lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=c1cc(Sc2ccc(-c3ccc(C(F)(F)F)cc3)cc2)[nH]c(=O)n1O
InChIKey: ZPFLJEHOPGJBFK-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 integrase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q7ZJM1
Assay: Inhibition of HIV integrase strand transfer activity using 5'-biotin/3'-Cy5-labeled DNA substrate preincubated for 5 mins followed by substrate addition measured after 30 mins by HTS assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 380.35, ALogP 3.61, HBA 5, HBD 2, PSA 75.09, QED 0.54
Compound (SMILES): Fc1ccc2[nH]cc(CCN3CCN(c4ccccc4-c4ccccc4F)CC3)c2c1
InChIKey: JLWIDAKJUHQHIW-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Displacement of [3H]LSD from recombinant human 5-HT7 receptor expressed in CHO cell membranes after 120 mins by TopCount scintillation counting method
Measurement: Ki = 2.3 nM (pChEMBL 8.640000343322754)
Descriptors: MW 417.5, ALogP 5.48, HBA 2, HBD 1, PSA 22.27, QED 0.46
Compound (SMILES): O=C(c1ccccc1)N1CCC[C@H](n2cnc(-c3cc(-c4nn[nH]c4C(F)(F)F)ccn3)c2)C1
InChIKey: JSHYFCYPEAAONQ-KRWDZBQOSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of recombinant human N-terminal GST-tagged JMJD2C (2 to 372 residues) expressed in baculovirus infected Sf9 cells using H3K9me3-biotin labelled peptide as substrate measured after 30 mins by Lance TR-FRET assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 467.46, ALogP 4.23, HBA 6, HBD 1, PSA 92.59, QED 0.49
Compound (SMILES): CC(Oc1cc(F)ccc1COc1ccnn1-c1cc(C(=O)O)ccn1)c1ccccc1
InChIKey: UQZWANPYQUOQKJ-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of recombinant human N-terminal GST-tagged JMJD2C (2 to 372 residues) expressed in baculovirus infected sf9 cells using H3K9me3-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by LANCE TR-FRET assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 433.44, ALogP 4.82, HBA 6, HBD 1, PSA 86.47, QED 0.43
Compound (SMILES): CC(C)(C)OC(=O)N1CCC2(CC1)CN(Cc1ccc(C(=O)NO)s1)c1ccccc12
InChIKey: SSEOONNFWOBUGO-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of human recombinant HDAC8 using fluor de Lys(R) as substrate after 90 mins by fluorescence-based assay
Measurement: IC50 = 1344 nM (pChEMBL 5.869999885559082)
Descriptors: MW 443.57, ALogP 4.16, HBA 6, HBD 2, PSA 82.11, QED 0.55
Compound (SMILES): CN1CCN(CC(=O)Nc2ccc(-c3ccnc(Nc4cccc(OCCCCCCC(=O)NO)c4)n3)cc2)CC1
InChIKey: ZTGQZVKHKYKKGE-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin) using Arg-His-Lys-Lys(Ac) as substrate preincubated with enzyme followed by substrate addition for 2 hrs and measured for 1.5 hrs at 15 mins time interval by fluorescence assay
Measurement: IC50 = 6.8 nM (pChEMBL 8.170000076293945)
Descriptors: MW 561.69, ALogP 3.91, HBA 9, HBD 4, PSA 131.95, QED 0.13
Compound (SMILES): CCCCCc1cc(O)c2c(c1)OC(C)(C)C1=C2C(OC(C)=O)C(C)(OC)CC1
InChIKey: QNQVIRAZQPCQEB-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]CP-55,940 from recombinant human full length CB2 receptor expressed in HEK293 cell membranes after 90 mins by topcount method
Measurement: IC50 = 1980 nM (pChEMBL 5.699999809265137)
Descriptors: MW 402.53, ALogP 5.18, HBA 5, HBD 1, PSA 64.99, QED 0.52
Compound (SMILES): CC(O)[C@@H](NC(=O)[C@H](Cc1ccc(OCc2ccccc2)cc1)NC(=O)OC(C)(C)C)C(=O)N[C@@H](C[C@]1(O)C(=O)Nc2ccccc21)C(=O)NCc1ccccc1
InChIKey: IURMTFSKTSDMFY-GWMWZFRLSA-N
Target: Proteasome subunit beta type-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P28065
Assay: Inhibition of human 20S immunoproteasome beta-1 using Ac-PAL-AMC as substrate incubated for 15 mins measured for 45 mins by fluorescence assay
Measurement: IC50 = 8800 nM (pChEMBL 5.059999942779541)
Descriptors: MW 779.89, ALogP 3.6, HBA 9, HBD 7, PSA 204.42, QED 0.09
Compound (SMILES): O=C(O)c1ccnc(-n2nccc2OCc2ccc(Cl)cc2/C=C/c2ccc(F)cc2)c1
InChIKey: BVUXJIUJKSADTM-DAFODLJHSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of recombinant human N-terminal GST-tagged JMJD2C (2 to 372 residues) expressed in baculovirus infected sf9 cells using H3K9me3-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by LANCE TR-FRET assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 449.87, ALogP 5.51, HBA 5, HBD 1, PSA 77.24, QED 0.38
Compound (SMILES): N#CC1(c2cc(Nc3nc(N[C@H]4CCC(F)(F)C4)nc(-n4ccc(C(F)(F)F)n4)n3)ccn2)CC1
InChIKey: WFGLMCWPQJGAJJ-ZDUSSCGKSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of DH1 R132H mutant homodimer (unknown origin) expressed in Sf9 cells pre-incubated for 1 hr before addition of alpha-KG followed by 60 mins incubation in presence of NADPH, NADP, diaphorase and resazurin by fluorescence spectrometry
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 491.43, ALogP 4.37, HBA 9, HBD 2, PSA 117.23, QED 0.49
Compound (SMILES): CC(=O)Nc1ccc(-c2ccnc(Nc3cccc(OCCCCCCC(=O)NO)c3)n2)cc1
InChIKey: JSSDNFQOZLHEQV-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin) using Arg-His-Lys-Lys(Ac) as substrate preincubated with enzyme followed by substrate addition for 2 hrs and measured for 1.5 hrs at 15 mins time interval by fluorescence assay
Measurement: IC50 = 1.8 nM (pChEMBL 8.739999771118164)
Descriptors: MW 463.54, ALogP 4.68, HBA 7, HBD 4, PSA 125.47, QED 0.17
Compound (SMILES): COc1cccc(Nc2cc(NC(=O)CCCC(=O)O)ncn2)c1
InChIKey: XGCIQQCBKZDMPK-UHFFFAOYSA-N
Target: Receptor tyrosine-protein kinase erbB-3 (SINGLE PROTEIN), Homo sapiens
UniProt: P21860
Assay: Inhibition of recombinant human GST-tagged EGFR L858R mutant cytoplasmic domain expressed in baculovirus expression system using FAM-labeled peptide as substrate after 10 mins by mobility shift assay
Measurement: IC50 = 31 nM (pChEMBL 7.510000228881836)
Descriptors: MW 330.34, ALogP 2.42, HBA 6, HBD 3, PSA 113.44, QED 0.68
Compound (SMILES): CSc1ncc2c(n1)Nc1n[nH]c(C)c1N=C2c1ccccc1
InChIKey: YXCGTDGQBHHSIT-UHFFFAOYSA-N
Target: Aurora kinase B (SINGLE PROTEIN), Homo sapiens
UniProt: Q96GD4
Assay: Inhibition of Aurora B (unknown origin) using STK S2 as substrate after 30 mins by HTRF assay
Measurement: IC50 = 894 nM (pChEMBL 6.050000190734863)
Descriptors: MW 322.4, ALogP 3.46, HBA 6, HBD 2, PSA 78.85, QED 0.44
Compound (SMILES): O=c1cc(Cc2ccc(-c3ccc(Cl)cc3Cl)cc2)[nH]c(=O)n1O
InChIKey: JOGJYXTVSSCEKJ-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of recombinant HIV1 reverse transcriptase RNase H expressed in Escherichia coli JM109 using RNA/DNA duplex substrate HTS1 as substrate
Measurement: IC50 = 9.2 nM (pChEMBL 8.039999961853027)
Descriptors: MW 363.2, ALogP 3.34, HBA 4, HBD 2, PSA 75.09, QED 0.7
Compound (SMILES): COc1cc(C(=O)N[C@@H]2CCCc3ccc(-c4cn5c(n4)CCC5)cc32)ccc1C
InChIKey: HMOMQPHKMPWUKJ-OAQYLSRUSA-N
Target: WD repeat-containing protein 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P61964
Assay: Inhibition of human WDR5 (22 to 334 residues) assessed as reduction in WRAD-mediated human MLL1 ( 3745 to 3969 residues) H3K4 methylation using human HeLa cells oligonucleosomes as substrate and 3H-SAM as methylation cofactor by radioisotope-based filter-binding assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 401.51, ALogP 4.62, HBA 4, HBD 1, PSA 56.15, QED 0.69
Compound (SMILES): Clc1cccc(-c2nc(NC3C4COCC43)nc(NC3C4COCC43)n2)n1
InChIKey: CBYBEVCADOLNTG-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP], mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P48735
Assay: In Vitro Assays for IDH2m R140Q Inhibitors: Compounds are assayed for IDH2 R140Q inhibitory activity through a cofactor depletion assay. Compounds are preincubated with enzyme, then the reaction is started by the addition of NADPH and α-KG, and allowed to proceed for 60 minutes under conditions previously demonstrated to be linear with respect for time for consumption of both cofactor and substrate. The reaction is terminated by the addition of a second enzyme, diaphorase, and a corresponding substrate, resazurin. Diaphorase reduces resazurin to the highly fluorescent resorufin with the concomitant oxidation of NADPH to NADP, both halting the IDH2 reaction by depleting the available cofactor pool and facilitating quantitation of the amount of cofactor remaining after a specific time period through quantitative production of an easily detected fluorophore.Specifically, into each of 12 wells of a 384-well plate, 1 μl of 100× compound dilution series is placed, followed by the addition of 40 μl of buffer (50 mM potassium phosphate (K2HPO4), pH 7.5; 150 mM NaCl; 10 mM MgCl2, 10% glycerol, 0.05% bovine serum albumin, 2 mM beta-mercaptoethanol) containing 0.25 μg/ml IDH2 R140Q protein. The test compound is then incubated for one hour at room temperature with the enzyme; before starting the IDH2 reaction with the addition of 10 μl of substrate mix containing 4 μM NADPH and 1.6 mM α-KG in the buffer described above. After a further 16 hours of incubation at room temperature, the reaction is halted and the remaining NADPH measured through conversion of resazurin to resorufin by the addition of 25 μl Stop Mix (36 μg/ml diaphorase enzyme and 60 μM resazurin; in buffer). After one minute of incubation the plate is read on a plate reader at Ex544/Em590.For determination of the inhibitory potency of compounds against IDH2 R140Q in an assay format similar to the above, a similar procedure is performed, except that the final testing concentration is 0.25 μg/ml IDH2 R140Q protein, 4 μM NADPH and 1.6 mM α-KG.For determination of the inhibitory potency of compounds against IDH2 R140Q in a high throughput screening format, a similar procedure is performed, except that 0.25 μg/ml IDH2 R140Q protein is utilized in the preincubation step, and the reaction is started with the addition of 4 μM NADPH and 8 μM α-KG.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 386.84, ALogP 1.7, HBA 8, HBD 2, PSA 94.08, QED 0.75
Compound (SMILES): Nc1oc2cnccc2c1Nc1ccc(F)c(Br)c1
InChIKey: KBJUOIUSOJGQLO-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of recombinant human TDO2 expressed in CHOK1 cells assessed as reduction in kynurenine formation using L-tryptophan as substrate measured after 2 hrs by LC/MS/MS analysis
Measurement: IC50 < 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 322.14, ALogP 4.06, HBA 4, HBD 2, PSA 64.08, QED 0.75
Compound (SMILES): CCOc1ccccc1CCn1cnc(-c2cc(-c3c[nH]nn3)ccn2)c1
InChIKey: YIGRHNBSMBEKHZ-UHFFFAOYSA-N
Target: Histone lysine demethylase PHF8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UPP1
Assay: Inhibition of recombinant human N-terminal FLAG-tagged PHF8 expressed in baculovirus infected Sf9 cells using H3K9mel-biotin labelled peptide as substrate measured after 15 mins by Lance TR-FRET assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 360.42, ALogP 3.37, HBA 6, HBD 1, PSA 81.51, QED 0.55
Compound (SMILES): COc1ccc2c(c1OC)C(OC)N(C)c1c-2ccc2cc3c(cc12)OCO3
InChIKey: LVWAKZBZWYHYCJ-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of human recombinant CYP1A2 expressed in HEK293 cells using 3-cyano-7-ethoxycoumarin substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins by fluorescence assay relative to control
Measurement: IC50 = 8930 nM (pChEMBL 5.050000190734863)
Descriptors: MW 379.41, ALogP 4.35, HBA 6, HBD 0, PSA 49.39, QED 0.67
Compound (SMILES): O=c1cc(-c2ccccc2)oc2cc(OCCCc3cn(CCOCCOCCOc4ccc(-c5oc6ccccc6c(=O)c5OCc5ccccc5)cc4)nn3)ccc12
InChIKey: VOROWDYQRAPUBO-UHFFFAOYSA-N
Target: Multidrug resistance-associated protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P33527
Assay: Inhibition of MRP1 (unknown origin) expressed in human 2008/MRP1 assessed as reversal of doxorubicin resistance after 5 days by MTS/PMS assay
Measurement: EC50 = 207.3 nM (pChEMBL 6.679999828338623)
Descriptors: MW 805.88, ALogP 8.53, HBA 12, HBD 0, PSA 137.28, QED 0.07
Compound (SMILES): O=C(N[C@H]1CCS[C@H]2CCC[C@@H](C(=O)O)N2C1=O)[C@H](Cc1ccccc1)SS[C@@H](Cc1ccccc1)C(=O)N[C@H]1CCS[C@H]2CCC[C@@H](C(=O)O)N2C1=O
InChIKey: AFPQGXPNGGHYHA-ALERXTORSA-N
Target: Angiotensin-converting enzyme (SINGLE PROTEIN), Homo sapiens
UniProt: P12821
Assay: Inhibition of human fully glycosylated ACE N-terminal domain expressed in CHO cells using MCA-RPPGFSAFK(Dnp)-OH as substrate preincubated for 15 mins followed by substrate addition measured after 10 mins by fluorescence spectrophotometric analysis
Measurement: IC50 = 2100 nM (pChEMBL 5.679999828338623)
Descriptors: MW 815.07, ALogP 4.42, HBA 10, HBD 4, PSA 173.42, QED 0.21
Compound (SMILES): CC(F)(F)c1cncc(-c2nc(NC3CC(F)(F)C3)nc(NC3CC(F)(F)C3)n2)n1
InChIKey: CDUYLYBNWORMLM-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132C mutant (unknown origin) expressed in human U87MG cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 433.36, ALogP 3.86, HBA 7, HBD 2, PSA 88.51, QED 0.67
Compound (SMILES): COc1ccccc1CNCCn1cnc(-c2cc(C(=O)O)ccn2)c1
InChIKey: HNCSOLMMKKZZJS-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of recombinant human N-terminal GST-tagged JMJD2C (2 to 372 residues) expressed in baculovirus infected sf9 cells using H3K9me3-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by LANCE TR-FRET assay
Measurement: IC50 <= 100 nM (pChEMBL 7)
Descriptors: MW 352.39, ALogP 2.44, HBA 6, HBD 2, PSA 89.27, QED 0.61
Compound (SMILES): O=C(O)[C@H]1[C@H](c2c(Cl)cccc2Cl)[C@H](C(=O)O[C@@H]2CCCC[C@H]2c2ccccc2)[C@H]1c1c(Cl)cccc1Cl
InChIKey: ASTDZMIALLAUDJ-NLWTXNOPSA-N
Target: Fatty acid-binding protein, brain (SINGLE PROTEIN), Homo sapiens
UniProt: O15540
Assay: Displacement of ANS from recombinant human N-terminal His-tagged FABP7 expressed in Escherichia coli BL21(DE3) after 20 mins by fluorescence assay
Measurement: Ki = 6320 nM (pChEMBL 5.199999809265137)
Descriptors: MW 592.35, ALogP 8.77, HBA 3, HBD 1, PSA 63.6, QED 0.29
Compound (SMILES): NC1=N[C@@]2(CO1)c1cc(NC(=O)c3ccc(Cl)cn3)ccc1Oc1cnc(C3=CCCOC3)cc12
InChIKey: ZXMNKHTXDORUCR-VWLOTQADSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in HEK293 cells at -80 mV holding potential by PatchXpress automated electrophysiology method
Measurement: IC50 = 900 nM (pChEMBL 6.050000190734863)
Descriptors: MW 489.92, ALogP 3.88, HBA 8, HBD 2, PSA 120.95, QED 0.57
Compound (SMILES): N#CC1(c2cc(Nc3nc(N[C@H]4CCC(F)(F)C4)nc(-c4cccc(C(F)(F)F)n4)n3)ccn2)CC1
InChIKey: FQOVWGJWJAOWBO-AWEZNQCLSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of DH1 R132C mutant homodimer (unknown origin) expressed in Sf9 cells pre-incubated for 1 hr before addition of alpha-KG followed by 60 mins incubation in presence of NADPH, NADP, diaphorase and resazurin by fluorescence spectrometry
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 502.45, ALogP 5.25, HBA 8, HBD 2, PSA 112.3, QED 0.44
Compound (SMILES): COc1cc(C(=O)NS(=O)(=O)c2cccc(C(F)(F)F)c2)ccc1Cc1cn(C)c2ccc(NC(=O)NC3CCCCC3)cc12
InChIKey: BCMLBMIEKQMGLP-UHFFFAOYSA-N
Target: Cysteinyl leukotriene receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y271
Assay: Antagonist potency at human CysLT1R expressed in African green monkey COS7 cells assessed as inhibition of LTD4-induced Ca2+ levels after 60 mins by fura-2/AM-fluorescence based spectrofluorimetry
Measurement: Kd = 5.012 nM (pChEMBL 8.300000190734863)
Descriptors: MW 642.7, ALogP 6.37, HBA 6, HBD 3, PSA 118.53, QED 0.21
Compound (SMILES): CCCCCCCC(O)CCCC(=O)[O-].[Na+]
InChIKey: JXKITCMSFKBCAI-UHFFFAOYSA-M
Target: Free fatty acid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O14842
Assay: Agonist activity at N-terminal FLAG-tagged/C-terminal eYFP-fused human FFA1 receptor expressed in HEK293T cells assessed as induction of beta-arrestin-2 recruitment after 15 mins by BRET assay
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 216.32, ALogP 2.96, HBA 2, HBD 2, PSA 57.53, QED 0.55
Compound (SMILES): CNc1ncc(C(=O)NC(c2ccccc2)c2ccccc2)c2nc(-c3ccco3)nn12
InChIKey: UHDZPXOSQNQCSS-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Antagonist activity at human adenosine A2B receptor expressed in CHO cell membranes assessed as inhibition of NECA-stimulated adenylyl cyclase activity by [alpha-32P]ATP based assay
Measurement: Ki = 10000 nM (pChEMBL 5)
Descriptors: MW 424.46, ALogP 3.95, HBA 7, HBD 2, PSA 97.35, QED 0.43
Compound (SMILES): Clc1cc(Cl)cc(-n2cnc(-c3cc4[nH]nnc4cn3)c2)c1
InChIKey: PXBUOEOSFSTIDA-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NHM5
Assay: FBXL10 Assay: The ability of test compounds to inhibit the activity of FBXL10 was determined in 384-well plate format under the following reaction conditions: 0.3 nM FBXL10, 30 nM H3K36me2-biotin labeled peptide (Anaspec cat #64442), 0.2 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, 5 μM ammonium iron(II) sulfate. Reaction product is determined quantitatively by AlphaScreen detection after the addition of detection reagents anti-H3K36me1 antibody, AlphaScreen® Streptavidin-coated Donor beads, and AlphaScreen® Protein A Acceptor beads in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA to final 10 μg/ml beads.The assay reaction was initiated by the following: 3 μl of the mixture of 90 nM H3K36me2-biotin labeled peptide and 0.6 μM alpha-ketoglutaric acid with 3 μl of 11-point serial diluted inhibitor in 3% DMSO are added to each well of 384 well Proxiplate (Perkin Elmer), followed by the addition of 3 μl of 0.9 nM FBXL10 to initiate the reaction. The reaction mixture is incubated at room temperature for 1 hour, and terminated by the addition of 3 μl of appropriate dilution of anti H3K36me1 antibody in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA. Plates will then incubated at room temperature for 40 minutes, followed by addition of 3 ul of 50 μg/ml AlphaScreen® Streptavidin-coated Donor beads and AlphaScreen® Protein A Acceptor beads in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA. Plates will then be read by EnVision Multilabel Reader in AlphaScreen mode after minimum 2 hour incubation at room temperature. The AlphaScreen signal for each well is used to determine inhibition constant (IC50).
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 331.17, ALogP 3.51, HBA 5, HBD 1, PSA 72.28, QED 0.61
Compound (SMILES): COc1cccc(NC(=O)Nc2cc(S(N)(=O)=O)cc([N+](=O)[O-])c2O)c1
InChIKey: DNIGLUHHUQKONI-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of carbonic anhydrase 9 (unknown origin) preincubated for 15 mins by stopped flow CO2 hydration assay
Measurement: Ki = 460 nM (pChEMBL 6.340000152587891)
Descriptors: MW 382.35, ALogP 1.6, HBA 7, HBD 4, PSA 173.89, QED 0.34
Compound (SMILES): CC[C@H](C)[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(N)=O)CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)O)[C@@H](C)O)C(C)C
InChIKey: ZDTMOXOTRBDQHN-QVJUSLJMSA-N
Target: Neuropeptide Y receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P50391
Assay: Displacement of [125I]-PP from human Y4R expressed in CHO-K1 cell membranes after 2 hrs by scintillation proximity assay
Measurement: Ki = 100 nM (pChEMBL 7)
Descriptors: MW 4064.54
Compound (SMILES): COc1cc2c(cc1O)CN(CCCCNC(=O)c1ccc(O)cc1)CC2
InChIKey: HTIHIBRTTCYUMB-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Antagonist activity at human dopamine D3 receptor assessed as inhibition of beta-arrestin recruitment by Tango assay
Measurement: EC50 = 420 nM (pChEMBL 6.380000114440918)
Descriptors: MW 370.45, ALogP 2.67, HBA 5, HBD 3, PSA 82.03, QED 0.65
Compound (SMILES): CC1(C)O[C@H]2O[C@H](CNCCCCCCCCCNc3c4c(nc5ccccc35)CCCC4)[C@H](O)[C@H]2O1
InChIKey: ZDIBXLSDOAFGQH-KKAKYAENSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Mus musculus
UniProt: P21836
Assay: Inhibition of mouse brain AChE
Measurement: IC50 = 5.1 nM (pChEMBL 8.289999961853027)
Descriptors: MW 511.71, ALogP 5.08, HBA 7, HBD 3, PSA 84.87, QED 0.32
Compound (SMILES): NC(=O)c1ccc(-c2nccc3c(Nc4ccc(F)c(Cl)c4)c(N)oc23)cc1
InChIKey: PZIOOGLTMJLKQE-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of recombinant human TDO2 expressed in CHOK1 cells assessed as reduction in kynurenine formation using L-tryptophan as substrate measured after 2 hrs by LC/MS/MS analysis
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 396.81, ALogP 4.71, HBA 5, HBD 3, PSA 107.17, QED 0.46
Compound (SMILES): Cl.O=C(CCCN1CCC(Cc2ccccc2)CC1)c1ccc(-c2ccccc2)cc1
InChIKey: FOKXFADDYWJNLC-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of electric eel AChE using acetylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition and measured after 2 mins by Ellman's method
Measurement: IC50 = 13940 nM (pChEMBL 4.860000133514404)
Descriptors: MW 397.56, ALogP 6.27, HBA 2, HBD 0, PSA 20.31, QED 0.42
Compound (SMILES): CCS(=O)(=O)NC(=O)c1ccc2c(-c3cnc(OCC(C)C)c(Cl)c3)cn(C)c2c1
InChIKey: PMZAJXSRPAMGQD-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Inhibition of Nav1.5 (unknown origin) expressed in HEK293 cells at -40 mV holding potential measured after 600 secs by patch clamp method
Measurement: IC50 = 5673 nM (pChEMBL 5.25)
Descriptors: MW 449.96, ALogP 4.01, HBA 6, HBD 1, PSA 90.29, QED 0.59
Compound (SMILES): C[C@H](Nc1nc(Nc2ccnc(C(F)(F)F)c2)nc(-n2ccc(C(F)(F)F)n2)n1)C(F)(F)F
InChIKey: ORPDRKJAHZEOLR-ZETCQYMHSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132C mutant (unknown origin) expressed in human U87MG cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 486.3, ALogP 4.6, HBA 8, HBD 2, PSA 93.44, QED 0.51
Compound (SMILES): Cn1cnc(-c2cc(C(=O)O)ccn2)c1-c1ccc(Cl)cc1C(F)(F)F
InChIKey: GOMLARFYKWXBIU-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of recombinant human N-terminal GST-tagged JMJD2C (2 to 372 residues) expressed in baculovirus infected sf9 cells using H3K9me3-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by LANCE TR-FRET assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 381.74, ALogP 4.52, HBA 4, HBD 1, PSA 68.01, QED 0.72
Compound (SMILES): CC(C)C[C@H](NC(=O)OC(C)(C)C)C(=O)N1CCC[C@@H]1C(=O)N1C(C(=O)O)C1C(=O)OCC1CCCCC1
InChIKey: NHGHQGULMGPVNX-BADMPUJESA-N
Target: Cruzipain (SINGLE PROTEIN), Trypanosoma cruzi
UniProt: P25779
Assay: Inhibition of Trypanosoma cruzi cruzain using Z-Phe-Arg-AMC as substrate by fluorometric assay
Measurement: Ki = 710 nM (pChEMBL 6.150000095367432)
Descriptors: MW 537.65, ALogP 2.7, HBA 7, HBD 2, PSA 142.32, QED 0.34
Compound (SMILES): NCCCCNC(=O)COc1ccc(CCCn2ncc3c2nc(N)n2nc(-c4ccco4)nc32)cc1
InChIKey: ZLNSJZCPMMZNSC-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of [125I]I-AB-MECA from recombinant human adenosine receptor A3 expressed in HEK293 cell membranes after 1 hr by FACS analysis
Measurement: Ki = 5990 nM (pChEMBL 5.21999979019165)
Descriptors: MW 503.57, ALogP 2.18, HBA 11, HBD 3, PSA 164.41, QED 0.22
Compound (SMILES): C[C@H](CC(=O)N1CCC(O)(Cn2cnc(NCCN3CCCC3)cc2=O)CC1)c1ccccc1
InChIKey: VJDZJAUBPMXVAF-OAQYLSRUSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q93009
Assay: Fluorescence Polarisation (FP) Homogeneous Assay: USP7 activity was monitored in a fluorescence polarisation (FP) homogeneous assay using the isopeptide ubiquitin-Lys-TAMRA substrate (U-558, Boston Biochem). Full-length USP7 was purchased from Boston Biochem (His6-USP7FL, E-519). Unless otherwise stated, all other reagents were purchased from Sigma-Aldrich. Enzymatic reactions were conducted in black flat-bottom polystyrene 384-well plates (Nunc) and 15 μL total volume. USP7 (2.5 nM, 5 μL) was incubated in assay buffer (50 mM HEPES (pH 7.2), 150 mM NaCl, 0.5 mM EDTA, 5 mM DTT, 0.05% BSA (w/v), 0.05% CHAPS) in the presence or absence of inhibitor (5 μl). Inhibitors were stored as 10 mM DMSO stocks in an inert environment (low humidity, dark, low oxygen, room temperature) using a Storage Pod System and serial dilutions were prepared in buffer just prior to the assay (from 200 to 0.1 μM, 8 dp curve). Following incubation at room temperature for 30 min, the enzymatic reactions were initiated by dispensing the Ub substrate (250 nM, 5 μL). FP was measured every 15 min over a period of 1.5 h (within the linear range of the assay) using a Synergy 4 plate reader (BioTek) exciting at 530 nm and measuring the amount of parallel and perpendicular light at 575 nm.
Measurement: IC50 < 250 nM (pChEMBL 6.6020002365112305)
Descriptors: MW 467.61, ALogP 2.3, HBA 7, HBD 2, PSA 90.7, QED 0.59
Compound (SMILES): FC(F)(F)c1[nH]nnc1-c1ccnc(-c2cn(CC3CCCc4ccccc43)cn2)c1
InChIKey: GZSKYQYFMMZVFA-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of recombinant human N-terminal GST-tagged JMJD2C (2 to 372 residues) expressed in baculovirus infected Sf9 cells using H3K9me3-biotin labelled peptide as substrate measured after 30 mins by Lance TR-FRET assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 424.43, ALogP 4.87, HBA 5, HBD 1, PSA 72.28, QED 0.51
Compound (SMILES): CN(c1ccc2nc(-c3ccc(Cl)cc3Cl)c(CN3CCN(C(=O)C(C)(C)O)CC3)n2c1)S(C)(=O)=O
InChIKey: BOULNMAIECOHND-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P11169
Assay: Inhibition of human GluT3 expressed in HEK293 cells assessed as reduction in 3H]-deoxy-D-glucose uptake incubated for 30 mins by scintillation counting method
Measurement: IC50 <= 1000 nM (pChEMBL 6)
Descriptors: MW 554.5, ALogP 3.12, HBA 7, HBD 1, PSA 98.46, QED 0.5
Compound (SMILES): Nc1oc2cnccc2c1Nc1cc(Cl)ccc1Cl
InChIKey: HNKDGHFFOLIGBX-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of recombinant human TDO2 expressed in CHOK1 cells assessed as reduction in kynurenine formation using L-tryptophan as substrate measured after 2 hrs by LC/MS/MS analysis
Measurement: IC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 294.14, ALogP 4.46, HBA 4, HBD 2, PSA 64.08, QED 0.73
Compound (SMILES): CC(O)[C@@H](NC(=O)OCc1ccccc1)C(=O)N[C@@H](C[C@]1(O)C(=O)Nc2ccccc21)C(=O)NCc1ccccc1
InChIKey: AILUPPFPYNWHMY-UATIKPPHSA-N
Target: Proteasome subunit beta type-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P28065
Assay: Inhibition of human 20S immunoproteasome beta-1 using Ac-PAL-AMC as substrate incubated for 15 mins measured for 45 mins by fluorescence assay
Measurement: IC50 = 24600 nM (pChEMBL 4.610000133514404)
Descriptors: MW 560.61, ALogP 1.69, HBA 7, HBD 6, PSA 166.09, QED 0.21
Compound (SMILES): CC1Cc2cnc(Nc3ccccc3)nc2-c2c1c(C(N)=O)nn2C
InChIKey: MGVIWAJZVGYINA-UHFFFAOYSA-N
Target: CDK6/cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Inhibition of CDK6/Cyclin D3 (unknown origin) using FAM-labeled peptide as substrate after 40 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 334.38, ALogP 2.38, HBA 6, HBD 2, PSA 98.72, QED 0.77
Compound (SMILES): CC(F)(F)c1nc(-c2nc(NC3CCC(F)(F)CC3)nc(NC3CCC(F)(F)CC3)n2)cs1
InChIKey: BCVWBQGSHAGBJM-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP], mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P48735
Assay: Inhibition of IDH2 R140Q mutant homodimer (unknown origin) expressed in Sf9 cells pre-incubated for 1 hr before addition of alpha-KG followed by 16 hrs incubation in presence of NADPH, NADP, diaphorase and resazurin by fluorescence spectrometry based cofactor depletion assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 494.51, ALogP 6.09, HBA 7, HBD 2, PSA 75.62, QED 0.47
Compound (SMILES): FC1(F)CCC(Nc2nc(NC3CCC(F)(F)CC3)nc(-c3ccnc(C(F)(F)F)n3)n2)CC1
InChIKey: VFDBHGHEXPAMBP-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of DH1 R132H mutant homodimer (unknown origin) expressed in Sf9 cells pre-incubated for 1 hr before addition of alpha-KG followed by 60 mins incubation in presence of NADPH, NADP, diaphorase and resazurin by fluorescence spectrometry
Measurement: IC50 >= 1000 nM (pChEMBL 6)
Descriptors: MW 493.43, ALogP 5.33, HBA 7, HBD 2, PSA 88.51, QED 0.54
Compound (SMILES): Cc1cc(Oc2nccc3occc23)ccc1-c1cccc2nccn12
InChIKey: PQMACIUZHAYTRR-UHFFFAOYSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Agonist activity at recombinant human D1 receptor expressed in HEK29T cells assessed as induction of stimulatory G-protein-mediated cAMP accumulation measured after 15 mins by Glosensor-based FLIPR assay
Measurement: EC50 = 2.7 nM (pChEMBL 8.569999694824219)
Descriptors: MW 341.37, ALogP 5.24, HBA 5, HBD 0, PSA 52.56, QED 0.45
Compound (SMILES): Cc1ccc2oc(-c3ccc(OCCOCCOCCn4cc(CCCCOc5ccc6c(=O)cc(-c7ccccc7)oc6c5)nn4)cc3)cc(=O)c2c1
InChIKey: JKYZGKWNGFTCMZ-UHFFFAOYSA-N
Target: Multidrug resistance-associated protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P33527
Assay: Inhibition of MRP1 (unknown origin) expressed in human 2008/MRP1 assessed as reversal of doxorubicin resistance after 5 days by MTS/PMS assay
Measurement: EC50 = 171 nM (pChEMBL 6.769999980926514)
Descriptors: MW 727.81, ALogP 7.65, HBA 11, HBD 0, PSA 128.05, QED 0.08
Compound (SMILES): Cc1cc(-c2nccc3c(Nc4ccc(F)c(F)c4)c(N)oc23)ccn1
InChIKey: IBDOWWWHLPYOLU-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of recombinant human TDO2 expressed in CHOK1 cells assessed as reduction in kynurenine formation using L-tryptophan as substrate measured after 2 hrs by LC/MS/MS analysis
Measurement: IC50 < 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 352.34, ALogP 4.8, HBA 5, HBD 2, PSA 76.97, QED 0.55
Compound (SMILES): CC(F)(F)c1cc(Nc2nc(N[C@@H]3CCC(F)(F)C3)nc(-c3cccc(C(F)(F)F)n3)n2)ccn1
InChIKey: RJZGABPOSOZJRY-GFCCVEGCSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132C mutant (unknown origin) expressed in human U87MG cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 501.41, ALogP 5.8, HBA 7, HBD 2, PSA 88.51, QED 0.41
Compound (SMILES): N#CC1(c2cc(Nc3nc(NC4CCC(F)(F)CC4)nc(-c4cncc(C(F)(F)F)n4)n3)ccn2)CC1
InChIKey: WXWZXGHGTPKZJP-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of IDH1 R132H/R132C mutant in human HT1080 cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 517.47, ALogP 5.03, HBA 9, HBD 2, PSA 125.19, QED 0.43
Compound (SMILES): CCOC(=O)c1ccc(-c2c(-c3cccc(C)n3)nn3c2C(C)C(C)(C)C3)cc1
InChIKey: TUQJLUVEHCATLN-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Mus musculus
UniProt: P00520
Assay: Inhibition of mouse ABL expressed in Sf9 insect cells using GGEAIYAAPFKK as substrate in presence of [gamma-33P]ATP
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 389.5, ALogP 5.24, HBA 5, HBD 0, PSA 57.01, QED 0.57
Compound (SMILES): COc1cccc2c1CCCC2Cn1cnc(-c2cc(-c3nn[nH]c3C(F)(F)F)ccn2)c1
InChIKey: KSHWDEXTHUSOBP-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NHM5
Assay: Inhibition of recombinant human C-terminal FLAG-tagged FBXL10 (1 to 650 residues) expressed in baculovirus infected Sf9 cells using H3K36me2-biotin labelled peptide as substrate measured after 1 hr by AlphaScreen assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 454.46, ALogP 4.88, HBA 6, HBD 1, PSA 81.51, QED 0.47
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@@H](NC(=O)[C@@H](N)Cc2ccc(O)cc2)CCC(=O)NCCCC[C@@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc2ccc(O)cc2)C(=O)O)[C@@H](C)O)C(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](Cc2cnc[nH]2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)CCCCCNC(=O)[C@H](CCCCN)NC1=O
InChIKey: QTDDOYSPIKOADE-BSUCQFSCSA-N
Target: Neuropeptide Y receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P50391
Assay: Displacement of [125I]-PP from human Y4R expressed in CHO-K1 cell membranes after 2 hrs by scintillation proximity assay
Measurement: Ki = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 2262.66
Compound (SMILES): C=CS(=O)(=O)N1CCCN(c2cc(NCCC(=O)O)nc(-c3ccccn3)n2)CC1
InChIKey: CPNWZGJHUIZVEZ-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P29375
Assay: Binding affinity to KDM5A ARID/PhD1 domain deletion mutant (1 to 588 residues) (unknown origin) by ITC assay
Measurement: Kd = 9000 nM (pChEMBL 5.050000190734863)
Descriptors: MW 432.51, ALogP 1.41, HBA 8, HBD 2, PSA 128.62, QED 0.64
Compound (SMILES): CCCCCC(=O)NC[C@@H](O)[C@@H](O)[C@@H]1OC(C(=O)O)=C[C@H](O)[C@H]1NC(C)=O
InChIKey: WZROZUPFCCVDFF-IQVWLFHZSA-N
Target: Sialidase-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99519
Assay: Inhibition of human NEU1 expressed in HEK293 cells using 4-MUNANA as substrate preincubated with compound for 0.25 hrs followed by substrate addition and measured after 0.5 hrs by fluorescence based analysis
Measurement: IC50 = 5000 nM (pChEMBL 5.300000190734863)
Descriptors: MW 388.42, ALogP -1.36, HBA 7, HBD 6, PSA 165.42, QED 0.25
Compound (SMILES): Cn1cnc(-c2cc(-c3nn[nH]n3)ccn2)c1-c1ccc(F)c(OCC(F)(F)F)c1
InChIKey: SFGZOXOAJXAEAX-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: JMJD2C Assay: The ability of test compounds to inhibit the activity of JMJD2C was determined in 384-well plate format under the following reaction conditions: 0.3 nM JMJD2C, 300 nM H3K9me3-biotin labeled peptide (Anaspec cat #64360), 2 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, and 2 μM ammonium iron(II) sulfate. Reaction product was determined quantitatively by TR-FRET after the addition of detection reagent Phycolink Streptavidin-allophycocyanin (Prozyme) and Europium-anti-di-methylated histone H3 lysine 9 (H3K9me2) antibody (PerkinElmer) in the presence of 5 mM EDTA in LANCE detection buffer (PerkinElmer) at a final concentration of 50 nM and 1 nM, respectively.The assay reaction was initiated by the following: 2 μl of the mixture of 900 nM H3K9me3-biotin labeled peptide and 6 μM alpha-ketoglutaric acid with 2 μl of 11-point serial diluted inhibitor in 3% DMSO were added to each well of the plate, followed by the addition of 2 μl of 0.9 nM JMJD2C to initiate the reaction. The reaction mixture was incubated at room temperature for 30 minutes, and terminated by the addition of 6 μl of 5 mM EDTA in LANCE detection buffer containing 100 nM Phycolink Streptavidin-allophycocyanin and 2 nM Europium-anti-H3K9me2 antibody. Plates were read by EnVisionMultilabel Reader in TR-FRET mode (excitation at 320 nm, emission at 615 nm and 665 nm) after 1 hour incubation at room temperature. A ratio was calculated (665/615) for each well and fitted to determine inhibition constant (IC50).
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 419.34, ALogP 3.41, HBA 7, HBD 1, PSA 94.4, QED 0.5
Compound (SMILES): Cc1[nH]nc(N)c1-c1ccc(Br)cc1
InChIKey: XBGQAVPNQRLZOV-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99558
Assay: Inhibition of recombinant human full-length N-terminal GST-fused/His6-tagged NIK (M1 to P947 residues) expressed in Sf9 insect cells using AKDVDQGSLCTSFVGTLQY peptide as substrate measured after 60 mins by ADP-Glo kinase assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 252.12, ALogP 2.73, HBA 2, HBD 2, PSA 54.7, QED 0.82
Compound (SMILES): Cc1cc(C#N)cc(C)c1Oc1nc(NC2CCN(Cc3ccc(N4CCCC4)cc3)CC2)nc2ccsc12
InChIKey: XLCBVJOBQQWYJB-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of wild-type HIV1 reverse transcriptase infected in human MT4 cells assessed as reduction in biotin-dUTP incorporation
Measurement: IC50 = 221 nM (pChEMBL 6.659999847412109)
Descriptors: MW 538.72, ALogP 6.65, HBA 8, HBD 1, PSA 77.31, QED 0.28
Compound (SMILES): Cc1cc(Cn2c(=O)c3cc(S(=O)(=O)NC4(C)CC4)ccc3n(Cc3cc(C)nn3C)c2=O)on1
InChIKey: SWIWJXUWGZZTFL-UHFFFAOYSA-N
Target: Poly(ADP-ribose) glycohydrolase (SINGLE PROTEIN), Homo sapiens
UniProt: Q86W56
Assay: PARG Assay: PARG In vitro assays were conducted in a total volume of 15 ul in a standard 384 well format. 5 ul of Human Full Length PARG (Produced internally by Astra Zeneca), used at a final reaction concentration of 80 pM, was added to 5 ul of Ribosylated PARP substrate (also produced internally by Astra Zeneca) at final reaction concentration of 4.5 nM in assay buffer (50 mM Tris pH7.4, 0.1 mg/ml BSA, 3 mM EDTA, 0.4 mM EGTA, 1 mM DTT, 0.01% Tween 20, 50 mM KCl). The reaction was incubated at room temperature for 10 minutes and then 5 ul detection reagent was added. Detection Reagent consists of 42 nM MAb Anti-6HIS XL665 (CisBio: 61HISXLB) and 2.25 nM Streptavidin Europium Cryptate (CisBio: 610SAKLB), both at 3× working stock concentrations (final concentrations of 14 nM and 0.75 nM respectively), in a detection buffer of 50 mM Tris pH7.4, BSA at 0.1 mg/ml and KF at 100 mM. Following incubation at room temperature for 60 minutes in the dark, TR-FRET signal was measured at Ex 340 and Em 665 and Em 620. A ratio was calculated as Em665/EM620×104 for each well and used to calculate percent inhibition for test compounds.
Measurement: IC50 = 38 nM (pChEMBL 7.420000076293945)
Descriptors: MW 498.57, ALogP 1.43, HBA 10, HBD 1, PSA 134.02, QED 0.41
Compound (SMILES): CCc1ccc(COC(=O)c2cnc(NC)n3nc(-c4ccco4)nc23)cc1
InChIKey: LHHCKUUYYUDSJU-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Antagonist activity at human adenosine A2B receptor expressed in CHO cell membranes assessed as inhibition of NECA-stimulated adenylyl cyclase activity by [alpha-32P]ATP based assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 377.4, ALogP 3.35, HBA 8, HBD 1, PSA 94.55, QED 0.51
Compound (SMILES): C#Cc1cc(Nc2c(N)oc3c(-c4ccccc4)nccc23)ccc1F
InChIKey: ZYSNIMKMPVZWPB-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of recombinant human TDO2 expressed in CHOK1 cells assessed as reduction in kynurenine formation using L-tryptophan as substrate measured after 2 hrs by LC/MS/MS analysis
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 343.36, ALogP 4.94, HBA 4, HBD 2, PSA 64.08, QED 0.52
Compound (SMILES): Cc1cc(-c2ccc3c(c2)CCC3N2CCC(N(C)C(=O)N[C@@H](C)c3ccc(-c4cnccn4)c(Cl)c3Cl)CC2)ncn1
InChIKey: RUUCIUOBMJBNIZ-UHWFRNQFSA-N
Target: Growth hormone secretagogue receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92847
Assay: Inverse agonist at recombinant human GHSR1a expressed in HEK293 cells assessed as decrease in IP1 accumulation after 1 hr by IP1-d2-based HTRF assay
Measurement: EC50 = 194 nM (pChEMBL 6.710000038146973)
Descriptors: MW 616.6, ALogP 7.07, HBA 6, HBD 1, PSA 87.14, QED 0.25
Compound (SMILES): CCCN1CC(=O)N2[C@H](Cc3c(n(Cc4ccc(C(=O)NO)cc4)c4ccccc34)[C@@H]2C)C1=O
InChIKey: PNSCXVKMXNVVCY-KSFYIVLOSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of human recombinant HDAC2 using RHKKAcAMC as substrate by fluorescence assay
Measurement: IC50 = 1870 nM (pChEMBL 5.730000019073486)
Descriptors: MW 460.53, ALogP 2.88, HBA 5, HBD 2, PSA 94.88, QED 0.45
Compound (SMILES): CC(=O)CC(=O)CC1(O)C(=O)Nc2ccccc21
InChIKey: XPSUBEFPBMRUAP-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of recombinant human TDO assessed as reduction in conversion of L-tryptophan to kynurenine by methylene blue dye based spectrometric method
Measurement: IC50 = 56120 nM (pChEMBL 4.25)
Descriptors: MW 247.25, ALogP 0.76, HBA 4, HBD 2, PSA 83.47, QED 0.77
Compound (SMILES): O=C1S/C(=C\c2ccc(Oc3ccc(F)cc3)cc2)C(=O)N1c1ccc(OCCCCCN2CCN(CC3CC3)CC2)cc1
InChIKey: ZROMFRHIPBBTBU-GIBOGKFOSA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit beta (SINGLE PROTEIN), Homo sapiens
UniProt: O14920
Assay: Inhibition of IKKbeta (unknown origin) using IkappaBalpha-derived 5FAMGRHDSGLDSMK-NH2 as substrate preincubated for 10 mins followed by substrate addition measured after 2 hrs by IMAP based TR-FRET assay
Measurement: IC50 = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 615.77, ALogP 7.44, HBA 7, HBD 0, PSA 62.32, QED 0.15
Compound (SMILES): C=C1C(=O)N[C@@H](C)C(=O)N(C)[C@@H](C)C(=O)N[C@@H]([C@H](OC(=O)[C@@H](NC(=O)c2ccccc2)[C@H](O)C(C)C)C(C)C)C(=O)N(C)[C@@H]([C@@H](C)OC)C(=O)O[C@H](C)[C@H](NC(C)=O)C(=O)O[C@H](Cc2ccccc2)C(=O)N1C
InChIKey: ZFNJRAXTBSDGTJ-ZYUHJPJISA-N
Target: Guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas (SINGLE PROTEIN), Homo sapiens
UniProt: Q5JWF2
Assay: Inhibition of Gs coupled adrenergic beta2 receptor in HEK293 cells assessed as reduction in isoproterenol-induced cAMP production pretreated for 1 hr followed by isoproterenol addition and measured after 30 mins by FRET assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 1022.16
Compound (SMILES): CC(C)c1ccccc1NC(=O)Nc1cc(S(N)(=O)=O)ccc1O
InChIKey: KXUXADXTCVSNDM-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human CA9 assessed as enzyme inhibitor complex formation preincubated for 15 mins and measured for 10 to 100 secs by phenol red dye based stopped-flow CO2 hydrase assay
Measurement: Ki = 179.7 nM (pChEMBL 6.75)
Descriptors: MW 349.41, ALogP 2.81, HBA 4, HBD 4, PSA 121.52, QED 0.63
Compound (SMILES): Nc1oc2c(Cl)nccc2c1Nc1ccc(F)c(Cl)c1
InChIKey: LNGPFHNSHDOTEE-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of recombinant human TDO2 expressed in CHOK1 cells assessed as reduction in kynurenine formation using L-tryptophan as substrate measured after 2 hrs by LC/MS/MS analysis
Measurement: IC50 < 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 312.13, ALogP 4.6, HBA 4, HBD 2, PSA 64.08, QED 0.68
Compound (SMILES): FC(F)c1ccnc(-c2nc(NC3CCC(F)(F)CC3)nc(NC3CCC(F)(F)CC3)n2)n1
InChIKey: KCKMAAKVFCQNEN-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP], mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P48735
Assay: Inhibition of IDH2 R140Q mutant homodimer (unknown origin) expressed in Sf9 cells pre-incubated for 1 hr before addition of alpha-KG followed by 16 hrs incubation in presence of NADPH, NADP, diaphorase and resazurin by fluorescence spectrometry based cofactor depletion assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 475.44, ALogP 5.25, HBA 7, HBD 2, PSA 88.51, QED 0.55
Compound (SMILES): CCCn1c(=O)c2c(nc3n2CCCN3CCc2ccc(OCC(=O)NCc3ccc(Cl)cc3)cc2)n(CCC)c1=O
InChIKey: OBCBOCPBZOTEPP-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Displacement of [3H]PSB-602 from human adenosine A2B receptor expressed in CHO cell membranes
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 593.13, ALogP 3.98, HBA 9, HBD 1, PSA 103.39, QED 0.27
Compound (SMILES): CC1(c2cccc3ccccc23)NC(=O)N(CC(O)CN2CCN(c3ccccc3C#N)CC2)C1=O
InChIKey: KAIYJBUQISWUCP-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Displacement of [3H]-5-carboxamidotryptamine from human 5-HT7B receptor expressed in HEK293 cell membranes after 1 hr by microbeta counting method
Measurement: Ki = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 483.57, ALogP 2.66, HBA 6, HBD 2, PSA 99.91, QED 0.52
Compound (SMILES): CSc1ncc2c(n1)Nc1n[nH]c(C)c1N=C2c1ccc(C)cc1
InChIKey: YDPCOTOJRODRFO-UHFFFAOYSA-N
Target: Aurora kinase A (SINGLE PROTEIN), Homo sapiens
UniProt: O14965
Assay: Inhibition of Aurora A (unknown origin) using STK S2 as substrate after 40 mins by HTRF assay
Measurement: IC50 = 70.6 nM (pChEMBL 7.150000095367432)
Descriptors: MW 336.42, ALogP 3.76, HBA 6, HBD 2, PSA 78.85, QED 0.43
Compound (SMILES): CCCOc1cccc2c(C(=O)c3ccc(OC)cc3)cn(CC3CCOCC3)c12
InChIKey: VPTHEUADMDCNSL-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Inverse agonist activity at N-terminal HA-tagged human CB2 receptor expressed in HEK293 cells transfected with YFP-Epac-RLuc assessed as increase in forskolin-stimulated cAMP level by BRET assay
Measurement: IC50 = 30.6 nM (pChEMBL 7.510000228881836)
Descriptors: MW 407.51, ALogP 5.1, HBA 5, HBD 0, PSA 49.69, QED 0.49
Compound (SMILES): CC(Nc1nc(N[C@H](C)C2CC2)nc(-c2cccc(C(F)(F)F)n2)n1)c1ccccn1
InChIKey: PVBOMIYGGWSXIY-PZORYLMUSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: In Vitro Assays for IDH1m (R132H or R132C): The following describes the experimental procedures that can be used to obtain data on columns 3 and 6 of Table 4.A test compound is prepared as 10 mM stock in DMSO and diluted to 50× final concentration in DMSO, for a 50 μl reaction mixture. IDH enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutaric acid is measured using a NADPH depletion assay. In the assay the remaining cofactor is measured at the end of the reaction with the addition of a catalytic excess of diaphorase and resazurin, to generate a fluorescent signal in proportion to the amount of NADPH remaining. IDH1-R132 homodimer enzyme is diluted to 0.125 μg/ml in 40 μl of Assay Buffer (150 mM NaCl, 20 mM Tris-Cl pH 7.5, 10 mM MgCl2, 0.05% BSA, 2 mM b-mercaptoethanol); 1 μl of test compound dilution in DMSO is added and the mixture is incubated for 60 minutes at room temperature. The reaction is started with the addition of 10 μl of Substrate Mix (20 μl NADPH, 5 mM alpha-ketoglutarate, in Assay Buffer) and the mixture is incubated for 90 minutes at room temperature. The reaction is terminated with the addition of 25 μl of Detection Buffer (36 μg/ml diaphorase, 30 mM resazurin, in 1× Assay Buffer), and is incubated for 1 minute before reading on a SpectraMax platereader at Ex544/Em590.Compounds are assayed for their activity against IDH1 R132C following the same assay as above with the following modifications: Assay Buffer is (50 mM potassium phosphate, pH 6.5; 40 mM sodium carbonate, 5 mM MgCl2, 10% glycerol, 2 mM b-mercaptoethanol, and 0.03% BSA). The concentration of NADPH and alpha-ketoglutarate in the Substrate Buffer is 20 μM and 1 mM, respectively.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 429.45, ALogP 4.73, HBA 7, HBD 2, PSA 88.51, QED 0.56