lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): OC[C@H]1O[C@@H](n2cnc3c(Nc4ccc(CNC(=S)Nc5ccc(N=C=S)cc5)cc4)ncnc32)[C@H](O)[C@@H]1O
InChIKey: QHBDGFBJMKRHNZ-UMCMBGNQSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Irreversible agonist activity at human adenosine A2B receptor expressed in Flp-In-CHO cells assessed as effect on forskolin-induced cAMP accumulation incubated for 30 mins by LANCE cAMP detection assay
Measurement: EC50 = 223.87 nM (pChEMBL 6.650000095367432)
Descriptors: MW 564.65, ALogP 2.4, HBA 12, HBD 6, PSA 161.97, QED 0.14
Compound (SMILES): COc1ccc(N2CCN(Cc3cc(=O)oc4cc(OCc5cccc(Br)c5)ccc34)CC2)cc1
InChIKey: QIMBUXAGULYNFZ-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 preincubated for 10 mins by stopped flow CO2 hydrase assay
Measurement: Ki = 360 nM (pChEMBL 6.440000057220459)
Descriptors: MW 535.44, ALogP 5.47, HBA 6, HBD 0, PSA 55.15, QED 0.29
Compound (SMILES): C[C@]1(c2cc(/C=C(\F)c3ccc(C#N)cn3)ccc2F)N=C(N)S[C@@]2(C(=O)N3CCCCC3)C[C@H]21
InChIKey: SWVMBKBHZPWAQL-VPLUUOPTSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: In Vitro Enzymatic BACE1 and BACE2 FRET (Fluorescence Resonance Energy Transfer) Assays: The cDNAs for both human recombinant BACE1 and 2 with C-terminal 6-His Tags were cloned into transient protein expression vectors, which were subsequently transfected into mammalian cell lines. These recombinant proteins were further purified using Ni-NTA affinity chromatography (Qiagen). The assay buffer used in these screens was 0.05M acetate, pH 4.5, 8% DMSO final, 100 uM genapol (which is a nonionic detergent, below its Critical Micelle Concentration). The Beta Secretase enzyme (0.02 nM for BACE1 and 0.64 nM for BACE2) is pre-incubated for one hour with inhibitors, typically in about 1 uL of DMSO according to a serial dilution, are added thereto. This assay is effectively started by the addition of FRET substrate (50 nM) and the combination is incubated for one hour. The FRET assay is terminated by addition of Tris buffer, which raises the pH to neutrality, and the fluorescence is determined. The FRET substrate is a peptide with commercially available fluorophore and quencher, on opposite sides of the BACE cleavage site. Proteolytic cleavage of the FRET substrate releases quenching of fluorescence (excitation 488 nm and emission 590 nm).
Measurement: IC50 = 0.863 nM (pChEMBL 9.0600004196167)
Descriptors: MW 493.58, ALogP 4.61, HBA 6, HBD 1, PSA 95.37, QED 0.67
Compound (SMILES): N#CC#Cc1cc(-c2nn(-c3nc(C(=O)O)cs3)c(CC3CC3)c2Cc2ccc(S(N)(=O)=O)c(F)c2)ccc1F
InChIKey: PGZYKDIEORGYJV-UHFFFAOYSA-N
Target: L-lactate dehydrogenase A chain (SINGLE PROTEIN), Homo sapiens
UniProt: P00338
Assay: Inhibition of GS[HiBiT]GS-tagged LDHA (unknown origin) expressed in HEK-293T cells measured after 1 hr by CESTA
Measurement: IC50 = 474 nM (pChEMBL 6.320000171661377)
Descriptors: MW 579.61, ALogP 4.04, HBA 8, HBD 2, PSA 151.96, QED 0.3
Compound (SMILES): Cc1cc(-c2ccc3nc(N)nn3c2)cc2c1C(=O)N([C@@H](C)C1CC1)C2
InChIKey: DNBUJELVNKASMK-LBPRGKRZSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: O00329
Assay: Inhibition of recombinant N-terminal GST-tagged full-length human PI3K p110delta/p85alpha co- expressed in Sf9 insect cells using phosphatidylinositol 4,5-bisphosphate as substrate preincubated for 60 mins followed by substrate addition and measured after 1 hr in presence of ATP by ADP-Glo lipid kinase assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 347.42, ALogP 3.04, HBA 5, HBD 1, PSA 76.52, QED 0.79
Compound (SMILES): CN(C)C(=O)c1ccccc1Nc1nc(Nc2ccc3nc(CN4CCCC4)[nH]c3c2)ncc1Cl
InChIKey: WTEVQSAOHYKUTI-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of N-terminal GST-tagged human EGFR cytoplasmic domain (669 to 1210 residues) expressed in baculovirus infected Sf21 insect cells using Srctide as substrate measured after 1 hr by mobility shift assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 491, ALogP 4.79, HBA 7, HBD 3, PSA 102.07, QED 0.34
Compound (SMILES): Fc1ccc(CCCCN2C3CCC2CN(c2ccc(Cl)cn2)C3)cc1
InChIKey: ZMDOIQGPLNKPIO-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]-ketanserin from human 5HT2A receptor by liquid scintillation counting
Measurement: Ki = 94 nM (pChEMBL 7.03000020980835)
Descriptors: MW 373.9, ALogP 4.55, HBA 3, HBD 0, PSA 19.37, QED 0.69
Compound (SMILES): O=C(Nc1ccc(Cl)cc1)C(=O)N1CCC(c2ccnc3ccc(F)cc23)CC1
InChIKey: BBNKZBRNGRLKCM-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 411.86, ALogP 4.37, HBA 3, HBD 1, PSA 62.3, QED 0.64
Compound (SMILES): O=c1oc2ccccc2cc1/C(CS(=O)(=O)c1ccccc1)=N/Nc1ccccc1
InChIKey: FBVOELWYHQIQAI-NJNXFGOHSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human CA12 preincubated for 6 hrs by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 1810 nM (pChEMBL 5.739999771118164)
Descriptors: MW 418.47, ALogP 4.08, HBA 6, HBD 1, PSA 88.74, QED 0.29
Compound (SMILES): CC(C)OC(=O)N1CCC(n2cc(C(=O)Nc3cc4cc(-c5cnn(C)c5)ccc4cn3)cn2)CC1
InChIKey: BLTBQJGRPVGLKM-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Kinase Assay: Briefly, recombinant GSK3β kinase, ATP and Ser/Thr peptide 09 are prepared in 1× Kinase buffer to final concentrations of 0.04 μg/mL, 46 μM, and 4 μM respectively. The mixture is allowed to incubate with the representative compounds for one hour at room temperature. All reactions were performed in duplicate. Unphosphorylated (0% Control) and phosphorylated (100% control) forms of Ser/Thr 18 serve as control reactions.After incubation, diluted Development Buffer is added to the reaction and allowed to further incubate for one hour at room temperature. The plate is read at Ex 400 Em 455 to detect the coumarin signal and Ex 400 Em 520 to measure the signal (EnVision Multilabel Plate Reader, PerkinElmer).
Measurement: EC50 = 4175 nM (pChEMBL 5.380000114440918)
Descriptors: MW 487.56, ALogP 4.27, HBA 8, HBD 1, PSA 107.17, QED 0.45
Compound (SMILES): COc1cc(OCc2ccnc(N)c2Cl)cc2sc(N[C@@H]3CCCC[C@H]3O)nc12
InChIKey: DICVVUCQTSNJLU-ZIAGYGMSSA-N
Target: Mast/stem cell growth factor receptor Kit (SINGLE PROTEIN), Homo sapiens
UniProt: P10721
Assay: Binding affinity to c-Kit (unknown origin) by kinome scan assay
Measurement: Kd = 30000 nM (pChEMBL 4.519999980926514)
Descriptors: MW 434.95, ALogP 4.23, HBA 8, HBD 3, PSA 102.52, QED 0.53
Compound (SMILES): CNCC[C@@H](Oc1cccc(N2CCN(C)CCC2=O)c1)c1cccs1
InChIKey: SOZQYEAKFLBWCU-GOSISDBHSA-N
Target: Voltage-dependent calcium channel subunit alpha-2/delta-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P54289
Assay: Binding Assay : Human α2δ-1 enriched membranes (2.5 μg) were incubated with 15 nM of radiolabeled [3H]-Gabapentin in assay buffer containing Hepes-KOH 10 mM, pH 7.4.NSB (non specific binding) was measured by adding 10 μM pregabalin. The binding of the test compound was measured in five different concentrations. After 60 min incubation at 27° C., binding reaction was terminated by filtering through Multiscreen GF/C (Millipore) presoaked in 0.5% polyethyleneimine in Vacuum Manifold Station, followed by 3 washes with ice-cold filtration buffer containing 50 mM Tris-HCl, pH 7.4.Filter plates were dried at 60° C. for 1 hour and 30 μl of scintillation cocktail were added to each well before radioactivity reading.Readings were performed in a Trilux 1450 Microbeta radioactive counter (Perkin Elmer).
Measurement: Ki = 1750 nM (pChEMBL 5.760000228881836)
Descriptors: MW 373.52, ALogP 3.15, HBA 5, HBD 1, PSA 44.81, QED 0.81
Compound (SMILES): c1ccc(CNCC[C@@H]2CCC[C@@H](c3ccccc3)C2)cc1
InChIKey: SSLAKSDPAPMJKU-GHTZIAJQSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q5U3Y7
Assay: Displacement of [3H]-di-o-tolylguanidine from sigma2 receptor in rat liver membrane incubated for 120 mins by liquid scintillation counting method relative to control
Measurement: Ki = 57 nM (pChEMBL 7.239999771118164)
Descriptors: MW 293.45, ALogP 5.14, HBA 1, HBD 1, PSA 12.03, QED 0.73
Compound (SMILES): Cc1cnc(OCCNCC2(F)CCN(C(=O)c3ccc(F)c(Cl)c3)CC2)nc1
InChIKey: BLJZKXJVIGQCID-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Biased agonist activity at human recombinant 5-HT1A receptor stably expressed in CHO-K1 cells assessed as inhibition of forskolin-induced cAMP accumulation after 40 mins by LANCE Ultra cAMP kit-based TR-FRET assay
Measurement: EC50 = 933.25 nM (pChEMBL 6.03000020980835)
Descriptors: MW 424.88, ALogP 3.19, HBA 5, HBD 1, PSA 67.35, QED 0.69
Compound (SMILES): Cc1ccc(-c2c3c(nn2C(C)C)CCNCC3)cc1
InChIKey: OLFYDDVREGSNQJ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P32305
Assay: Displacement of [3H]-CT from rat 5-HT7 receptor expressed in HEK293 cells by competitive radioligand binding assay
Measurement: Ki = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 269.39, ALogP 3.13, HBA 3, HBD 1, PSA 29.85, QED 0.91
Compound (SMILES): C[C@@H]1CN(c2ccc(C(C)(C)O)nc2)CCN1c1cccc(C(=O)NC2C3CC4CC2CC(O)(C4)C3)n1
InChIKey: UNRPWLPNKUXWDT-JMBJFCBPSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in pooled human liver microsomes using mephenytoin as substrate in presence of NADPH incubated for 10 mins by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 505.66, ALogP 3.09, HBA 7, HBD 3, PSA 101.82, QED 0.57
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(C)CC2)c1[nH]c(-c2ccc(-c3cccnc3)cc2)nc1C#N
InChIKey: BWTPSSSOMLHHKD-IZLXSDGUSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of HDAC3 (unknown origin)
Measurement: IC50 = 0.3 nM (pChEMBL 9.520000457763672)
Descriptors: MW 552.72, ALogP 5.83, HBA 6, HBD 2, PSA 114.77, QED 0.27
Compound (SMILES): CN(C)CCN1C(=O)c2ccccc2/C=C\c2ccccc21
InChIKey: YFINOLWYBYMFPQ-QXMHVHEDSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Binding affinity to 5HT1A receptor (unknown origin)
Measurement: Ki = 77200 nM (pChEMBL 4.110000133514404)
Descriptors: MW 292.38, ALogP 3.38, HBA 2, HBD 0, PSA 23.55, QED 0.87
Compound (SMILES): Cc1cc(Cl)cc(N2C=Nc3cc(C)c(-c4cccc(F)c4O)cc3C2C(=O)N(C)C[C@@H]2CCCN2)c1
InChIKey: FGVUWBKWBAZBPK-SVQMELKDSA-N
Target: Somatostatin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P30874
Assay: Agonist activity at SST2 (unknown origin)
Measurement: EC50 = 0.7943 nM (pChEMBL 9.100000381469727)
Descriptors: MW 521.04, ALogP 5.9, HBA 5, HBD 2, PSA 68.17, QED 0.44
Compound (SMILES): Cc1ccccc1N1CCN(C(=O)C2CN(C(=O)C3CCCCC3)Cc3cc(Cl)ccc32)CC1
InChIKey: RBIRVXJGAJBPAV-UHFFFAOYSA-N
Target: Vasopressin V1a receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P37288
Assay: Antagonist activity at human V1a receptor expressed in human 1321N1 cells assessed as decrease in Arg8-vasopressin-stimulated calcium flux by fluorometric calcium assay
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 480.05, ALogP 5, HBA 3, HBD 0, PSA 43.86, QED 0.62
Compound (SMILES): CC1(CNc2cc(F)c(S(=O)(=O)Nc3nccs3)cc2Cl)CCCN1
InChIKey: AYTPMWAPDMTVKH-UHFFFAOYSA-N
Target: Sodium channel protein type 8 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQD0
Assay: Inhibition of human Nav1.6 alpha expressed in HEK293 cells incubated for 5 mins with 6 consecutive train pulses to -10 mV at 0.1 Hz and holding potential of -65 mV by Qube-automated patch clamp assay
Measurement: IC50 = 860 nM (pChEMBL 6.070000171661377)
Descriptors: MW 404.92, ALogP 3.29, HBA 6, HBD 3, PSA 83.12, QED 0.69
Compound (SMILES): Nc1nnc(-c2ccccc2O)cc1N1CCNCC1
InChIKey: SZKHGLTYXIDOFH-UHFFFAOYSA-N
Target: SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P51531
Assay: Inhibition of SMARCA2 BD (unknown origin)
Measurement: IC50 = 370 nM (pChEMBL 6.429999828338623)
Descriptors: MW 271.32, ALogP 0.84, HBA 6, HBD 3, PSA 87.3, QED 0.75
Compound (SMILES): Cc1ccc(NC(=O)NCCS(=O)(=O)Nc2ccc(S(N)(=O)=O)cc2)cc1
InChIKey: YDAOBULQBPBUCA-UHFFFAOYSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Inhibition of recombinant human carbonic anhydrase 7 incubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 737.7 nM (pChEMBL 6.130000114440918)
Descriptors: MW 412.49, ALogP 1.21, HBA 5, HBD 4, PSA 147.46, QED 0.54
Compound (SMILES): CNCCC(Oc1cccc(N2CCN(C)c3nc(N(C)C)ncc3C2=O)c1)c1cccs1
InChIKey: YCGNFTGPXBAEMC-UHFFFAOYSA-N
Target: Voltage-dependent calcium channel subunit alpha-2/delta-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P54289
Assay: Binding Assay: α2δ-1: Binding Assay to Human α2δ-1 Subunit of Cav2.2 Calcium Channel.Human α2δ-1 enriched membranes (2.5 μg) were incubated with 15 nM of radiolabeled [3H]-Gabapentin in assay buffer containing Hepes-KOH 10 mM, pH 7.4.NSB (non specific binding) was measured by adding 10 μM pregabalin. After 60 min incubation at 27° C., binding reaction was terminated by filtering through Multiscreen GF/C (Millipore) presoaked in 0.5% polyethyleneimine in Vacuum Manifold Station, followed by 3 washes with ice-cold filtration buffer containing 50 mM Tris-HCl, pH 7.4.Filter plates were dried at 60° C. for 1 hour and 30 μl of scintillation cocktail were added to each well before radioactivity reading.Readings were performed in a Trilux 1450 Microbeta radioactive counter (Perkin Elmer).
Measurement: Ki = 1750 nM (pChEMBL 5.760000228881836)
Descriptors: MW 466.61, ALogP 3.43, HBA 8, HBD 1, PSA 73.83, QED 0.55
Compound (SMILES): NS(=O)(=O)c1ccc(NC(=O)CSC(=S)N2CCN(c3ccc([N+](=O)[O-])cc3)CC2)cc1
InChIKey: CLELFAQDDCZPPC-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human erythrocyte CA2 using 4-nitrophenyl acetate as substrate by Lineweaver-Burk plot analysis
Measurement: Ki = 2027 nM (pChEMBL 5.690000057220459)
Descriptors: MW 495.61, ALogP 2.02, HBA 8, HBD 2, PSA 138.88, QED 0.35
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CS)NC(=O)[C@H](Cc1ccccc1)NC(=O)CNC(=O)[C@H](CS)NC(=O)[C@@H](N)Cc1ccc(O)cc1)C(=O)N[C@@H](Cc1ccccc1)C(N)=O
InChIKey: HTRPGUCLEKHUTO-TZPCGENMSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Agonist activity at kappa opioid receptor (unknown origin) expressed in HEK293-A cells assessed as inhibition of forskolin-stimulated cAMP accumulation incubated for 30 mins by competition PKA binding assay
Measurement: EC50 = 184 nM (pChEMBL 6.739999771118164)
Descriptors: MW 1119.34
Compound (SMILES): Nc1nc2ccccn2c1-c1ccc(O)cc1
InChIKey: YAVLEYZGIQRBDK-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: P54578
Assay: Inhibition of USP14 (unknown origin)
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 225.25, ALogP 2.29, HBA 4, HBD 2, PSA 63.55, QED 0.67
Compound (SMILES): COc1ccc(C(=O)Nc2nc(-c3ccccc3)c(-c3nc4ccccc4c(=O)n3-c3ccc(OC)cc3)s2)cc1
InChIKey: UFKAMNUQGBWBJM-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Rattus norvegicus
UniProt: P30543
Assay: Displacement of [3H]MSX2 from adenosine receptor A2A in rat brain striatum membranes incubated for 30 mins by radioligand competition assay
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 560.64, ALogP 6.45, HBA 8, HBD 1, PSA 95.34, QED 0.24
Compound (SMILES): Cc1c(C(=O)/C=C/Nc2cc(Cl)c(S(N)(=O)=O)cc2S(N)(=O)=O)sc2nc3ccccc3n12
InChIKey: JXTWQUKZLNDKPN-VOTSOKGWSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human CA12 preincubated for 15 mins prior to testing by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 6.1 nM (pChEMBL 8.210000038146973)
Descriptors: MW 526.02, ALogP 2.61, HBA 9, HBD 3, PSA 166.72, QED 0.26
Compound (SMILES): Cc1cc(/C=C/C#N)cc(C)c1Oc1nc(Nc2ccc(CN3CCN(S(N)(=O)=O)CC3)cc2)nc2sccc12
InChIKey: FXIKTRNSOFEJNE-ONEGZZNKSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of reverse transcriptase E138K mutant in HIV-1 infected in human MT4 cells assessed as reduction in virus-induced cytopathic effect incubated for 5 days by MTT assay
Measurement: EC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 575.72, ALogP 4.7, HBA 9, HBD 2, PSA 137.47, QED 0.29
Compound (SMILES): CNC(=O)c1cnc2[nH]ccc2c1NCC1CCN(Cc2ccc(Cl)cc2)CC1
InChIKey: JYFUVKPUCJATNL-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of recombinant TYK2 (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 = 48.9 nM (pChEMBL 7.309999942779541)
Descriptors: MW 411.94, ALogP 3.9, HBA 4, HBD 3, PSA 73.05, QED 0.57
Compound (SMILES): N#Cc1ccc(/C=C/C(=O)Nc2ccc3c(c2)C=CS(=O)(=O)O3)cc1
InChIKey: ARJYJMVBLZXLQL-VMPITWQZSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 assessed as inhibition constant preincubated with enzyme for 10 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 519.9 nM (pChEMBL 6.28000020980835)
Descriptors: MW 352.37, ALogP 2.9, HBA 5, HBD 1, PSA 96.26, QED 0.68
Compound (SMILES): CCCCCCCC/C=C\CCCCCCCC(=O)OC[C@@H](COCc1ccccc1)OP(=O)(O)OC[C@H](N)C(=O)O
InChIKey: CLPCIRZHATVKCL-BDZCPYMJSA-N
Target: Putative P2Y purinoceptor 10 (SINGLE PROTEIN), Mus musculus
UniProt: Q8BFU7
Assay: Agonist activity at mouse P2Y10 expressed in HEK293 cells co-transfected with AP-TGFalpha/Galphaq/i1 assessed as induction of ectodomain shedding of membrane bound AP-TGFalpha after 1 hr by p-NPP substrate based microplate reader analysis
Measurement: EC50 = 1380.38 nM (pChEMBL 5.860000133514404)
Descriptors: MW 613.73, ALogP 6.7, HBA 8, HBD 3, PSA 154.61, QED 0.04
Compound (SMILES): CC(C)N1CCC(c2ccc(/C(=C(/CCCO)c3ccc(F)cc3)c3ccc(O)cc3)cc2)CC1.Cl
InChIKey: ZGYAUKANTNTUQP-FJISBNMDSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Binding affinity to ERalpha (unknown origin) by TR-FRET assay
Measurement: IC50 = 2494 nM (pChEMBL 5.599999904632568)
Descriptors: MW 473.63, ALogP 6.85, HBA 3, HBD 2, PSA 43.7, QED 0.35
Compound (SMILES): O=c1c2cc(Cl)ccc2oc2ccc(OCCCCCCN3CCCCCC3)cc12
InChIKey: IGORWQONHHRXPZ-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of recombinant human MAO-B expressed in baculovirus infected BTI cells using p-tyramine as substrate by fluorometric assay
Measurement: IC50 = 1387 nM (pChEMBL 5.860000133514404)
Descriptors: MW 427.97, ALogP 6.41, HBA 4, HBD 0, PSA 42.68, QED 0.31
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 inhibition of forskolin-induced cAMP accumulation after 40 mins by LANCE Ultra cAMP kit-based TR-FRET assay
Measurement: EC50 = 562.34 nM (pChEMBL 6.25)
Descriptors: MW 438.9, ALogP 4.1, HBA 4, HBD 1, PSA 50.8, QED 0.63
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 1a 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 = 0.47 nM (pChEMBL 9.329999923706055)
Descriptors: MW 863.03, ALogP 7.63, HBA 8, HBD 4, PSA 174.64, QED 0.1
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: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of HDAC3 (unknown origin) by fluorescence based assay
Measurement: IC50 = 1440.5 nM (pChEMBL 5.840000152587891)
Descriptors: MW 607.71, ALogP 5.31, HBA 7, HBD 5, PSA 151.47, QED 0.14
Compound (SMILES): Nc1nn2cc(-c3ccc(Cl)cc3)[nH]c2c1/N=N/c1ccc(S(N)(=O)=O)cc1
InChIKey: KBRGTQDAHIIWBV-GHVJWSGMSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 preincubated with enzyme for 15 mins by phenol red dye based stopped flow CO2 hydrase assay
Measurement: Ki = 36.5 nM (pChEMBL 7.440000057220459)
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: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity at human MOR expressed in CHO cell membranes incubated for 60 mins scintillation counting assay
Measurement: EC50 = 1.45 nM (pChEMBL 8.84000015258789)
Descriptors: MW 432.47, ALogP 0.72, HBA 7, HBD 4, PSA 128.56, QED 0.51
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: Ki = 4.7 nM (pChEMBL 8.329999923706055)
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: PI3K p110 beta/p85 alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of recombinant human PI3K p110beta/p85alpha using phosphatidylinositol 4,5-bisphosphate as substrate preincubated for 15 mins followed by addition of ATP and measured after 30 mins by fluorescence polarisation assay
Measurement: Ki = 11 nM (pChEMBL 7.960000038146973)
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 4B (SINGLE PROTEIN), Homo sapiens
UniProt: Q07343
Assay: Inhibition of human PDE4B 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 CLK4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HAZ1
Assay: Inhibition of human recombinant CLK4 using YRRAAVPPSPSLS 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 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Inhibition of recombinant human carbonic anhydrase 7 preincubated with enzyme for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 510 nM (pChEMBL 6.289999961853027)
Descriptors: MW 335.93, ALogP 1.27, HBA 4, HBD 2, PSA 74.6, QED 0.55
Compound (SMILES): O=S(=O)(N[C@@H]1CCN(CCCc2noc3ccccc23)C1)c1ccc2ccccc2c1
InChIKey: QGVGRVIBOJVENZ-HXUWFJFHSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-methylspiperone from recombinant human D2 receptor expressed in CHOK1 cell membranes measured after 60 mins by microbeta counting method
Measurement: Ki = 0.1995 nM (pChEMBL 9.699999809265137)
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: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of human TDO expressed in Escherichia coli Rosetta using tryptophan as substrate incubated for 1 hr by methylene blue based assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
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 (High ATP Concentration): 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 (1.5 nM CDK9/CycT1, 5 mM 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 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 445.95, ALogP 3.31, HBA 6, HBD 3, PSA 109.14, QED 0.67
Compound (SMILES): Nc1cc([C@H](CCN[C@H]2C[C@@H](c3ccccc3)c3ccccc32)c2ccccc2)c2nn[nH]c2n1
InChIKey: PUZMDZNRNPQCRQ-DSBYRVASSA-N
Target: Eosinophil peroxidase (SINGLE PROTEIN), Homo sapiens
UniProt: P11678
Assay: Inhibition of human EPX bromination activity using tyrosine as substrate by measuring 3-bromo tyrosine formation incubated for 10 mins
Measurement: IC50 = 92 nM (pChEMBL 7.039999961853027)
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: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of recombinant TYK2 (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 = 586 nM (pChEMBL 6.230000019073486)
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 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: HDAC Inhibition: These SAR data indicate that a tripartite structure of this scaffold with a central C(O)NHNH unit flanked by a phenyl group and a short aliphatic chain increases HDAC inhibition. As for the phenyl group, the presence of a relatively bulky substituent at the para position relative to the carbonyl group also affords potent HDAC inhibitors.
Measurement: IC50 = 1910 nM (pChEMBL 5.71999979019165)
Descriptors: MW 222.29, ALogP 1.73, HBA 3, HBD 2, PSA 50.36, QED 0.57
Compound (SMILES): CNC(=O)c1cnc2[nH]ccc2c1NC1CCCN(Cc2ccc(C#N)cc2)CC1
InChIKey: KJXRBJQOXNHDRP-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of recombinant TYK2 (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 = 120 nM (pChEMBL 6.920000076293945)
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: Neurotensin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30989
Assay: Displacement of [125I]-neurotensin from human recombinant NTS1 stably expressed in CHO-K1 cell membranes incubated for 60 mins by gamma counter method
Measurement: Ki = 59 nM (pChEMBL 7.230000019073486)
Descriptors: MW 1338.66
Compound (SMILES): Cc1ccnc2c1CC[C@@H]1CNCCN21
InChIKey: WCZLKBAQARPHLD-SNVBAGLBSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
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 = 2.95 nM (pChEMBL 8.529999732971191)
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 GS[HiBiT]GS-tagged LDHA (unknown origin) expressed in HEK-293T cells measured after 1 hr by CESTA
Measurement: IC50 = 89 nM (pChEMBL 7.050000190734863)
Descriptors: MW 624.69, ALogP 4.55, HBA 8, HBD 2, PSA 137.4, QED 0.27
Compound (SMILES): COc1cc(/C=C/C(=O)Nc2ccc3oc(=O)ccc3c2)cc(OC)c1OC
InChIKey: JLBSOIAPINYYML-XBXARRHUSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 assessed as inhibition constant preincubated with enzyme for 10 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 149.3 nM (pChEMBL 6.829999923706055)
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-sensitive MEL1617 cells assessed as reduction in STAT3 transcriptional activity measured after 12 hrs by Dual-luciferase reporter gene assay
Measurement: IC50 = 10300 nM (pChEMBL 4.989999771118164)
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: Voltage-dependent calcium channel subunit alpha-2/delta-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P54289
Assay: Binding Assay : Human α2δ-1 enriched membranes (2.5 μg) were incubated with 15 nM of radiolabeled [3H]-Gabapentin in assay buffer containing Hepes-KOH 10 mM, pH 7.4.NSB (non specific binding) was measured by adding 10 μM pregabalin. The binding of the test compound was measured in five different concentrations. After 60 min incubation at 27° C., binding reaction was terminated by filtering through Multiscreen GF/C (Millipore) presoaked in 0.5% polyethyleneimine in Vacuum Manifold Station, followed by 3 washes with ice-cold filtration buffer containing 50 mM Tris-HCl, pH 7.4.Filter plates were dried at 60° C. for 1 hour and 30 μl of scintillation cocktail were added to each well before radioactivity reading.Readings were performed in a Trilux 1450 Microbeta radioactive counter (Perkin Elmer).
Measurement: Ki = 1750 nM (pChEMBL 5.760000228881836)
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: Binding affinity to human GPX4 assessed as dissociation constant by MST assay
Measurement: Kd = 43.7 nM (pChEMBL 7.360000133514404)
Descriptors: MW 440.88, ALogP 3.21, HBA 5, HBD 1, PSA 88.7, QED 0.5
Compound (SMILES): NS(=O)(=O)c1ccc(NC(=O)CSC(=S)N2CCN(c3ccccn3)CC2)cc1
InChIKey: XAMNSCDFHCYFPT-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human erythrocyte CA2 using 4-nitrophenyl acetate as substrate by Lineweaver-Burk plot analysis
Measurement: Ki = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 451.6, ALogP 1.51, HBA 7, HBD 2, PSA 108.63, QED 0.66
Compound (SMILES): Oc1cncc(-c2ccc3[nH]nc(-c4nc5c(-c6cccc(F)c6)ccnc5[nH]4)c3c2)c1
InChIKey: BZXOXNSMVCRHKP-UHFFFAOYSA-N
Target: Proto-oncogene Wnt-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P04628
Assay: The screening assay for Wnt activity: Reporter cell lines can be generated by stably transducing cancer cell lines (e.g., colon cancer) or primary cells (e.g., IEC-6 intestinal cells) with a lentiviral construct that includes a Wnt-responsive promoter driving expression of the firefly luciferase gene.SW480 colon carcinoma cells were transduced with a lentiviral vector expressing luciferase with a human Sp5 promoter consisting of a sequence of eight TCF/LEF binding sites. SW480 cells stably expressing the Sp5-Luc reporter gene and a hygromycin resistance gene were selected by treatment with 150 μg/ml of hygromycin for 7 days. These stably transduced SW480 cells were expanded in cell culture and used for all further screening activities. For Sp5-Luc reporter gene assays, the cells were plated at 10,000 cells/well in 96-well plates with growth medium containing 10% fetal calf serum and incubated overnight at 37° C. and 5% CO2. Each compound was dissolved in DMSO as a 10 mM stock in standard j-vials and used to prepare compound source plates in dose-response format with 3-fold serial dilutions and a 10 mM top concentration. Compound transfer from serially diluted source plates to assay plates containing the cells was accomplished using a pintool (Multimek 96, Beckman equipped with V&P Scientific FP1S50H pins) based liquid handling protocol. This protocol used a slotted pin to transfer 50 nl of compound from a source plate well to an assay plate well containing 50 μl of cells in growth medium. The 1000-fold dilution resulted in a final DMSO concentration of 0.1% on the cells in each well. Control wells received 50 nl of DMSO treatment for normalization and calculating IC50 values. The treated cells were incubated at 37° C. and 5% CO2 for an additional forty-two hours. Following incubation, the growth medium was removed and 50 μl of BrightGlo luminescence reagent (Promega) was added to each well of the 96-well assay plates. The plates were placed on an orbital shaker for 5 min and then luminescence was quantified on the Victor3 (Perkin Elmer) plate reader. Readings were normalized to DMSO only treated cells, and normalized activities were utilized for IC50 calculations using the dose-response log (inhibitor) vs. responsevariable slope (four parameters) nonlinear regression feature available in GraphPad Prism 5.0 or 6.0.
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
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 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 incubated for 6 hrs prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 5.3 nM (pChEMBL 8.279999732971191)
Descriptors: MW 327.28, ALogP 3.46, HBA 4, HBD 0, PSA 56.26, QED 0.75
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 inhibition of forskolin-induced cAMP accumulation after 40 mins by LANCE Ultra cAMP kit-based TR-FRET assay
Measurement: EC50 = 42.66 nM (pChEMBL 7.369999885559082)
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 M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: Displacement of [3H]-NMS from muscarinic M1 receptor (unknown origin) expressed in CHO-K1 cell membranes assessed as inhibition constant by radioligand competition analysis
Measurement: Ki = 1122.02 nM (pChEMBL 5.949999809265137)
Descriptors: MW 287.39, ALogP 2.92, HBA 4, HBD 1, PSA 45.23, QED 0.94
Compound (SMILES): CNCCC(Oc1cccc(N2CCN(C)c3cnccc3C2=O)c1)c1cccs1
InChIKey: SFDCNWPOHFHZDB-UHFFFAOYSA-N
Target: Voltage-dependent calcium channel subunit alpha-2/delta-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P54289
Assay: Binding Assay : Human α2δ-1 enriched membranes (2.5 μg) were incubated with 15 nM of radiolabeled [3H]-Gabapentin in assay buffer containing Hepes-KOH 10 mM, pH 7.4.NSB (non specific binding) was measured by adding 10 μM pregabalin. The binding of the test compound was measured in five different concentrations. After 60 min incubation at 27° C., binding reaction was terminated by filtering through Multiscreen GF/C (Millipore) presoaked in 0.5% polyethyleneimine in Vacuum Manifold Station, followed by 3 washes with ice-cold filtration buffer containing 50 mM Tris-HCl, pH 7.4.Filter plates were dried at 60° C. for 1 hour and 30 μl of scintillation cocktail were added to each well before radioactivity reading.Readings were performed in a Trilux 1450 Microbeta radioactive counter (Perkin Elmer).
Measurement: Ki = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 422.55, ALogP 3.97, HBA 6, HBD 1, PSA 57.7, QED 0.62
Compound (SMILES): O=C(NO)c1ccc(NC(=O)c2ccc(C3CC3)cc2)cc1
InChIKey: AZQYECILTLBYIV-UHFFFAOYSA-N
Target: Histone deacetylase 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96DB2
Assay: Inhibition of recombinant full length human HDAC11 expressed in SF9 baculovirus using FAM- labelled acetylated peptide as substrate measured by Electrophoretic mobility shift assay
Measurement: IC50 = 704 nM (pChEMBL 6.150000095367432)
Descriptors: MW 296.33, ALogP 2.94, HBA 3, HBD 3, PSA 78.43, QED 0.6
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: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of His6/TEV fused-GST-tagged Flt3 (unknown origin) (H564 to S993 residues) using Axltide (CKKSRGDYMTMQJ-acid) peptide as substrate preincubated for 30 mins followed by substrate and ATP addition at Km concentration measured after 75 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): c1cncc(-c2ccnc3[nH]c(-c4n[nH]c5ncc(-c6cncc(CN7CCCCC7)c6)cc45)cc23)c1
InChIKey: OLBDNEBUSBYBHZ-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 = 69 nM (pChEMBL 7.159999847412109)
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: Collagenase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P45452
Assay: Inhibition of recombinant human MMP13 (104 to 274 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 = 41000 nM (pChEMBL 4.389999866485596)
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 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UKV0
Assay: Inhibition of HDAC9 (unknown origin) using Boc Lys(TFA) as substrate by fluorogenic assay
Measurement: IC50 = 70 nM (pChEMBL 7.159999847412109)
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: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of BRD4 (unknown origin) by radiometric ATP-competitive kinase assay
Measurement: IC50 = 109.3 nM (pChEMBL 6.960000038146973)
Descriptors: MW 573.75, ALogP 4.79, HBA 10, HBD 2, PSA 113.33, QED 0.39
Compound (SMILES): COc1ccc(OC)c(-c2nnc(-c3cccc(S(N)(=O)=O)c3)o2)c1
InChIKey: YRABJYQCLKEVCS-UHFFFAOYSA-N
Target: Carbonic anhydrase 13 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N1Q1
Assay: Inhibition of recombinant human carbonic anhydrase 13 by stopped flow CO2 hydrase assay
Measurement: Ki = 31.4 nM (pChEMBL 7.5)
Descriptors: MW 361.38, ALogP 2.07, HBA 7, HBD 1, PSA 117.54, QED 0.74
Compound (SMILES): CN(C)Cc1nc2ccc(Nc3ncc(Cl)c(Nc4ccccc4NS(C)(=O)=O)n3)cc2[nH]1
InChIKey: OHMKUKNYYOHYNP-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of N-terminal GST-tagged human EGFR cytoplasmic domain (669 to 1210 residues) expressed in baculovirus infected Sf21 insect cells using Srctide as substrate measured after 1 hr by mobility shift assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
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 CLK4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HAZ1
Assay: Inhibition of human recombinant CLK4 using YRRAAVPPSPSLS 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: Macrophage metalloelastase (SINGLE PROTEIN), Homo sapiens
UniProt: P39900
Assay: Inhibition of human recombinant MMP12 using Mca-Lys-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 substrate by spectrophotometry
Measurement: Ki = 11.8 nM (pChEMBL 7.929999828338623)
Descriptors: MW 336.39, ALogP 1.36, HBA 4, HBD 4, PSA 115.73, QED 0.4
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 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in pooled human liver microsomes using mephenytoin as substrate in presence of NADPH incubated for 10 mins by LC-MS/MS analysis
Measurement: IC50 = 3700 nM (pChEMBL 5.429999828338623)
Descriptors: MW 524.69, ALogP 2.87, HBA 7, HBD 2, PSA 102.84, QED 0.62
Compound (SMILES): CN1CCN(c2ccc(C(=O)Nc3cc4cc(-c5cnn6c5CN(CCF)CC6)ccc4cn3)cn2)CC1
InChIKey: OJQUMPNKISYUBU-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: GSK3 beta kinase assay: Briefly, recombinant GSK3β kinase, ATP and Ser/Thr peptide 09 are prepared in 1× Kinase buffer to final concentrations of 0.04 μg/mL, 46 μM, and 4 μM respectively. The mixture is allowed to incubate with the representative compounds for one hour at room temperature. All reactions were performed in duplicate. Unphosphorylated (0% Control) and phosphorylated (100% control) forms of Ser/Thr 18 serve as control reactions. After incubation, diluted Development Buffer is added to the reaction and allowed to further incubate for one hour at room temperature. The plate is read at Ex 400 Em 455 to detect the coumarin signal and Ex 400 Em 520 to measure the signal (EnVision Multilabel Plate Reader, PerkinElmer). The Emission ratio (Em) is calculated as a ratio of the coumarin (C) emission signal (at 445 nm)/Fluorescein (F) emission signal (at 520 nm). The percent phosphorylation is then calculated using the following formula: [1−((Em ratio×F100%)−C100%)/((C0%−C100%)+(Em ratio×(F100%−F0%)))].
Measurement: EC50 = 780 nM (pChEMBL 6.110000133514404)
Descriptors: MW 514.61, ALogP 3.28, HBA 8, HBD 1, PSA 82.42, QED 0.42
Compound (SMILES): CCn1nc2c(c1Nc1nc(-c3ccc(-n4cnc(C)c4)c(OC)n3)cs1)CCC2(C)C
InChIKey: QVXGQFQOUQCCDN-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of recombinant CYP2C9 (unknown origin) by fluorescence-based assay
Measurement: IC50 = 48000 nM (pChEMBL 4.320000171661377)
Descriptors: MW 449.58, ALogP 4.89, HBA 9, HBD 1, PSA 82.68, QED 0.45
Compound (SMILES): COc1ccc2cc3[n+](cc2c1OCc1ccc2ccccc2c1)CCc1cc2c(cc1-3)OCO2.[Br-]
InChIKey: CIFGXRFRTRCQAC-UHFFFAOYSA-M
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Mixed inhibition of human butyrylcholinesterase assessed as affinity towards free enzyme using butyrylthiocholine iodide as substrate measured by Ellman's method based Lineweaver-Burk plot analysis
Measurement: Ki = 8.34 nM (pChEMBL 8.079999923706055)
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: Lysophosphatidylserine lipase ABHD12 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N2K0
Assay: Inhibition of human ABHD12 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 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 133 nM (pChEMBL 6.880000114440918)
Descriptors: MW 533.01, ALogP 4.84, HBA 8, HBD 2, PSA 124.49, QED 0.23