lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=C1NCc2c(-c3cnc4[nH]cc(Cc5ccccc5)c4c3)c[nH]c21
InChIKey: QHODOVGQIJJDRT-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of c-Met phosphorylation at Tyr 1234/Tyr1235 residues in human NCI-H1993 cells incubated for 4 hrs by HTRF assay
Measurement: IC50 = 21880 nM (pChEMBL 4.659999847412109)
Descriptors: MW 328.38, ALogP 3.39, HBA 2, HBD 3, PSA 73.57, QED 0.54
Compound (SMILES): CS(=O)(=O)NCc1cc(F)cc(-c2nccc3[nH]c(-c4n[nH]c5ncc(-c6cncc(OCc7ccccc7)c6)cc45)cc23)c1
InChIKey: UIMLVOCSMYXZFD-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 = 329 nM (pChEMBL 6.480000019073486)
Descriptors: MW 619.68, ALogP 6, HBA 7, HBD 3, PSA 138.54, QED 0.18
Compound (SMILES): COc1ccc(OCCNCC2(F)CCN(C(=O)c3ccc(F)c(Cl)c3)CC2)cc1
InChIKey: RPMCBOIGGLBGEL-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Biased agonist activity at human 5-HT1A receptor stably expressed in CHO-K1 cells assessed as increase in ERK1/2 phosphorylation after 15 mins by Alphalisa assay
Measurement: EC50 = 20.89 nM (pChEMBL 7.679999828338623)
Descriptors: MW 438.9, ALogP 4.1, HBA 4, HBD 1, PSA 50.8, QED 0.63
Compound (SMILES): NS(=O)(=O)c1ccc(-n2nc(C(=O)O)cc2-c2ccc(Cl)s2)cc1
InChIKey: MBYVVQGJJDBRKH-UHFFFAOYSA-N
Target: Polyunsaturated fatty acid 5-lipoxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P09917
Assay: Inhibition of 5-LOX (unknown origin) using arachidonic acid as substrate preincubated for 5 mins followed by substrate addition and measured after 10 mins
Measurement: IC50 = 4960 nM (pChEMBL 5.300000190734863)
Descriptors: MW 383.84, ALogP 2.6, HBA 6, HBD 2, PSA 115.28, QED 0.72
Compound (SMILES): COC(=O)N[C@H](C(=O)N1CCC[C@H]1c1ncc(C#CC#Cc2ccc(-c3cnc([C@@H]4CCCN4C(=O)[C@@H](NC(=O)OC)C(C)C)[nH]3)cc2-c2cccc(-c3ccccc3)c2)[nH]1)C(C)C.Cl.Cl
InChIKey: CUSIGCMDCJYENH-PLGVYSAESA-N
Target: Nonstructural protein 5A (SINGLE PROTEIN), Hepatitis C virus
UniProt: Q5L478
Assay: Inhibition of HCV genotype 4a NS5A infected in Huh7 cells assessed as reduction in viral replication incubated 3 days and measured by bright Glo-luciferase reporter gene assay
Measurement: IC50 = 0.0192 nM (pChEMBL 10.720000267028809)
Descriptors: MW 863.03, ALogP 7.63, HBA 8, HBD 4, PSA 174.64, QED 0.1
Compound (SMILES): Clc1ccc(C(Cn2ccnc2)OCc2ccsc2)c(Cl)c1
InChIKey: WSCZZAJFIDKWCY-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of human N-terminal IDO1 expressed in Escherichia coli BL21 A1 cells using L-tryptophan as substrate measured after 30 mins by HPLC analysis
Measurement: IC50 = 63600 nM (pChEMBL 4.199999809265137)
Descriptors: MW 353.27, ALogP 5.21, HBA 4, HBD 0, PSA 27.05, QED 0.61
Compound (SMILES): CC(C)Oc1ccc(C(C)(C)O)cc1-c1cn(C)c(=O)c2[nH]c(C(=O)NCc3ccc(C(=O)Nc4ccccc4N)cc3)cc12
InChIKey: SFYLADBQGNFSOV-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of His-tagged BRD4 bromodomain 2 (unknown origin) using [Lys (5,8,12,16) Ac] H4(1-21) as substrate by fluorescence based assay
Measurement: IC50 = 2.1 nM (pChEMBL 8.680000305175781)
Descriptors: MW 607.71, ALogP 5.31, HBA 7, HBD 5, PSA 151.47, QED 0.14
Compound (SMILES): COc1ccc2cc3[n+](cc2c1OCc1ccc(Cl)c(Cl)c1)CCc1cc2c(cc1-3)OCO2.[Br-]
InChIKey: QISNLKFKSGXOTH-UHFFFAOYSA-M
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human butyrylcholinesterase in plasma using butyrylthiocholineiodide as substrate preincubated with enzyme for 5 mins followed by substrate addition and measured at 2 mins interval by Ellman's method
Measurement: IC50 = 3600 nM (pChEMBL 5.440000057220459)
Descriptors: MW 481.36, ALogP 5.97, HBA 4, HBD 0, PSA 40.8, QED 0.34
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@@H](O)[C@H](N)Cc1ccccc1)C(=O)Nc1ccn([C@@H]2O[C@H](CO)[C@@H](O)C2(F)F)c(=O)n1.Cl
InChIKey: ZRPZMLHRWYUDSA-KBLZJMLGSA-N
Target: Aminopeptidase N (SINGLE PROTEIN), Sus scrofa
UniProt: P15145
Assay: Inhibition of porcine kidney microsomal CD13 using L-leucine-p-nitroanilide as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by microplate reader analysis
Measurement: IC50 = 8750 nM (pChEMBL 5.059999942779541)
Descriptors: MW 553.56, ALogP -0.47, HBA 10, HBD 6, PSA 189.03, QED 0.21
Compound (SMILES): Nc1nn2cc(-c3ccc(Cl)cc3)[nH]c2c1/N=N/c1ccc(S(N)(=O)=O)cc1
InChIKey: KBRGTQDAHIIWBV-GHVJWSGMSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 preincubated with enzyme for 15 mins by phenol red dye based stopped flow CO2 hydrase assay
Measurement: Ki = 16.6 nM (pChEMBL 7.78000020980835)
Descriptors: MW 415.87, ALogP 3.63, HBA 7, HBD 3, PSA 143.99, QED 0.44
Compound (SMILES): CO[C@@]12CC[C@@H](N[C@@H](CC(=O)O)C(=O)O)[C@@H]3Oc4c(O)ccc5c4[C@@]31CCN(C)[C@@H]2C5
InChIKey: MNYBENXVWGLZEJ-YQSLKQGWSA-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 = 351 nM (pChEMBL 6.460000038146973)
Descriptors: MW 432.47, ALogP 0.72, HBA 7, HBD 4, PSA 128.56, QED 0.51
Compound (SMILES): COc1cccc(CNC2CCN(Cc3ccccc3)C2)c1OC
InChIKey: FUJGEURJBFJMHI-UHFFFAOYSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of human BACE-1 by FRET assay
Measurement: IC50 = 2856 nM (pChEMBL 5.539999961853027)
Descriptors: MW 326.44, ALogP 3.07, HBA 4, HBD 1, PSA 33.73, QED 0.85
Compound (SMILES): CCCc1cc(O)c2c(c1)OC(C)(C)[C@@H]1CCC(CO)=C[C@@H]21
InChIKey: UWBCYGUAEGZJRC-HUUCEWRRSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]-CP-55,940 from recombinant human CB2R expressed in HEK293 cell membranes after 90 mins
Measurement: IC50 = 29.8 nM (pChEMBL 7.53000020980835)
Descriptors: MW 302.41, ALogP 3.93, HBA 3, HBD 2, PSA 49.69, QED 0.83
Compound (SMILES): CS(=O)(=O)N1CC[C@](CO)(Nc2cc(-c3cnc(N)nc3)nc(N3CCOCC3)n2)C1
InChIKey: QBDMEXDBIHVBTA-SFHVURJKSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of recombinant human N-terminal Myr signal and C-terminal Flag-tagged PI3K p110alpha expressed in rat Rat1 cells
Measurement: IC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 450.53, ALogP -0.84, HBA 11, HBD 3, PSA 159.69, QED 0.5
Compound (SMILES): COc1ccc(-c2ccc3c(c2)COC3=O)n2nc(C3(C(=O)OCC(C)C)CC3)nc12
InChIKey: LUUUHUYQTLUIDG-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: P27815
Assay: Inhibition of human PDE4A catalytic domain using cAMP and FAM-conjugated cAMP by IMAP FRET progressive binding assay
Measurement: IC50 = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 421.45, ALogP 3.31, HBA 8, HBD 0, PSA 92.02, QED 0.56
Compound (SMILES): Cn1cc(-c2ccc3occ(-c4ccc(C(C)(C)C)cc4)c3n2)cn1
InChIKey: VQJUNEANVUYHDU-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of human full length recombinant CLK3 using ERMRPRKRQGSVR substrate by radiometric scintillation assay
Measurement: IC50 > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 331.42, ALogP 5.19, HBA 4, HBD 0, PSA 43.85, QED 0.51
Compound (SMILES): O=C1c2cc(Br)cc(Br)c2C(=O)C1(O)O
InChIKey: PIVDGZKJNCLWFF-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 > 100000 nM (pChEMBL 4)
Descriptors: MW 335.93, ALogP 1.27, HBA 4, HBD 2, PSA 74.6, QED 0.55
Compound (SMILES): Cc1cc(NC2CCc3cc(Br)ccc3C2)n2nc(C(C)(F)F)nc2n1
InChIKey: KUSWFJYHVKCDSX-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (quinone), mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q02127
Assay: Inhibition of N-terminal His6-tagged human DHODH expressed in Escherichia coli BL21 using L-DHO as substrate and CoQ as co-substrate by DCIP dye based spectrophotometric assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 422.28, ALogP 4.28, HBA 5, HBD 1, PSA 55.11, QED 0.69
Compound (SMILES): O=S(=O)(N[C@@H]1CCN(CCCc2noc3ccccc23)C1)c1ccc2ccccc2c1
InChIKey: QGVGRVIBOJVENZ-HXUWFJFHSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Displacement of [3H]-LSD from recombinant human 5HT7 receptor expressed in CHOK1 cell membranes measured after 120 mins by microbeta counting method
Measurement: Ki = 5.495 nM (pChEMBL 8.260000228881836)
Descriptors: MW 435.55, ALogP 3.97, HBA 5, HBD 1, PSA 75.44, QED 0.48
Compound (SMILES): Cn1cc(-c2ccc(NC(=O)N3CCC(C(=O)/C(=N/O)Nc4ccc(F)c(Br)c4)CC3)cc2)cn1
InChIKey: OSCFYQVPHNZVGU-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of human IDO1 expressed in Escherichia coli Rosetta using tryptophan as substrate incubated for 1 hr by methylene blue based assay
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 543.4, ALogP 4.7, HBA 6, HBD 3, PSA 111.85, QED 0.19
Compound (SMILES): CC(=O)N[C@@H]1CCC[C@H](C(=O)Nc2cc(-c3cnn4c3CC(C)(C)C4O)c(Cl)cn2)C1
InChIKey: SLBMMPZICNYISW-MOUIRZPISA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Kinase Assay (ATP Concentration at Km): Activity of CDK9 was determined in-vitro using a mobility shift assay on a Caliper LC3000 reader (Caliper/PerkinElmer), which measures fluorescence of a phosphorylated and unphosphorylated fluorescent peptide substrate and calculates a ratiometric value to determine percent turnover. Phosphorylation of the peptide in the presence and absence of the compound of interest was determined. Enzyme/substrate/adenosine triphosphate (ATP) mix (3 nM CDK9/CycT1, 6 μM ATP, 1.5 μM CDK9 peptide substrate (FITC-X-GSRTPMY-NH2 (X: epsilon aminocaproic acid)), 50 mM HEPES (pH7.2), 1 mM dithiothreitol, 0.01% tween 20, 50 μg/mL bovine serum albumin, (final assay concentration)) (5 μl) was preincubated with 2 μl of compound for 15 minutes at 25° C. Reactions were initiated with 5 μl of 24 mM MgCl2 (10 mM final assay concentration) in buffer (50 mM HEPES (pH7.2), 1 mM dithiothreitol, 0.01% tween 20, 50 μg/mL bovine serum albumin, (final assay concentration) and incubated at 25° C. for 90 minutes and reactions were stopped by addition of 5 μl of Stop mix consisting of 65 mM HEPES (pH7.2), 35.5 mM EDTA, 0.227% Coatin Reagent 3 (Caliper/PerkinElmer), and 0.003% Tween. Phosphorylated and unphosphorylated substrate was detected by a Caliper LC3000 reader (Caliper/PerkinElmer) in the presence of separation buffer consisting of 100 mM HEPES (pH7.2), 15.8 mM EDTA, 0.1% Coatin Reagent 3 (Caliper/PerkinElmer), 0.015% Brij-35, 5% DMSO, and 5.6 mM MgCl2.
Measurement: IC50 < 4 nM (pChEMBL 8.39799976348877)
Descriptors: MW 445.95, ALogP 3.31, HBA 6, HBD 3, PSA 109.14, QED 0.67
Compound (SMILES): COc1ccc(C(=O)N[C@H](C)[C@H]2CC[C@@H](c3ccnc4ccc(F)cc43)CC2)cc1N1CCOCC1
InChIKey: CEZMCQZDXYRVDR-NJYVYQBISA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in IFNgamma-stimulated human HeLa cells preincubated for 2 hrs followed by IFNgamma stimulation and measured after 18 hrs by
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 491.61, ALogP 5.31, HBA 5, HBD 1, PSA 63.69, QED 0.51
Compound (SMILES): CCCC(CCC)C(=O)OC(CCCN1CCC(O)(c2ccc(Cl)cc2)CC1)c1ccc(F)cc1
InChIKey: ZMMTZQWVQFDIBG-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P19020
Assay: Displacement of [3H]-7-OH-DPAT from DRD3 in rat olfactory tubercle by scintillation counting
Measurement: Ki > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 504.09, ALogP 7.04, HBA 4, HBD 1, PSA 49.77, QED 0.32
Compound (SMILES): Nc1cc([C@H](CCN[C@H]2C[C@@H](c3ccccc3)c3ccccc32)c2ccccc2)c2nn[nH]c2n1
InChIKey: PUZMDZNRNPQCRQ-DSBYRVASSA-N
Target: Lactoperoxidase (SINGLE PROTEIN), Homo sapiens
UniProt: P22079
Assay: Inhibition of LPO (unknown origin)
Measurement: IC50 > 62000 nM (pChEMBL 4.208000183105469)
Descriptors: MW 460.59, ALogP 5.32, HBA 5, HBD 3, PSA 92.51, QED 0.31
Compound (SMILES): CNC(=O)c1cnc2[nH]ccc2c1NC1CCN(Cc2ccccc2)CC1
InChIKey: GHEPXWWYKLYEIC-UHFFFAOYSA-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 = 690 nM (pChEMBL 6.159999847412109)
Descriptors: MW 363.47, ALogP 3, HBA 4, HBD 3, PSA 73.05, QED 0.65
Compound (SMILES): CCCCNNC(=O)c1ccc(OC)cc1
InChIKey: RFMNSSZOADXOBU-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of HDAC2 (unknown origin) using acetylated 7-amino-4-methylcoumarin (AMC) as peptide substrate measured after 20 mins by fluorescence based analysis
Measurement: IC50 = 2520 nM (pChEMBL 5.599999904632568)
Descriptors: MW 222.29, ALogP 1.73, HBA 3, HBD 2, PSA 50.36, QED 0.57
Compound (SMILES): CC(=O)Nc1ccc(-c2c(-c3ccc(F)cc3)nc([S+](C)[O-])n2C)cn1
InChIKey: GCFIASDOZHNRKP-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 10 (SINGLE PROTEIN), Homo sapiens
UniProt: P53779
Assay: Inhibition of JNK3 (unknown origin)
Measurement: IC50 = 700 nM (pChEMBL 6.159999847412109)
Descriptors: MW 372.43, ALogP 2.98, HBA 5, HBD 1, PSA 82.87, QED 0.71
Compound (SMILES): CNC(=O)c1cnc2[nH]ccc2c1NC1CCCN(Cc2ccc(C#N)cc2)CC1
InChIKey: KJXRBJQOXNHDRP-UHFFFAOYSA-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 = 343 nM (pChEMBL 6.460000038146973)
Descriptors: MW 402.5, ALogP 3.26, HBA 5, HBD 3, PSA 96.84, QED 0.61
Compound (SMILES): Cc1cc(O)cc(C)c1C[C@H](N)C(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@H]1Cc2ccccc2CN(CCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N2CCC[C@H]2C(=O)N[C@@H](Cc2cccc(O)c2)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)O)C(C)(C)C)C1=O
InChIKey: WAASVRUAWVMHCV-QRURJPQPSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Displacement of [3H]-U69593 from recombinant human kappa opioid receptor expressed in CHO cell membrane incubated for 60 mins by liquid scintillation counting method
Measurement: Ki = 70.9 nM (pChEMBL 7.150000095367432)
Descriptors: MW 1338.66
Compound (SMILES): CN1CCC[C@H]1[C@@H]1COc2c(cccc2-c2ccccc2)O1
InChIKey: BDLDCLXBYPQVTB-WMZOPIPTSA-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 = 640 nM (pChEMBL 6.190000057220459)
Descriptors: MW 295.38, ALogP 3.59, HBA 3, HBD 0, PSA 21.7, QED 0.84
Compound (SMILES): Cc1ccnc2c1CC[C@@H]1CNCCN21
InChIKey: WCZLKBAQARPHLD-SNVBAGLBSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Radioligand Binding Assay: Radioligand binding assays were performed using the commercially available 5-HT2 receptor agonist [125I]DOI as the radioligand and nonspecific binding was determined in the presence of unlabeled DOI at a saturating concentration of 10 μM. Competition experiments utilized 5-HT2 receptor expressing HEK293 cell membranes obtained as described in Example 3 (15-25 μg membrane protein/well) and radioligand at final assay concentrations of 0.4 to 0.6 nM. Experiments comprised addition of 95 μL of assay buffer (20 mM HEPES, pH 7.4, 10 mM MgCl2), 50 μL of membranes, 50 μL of radioligand stock, and 5 μL of test compound diluted in assay buffer to 96-well microtiter plates, which were then incubated for 1 h at room temperature. Assay incubations were terminated by rapid filtration through PerkinElmer F/C filtration plates under reduced pressure using a 96-well Packard filtration apparatus, followed by washing three times with ice cold assay buffer. Plates were then dried at 45° C. for a minimum of 2 h. Finally, 25 μL of BetaScint scintillation cocktail was added to each well and the plates were counted in a Packard TopCount scintillation counter. In each competition study, test compounds were dosed at ten concentrations with triplicate determinations at each test concentration.
Measurement: Ki = 2.47 nM (pChEMBL 8.609999656677246)
Descriptors: MW 203.29, ALogP 1.11, HBA 3, HBD 1, PSA 28.16, QED 0.68
Compound (SMILES): NS(=O)(=O)c1ccc(Cc2c(-c3ccc(F)c(C#CC4CCOC4)c3)nn(-c3nc(C(=O)O)cs3)c2CC2CC2)cc1F
InChIKey: ZMLIIPMBEKOVMP-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 = 831 nM (pChEMBL 6.079999923706055)
Descriptors: MW 624.69, ALogP 4.55, HBA 8, HBD 2, PSA 137.4, QED 0.27
Compound (SMILES): O=C(NC1CC1)c1nc2cccnc2n1-c1ccc(Cl)c(Cl)c1
InChIKey: LZTJYRYBQLTRFF-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4B (SINGLE PROTEIN), Homo sapiens
UniProt: Q07343
Assay: Inhibition of recombinant human C-terminal His-tagged N-terminal GST-tagged PDE4B2 expressed in baculovirus infected Sf9 cells by radioligand binding assay
Measurement: IC50 = 630 nM (pChEMBL 6.199999809265137)
Descriptors: MW 347.2, ALogP 3.62, HBA 4, HBD 1, PSA 59.81, QED 0.79
Compound (SMILES): C[C@]1(c2ccccc2)CN(C(=O)c2ccccc2)C[C@H]1c1ccc(C(O)(C(F)(F)F)C(F)(F)F)cc1
InChIKey: QGXLQHDKLPYLDY-LADGPHEKSA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Activation of PXR (unknown origin)
Measurement: EC50 = 740 nM (pChEMBL 6.130000114440918)
Descriptors: MW 507.47, ALogP 6.2, HBA 2, HBD 1, PSA 40.54, QED 0.43
Compound (SMILES): COc1cc(/C=C/C(=O)Nc2ccc3oc(=O)ccc3c2)cc(OC)c1OC
InChIKey: JLBSOIAPINYYML-XBXARRHUSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 assessed as inhibition constant preincubated with enzyme for 10 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 156.7 nM (pChEMBL 6.800000190734863)
Descriptors: MW 381.38, ALogP 3.47, HBA 6, HBD 1, PSA 87, QED 0.52
Compound (SMILES): C=CCn1c(SCC(=O)Nc2ccc(/C(C)=N\O)cc2)nnc1-c1cc(-c2ccccc2)nc2ccccc12
InChIKey: KHOUPLYHJRQMOU-OJYCWLPVSA-N
Target: Signal transducer and activator of transcription 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P40763
Assay: Inhibition of STAT3 in human SB-590885-resistant 451Lu cells assessed as reduction in STAT3 transcriptional activity measured after 12 hrs by Dual-luciferase reporter gene assay
Measurement: IC50 = 4700 nM (pChEMBL 5.329999923706055)
Descriptors: MW 534.65, ALogP 6.28, HBA 8, HBD 2, PSA 105.29, QED 0.08
Compound (SMILES): CNCCC(Oc1cccc(N2CCN(C)c3cccnc3C2=O)c1)c1cccs1
InChIKey: DXVNGVMZAPBUCS-UHFFFAOYSA-N
Target: Sodium-dependent noradrenaline transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P23975
Assay: Inhibition of human NET expressed in HEK293 cells assessed as reduction in ASP+ uptake incubated for 20 mins before ASP+ addition and measured after 90 mins by scintillation counting method
Measurement: IC50 = 213 nM (pChEMBL 6.670000076293945)
Descriptors: MW 422.55, ALogP 3.97, HBA 6, HBD 1, PSA 57.7, QED 0.62
Compound (SMILES): COC(=O)c1ccc([C@H]2c3[nH]c4ccccc4c3C[C@H](C(=O)OC)N2C(=O)CCl)cc1
InChIKey: TXJZRSRTYPUYRW-NQIIRXRSSA-N
Target: Phospholipid hydroperoxide glutathione peroxidase GPX4 (SINGLE PROTEIN), Homo sapiens
UniProt: P36969
Assay: Inhibition of GPX4 (unknown origin) incubated for 1 hrs in presence of glutathione and glutathione reductase by microplate reader analysis
Measurement: IC50 = 8420 nM (pChEMBL 5.079999923706055)
Descriptors: MW 440.88, ALogP 3.21, HBA 5, HBD 1, PSA 88.7, QED 0.5
Compound (SMILES): CCC(=O)Nc1cncc(-c2cnc3[nH]nc(-c4cc5c(-c6cccnc6)cccc5[nH]4)c3c2)c1
InChIKey: QHDMTWOMJZZFQS-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 = 538 nM (pChEMBL 6.269999980926514)
Descriptors: MW 459.51, ALogP 5.58, HBA 5, HBD 3, PSA 112.24, QED 0.31
Compound (SMILES): CN(c1ccccc1)c1cc[n+](Cc2ccc(-c3ccccc3)cc2)c2cc(Cl)ccc12.[Br-]
InChIKey: MZZNCOYGGXEQPY-UHFFFAOYSA-M
Target: Choline kinase alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P35790
Assay: Inhibition of human CKalpha1 assessed as reduction in 14C incorporation from [methyl-14C]choline to phosphatidylcholine using [methyl-14C]choline as substrate preincubated for 5 mins in presence of ATP and MgCl2 followed by substrate addition and measured after 10 mins by liquid scintillation counting method relative to control
Measurement: IC50 = 12550 nM (pChEMBL 4.900000095367432)
Descriptors: MW 435.98, ALogP 7.26, HBA 1, HBD 0, PSA 7.12, QED 0.26
Compound (SMILES): NS(=O)(=O)c1ccc(NC(=O)CSC(=S)N2CCN(c3ccccn3)CC2)cc1
InChIKey: XAMNSCDFHCYFPT-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 = 164 nM (pChEMBL 6.789999961853027)
Descriptors: MW 451.6, ALogP 1.51, HBA 7, HBD 2, PSA 108.63, QED 0.66
Compound (SMILES): COc1cncc(C#Cc2c[nH]nc2C(=O)Nc2ccc(OC3CCN(C)CC3)nc2)c1
InChIKey: OCNNWLACMXRHHM-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 > 10000 nM (pChEMBL 5)
Descriptors: MW 432.48, ALogP 2.33, HBA 7, HBD 2, PSA 105.26, QED 0.6
Compound (SMILES): Oc1cncc(-c2ccc3[nH]nc(-c4nc5c(-c6cccc(F)c6)ccnc5[nH]4)c3c2)c1
InChIKey: BZXOXNSMVCRHKP-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 = 45 nM (pChEMBL 7.349999904632568)
Descriptors: MW 422.42, ALogP 5.07, HBA 5, HBD 3, PSA 103.37, QED 0.37
Compound (SMILES): O=S1(=O)C=Cc2cc(-c3ccc(C(F)(F)F)cc3)cnc2O1
InChIKey: WLXAVZGEPMKPOR-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 incubated for 6 hrs prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 70.1 nM (pChEMBL 7.150000095367432)
Descriptors: MW 327.28, ALogP 3.46, HBA 4, HBD 0, PSA 56.26, QED 0.75
Compound (SMILES): NC(=O)c1sc(-c2ccnc(NC(=O)C3CC3)c2)nc1OCCc1cn(-c2c3c(nc4ccccc24)CCCC3)nn1
InChIKey: ZLMGZYYGAKQJDG-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of recombinant human N-terminal His6-tagged GSK-3beta H350L mutant expressed in baculovirus infected Sf21 cells using GSM as substrate incubated for 30 mins in presence of ATP by kinase-glo luminescence assay
Measurement: IC50 = 6.5 nM (pChEMBL 8.1899995803833)
Descriptors: MW 580.67, ALogP 4.28, HBA 10, HBD 2, PSA 150.8, QED 0.26
Compound (SMILES): O=S(=O)(N1CCC(Nc2ncnc3ccc(C(c4ccc(Cl)cc4)c4ccc(Cl)cc4)cc23)CC1)C(F)(F)F
InChIKey: RWFZLPYQONOIGR-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Inverse agonist activity at human CB1 receptor expressed in HEK293 cells assessed as forskolin-stimulated cAMP accumulation after 30 mins by HTRF assay
Measurement: EC50 = 4.6 nM (pChEMBL 8.34000015258789)
Descriptors: MW 595.47, ALogP 6.84, HBA 5, HBD 1, PSA 75.19, QED 0.25
Compound (SMILES): Fc1ccc(C(SCCN2CCC(NCc3ccccc3)CC2)c2ccc(F)cc2)cc1
InChIKey: KXWRPRLNAZIISP-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 = 60.9 nM (pChEMBL 7.210000038146973)
Descriptors: MW 452.61, ALogP 6.04, HBA 3, HBD 1, PSA 15.27, QED 0.43
Compound (SMILES): O=C(c1ccccc1)c1cc(O)c(-c2ccc3c(c2)OCCO3)c(O)c1
InChIKey: ZQHNJJPYLZPVGE-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Inverse agonist activity at human recombinant cannabinoid CB2 receptor expressed in HEK cells transfected with CNG assessed as increase in cAMP level measured up to 1 hr by ACTOne membrane potential dye based assay
Measurement: EC50 = 4897.79 nM (pChEMBL 5.309999942779541)
Descriptors: MW 348.35, ALogP 3.77, HBA 5, HBD 2, PSA 75.99, QED 0.7
Compound (SMILES): O=C(c1ccc(F)c(Cl)c1)N1CCC(F)(CNCCOc2ccc(F)cc2)CC1
InChIKey: UVGOPVMDNYVNOI-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Biased agonist activity at human 5-HT1A receptor stably expressed in CHO-K1 cells assessed as increase in ERK1/2 phosphorylation after 15 mins by Alphalisa assay
Measurement: EC50 = 5.754 nM (pChEMBL 8.239999771118164)
Descriptors: MW 426.87, ALogP 4.23, HBA 3, HBD 1, PSA 41.57, QED 0.67
Compound (SMILES): O=C(CCN1CCCc2ccccc21)Nc1nccs1
InChIKey: RPQDEUULIGRPHF-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]-NMS from muscarinic M2 receptor (unknown origin) expressed in CHO-K1 cell membranes assessed as inhibition constant by radioligand competition analysis
Measurement: Ki = 3467.37 nM (pChEMBL 5.460000038146973)
Descriptors: MW 287.39, ALogP 2.92, HBA 4, HBD 1, PSA 45.23, QED 0.94
Compound (SMILES): C[C@H](NC(=O)Cn1nc2c(I)ccnn2c1=O)c1ccc(OC(F)(F)F)cc1
InChIKey: ANLLKEQWCAFUCO-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 >= 100 nM (pChEMBL 7)
Descriptors: MW 507.21, ALogP 2.27, HBA 7, HBD 1, PSA 90.52, QED 0.54
Compound (SMILES): CNCCC(Oc1cccc(N2CCN(C)c3cnccc3C2=O)c1)c1cccs1
InChIKey: SFDCNWPOHFHZDB-UHFFFAOYSA-N
Target: Sodium-dependent noradrenaline transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P23975
Assay: Inhibition of human NET expressed in HEK293 cells assessed as reduction in ASP+ uptake incubated for 20 mins before ASP+ addition and measured after 90 mins by scintillation counting method
Measurement: IC50 = 341 nM (pChEMBL 6.46999979019165)
Descriptors: MW 422.55, ALogP 3.97, HBA 6, HBD 1, PSA 57.7, QED 0.62
Compound (SMILES): Cc1cnc(Nc2ccc3c(c2)CCN(CCO)C3)nc1-c1cnn(C(C)C)c1
InChIKey: LMPWKFOZVIGRJF-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 ITD mutant in human MOLM13 cells assessed as reduction in cell viability incubated for 72 hrs by MTT assay
Measurement: IC50 = 1260 nM (pChEMBL 5.900000095367432)
Descriptors: MW 392.51, ALogP 3.32, HBA 7, HBD 2, PSA 79.1, QED 0.67
Compound (SMILES): Cc1n[nH]c2ccc(-c3cncc(N4CC(C)(N)C4)n3)cc12
InChIKey: GVLDGIHQNWBDIR-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 = 3400 nM (pChEMBL 5.46999979019165)
Descriptors: MW 294.36, ALogP 1.87, HBA 5, HBD 2, PSA 83.72, QED 0.75
Compound (SMILES): O=C(NO)c1ccc(NC(=O)c2ccc(C3CC3)cc2)cc1
InChIKey: AZQYECILTLBYIV-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant full length human HDAC8 expressed in SF9 baculovirus using FAM- labelled acetylated peptide as substrate measured by Electrophoretic mobility shift assay
Measurement: IC50 = 20.4 nM (pChEMBL 7.690000057220459)
Descriptors: MW 296.33, ALogP 2.94, HBA 3, HBD 3, PSA 78.43, QED 0.6
Compound (SMILES): Cc1cc(/C=C/C(=O)O)c(C)n1-c1ccc(C(C)(C)C)cc1
InChIKey: SQSSNDLMMQDSMJ-IZZDOVSWSA-N
Target: Bile acid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RI1
Assay: Binding affinity to recombinant FXR-LBD (unknown origin) expressed in Escherichia coli BL21 (DE3) gold cells by isothermal titration calorimetry
Measurement: Kd = 4000 nM (pChEMBL 5.400000095367432)
Descriptors: MW 297.4, ALogP 4.49, HBA 2, HBD 1, PSA 42.23, QED 0.85
Compound (SMILES): CNC(=O)c1sc(N2CC3CC2(CNC(=O)c2c[nH]c4ncc(C(F)(F)F)cc24)C3)nc1C(F)(F)F
InChIKey: GKFUTHVAVQPTFA-UHFFFAOYSA-N
Target: Tyrosine-protein kinase receptor TYRO3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06418
Assay: Inhibition of GST-tagged Tyro3 (unknown origin) (453 to 890 residues) using Axltide (KKSRGDYMTMQIG-acid) peptide as substrate preincubated for 30 mins followed by substrate and ATP addition at Km concentration measured after 180 mins by RapidFire LC-MS analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 532.47, ALogP 3.82, HBA 6, HBD 3, PSA 103.01, QED 0.43
Compound (SMILES): C=CC(=O)NCC1NC(=O)[C@@H](NC(C)=O)CCCCNC(=O)C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H]2CCCCNC(=O)C[C@@H](C(=O)N[C@@H](Cc3ccccc3)C(N)=O)NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@H]([C@@H](C)CC)NC2=O)NC(=O)[C@H](C)NC(=O)[C@H]([C@@H](C)CC)NC1=O
InChIKey: NCAPDVHCWFIPPZ-ZJWAASNJSA-N
Target: Bcl-2-related protein A1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16548
Assay: Covalent binding affinity to human Bcl2A1 by FBid based FP assay
Measurement: Ki = 30.5 nM (pChEMBL 7.519999980926514)
Descriptors: MW 1664.89
Compound (SMILES): CC(C)(C)C(=O)Nc1sc2c(c1C(N)=O)CCC(C(C)(C)C)C2
InChIKey: QJDASIZKRQHFFS-UHFFFAOYSA-N
Target: Anoctamin-2 (SINGLE PROTEIN), Mus musculus
UniProt: Q8CFW1
Assay: Inhibition of GFP-fused mouse ANO2 channel expressed in HEK293A cells assessed as inhibition of channel current amplitude at membrane potential of +80 mV by patch clamp electrophysiology assay
Measurement: IC50 = 15430 nM (pChEMBL 4.809999942779541)
Descriptors: MW 336.5, ALogP 3.98, HBA 3, HBD 2, PSA 72.19, QED 0.86
Compound (SMILES): c1cncc(-c2ccnc3[nH]c(-c4n[nH]c5ncc(-c6cncc(CN7CCCCC7)c6)cc45)cc23)c1
InChIKey: OLBDNEBUSBYBHZ-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 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 486.58, ALogP 5.61, HBA 6, HBD 2, PSA 99.27, QED 0.33
Compound (SMILES): Cc1ccc(-c2cc(Nc3ccccc3)c3c(=O)[nH]c4ccccc4c3c2)cc1
InChIKey: MBXJDZFFRJRWBY-UHFFFAOYSA-N
Target: Matrix metalloproteinase-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P14780
Assay: Inhibition of recombinant human MMP9 (107 to 449 residues) using Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 expressed in Escherichia coli expression system as substrate incubated for 15 mins followed by substrate addition and measured after 2 to 4 hrs by fluorescence based assay
Measurement: IC50 = 37500 nM (pChEMBL 4.429999828338623)
Descriptors: MW 376.46, ALogP 6.4, HBA 2, HBD 2, PSA 44.89, QED 0.36
Compound (SMILES): O=C(NCCN1CCCC1)c1ccc(-c2noc(C(F)(F)F)n2)cc1
InChIKey: PVQMNPDPHHUNAN-UHFFFAOYSA-N
Target: Histone deacetylase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8WUI4
Assay: Inhibition of HDAC7 (unknown origin) using Boc Lys(TFA) as substrate by fluorogenic assay
Measurement: IC50 = 140 nM (pChEMBL 6.849999904632568)
Descriptors: MW 354.33, ALogP 2.58, HBA 5, HBD 1, PSA 71.26, QED 0.89
Compound (SMILES): CC[C@@H]1c2nnc(C)n2-c2cnc(Nc3ccc(C(=O)NC4CCN(C)CC4)cc3OC)nc2N1CC1CCCCC1
InChIKey: QUMCIHKVKQYNPA-RUZDIDTESA-N
Target: Serine/threonine-protein kinase PLK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53350
Assay: Inhibition of PLK1 (unknown origin) by radiometric ATP-competitive kinase assay
Measurement: IC50 = 22.3 nM (pChEMBL 7.650000095367432)
Descriptors: MW 573.75, ALogP 4.79, HBA 10, HBD 2, PSA 113.33, QED 0.39
Compound (SMILES): C/C=C/C(=O)Nc1ccc(-c2cc(Nc3ccc(N4CCOCC4)cc3)ncn2)cc1
InChIKey: ISGHGKARQYJBTN-NSCUHMNNSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of recombinant human GST-tagged JAK1 cytoplasmic domain (866 to 1154 residues) expressed in baculovirus expression system using TK-substrate-biotin preincubated for 5 mins followed by substrate addition and measured after 30 mins by HTRF assay
Measurement: IC50 = 321 nM (pChEMBL 6.489999771118164)
Descriptors: MW 415.5, ALogP 4.24, HBA 6, HBD 2, PSA 79.38, QED 0.59
Compound (SMILES): COc1ccc(OC)c(-c2nnc(-c3cccc(S(N)(=O)=O)c3)o2)c1
InChIKey: YRABJYQCLKEVCS-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 by stopped flow CO2 hydrase assay
Measurement: Ki = 76.8 nM (pChEMBL 7.119999885559082)
Descriptors: MW 361.38, ALogP 2.07, HBA 7, HBD 1, PSA 117.54, QED 0.74
Compound (SMILES): CC#CC(=O)N1CCC[C@@H]1c1nc(-c2ccc(C(=O)Nc3ccccn3)cc2)c2c(N)nccn12
InChIKey: WDENQIQQYWYTPO-LJQANCHMSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of GST-tagged human EGFR (668 to 1210 residues) expressed in baculovirus expression system using poly-Glu-Tyr (4:1) as substrate incubated for 1 hrs by ELISA
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 465.52, ALogP 3.31, HBA 7, HBD 2, PSA 118.51, QED 0.45
Compound (SMILES): CN(C)Cc1nc2ccc(Nc3ncc(Cl)c(Nc4ccccc4NS(C)(=O)=O)n3)cc2[nH]1
InChIKey: OHMKUKNYYOHYNP-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of human N-terminal GST-fused ALK G1202R mutant cytoplasmic domain (1058 to 1620 residues) expressed in baculovirus infected Sf21 insect cells using Srctide as substrate measured after 1 hr by mobility shift assay
Measurement: IC50 = 8.2 nM (pChEMBL 8.09000015258789)
Descriptors: MW 486.99, ALogP 3.93, HBA 8, HBD 4, PSA 127.93, QED 0.29
Compound (SMILES): CC(C)(C)c1ccc(-c2coc3ccc(-c4cnsc4)nc23)cc1
InChIKey: GEXQRIJEFKNHPX-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of human full length recombinant CLK3 using ERMRPRKRQGSVR substrate by radiometric scintillation assay
Measurement: IC50 > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 334.44, ALogP 5.92, HBA 4, HBD 0, PSA 38.92, QED 0.46
Compound (SMILES): CC(C)C[C@H](CC(=O)NO)C(=O)N[C@@H](Cc1ccccc1)C(=O)O
InChIKey: TYZVGHNHMXVHTN-KGLIPLIRSA-N
Target: Matrix metalloproteinase-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P14780
Assay: Inhibition of human recombinant MMP9 using Mca-Lys-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 substrate by spectrophotometry
Measurement: Ki = 125 nM (pChEMBL 6.900000095367432)
Descriptors: MW 336.39, ALogP 1.36, HBA 4, HBD 4, PSA 115.73, QED 0.4
Compound (SMILES): CNc1nc2nc3c1[nH]c(=O)n3Cc1cccc(c1)OCCCCCO2
InChIKey: VRGRKKSAGJKMRY-UHFFFAOYSA-N
Target: Oxidized purine nucleoside triphosphate hydrolase (SINGLE PROTEIN), Homo sapiens
UniProt: P36639
Assay: Inhibition of MTH1 (unknown origin) using 8-oxo-dGTP as substrate preincubated for 15 mins followed by substrate addition and measured after 20 mins by PPiLight detection reagent based luminescence assay
Measurement: IC50 = 0.3 nM (pChEMBL 9.520000457763672)
Descriptors: MW 355.4, ALogP 2.15, HBA 7, HBD 2, PSA 94.06, QED 0.69
Compound (SMILES): C[C@@H]1CN(c2ccc(S(C)(=O)=O)cc2)CCN1c1cccc(C(=O)NC2C3CC4CC2CC(O)(C4)C3)n1
InChIKey: AKFNADJKXYYHSU-WHPWKXGYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in pooled human liver microsomes using diclofenac as substrate in presence of NADPH incubated for 10 mins by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 524.69, ALogP 2.87, HBA 7, HBD 2, PSA 102.84, QED 0.62
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(CC)CC2)c1ncc(-c2cc(C(F)(F)F)ccc2OC)[nH]1
InChIKey: HSFRSCKOBBRJQG-RPWUZVMVSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of HDAC3 (unknown origin) using compound purified by microgram-scale HPLC work-flow
Measurement: IC50 = 0.7 nM (pChEMBL 9.149999618530273)
Descriptors: MW 562.68, ALogP 6.31, HBA 5, HBD 2, PSA 87.32, QED 0.28
Compound (SMILES): c1cncc(-c2cc3c(-c4cc5cnccc5[nH]4)n[nH]c3cn2)c1
InChIKey: ZFQVDMYZDIWCEU-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 = 88 nM (pChEMBL 7.059999942779541)
Descriptors: MW 312.34, ALogP 3.56, HBA 4, HBD 2, PSA 83.14, QED 0.52
Compound (SMILES): CN1CCN(c2ccc(C(=O)Nc3cc4cc(-c5cnn6c5CN(CCF)CC6)ccc4cn3)cn2)CC1
InChIKey: OJQUMPNKISYUBU-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 = 81 nM (pChEMBL 7.090000152587891)
Descriptors: MW 514.61, ALogP 3.28, HBA 8, HBD 1, PSA 82.42, QED 0.42
Compound (SMILES): Br.N=C(N)SCc1ccc(CN2C(=O)C(=O)c3cc(Cl)ccc32)cc1
InChIKey: MHQGESGQFKPTIY-UHFFFAOYSA-N
Target: Aldehyde dehydrogenase, dimeric NADP-preferring (SINGLE PROTEIN), Homo sapiens
UniProt: P30838
Assay: Inhibition of ALDH3A1 (unknown origin) assessed as NADH formation using 4-nitrobenzaldehyde as substrate
Measurement: IC50 = 3067 nM (pChEMBL 5.510000228881836)
Descriptors: MW 359.84, ALogP 3.2, HBA 4, HBD 2, PSA 87.25, QED 0.5
Compound (SMILES): CCn1nc2c(c1Nc1nc(-c3ccc(-n4cnc(C)c4)c(OC)n3)cs1)CCC2(C)C
InChIKey: QVXGQFQOUQCCDN-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of recombinant CYP1A2 (unknown origin) by fluorescence-based assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 449.58, ALogP 4.89, HBA 9, HBD 1, PSA 82.68, QED 0.45
Compound (SMILES): O=C(N[C@@H](CCCCNC(=O)c1ccccc1OCC(F)(F)F)c1ncc(-c2ccc3ccccc3c2)[nH]1)c1cncs1
InChIKey: CCXFNJSHGTUHNE-DEOSSOPVSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of human recombinant full length FLAG-tagged HDAC3 expressed in HEK293F cells in using BML-KI104 as substrate in presence of SAHA as inhibitor preincubated for 3 hrs followed by addition of substrate measured after 30 mins by fluorescence based assay
Measurement: IC50 = 12000 nM (pChEMBL 4.920000076293945)
Descriptors: MW 607.66, ALogP 6.7, HBA 6, HBD 3, PSA 109, QED 0.14
Compound (SMILES): N#Cc1ccc(OCc2nc(C(=O)NCC(=O)N3CC(F)(F)C[C@H]3C#N)cs2)cc1
InChIKey: JVPUEBYYUCOOCE-ZDUSSCGKSA-N
Target: Prolyl endopeptidase (SINGLE PROTEIN), Homo sapiens
UniProt: P48147
Assay: Inhibition of PREP (unknown origin) using AMC substrate by fluorometric assay
Measurement: IC50 = 70 nM (pChEMBL 7.159999847412109)
Descriptors: MW 431.42, ALogP 2.08, HBA 7, HBD 1, PSA 119.11, QED 0.75
Compound (SMILES): COc1ccc2cc3[n+](cc2c1OCc1ccc2ccccc2c1)CCc1cc2c(cc1-3)OCO2.[Br-]
InChIKey: CIFGXRFRTRCQAC-UHFFFAOYSA-M
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human butyrylcholinesterase in plasma using butyrylthiocholineiodide as substrate preincubated with enzyme for 5 mins followed by substrate addition and measured at 2 mins interval by Ellman's method
Measurement: IC50 = 1260 nM (pChEMBL 5.900000095367432)
Descriptors: MW 462.53, ALogP 5.82, HBA 4, HBD 0, PSA 40.8, QED 0.32
Compound (SMILES): O=C(c1ccc(Sc2ccccc2)cc1)C1CCN(C(=O)c2cc(O)ccc2F)CC1
InChIKey: SYKQOVVZSRWKHB-UHFFFAOYSA-N
Target: Monoacylglycerol lipase ABHD6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BV23
Assay: Inhibition of human ABHD6 expressed in HEK293 cells using [3H]2-OG as substrate preincubated for 30 mins followed by substrate addition and measured after 5 mins by liquid scintillation spectroscopy
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 435.52, ALogP 5.42, HBA 4, HBD 1, PSA 57.61, QED 0.54
Compound (SMILES): COc1ccc(/C=N/Nc2ncnc3c2c(-c2ccc(Cl)cc2)cn3-c2ccc(S(N)(=O)=O)cc2)cc1
InChIKey: AGYOQXUERREJAL-XAZZYMPDSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 159.6 nM (pChEMBL 6.800000190734863)
Descriptors: MW 533.01, ALogP 4.84, HBA 8, HBD 2, PSA 124.49, QED 0.23
Compound (SMILES): CC1CCCCN1C(=O)CCN1CCCc2ccccc21
InChIKey: OYQSJQCVYUUOTR-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]-NMS from muscarinic M2 receptor (unknown origin) expressed in CHO-K1 cell membranes assessed as inhibition constant by radioligand competition analysis
Measurement: Ki = 3235.94 nM (pChEMBL 5.489999771118164)
Descriptors: MW 286.42, ALogP 3.23, HBA 2, HBD 0, PSA 23.55, QED 0.85
Compound (SMILES): Cn1cc(Nc2nccc(N3CC4CCC(C3)N4C(=O)[C@@H]3CC3(F)F)n2)cn1
InChIKey: BUWBRTXGQRBBHG-RUXDESIVSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of recombinant human JAK3 assessed as phosphorylation level in presence of 1 mM ATP
Measurement: IC50 = 6494 nM (pChEMBL 5.190000057220459)
Descriptors: MW 389.41, ALogP 1.79, HBA 7, HBD 1, PSA 79.18, QED 0.86
Compound (SMILES): COc1ccc(-c2c(-c3ccc(C#N)cc3)nc(N3CCC(N)CC3)n(C)c2=O)cc1
InChIKey: UHPMAJMYBCEHQQ-UHFFFAOYSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: In Vitro Enzyme Inhibition Assay: The enzymatic assay of LSD1 activity is based on Time Resolved-Fluorescence Resonance Energy Transfer (TR-FRET) detection. The inhibitory properties of compounds to LSD1 were determined in 384-well plate format under the following reaction conditions: 0.1-0.5 nM LSD1, 50 nM H3K4mel-biotin labeled peptide (Anaspec cat #64355), 2 μM FAD in assay buffer of 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA. Reaction product was determined quantitatively by TR-FRET after the addition of detection reagent Phycolink Streptavidin-allophycocyanin (Prozyme) and Europium-anti-unmodified histone H3 lysine 4 (H3K4) antibody (PerkinElmer) in the presence of LSD1 inhibitor such as 1.8 mM of Tranylcypromine hydrochloride (2-PCPA) in LANCE detection buffer (PerkinElmer) to final concentration of 12.5 nM and 0.25 nM respectively.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 415.5, ALogP 2.92, HBA 7, HBD 1, PSA 97.17, QED 0.7
Compound (SMILES): Nc1nn2cc(-c3ccc(Br)cc3)[nH]c2c1/N=N/c1ccc(S(N)(=O)=O)cc1
InChIKey: XQQUUIQYQFCYDD-GHVJWSGMSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 preincubated with enzyme for 15 mins by phenol red dye based stopped flow CO2 hydrase assay
Measurement: Ki = 44.9 nM (pChEMBL 7.349999904632568)
Descriptors: MW 460.32, ALogP 3.74, HBA 7, HBD 3, PSA 143.99, QED 0.4
Compound (SMILES): FC1(F)CCN(Cc2cncc(-c3ccc4[nH]nc(-c5cc6c(-c7ccccn7)cccc6[nH]5)c4n3)c2)C1
InChIKey: YZZYRGCQGLYBDZ-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 = 142 nM (pChEMBL 6.849999904632568)
Descriptors: MW 507.55, ALogP 6.07, HBA 5, HBD 2, PSA 86.38, QED 0.3
Compound (SMILES): Cl.OCCC/C(=C(\c1ccc(O)cc1)c1ccc(OCCN2CC2)cc1)c1ccccc1
InChIKey: KOVNLGSITVPOLE-JTHROIFXSA-N
Target: Steroid hormone receptor ERR2 (SINGLE PROTEIN), Homo sapiens
UniProt: O95718
Assay: Binding affinity to GST-tagged ERRbeta LBD (unknown origin) using fluorescein PGC1alpha as coactivator incubated for 1 hr by LanthaScreen TR-FRET co-regulator assay
Measurement: IC50 = 3723 nM (pChEMBL 5.429999828338623)
Descriptors: MW 415.53, ALogP 4.82, HBA 4, HBD 2, PSA 52.7, QED 0.37
Compound (SMILES): COc1cc2c(cc1Nc1ncc(Cl)c(Nc3ccccc3S(=O)(=O)C(C)C)n1)CN(S(N)(=O)=O)CC2
InChIKey: GUVYVRSFYHAUGS-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibitory Activity Against Anaplastic Lymphoma Kinase (ALK): A proliferation inhibitory activity against the ALK of the compound represented by Chemical Formula 1 according to the present invention at an enzyme level, the following experiment was performed.In order to measure the inhibitory activity against the ALK, the compounds (2 μl) prepared in Examples 1 to 106 were added to Greiner 96 well round bottom plates, respectively, and the ALK enzyme (1 μl) and biotin-adhered peptide substrate (2 μl) were mixed for 15 minutes, and then, the plates were cultured. An ATP solution (5 μl) was added thereto, and then, a kinase reaction was performed at room temperature for 30 minutes. Streptavidin-adhered XL 665 (5 μl) and europium (Eu3+)-adhered anti-phosphotyrosine antibody (5 μl) dissolved in ethylenediaminetetraacetic acid solution was added to the reaction solution to stop the reaction, and cultured for 1 hour, and analyzed by using homogeneous time-resolved fluorescence (HTRF, Cisbio) The compounds were read in a wavelength range of 615/665 nm using a Wallac Envision 2103 instrument. The IC50 of each of the test compounds subjected to the above experiment was implemented using prism (version 5.01, GraphPad) software.Accordingly, IC50 of each of the compounds that reduce an ALK enzyme activity and a cell activity of L1196M (a non-small cell lung cancer cell including an ALK enzyme) to 50% was calculated, and as a result, it was found that all of the compounds prepared in Examples 1 to 106 according to the present invention had IC50 values of 0.01 μM or less.
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 567.09, ALogP 3.37, HBA 9, HBD 3, PSA 156.61, QED 0.37
Compound (SMILES): C[C@H](NC(=O)Cn1nc2c(N3CCC34CN(C)C4)cccn2c1=O)c1ccc(Cl)c(F)c1
InChIKey: PGJOBKWNEUVOKP-AWEZNQCLSA-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 = 10 nM (pChEMBL 8)
Descriptors: MW 458.93, ALogP 2.06, HBA 7, HBD 1, PSA 74.88, QED 0.63