
InChIKey: HXSDKMUJXCRATG-GOSISDBHSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin) using Tyr 04 peptide as substrate incubated for 1 hr by Z'-LYTE assay
Measurement: IC50 = 0.8 nM (pChEMBL 9.100000381469727)
Descriptors: MW 360.42, ALogP 3.78, HBA 5, HBD 3, PSA 83.06, QED 0.49
Compound (SMILES): CC(=O)n1ccc2cc(C(=O)N3CCCC(c4ccnc5ncnn45)C3)ccc21
InChIKey: ACILVPXHSUHXNS-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9QYJ6
Assay: Inhibition of 6xHis-tagged rat recombinant PDE10A2 expressed in Sf9 cells in presence of [3H]-cAMP and cAMP incubated for 60 mins by scintillation counting method
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 388.43, ALogP 2.76, HBA 7, HBD 0, PSA 85.39, QED 0.53
Compound (SMILES): C[C@](O)(Cn1cc(F)cn1)C(=O)Nc1ccc(C#N)c(C(F)(F)F)c1
InChIKey: YDRMSDHDYRAUBR-AWEZNQCLSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Antagonist activity at recombinant human AR expressed in HEK293 cells assessed as inhibition of R1881-induced transcriptional activity measured after 24 hrs by dual luciferase reporter gene assay
Measurement: IC50 = 199 nM (pChEMBL 6.699999809265137)
Descriptors: MW 356.28, ALogP 2.3, HBA 5, HBD 2, PSA 90.94, QED 0.82
Compound (SMILES): COc1ccc(C2CC(c3ccccc3)=NN2C(=O)Cn2c(=O)oc3ccccc32)cc1OC
InChIKey: LENBDQFFJSXNPK-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of recombinant human MAO-A assessed as inhibition constant by Lineweaver-Burk plot analysis
Measurement: Ki = 850 nM (pChEMBL 6.070000171661377)
Descriptors: MW 457.49, ALogP 3.99, HBA 7, HBD 0, PSA 86.27, QED 0.44
Compound (SMILES): N#CC1(NC(=O)[C@H](Cc2ccccc2)NS(=O)(=O)c2ccccc2Cl)CC1
InChIKey: GVODRVUWACIZOR-INIZCTEOSA-N
Target: Procathepsin L (SINGLE PROTEIN), Homo sapiens
UniProt: P07711
Assay: Inhibition of human cathepsin L using Phe-Arg-pNA as substrate measured after 60 mins by spectrophotometric assay
Measurement: Ki = 156 nM (pChEMBL 6.809999942779541)
Descriptors: MW 403.89, ALogP 2.4, HBA 4, HBD 2, PSA 99.06, QED 0.74
Compound (SMILES): CO[C@@]12CC[C@@H](N[C@H](Cc3ccccc3)C(=O)O)[C@@H]3Oc4c(O)ccc5c4[C@@]31CCN(C)[C@@H]2C5
InChIKey: SILMEZJWWQTRJT-STVOXHSWSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Cavia porcellus
UniProt: P41144
Assay: Displacement of [3H]U69,593 from kappa opioid receptor in guinea-pig brain membranes incubated for 30 mins by liquid scintillation counting method
Measurement: Ki = 139 nM (pChEMBL 6.860000133514404)
Descriptors: MW 464.56, ALogP 2.48, HBA 6, HBD 3, PSA 91.26, QED 0.61
Compound (SMILES): CC(C)(C)CN1CCC(NCCSC(c2ccc(F)cc2)c2ccc(F)cc2)CC1
InChIKey: HVYCZHSOZAMKOW-UHFFFAOYSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Cavia porcellus
UniProt: Q60492
Assay: Displacement of [3H](+)-pentazocine from sigma 1 receptor in guinea pig brain cortex membranes after 120 mins by scintillation counting analysis
Measurement: Ki = 315 nM (pChEMBL 6.5)
Descriptors: MW 432.62, ALogP 5.89, HBA 3, HBD 1, PSA 15.27, QED 0.52
Compound (SMILES): CCS(=O)(=O)c1cnc(CNc2nc3cnc(-c4c(C)ncnc4C4CC4)nc3n([C@@H](C)C3CC3)c2=O)nc1
InChIKey: XXMJJXJUBYEROS-HNNXBMFYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Antagonist activity at RORgamma in human whole blood derived CD4-positive T cells assessed as inhibition of IL-17 secretion from differentiated Th17 cells preincubated for 1 hr and measured after 48 hrs
Measurement: IC50 = 49 nM (pChEMBL 7.309999942779541)
Descriptors: MW 547.65, ALogP 3, HBA 12, HBD 1, PSA 158.4, QED 0.33
Compound (SMILES): O=c1c2cc(Cl)ccc2oc2ccc(OCCCCCN3CCCCCC3)cc12
InChIKey: JREXJAZIYYZNSO-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BChE using BTCI as substrate incubated for 5 mins followed by substrate addition and measured after 5 mins by spectrophotometric based Ellman's method
Measurement: IC50 = 394 nM (pChEMBL 6.409999847412109)
Descriptors: MW 413.95, ALogP 6.02, HBA 4, HBD 0, PSA 42.68, QED 0.35
Compound (SMILES): COc1cccc2nnn(CC(=O)N[C@@H](C)c3ccc(OC(F)F)cc3)c(=O)c12
InChIKey: CBWQJOMWISNROA-NSHDSACASA-N
Target: Probable G-protein coupled receptor 139 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6DWJ6
Assay: Agonist activity at human GPR139 expressed in CHO-TRex cells assessed as stimulation of calcium signalling incubated for 15 mins by FLIPR assay
Measurement: EC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 404.37, ALogP 2.28, HBA 7, HBD 1, PSA 95.34, QED 0.65
Compound (SMILES): CCOP(=O)(OCC)c1ccc2[nH]cc(-c3nc(N[C@H]4CCCNC4)ncc3C(F)(F)F)c2c1
InChIKey: BVQPDSLIPWTEIC-AWEZNQCLSA-N
Target: CDK12/Cyclin K (PROTEIN COMPLEX), Homo sapiens
UniProt: O75909
Assay: Inhibition of CDK12 (686 to 1082 residues) /Cyclin K (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 3 hrs
Measurement: IC50 >= 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 497.46, ALogP 4.7, HBA 7, HBD 3, PSA 101.16, QED 0.39
Compound (SMILES): Cn1cncc1-c1ccc2cnc(NC(=O)c3ccc(F)cc3)cc2c1
InChIKey: ZTSBOGNTMIHVRH-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 346.37, ALogP 4.03, HBA 4, HBD 1, PSA 59.81, QED 0.61
Compound (SMILES): C[C@H](NC(=O)Cn1nc2cc(Cl)ccn2c1=O)c1ccc(OC(F)(F)F)cc1
InChIKey: IADVTJHARCIQEO-JTQLQIEISA-N
Target: Probable G-protein coupled receptor 139 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6DWJ6
Assay: Agonist activity at human GPR139 expressed in CHO-K1 cells assessed as induction of beta-arrestin 2 recruitment incubated for 90 mins by PathHunter assay
Measurement: EC50 < 1 nM (pChEMBL 9)
Descriptors: MW 414.77, ALogP 2.93, HBA 6, HBD 1, PSA 77.63, QED 0.7
Compound (SMILES): O=C(Nc1cc(C(F)(F)F)cc(C(F)(F)F)c1)C(c1ccccc1)S(=O)(=O)O
InChIKey: ONDIAWAXPRNPRA-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 13 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12923
Assay: Inhibition of His-tagged FAP1 (unknown origin) expressed in Escherichia coli BL21 cells using para-nitrophenyl phosphate as substrate incubated for 5 to 10 mins by microplate reader based spectrophotometric analysis
Measurement: IC50 = 76000 nM (pChEMBL 4.119999885559082)
Descriptors: MW 427.32, ALogP 4.29, HBA 3, HBD 2, PSA 83.47, QED 0.56
Compound (SMILES): C=CC(=O)Nc1cc2c(Nc3cccc(Cl)c3F)ncnc2cc1OCc1cn(CCCCC(=O)NO)nn1
InChIKey: ATEKSUDRIVWTTK-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of HDAC1 (unknown origin)
Measurement: IC50 = 132 nM (pChEMBL 6.880000114440918)
Descriptors: MW 554.97, ALogP 4.14, HBA 10, HBD 4, PSA 156.18, QED 0.09
Compound (SMILES): Nc1ncnc2c1ncn2[C@H]1C[C@@H]2OP(=O)(O)OC[C@H]3O[C@@H](n4cnc5c(O)ncnc54)C[C@@H]3OP(=O)(O)OC[C@H]2O1
InChIKey: BAEJKTUPWJXHEZ-PRSXHHODSA-N
Target: Stimulator of interferon genes protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q86WV6
Assay: Activation of STING in human THP-1-Dual cells assessed as induction of type I IFNs by measuring stimulation of NF-kappaB pathway incubated for 48 hrs by luciferase reporter gene assay
Measurement: EC50 = 62300 nM (pChEMBL 4.210000038146973)
Descriptors: MW 627.4, ALogP 0.55, HBA 18, HBD 4, PSA 263.43, QED 0.22
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2C[C@H](Nc3ncc4ccccc4n3)[C@@H](C)C2)cc1
InChIKey: GRBMJJYBCNETMC-YWZLYKJASA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51948
Assay: Inhibition of CDK7/cyclin H/MAT1 (unknown origin) assessed as incoporation of [33]Pi using RBER-IRStide as substrate and in presence of [gamma-33P]-ATP measured after 60 mins by microplate scintillation counter
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 401.47, ALogP 3.33, HBA 5, HBD 2, PSA 87.22, QED 0.64
Compound (SMILES): CCC(=O)N(Cc1ccco1)C1(C(=O)NCCc2cccc(F)c2)CCN(CCc2ccccc2)CC1
InChIKey: NLYJPYOXSQKJEH-UHFFFAOYSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at EA-fragment beta-arrestin-tagged human DOR expressed in human U2OS cell membranes assessed as stimulation of [35S]-GTPgammaS binding after 60 mins by beta-galactosidase based scintillation counting method
Measurement: EC50 = 3328 nM (pChEMBL 5.480000019073486)
Descriptors: MW 505.63, ALogP 4.59, HBA 4, HBD 1, PSA 65.79, QED 0.41
Compound (SMILES): CC(C)CC(=O)Nc1cncc(-c2cnc3[nH]nc(-c4cc5c(-c6cccnc6)ccnc5[nH]4)c3c2)c1
InChIKey: BCOCZYTVGLGCEA-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 9838 nM (pChEMBL 5.010000228881836)
Descriptors: MW 488.56, ALogP 5.61, HBA 6, HBD 3, PSA 125.13, QED 0.28
Compound (SMILES): CN1CCC[C@H]1[C@@H]1COc2cc([N+](=O)[O-])ccc2O1
InChIKey: RGJUMUZTONCAMS-GWCFXTLKSA-N
Target: Neuronal acetylcholine receptor; alpha4/beta2 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P09483
Assay: Displacement of [3H]-Epibatidine from alpha4beta2 nAChR in rat cerebral cortex membrane preincubated for 5 mins followed by [3H]-Epibatidine addition and measured after overnight incubation by liquid scintillation beta counter analysis
Measurement: Ki = 46000 nM (pChEMBL 4.340000152587891)
Descriptors: MW 264.28, ALogP 1.83, HBA 5, HBD 0, PSA 64.84, QED 0.6
Compound (SMILES): CCc1cnc(N[C@H]2CCCNC2)nc1-c1c[nH]c2c(S(=O)(=O)C(C)C)cccc12
InChIKey: WCEMNRJMILXDIH-INIZCTEOSA-N
Target: CDK12/Cyclin K (PROTEIN COMPLEX), Homo sapiens
UniProt: O75909
Assay: Inhibition of CDK12 (686 to 1082 residues) /Cyclin K (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 3 hrs
Measurement: IC50 >= 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 427.57, ALogP 3.53, HBA 6, HBD 3, PSA 99.77, QED 0.56
Compound (SMILES): CC(=O)O[C@@H]1C[C@H](NC(=O)c2ccccc2)C(=O)[C@H]2[C@@]1(C)CC[C@H]1C(=O)O[C@H](c3ccoc3)C[C@]21C
InChIKey: GSUYLEUILULBTA-OONXLWFASA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at human delta opiod receptor expressed in CHO-K1 cells assessed as increase in forskolin induced cAMP production measured after 30 mins by HitHunter luminescence based assay
Measurement: EC50 = 690 nM (pChEMBL 6.159999847412109)
Descriptors: MW 493.56, ALogP 4.01, HBA 7, HBD 1, PSA 111.91, QED 0.64
Compound (SMILES): FC(F)(F)c1cnc(N[C@H]2CCCNC2)nc1-c1c[nH]c2ccc(Cl)cc12
InChIKey: ZVQWWSRTRLSWBL-NSHDSACASA-N
Target: CDK12/Cyclin K (PROTEIN COMPLEX), Homo sapiens
UniProt: O75909
Assay: Inhibition of CDK12 (686 to 1082 residues) /Cyclin K (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 3 hrs
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 395.82, ALogP 4.46, HBA 4, HBD 3, PSA 65.63, QED 0.61
Compound (SMILES): Cl.Cl.O=C(Nc1ccc(O[C@@H]2CCNC2)c(-c2cccc(-c3nn[nH]n3)c2)c1)c1ccc(O[C@H]2CCNC2)c(-c2ccc3ccsc3c2)c1
InChIKey: ATQXLHLDQNXZAH-KKXMJGKMSA-N
Target: beta-catenin-B-cell lymphoma 9 protein complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O00512
Assay: Inhibition of protein interaction between beta-catenin (unknown origin)/BCL9 in human SW480 cells transfected with beta-catenin assessed as reduction in Wnt/beta-catenin transactivation incubated for 24 hrs by Wnt-responsive TOP-Flash luciferase reporter assay
Measurement: IC50 = 43000 nM (pChEMBL 4.369999885559082)
Descriptors: MW 643.77, ALogP 6.15, HBA 9, HBD 4, PSA 126.08, QED 0.15
Compound (SMILES): O=C(CCl)Nc1ccc2sc(C(=O)NCc3cccc(NC(=O)c4cccs4)c3)c(OCc3ccccc3)c2c1
InChIKey: CEWXICCLFQTXRG-UHFFFAOYSA-N
Target: Sentrin-specific protease 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96HI0
Assay: Inhibition of recombinant human SNEP5 (567 to 755 residues) expressed in Escherichia coli (DE3) cells using RanGAP-SUMO2 substrate preincubated for 10 mins followed by substrate addition and measured after 25 min by Coomassie blue staining based SDS-PAGE analysis
Measurement: IC50 = 5700 nM (pChEMBL 5.239999771118164)
Descriptors: MW 590.13, ALogP 6.9, HBA 6, HBD 3, PSA 96.53, QED 0.15
Compound (SMILES): C=CC(=O)N1CCC=C(c2ccc(C(C)C(=O)Nc3cc(C4CC4)[nH]n3)cc2F)C1
InChIKey: HXKPNDMPSKRYFH-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7 (unknown origin) using ULight -mylein basic protein as substrate preincubated for 60 mins bu LANCE-TR-FRET assay
Measurement: IC50 = 440 nM (pChEMBL 6.360000133514404)
Descriptors: MW 408.48, ALogP 3.97, HBA 3, HBD 2, PSA 78.09, QED 0.71
Compound (SMILES): Nc1ncc(-c2ccc3c(c2)CC[C@@H]3C(=O)O)cc1-c1ccc(Cl)cc1
InChIKey: GWSFVTDGWLQLIO-SFHVURJKSA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O95819
Assay: Inhibition of MAP4K4 in human GripTite 293 MSR cells assessed as reduction in TRAF2 Ser/Thr phosphorylation incubated for 1.5 hrs by ELISA
Measurement: IC50 = 103 nM (pChEMBL 6.989999771118164)
Descriptors: MW 364.83, ALogP 4.77, HBA 3, HBD 2, PSA 76.21, QED 0.7
Compound (SMILES): COc1ccc(N2CCOCC2)c2sc(NC(=O)N3CCC(F)CC3)nc12
InChIKey: BDQMFCOBESCDSN-UHFFFAOYSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30542
Assay: Displacement of [3H]-DPCPX from recombinant human A1 receptor expressed in CHO-K1 cells incubated for 70 mins by liquid scintillation counting method
Measurement: Ki = 591 nM (pChEMBL 6.230000019073486)
Descriptors: MW 394.47, ALogP 3.11, HBA 6, HBD 1, PSA 66.93, QED 0.87
Compound (SMILES): Cc1cccc2c(-c3nc(N[C@H]4CCCNC4)ncc3F)c[nH]c12
InChIKey: FIBSRCUVZPVZGR-LBPRGKRZSA-N
Target: CDK12/Cyclin K (PROTEIN COMPLEX), Homo sapiens
UniProt: O75909
Assay: Inhibition of CDK12 (686 to 1082 residues) /Cyclin K (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 3 hrs
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 325.39, ALogP 3.24, HBA 4, HBD 3, PSA 65.63, QED 0.69
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CS)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)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](CS)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)C(C)(C)NC(=O)[C@@H](N)Cc1c[nH]cn1)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)O)[C@@H](C)CC)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCCN)C(=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(=O)NCCOCCOCC(=O)NCCOCCOCC(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)NCC(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](Cc1ccccc1)C(N)=O
InChIKey: ZBESYBJCRRZHKO-ZWYWDEOFSA-N
Target: Gastrin/cholecystokinin type B receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P32239
Assay: Agonist activity at human CCK-2R expressed in HEK293 cells assessed as stimulation of ERK phosphorylation incubated for 5 mins
Measurement: EC50 = 8.3 nM (pChEMBL 8.079999923706055)
Descriptors: MW 5341.93
Compound (SMILES): O=C(c1ccc(OCCCN2CCN(c3ccncc3)CC2)cc1)C1CC1
InChIKey: MHFUOIGTIQCKRH-UHFFFAOYSA-N
Target: Histamine H2 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P25021
Assay: Displacement of [3H]UR-DE257 from Gsalphas-coupled human H2R expressed in Sf9 cell membranes measured after 60 mins by scintillation counting analysis
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 365.48, ALogP 3.27, HBA 5, HBD 0, PSA 45.67, QED 0.53
Compound (SMILES): COc1cccc(-c2cncc3[nH]c(-c4n[nH]c5ccc(-c6cccnc6)nc45)nc23)c1
InChIKey: AWDCQQISBRFLGK-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 419.45, ALogP 4.63, HBA 6, HBD 2, PSA 105.26, QED 0.43
Compound (SMILES): CCc1cnc(N[C@H]2CCCNC2)nc1-c1n[nH]c2cc(C#N)ccc12
InChIKey: GQMFXBDTIABAEJ-AWEZNQCLSA-N
Target: CDK12/Cyclin K (PROTEIN COMPLEX), Homo sapiens
UniProt: O75909
Assay: Inhibition of CDK12 (686 to 1082 residues) /Cyclin K (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 3 hrs
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 347.43, ALogP 2.62, HBA 6, HBD 3, PSA 102.31, QED 0.67
Compound (SMILES): CN(C)c1cncc(-c2ccc3[nH]nc(-c4nc5c(-c6cccc(F)c6)cncc5[nH]4)c3n2)c1
InChIKey: FMEQEXAKKJQWLQ-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 450.48, ALogP 4.83, HBA 6, HBD 2, PSA 99.27, QED 0.4
Compound (SMILES): CNC(=O)c1[nH]c(C)c2c1CCCCC2=O
InChIKey: PZYBAQLWKWXUON-UHFFFAOYSA-N
Target: CREB-binding protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q92793
Assay: Binding affinity to CBP (unknown origin) assessed as dissociation constant by ITC analysis
Measurement: Kd = 28900 nM (pChEMBL 4.539999961853027)
Descriptors: MW 220.27, ALogP 1.59, HBA 2, HBD 2, PSA 61.96, QED 0.71
Compound (SMILES): CC(C)(C)CC(=O)Nc1cncc(-c2ccc3[nH]nc(-c4nc5ccncc5[nH]4)c3c2)c1
InChIKey: BMCUWCAUBUKQQR-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 65 nM (pChEMBL 7.190000057220459)
Descriptors: MW 425.5, ALogP 4.94, HBA 5, HBD 3, PSA 112.24, QED 0.38
Compound (SMILES): C[C@H](NC(=O)Cn1nc2c(C(F)F)nccn2c1=O)c1ccc(OC(F)(F)F)cc1
InChIKey: JEZBXEYTBJAMHK-VIFPVBQESA-N
Target: Probable G-protein coupled receptor 139 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6DWJ6
Assay: Agonist activity at human GPR139 expressed in CHO-K1 cells assessed as induction of beta-arrestin 2 recruitment incubated for 90 mins by PathHunter assay
Measurement: EC50 < 1 nM (pChEMBL 9)
Descriptors: MW 431.32, ALogP 2.6, HBA 7, HBD 1, PSA 90.52, QED 0.61
Compound (SMILES): CCC(=O)Nc1cncc(-c2ccc3[nH]nc(-c4nc5c(-c6ccsc6)cncc5[nH]4)c3c2)c1
InChIKey: PRUHFTXFFVARDU-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 64 nM (pChEMBL 7.190000057220459)
Descriptors: MW 465.54, ALogP 5.64, HBA 6, HBD 3, PSA 112.24, QED 0.3
Compound (SMILES): O=C(Nc1c[nH]nc1C(=O)Nc1cncc(-c2cccc(F)c2)c1)c1cncc(OC2CCNCC2)c1
InChIKey: GZVNTYHVMHCXBO-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 4305 nM (pChEMBL 5.369999885559082)
Descriptors: MW 501.52, ALogP 3.64, HBA 7, HBD 4, PSA 133.92, QED 0.3
Compound (SMILES): NS(=O)(=O)c1ccc(NC(=O)CSC(=S)N2CCN(Cc3ccc(F)cc3)CC2)cc1
InChIKey: ABZBORHAEWIHGS-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of human erythrocyte CA1 b using 4-nitrophenyl acetate as substrate by Lineweaver-Burk plot analysis
Measurement: Ki = 299 nM (pChEMBL 6.519999980926514)
Descriptors: MW 482.63, ALogP 2.25, HBA 6, HBD 2, PSA 95.74, QED 0.61
Compound (SMILES): CC(C)c1ccc(NC(=O)OC2CCN(Cc3ccccc3)CC2)cc1
InChIKey: RUFCJFOENLCATM-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human BuchE using butyrylthiocholine iodide as substrate preincubated for 30 mins followed by substrate addition by Ellman's method
Measurement: IC50 = 1740 nM (pChEMBL 5.760000228881836)
Descriptors: MW 352.48, ALogP 5.02, HBA 3, HBD 1, PSA 41.57, QED 0.82
Compound (SMILES): Cc1ccc(/C(=C(\CCCO)c2ccccc2)c2ccc(C3CNC3)cc2)cc1.Cl
InChIKey: NSKPLCNOGVCTPE-JTHROIFXSA-N
Target: Steroid hormone receptor ERR2 (SINGLE PROTEIN), Homo sapiens
UniProt: O95718
Assay: Binding affinity to ERRbeta (unknown origin) by TR-FRET assay
Measurement: IC50 = 9120 nM (pChEMBL 5.039999961853027)
Descriptors: MW 383.54, ALogP 5.41, HBA 2, HBD 2, PSA 32.26, QED 0.53
Compound (SMILES): N#CSCCNC(=O)c1ccc(Oc2ccc(Cl)cc2NS(=O)(=O)c2ccc(Cl)c(C(F)(F)F)c2)cc1
InChIKey: FKIPEBVDUWFIIM-UHFFFAOYSA-N
Target: C-C chemokine receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P41597
Assay: Displacement of [3H]-CCR2-RA-(R) from human CCR2b expressed in human U2OS cell membranes pre-incubated for 0 hrs before radio ligand addition and measured after 20 mins by scintillation counting method
Measurement: Ki = 1.995 nM (pChEMBL 8.699999809265137)
Descriptors: MW 590.43, ALogP 6.55, HBA 6, HBD 2, PSA 108.29, QED 0.22
Compound (SMILES): CC/C=C\C/C=C\C/C=C\C/C=C\C/C=C\CCCC(=O)NCc1ccccc1
InChIKey: VIMYRMWXQWTCCQ-JLNKQSITSA-N
Target: Bifunctional epoxide hydrolase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34913
Assay: Inhibition of recombinant human sEH expressed in baculovirus expression system using MNPC as substrate by fluorescence-based assay
Measurement: IC50 = 111 nM (pChEMBL 6.960000038146973)
Descriptors: MW 391.6, ALogP 7.22, HBA 1, HBD 1, PSA 29.1, QED 0.25
Compound (SMILES): Nc1ccccc1NC(=O)CNC(=O)/C(Cc1ccc(O)c(Br)c1)=N/O
InChIKey: SSOFSCHSYLOVMU-HYARGMPZSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of recombinant full length C-terminal FLAG-tagged human HDAC2 expressed in baculovirus infected Sf9 cells using Boc-Lys(Ac)-AMC as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by fluorescence based assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 421.25, ALogP 1.86, HBA 6, HBD 5, PSA 137.04, QED 0.21
Compound (SMILES): COc1ccc(-c2cc(OC(C)=O)c3c(-c4cccs4)c(N(C(C)=O)C(C)=O)oc3c2)cc1
InChIKey: BQDSZKNDEHZKOL-UHFFFAOYSA-N
Target: ATP-dependent translocase ABCB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08183
Assay: Inhibition of ABCB1 in FLp-In-293 cells assessed as potentiation of paclitaxel-induced cytotoxicity by measuring paclitaxel IC50 at 2.5 uM measured after 72 hrs by SRB assay (Rvb = 11.8 +/- 1.13 nM)
Measurement: IC50 = 10.5 nM (pChEMBL 7.980000019073486)
Descriptors: MW 463.51, ALogP 5.66, HBA 7, HBD 0, PSA 86.05, QED 0.28
Compound (SMILES): COc1cccc([C@@H](C)NC(=O)c2ccc3c(c2)c(=O)[nH]c2cnccc23)c1
InChIKey: LKMNKIPZENZTEM-CYBMUJFWSA-N
Target: Rho-associated protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75116
Assay: In Vitro Assay: The effectiveness of compounds of the present invention as ROCK inhibitors can be determined in a 30 μL assay containing 20 mM HEPES, pH 7.5, 20 mM MgCl2, 0.015% Brij-35, 4 mM DTT, 5 μM ATP and 1.5 μM peptide substrate (FITC-AHA-AKRRRLSSLRA-OH). Compounds were dissolved in DMSO so that the final concentration of DMSO was <2%, and the reaction was initiated with Rho kinase variants. After incubation, the reaction was terminated by the addition of EDTA and the phosphorylated and non-phosphorylated peptides separated using a LABCHIP® 3000 Reader (Caliper Life Sciences). Controls consisted of assays that did not contain compound, and backgrounds consisted of assays that contained enzyme and substrate but had EDTA from the beginning of the reaction to inhibit kinase activity. Compounds were tested in dose-response format, and the inhibition of kinase activity was calculated at each concentration of compound. The inhibition data were fit using a curve-fitting program to determine the IC50; i.e., the concentration of compound required to inhibit 50% of kinase activity.
Measurement: IC50 = 583 nM (pChEMBL 6.230000019073486)
Descriptors: MW 373.41, ALogP 3.58, HBA 4, HBD 2, PSA 84.08, QED 0.54
Compound (SMILES): COc1ccc2c(c1)C(=O)C(O)(O)C2=O
InChIKey: CHRLGTHYCGMMQQ-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of recombinant human carbonic anhydrase 4 preincubated with enzyme for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 74300 nM (pChEMBL 4.130000114440918)
Descriptors: MW 208.17, ALogP -0.24, HBA 5, HBD 2, PSA 83.83, QED 0.49
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](C(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](N)CCCCN)C(C)C)CSSC[C@H](N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(=O)O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)O)CSSC[C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc2c[nH]c3ccccc23)C(=O)O)NC1=O
InChIKey: IPGWRVNPJSUZJT-DDYAFKAXSA-N
Target: Relaxin-3 receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TDU9
Assay: Agonist activity at human RXFP4 expressed in CHO-K1 cells assessed as reduction in forskolin-induced cAMP production by pCRE beta-galactosidase reporter assay
Measurement: EC50 = 100 nM (pChEMBL 7)
Descriptors: MW 4229.93
Compound (SMILES): CCC(=O)Nc1cncc(-c2cnc3[nH]nc(-c4nc5c(-c6ccc(F)cc6)cncc5[nH]4)c3c2)c1
InChIKey: GKSHRCNLHWKGMH-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 37 nM (pChEMBL 7.429999828338623)
Descriptors: MW 478.49, ALogP 5.11, HBA 6, HBD 3, PSA 125.13, QED 0.32
Compound (SMILES): CCCS(=O)(=O)Nc1ccc(F)c(C(=O)c2n[nH]c3ncc(-c4ccccc4F)cc23)c1F
InChIKey: PYPLZNBMAJVTNZ-UHFFFAOYSA-N
Target: Dual specificity mitogen-activated protein kinase kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P45985
Assay: Inhibition of MEKK2 (unknown origin) using casein as substrate in presence of [gamma-33P]-ATP by scintillation counter assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 474.46, ALogP 4.42, HBA 5, HBD 2, PSA 104.81, QED 0.39
Compound (SMILES): COc1ccc(-c2cc(OC(C)=O)c3c(-c4cccs4)c(NC(=O)c4ccccc4C)oc3c2)cc1
InChIKey: KFIFBXUHWWIHKN-UHFFFAOYSA-N
Target: ATP-dependent translocase ABCB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08183
Assay: Inhibition of ABCB1 in FLp-In-293 cells assessed as potentiation of paclitaxel-induced cytotoxicity by measuring paclitaxel IC50 at 2.5 uM measured after 72 hrs by SRB assay (Rvb = 11.8 +/- 1.13 nM)
Measurement: IC50 = 9.1 nM (pChEMBL 8.039999961853027)
Descriptors: MW 497.57, ALogP 7.32, HBA 6, HBD 1, PSA 77.77, QED 0.2
Compound (SMILES): C[C@H]1C[C@@H](c2ccncc2NC(=O)c2csc(-c3c(F)cccc3F)n2)C[C@@H](O)[C@]1(C)O
InChIKey: AKCBESCJVOEVGC-APWSAUDXSA-N
Target: Serine/threonine-protein kinase pim-3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86V86
Assay: Inhibition of PIM3 (unknown origin) using Bad peptide NH2-AGAGRSRHSSYPAGT-OH as substrate measured after 10 mins in presence of ATP by luciferase-luciferin based Kinase-Glo luminescence assay
Measurement: Ki < 3 nM (pChEMBL 8.52299976348877)
Descriptors: MW 459.52, ALogP 4.36, HBA 6, HBD 3, PSA 95.34, QED 0.54
Compound (SMILES): CNC(=O)c1cnc2[nH]ccc2c1N[C@H]1CCN(Cc2ccc(Cl)cc2)[C@@H](C)C1
InChIKey: ZAVSMABHFLBCSH-YOEHRIQHSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of recombinant JAK3 (unknown origin) using GFP-STAT1 as substrate incubated for 1 hr followed by anti-pSTAT1 antibody addition and measured after 30 mins by Lanthascreen TR-FRET assay
Measurement: IC50 = 2.31 nM (pChEMBL 8.640000343322754)
Descriptors: MW 411.94, ALogP 4.04, HBA 4, HBD 3, PSA 73.05, QED 0.59
Compound (SMILES): COCC#Cc1cc(-c2nn(-c3nc(C(=O)O)cs3)c(CC3CC3)c2Cc2ccc(S(N)(=O)=O)c(F)c2)ccc1F
InChIKey: BILQDTWZUULZFS-UHFFFAOYSA-N
Target: L-lactate dehydrogenase A chain (SINGLE PROTEIN), Homo sapiens
UniProt: P00338
Assay: Inhibition of LDHA in human MIA PaCa-2 cells assessed as decrease in lactate production incubated for 2 hrs by lactate oxidase-coupled fluorescence based assay
Measurement: IC50 = 525 nM (pChEMBL 6.28000020980835)
Descriptors: MW 598.65, ALogP 4.16, HBA 8, HBD 2, PSA 137.4, QED 0.28
Compound (SMILES): O=c1cc(CN2CCN(Cc3ccccc3)CC2)c2ccc(OCc3ccccc3[N+](=O)[O-])cc2o1
InChIKey: HIGSDGAFMUAOTF-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 preincubated for 10 mins by stopped flow CO2 hydrase assay
Measurement: Ki = 930 nM (pChEMBL 6.03000020980835)
Descriptors: MW 485.54, ALogP 4.6, HBA 7, HBD 0, PSA 89.06, QED 0.2
Compound (SMILES): CC[C@H]1CN(C(=O)NCC(F)(F)F)C[C@H]1C1C=NC2=CN=C3NC=CC3N21
InChIKey: DJNQPYNEIBMPBA-ZFDZMSFRSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of recombinant human GST-tagged JAK1 catalytic domain (845 to 1142 residues) expressed in Sf9 insect cells using Biotin-TYR2 (Biotin-(Ahx)-AEEEYFFLFA-amide) as substrate
Measurement: IC50 = 47 nM (pChEMBL 7.329999923706055)
Descriptors: MW 382.39, ALogP 1.67, HBA 5, HBD 2, PSA 72.33, QED 0.78
Compound (SMILES): Fc1ccc(CCCCN2CCN(c3ccc(-c4ccccc4)cn3)CC2)cc1
InChIKey: VAVQKONBNVLSBI-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]-N-methylspiperone from human dopamine D3 receptor by liquid scintillation counting
Measurement: Ki = 2089 nM (pChEMBL 5.679999828338623)
Descriptors: MW 389.52, ALogP 5.03, HBA 3, HBD 0, PSA 19.37, QED 0.53
Compound (SMILES): FCCc1cnc(N[C@H]2CCCNC2)nc1-c1c[nH]c2ccccc12
InChIKey: JFCFXMMAWHGRMB-AWEZNQCLSA-N
Target: CDK12/Cyclin K (PROTEIN COMPLEX), Homo sapiens
UniProt: O75909
Assay: Inhibition of CDK12 (686 to 1082 residues) /Cyclin K (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 3 hrs
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 339.42, ALogP 3.3, HBA 4, HBD 3, PSA 65.63, QED 0.67
Compound (SMILES): COc1cc(NC(=O)Nc2cc(C(C)(C)C)on2)ccc1Nc1ncnc2c1OCCN2
InChIKey: XWKBEUKRCQPJPK-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase receptor Ret (SINGLE PROTEIN), Homo sapiens
UniProt: P07949
Assay: Inhibition of recombinant human RET using KKKSPGEYVNIEFG as substrate incubated for 15 mins followed by Mg/ATP addition and measured after 40 mins by [gamma-33P]-ATP assay
Measurement: IC50 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 439.48, ALogP 3.96, HBA 9, HBD 4, PSA 135.46, QED 0.47
Compound (SMILES): Cn1cc(-c2ccc3c(Nc4ccc(NC(=O)Nc5cccc(F)c5)cc4)ncnc3c2)cn1
InChIKey: UXYIPHKBTFKDMP-UHFFFAOYSA-N
Target: Mast/stem cell growth factor receptor Kit (SINGLE PROTEIN), Homo sapiens
UniProt: P10721
Assay: Inhibition of KIT (unknown origin)
Measurement: IC50 = 12.04 nM (pChEMBL 7.920000076293945)
Descriptors: MW 453.48, ALogP 5.56, HBA 6, HBD 3, PSA 96.76, QED 0.32
Compound (SMILES): O=C(NO)c1ccc(CNC(=O)c2c(F)c(F)c(F)c(F)c2F)cc1
InChIKey: KMHKOOKREYIIBC-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of recombinant full length human HDAC3 expressed in SF9 baculovirus using FAM- labelled acetylated peptide as substrate measured by Electrophoretic mobility shift assay
Measurement: IC50 = 215 nM (pChEMBL 6.670000076293945)
Descriptors: MW 360.24, ALogP 2.43, HBA 3, HBD 3, PSA 78.43, QED 0.26
Compound (SMILES): CN1CCC[C@H]1[C@H]1COc2c(cccc2-c2ccccc2)O1
InChIKey: BDLDCLXBYPQVTB-FUHWJXTLSA-N
Target: Neuronal acetylcholine receptor; alpha4/beta2 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P09483
Assay: Displacement of [3H]-Epibatidine from alpha4beta2 nAChR in rat cerebral cortex membrane preincubated for 5 mins followed by [3H]-Epibatidine addition and measured after overnight incubation by liquid scintillation beta counter analysis
Measurement: Ki = 7300 nM (pChEMBL 5.139999866485596)
Descriptors: MW 295.38, ALogP 3.59, HBA 3, HBD 0, PSA 21.7, QED 0.84
Compound (SMILES): FC1(F)CCN(Cc2cncc(-c3cc4c(-c5cc6cccnc6[nH]5)n[nH]c4cn3)c2)C1
InChIKey: UZTQLBFRFIMMPV-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 203 nM (pChEMBL 6.690000057220459)
Descriptors: MW 431.45, ALogP 4.4, HBA 5, HBD 2, PSA 86.38, QED 0.44
Compound (SMILES): CC1CCN(CCCCCOc2ccc3oc4cc(Cl)ccc4c(=O)c3c2)CC1
InChIKey: KIAUCSPOPNRBJQ-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BChE using BTCI as substrate incubated for 5 mins followed by substrate addition and measured after 5 mins by spectrophotometric based Ellman's method
Measurement: IC50 = 1610 nM (pChEMBL 5.789999961853027)
Descriptors: MW 413.95, ALogP 5.88, HBA 4, HBD 0, PSA 42.68, QED 0.36
Compound (SMILES): CS(=O)(=O)Cc1ccc2c(-c3nc(N[C@H]4CCCNC4)ncc3C(F)(F)F)c[nH]c2c1
InChIKey: FPUINILIGYYXCJ-ZDUSSCGKSA-N
Target: CDK12/Cyclin K (PROTEIN COMPLEX), Homo sapiens
UniProt: O75909
Assay: Inhibition of CDK12 (686 to 1082 residues) /Cyclin K (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 3 hrs
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 453.49, ALogP 3.35, HBA 6, HBD 3, PSA 99.77, QED 0.55
Compound (SMILES): Nc1nc(-c2ccc(NC(=O)CCC(=O)O)cc2)cn2c(=O)n(-c3ccccc3)nc12
InChIKey: WBXYUQQMXZEFHT-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of [3H]-HEMADO from human A3 receptor stably expressed in CHO cell membranes by radioligand competitive binding assay
Measurement: Ki = 6957 nM (pChEMBL 5.159999847412109)
Descriptors: MW 418.41, ALogP 1.93, HBA 8, HBD 3, PSA 144.61, QED 0.43
Compound (SMILES): Cn1cc(-c2nc(N[C@H]3CCCNC3)ncc2C(F)(F)F)c2cccc(C#N)c21
InChIKey: PDGXKNHBQVYZDZ-ZDUSSCGKSA-N
Target: CDK12/Cyclin K (PROTEIN COMPLEX), Homo sapiens
UniProt: O75909
Assay: Inhibition of CDK12 (686 to 1082 residues) /Cyclin K (unknown origin) using 5-FAM-CDK9tide peptide substrate incubated for 3 hrs
Measurement: IC50 >= 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 400.41, ALogP 3.69, HBA 6, HBD 2, PSA 78.56, QED 0.7
Compound (SMILES): CCCC[C@H](NC(C)=O)C(=O)N[C@H]1CC(=O)NCCCC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](Cc2cccc(-c3ccc4ccccc4c3)c2)NC(=O)[C@H](Cc2cnc[nH]2)NC1=O
InChIKey: AUTMNYLYUILQAZ-YJLRWSCOSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Agonist activity at human MC4R expressed in HEK293 cells expressing the GScAMP22F cAMP reporter assessed as effect on cAMP accumulation by cAMP split-luciferase reporter gene assay
Measurement: EC50 = 40.74 nM (pChEMBL 7.389999866485596)
Descriptors: MW 1150.36
Compound (SMILES): Cn1c(=O)n(CC(=O)N2CC(F)C2)c2cc(-c3cccc(C(F)(F)F)c3)cnc21
InChIKey: QTYKGDXOIZZLMC-UHFFFAOYSA-N
Target: Glutamate NMDA receptor; GRIN1/GRIN2B (PROTEIN COMPLEX), Homo sapiens
UniProt: Q05586
Assay: Biological Assay (standard): NMDA receptors are ion channels that are highly permeable to Ca2+ ions, rendering it possible to monitor NMDA receptor function using cell-based calcium flux assay. In this assay, co-agonists glutamate and glycine are added to cells heterologously expressing human GluN1/GluN2B NMDA receptors to initiate cellular Ca2+ influx. The time course of the changes in intracellular calcium is measured using a fluorescent dye and a FLIPR (Fluorometric Imaging Plate Reader) device.Twenty four hours before measurements, the expression of the NMDA receptors in the stable cell line is induced with Tet-On inducible system in the presence of a non-selective NMDA receptor blocker. On the day of the experiment, cell culture media is carefully washed and the cells are loaded with Calcium 5 Dye Kit (Molecular Devices) in dye loading buffer containing 137 mM NaCl, 4 mM KCl, 2 mM CaCl2), 0.5 mM MgCl2, 10 mM HEPES and 5 mM D-glucose; pH 7.4. After 1 h incubation at the room temperature, the dye is washed away with the assay buffer (137 mM NaCl, 4 mM KCl, 2 mM CaCl2), 0.01 mM EDTA, 10 mM HEPES and 5 mM D-glucose; pH 7.4) In the FLIPR TETRA reader, various concentrations of the test compounds are added to the cells for 5 min while fluorescence is monitored to detect potential agonist activity. Next, co-agonists, glutamate and glycine are added for another 5 minutes. The concentration of glutamate corresponding to ~EC40 used to maximize the assay's signal window and ability to detect NMDA receptor antagonists and negative allosteric modulators. A saturating concentration (10 μM) of glycine is also present in the assay. A non-selective NMDA receptor antagonist, (+)MK-801 is used as a positive control for antagonist activity. The fluorescent signal in the presence of test compounds is quantified and normalized to the signal defined by the appropriate control wells.
Measurement: IC50 = 65 nM (pChEMBL 7.190000057220459)
Descriptors: MW 408.36, ALogP 2.6, HBA 5, HBD 0, PSA 60.13, QED 0.63
Compound (SMILES): O=C(/C(=N/O)Nc1ccc(F)c(Br)c1)c1cccs1
InChIKey: FOAZDLNPJRWJGK-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of human TDO expressed in Escherichia coli Rosetta using tryptophan as substrate incubated for 1 hr by methylene blue based assay
Measurement: IC50 = 63091 nM (pChEMBL 4.199999809265137)
Descriptors: MW 343.18, ALogP 3.73, HBA 4, HBD 2, PSA 61.69, QED 0.29
Compound (SMILES): COC(=O)c1ccc(-n2nc(-c3ccco3)cc2N)cc1
InChIKey: CKYRQRCQUDZFGL-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23219
Assay: Inhibition of COX1 in human OVCAR-3 cells assessed as reduction in PGE2 level incubated for 30 mins by ELISA
Measurement: IC50 = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 283.29, ALogP 2.5, HBA 6, HBD 1, PSA 83.28, QED 0.75
Compound (SMILES): CCCCCn1c(-c2ccco2)nc2c(NCCCOC)ccnc21
InChIKey: MAPVIKPJVDLTQE-UHFFFAOYSA-N
Target: High affinity 3',5'-cyclic-AMP phosphodiesterase 7A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13946
Assay: Inhibition of human recombinant PDE7A using cAMP as substrate incubated for 20 mins measured by Kinase Glo reagent based microplate reader assay
Measurement: IC50 = 34200 nM (pChEMBL 4.46999979019165)
Descriptors: MW 342.44, ALogP 4.33, HBA 6, HBD 1, PSA 65.11, QED 0.56