lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CCc1cc(O)c(F)cc1-c1cc(N(C)CCO)c2nc(N)ncc2c1
InChIKey: SXJRNQUKDNTVAI-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of GST-tagged recombinant human JAK2 (808 to 1132 residues) expressed in baculovirus expression system using ULight-JAK-1 Tyr1023 peptide as substrate preincubated for 30 mins followed by substrate addition and further incubated for 20 mins in presence of ATP by FRET assay
Measurement: IC50 = 12.59 nM (pChEMBL 7.900000095367432)
Descriptors: MW 356.4, ALogP 2.71, HBA 6, HBD 3, PSA 95.5, QED 0.65
Compound (SMILES): C[C@@]1(S(C)(=O)=O)CC[C@@](CF)(c2cc(NC(=O)c3cc4c(cn3)OCO4)ccc2F)N=C1N
InChIKey: IENHUNDDRIGOLX-NHCUHLMSSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of BACE1 in human SNKBE2 cells expressing wild type APP695 assessed as reduction in amyloid beta 42 secretion incubated for 18 hrs by sandwich ELISA
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 480.49, ALogP 2.32, HBA 8, HBD 2, PSA 132.97, QED 0.67
Compound (SMILES): CCNC(=N)NC(=O)Nc1c(CC)cc(C(=O)NC(C)C)cc1CC
InChIKey: YNLDPQYFFGLCQF-UHFFFAOYSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Inhibition of human Nav1.5 expressed in HEK cells by patch clamp method
Measurement: IC50 = 22400 nM (pChEMBL 4.650000095367432)
Descriptors: MW 347.46, ALogP 2.62, HBA 3, HBD 5, PSA 106.11, QED 0.4
Compound (SMILES): C[C@@H](Cn1c(=O)[nH]/c(=N\c2ccc(Oc3ccccn3)cc2)n(Cc2ccc(Cl)cc2)c1=O)C(=O)O
InChIKey: SKZQFKBIJUXXCG-INIZCTEOSA-N
Target: P2X purinoceptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P51575
Assay: Antagonist activity at P2X1 receptor (unknown origin)
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 507.93, ALogP 3.18, HBA 8, HBD 2, PSA 131.57, QED 0.38
Compound (SMILES): C=CC(=O)N1CCN(CCCCCn2nc(-c3ccc(OC(C)C)cc3)c3c(N)ncnc32)CC1
InChIKey: BLOJECJRRVAFOT-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of human FGFR3 (450 to 758 residues) expressed in Escherichia coli BL21 (DE3) by HTRF assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 477.61, ALogP 3.36, HBA 8, HBD 1, PSA 102.4, QED 0.35
Compound (SMILES): [3H]c1cncc(C(=O)Nc2nc(-c3cc(C)cc(C)c3)c(-c3ccncc3)s2)c1
InChIKey: YDXZLBYHXZOWOC-WJULDGBESA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P28647
Assay: Binding affinity to rat adenosine A3 receptor expressed in HEK293 cells measured by radioligand binding assay
Measurement: Kd = 2.8 nM (pChEMBL 8.550000190734863)
Descriptors: MW 386.48, ALogP 5.14, HBA 5, HBD 1, PSA 67.77, QED 0.53
Compound (SMILES): Cc1cc(-c2ccc(OC[C@@](C)(N)CC(C)C)c(C(F)F)n2)ccn1
InChIKey: CQKGLFXBOCVPLN-IBGZPJMESA-N
Target: AP2-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q2M2I8
Assay: AAK1 Kinase Assay: The assays were performed in U-bottom 384-well plates. The final assay volume was 30 μl prepared from 15 μl additions of enzyme and substrates (fluoresceinated peptide (5-FAM)-Aha-KEEQSQITSQVTGQIGWR-NH2 and ATP) and test compounds in assay buffer (10 mM Tris-HCL pH 7.4, 10 mM MgCl2, 0.01% Tween-20 and 1.0 mM DTT). The reactions were initiated by the combination of bacterially expressed, GST-Xa-hAAK1 with substrates and test compounds. The reactions were incubated at room temperature for 3 hours and terminated by adding 60 μl of 35 mM EDTA buffer to each sample. The reactions were analyzed on the Caliper LabChip 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison to EDTA quenched control reactions for 100% inhibition and vehicle-only reactions for 0% inhibition. The final concentration of reagents in the assays are ATP, 22 μM; (5-FAM)-Aha-KEEQSQITSQVTGQIGWR-NH2, 1.5 μM; GST-Xa-hAAK1, 3.5 nM; and DMSO, 1.6%. Dose response curves were generated to determine the concentration required inhibiting 50% of kinase activity (IC50). Compounds were dissolved at 10 mM in dimethylsulfoxide (DMSO) and evaluated at eleven concentrations. IC50 values were derived by non-linear regression analysis.
Measurement: IC50 = 3.2 nM (pChEMBL 8.489999771118164)
Descriptors: MW 349.42, ALogP 4.53, HBA 4, HBD 1, PSA 61.03, QED 0.8
Compound (SMILES): C=CC(=O)Nc1cc(Nc2nccc(Nc3cn(C)c4ccccc34)n2)c(OC)cc1N(C)CCN(C)C(=O)OC
InChIKey: AHOQUNYTDVRQHT-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of wild type EGFR (unknown origin) using flurogenic substrate in presence of ATP by HTRF assay
Measurement: IC50 = 2909 nM (pChEMBL 5.539999961853027)
Descriptors: MW 558.64, ALogP 4.72, HBA 10, HBD 3, PSA 125.88, QED 0.22
Compound (SMILES): COc1cccc(-c2nc3sccn3c2-c2ccnc(NCCNS(=O)(=O)c3ccc(C)cc3)n2)c1
InChIKey: KNHDWAHCQKUXFX-UHFFFAOYSA-N
Target: RAF proto-oncogene serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P04049
Assay: Inhibition of human wild type CRAF using myelin basic protein as substrate in presence of [gamma-33P]ATP incubated for 40 mins by scintillation counting method
Measurement: IC50 = 163 nM (pChEMBL 6.789999961853027)
Descriptors: MW 520.64, ALogP 4.23, HBA 9, HBD 2, PSA 110.51, QED 0.28
Compound (SMILES): Cn1ccc(-c2cn([C@H]3C[C@H](O)[C@@H](COc4ccc5ccc(NC6CC6)nc5c4)O3)c3ncnc(N)c23)n1
InChIKey: YMKOHBLIWAKQFU-WMTXJRDZSA-N
Target: N6-adenosine-methyltransferase catalytic subunit (SINGLE PROTEIN), Homo sapiens
UniProt: Q86U44
Assay: Inhibition of METTL3-mediated m6A methylation in human MOLM-13 cells assessed as reduction in mRNA level measured after 24 hrs by LC-MS/MS analysis
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 512.57, ALogP 3.26, HBA 11, HBD 3, PSA 138.16, QED 0.3
Compound (SMILES): Cn1cc(Nc2nccc(-c3ccc4c(c3)CCCCC4NC(=O)c3nc(C(C)(C)C)no3)n2)cn1
InChIKey: LJSVDEOHWCABIZ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of human BTK using fluorescein-labeled polyGAT peptide as substrate incubated for 30 mins by FRET assay
Measurement: IC50 = 0.3 nM (pChEMBL 9.520000457763672)
Descriptors: MW 486.58, ALogP 4.5, HBA 9, HBD 2, PSA 123.65, QED 0.4
Compound (SMILES): CN1C(=O)CNC(=O)[C@@H](NC(=O)[C@@H](N)Cc2ccc(O)cc2)CCCCNC(=O)C[C@H](C(=O)N2CCC[C@H]2C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc2ccccc2)C(N)=O)NC(=O)[C@@H]1Cc1ccccc1
InChIKey: GSGQKVJVZLVGIE-IXKZDAGASA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at DOR (unknown origin) expressed in HEK293-A cells assessed as inhibition of forskolin-induced cAMP accumulation preincubated for 30 mins in presence of 3-isobutyl-1-methylxanthine followed by forskolin and compound addition by competitive PKA binding assay
Measurement: EC50 = 912.01 nM (pChEMBL 6.039999961853027)
Descriptors: MW 1152.32
Compound (SMILES): CCN(CC)S(=O)(=O)/N=C(/N=C(/C)N)N1C[C@H](c2ccccc2)C(c2ccc(Cl)cc2)=N1
InChIKey: LGOBCRUUMMNHGQ-HXUWFJFHSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Antagonist activity at human CB1R expressed in CHO-K1 cell membranes assessed as stimulation of [35S]-GTPgammaS binding by liquid scintillation counting method
Measurement: IC50 = 1.2 nM (pChEMBL 8.920000076293945)
Descriptors: MW 475.02, ALogP 3.46, HBA 3, HBD 1, PSA 103.72, QED 0.51
Compound (SMILES): CC(C)C[C@@H]1NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]2CSSC[C@H](NC(=O)[C@@H](N)Cc3ccc(O)cc3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc3ccccc3)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N3CCC[C@H]3C(=O)N[C@H]3CSSC[C@H](NC(=O)[C@H](C(C)C)NC1=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1c[nH]c4ccccc14)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1c[nH]c4ccccc14)C(N)=O)CSSC[C@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)O)NC3=O)C(=O)N2
InChIKey: XEQFZSRNLOMEGR-ACEGBTHOSA-N
Target: Sodium channel protein type 8 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQD0
Assay: Inhibition of human Nav1.6 stably expressed in cells with train pulses to -20 mV at 0.1 Hz and holding potential of -85 mV by whole-cell Qube-automated patch clamp assay
Measurement: IC50 = 1185 nM (pChEMBL 5.929999828338623)
Descriptors: MW 3631.44
Compound (SMILES): CCN(C)c1nc(=O)n(-c2cccnc2)c2cc(Cl)ccc12
InChIKey: RFOSOYYKBITPCA-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes
Measurement: IC50 = 24000 nM (pChEMBL 4.619999885559082)
Descriptors: MW 314.78, ALogP 2.89, HBA 5, HBD 0, PSA 51.02, QED 0.75
Compound (SMILES): CC1(C)Oc2c(ncnc2Nc2ccc(NC(=O)Nc3cc(C(C)(C)C)nn3C(C)(C)C)cc2)NC1=O
InChIKey: MUXQFSYRCBSGNN-UHFFFAOYSA-N
Target: NT-3 growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16288
Assay: Inhibition of wild type TrkC (unknown origin) using poly(Glu: Tyr) as substrate preincubated for 15 mins followed by substrate addition and further incubated for 30 mins in presence of [gamma-33P]ATP by scintillation counting method
Measurement: IC50 = 459 nM (pChEMBL 6.340000152587891)
Descriptors: MW 506.61, ALogP 5.22, HBA 8, HBD 4, PSA 135.09, QED 0.38
Compound (SMILES): CCN(C)CCc1cn(C)c2cccc(O)c12
InChIKey: RPANRDIQVPPKGG-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Modulation of human 5HT2C expressed in HEK293T cells co-transfected with Galphaq-RLuc8, Ggamma1-GFP2 and Gbeta1 assessed as dissociation of Galphaq from Ggamma1 preincubated for 1 hr followed by addition of coelenterazine 400a substrate and measured after 15 mins by BRET assay
Measurement: IC50 = 2.8 nM (pChEMBL 8.550000190734863)
Descriptors: MW 232.33, ALogP 2.38, HBA 3, HBD 1, PSA 28.4, QED 0.88
Compound (SMILES): COc1ccc(-c2cc(Nc3ccnc(N4CCOCC4)n3)on2)cc1
InChIKey: WRCGBYNVBFVRTN-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using midazolam as substrate
Measurement: IC50 = 30040 nM (pChEMBL 4.519999980926514)
Descriptors: MW 353.38, ALogP 2.72, HBA 8, HBD 1, PSA 85.54, QED 0.75
Compound (SMILES): CN(C)S(=O)(=O)Nc1ccc(OCc2ccccc2)cc1
InChIKey: VOOWYFBNDLFQKS-UHFFFAOYSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Antagonist activity against human androgen receptor expressed in human LNCap cells trasfected with ARR2PB-eGFP cells incubated for 3 days by fluorescence based AR transcription assay
Measurement: IC50 = 470 nM (pChEMBL 6.329999923706055)
Descriptors: MW 306.39, ALogP 2.48, HBA 3, HBD 1, PSA 58.64, QED 0.89
Compound (SMILES): COCCN1CCC(c2cc(CN(C)C(=O)c3cccc(Oc4ccccc4)c3)ccn2)CC1
InChIKey: IQCHVVCQDZOLHI-UHFFFAOYSA-N
Target: Histone-arginine methyltransferase CARM1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86X55
Assay: Affinity Biochemical interaction: (Scintillation proximity assay (SPA)) EUB0000255b CARM1
Measurement: IC50 = 2500 nM (pChEMBL 5.599999904632568)
Descriptors: MW 459.59, ALogP 4.97, HBA 5, HBD 0, PSA 54.9, QED 0.45
Compound (SMILES): COC[C@@H](CC(C)C)NC1=N/C(=C\c2ccc3ncsc3c2)C(=O)N1C
InChIKey: VCCCOYOXNKTQFO-MEFZMRIGSA-N
Target: Dual specificity protein kinase CLK4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HAZ1
Assay: Inhibition of human CLK4 assessed as incorporation of 33Pi using [gamma-33P]-ATP measured after 60 mins by microplate scintillation counting based radiometric analysis
Measurement: IC50 = 11.6 nM (pChEMBL 7.940000057220459)
Descriptors: MW 372.49, ALogP 3.12, HBA 6, HBD 1, PSA 66.82, QED 0.79
Compound (SMILES): CCCCn1c(=O)c2nc(C34CCC(C(=O)NCCCN=[N+]=[N-])(CC3)CC4)[nH]c2n(CCCNC(=O)c2ccc(S(=O)(=O)O)cc2)c1=O
InChIKey: YYGSISGTSGWHBY-UHFFFAOYSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30542
Assay: Binding affinity to human Adenosine A1 receptor expressed in Flp-In-CHO cell membrane by microbeta scintillation counting method
Measurement: Ki = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 683.79, ALogP 3.16, HBA 10, HBD 4, PSA 234.01, QED 0.06
Compound (SMILES): CC(=O)N[C@H]1CSSC[C@@H]2NC(=O)[C@@H]3CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc4c[nH]c5ccccc45)C(N)=O)NC(=O)[C@H](Cc4c[nH]c5ccccc45)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CSSC[C@H](NC(=O)[C@@H]4CCCN4C(=O)[C@H](CCCCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc4ccccc4)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(N)=O)NC1=O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N3)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC2=O
InChIKey: MPUWQZBODXNWIK-CIPWDXRLSA-N
Target: Sodium channel protein type 8 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQD0
Assay: Inhibition of human Nav1.6 stably expressed in cells with train pulses to -20 mV at 0.1 Hz and holding potential of -85 mV by whole-cell Qube-automated patch clamp assay
Measurement: IC50 > 17000 nM (pChEMBL 4.769999980926514)
Descriptors: MW 3570.31
Compound (SMILES): Cc1cc(O)cc(C)c1C[C@H](N)C(=O)N[C@H]1CSSC[C@@H](C(=O)NCC(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@H](CCCNC(=N)N)C(=O)O)NC(=O)[C@H](Cc2ccc(Cl)cc2)NC(=O)[C@H](Cc2ccccc2)NC1=O
InChIKey: WRYFWSWPLXEAEH-PZHYQFSJSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P34975
Assay: Displacement of [3H]-U69593 from KOR in Wistar rat brain membranes measured after 1 hr by scintillation counting method
Measurement: Ki = 4303 nM (pChEMBL 5.369999885559082)
Descriptors: MW 1111.75
Compound (SMILES): O=C(CCC1CCN(Cc2ccccc2)CC1)c1ccc(N2CCN(CCCCc3c[nH]c4ccc(Br)cc34)CC2)cc1
InChIKey: YBNPWOYOYCFQFX-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Agonist activity at human 5-HT1A receptor expressed in HEK293 cells incubated for 60 mins by Eu-cAMP tracer based LANCE ultra cAMP assay
Measurement: EC50 = 169 nM (pChEMBL 6.769999980926514)
Descriptors: MW 641.7, ALogP 7.95, HBA 4, HBD 1, PSA 42.58, QED 0.13
Compound (SMILES): C=CC(=O)N1CCC2(CC1)CNC(=O)c1cc(-c3nc(Nc4ccccc4OC)ncc3C)[nH]c12
InChIKey: OFCZHXDIAWONMM-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGF-induced phosphorylation of EGFR T790M/L858R double mutant in human NCI-H1975 cells preincubated for 120 mins followed by EGF stimulation and measured after 10 mins by ELISA
Measurement: EC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 472.55, ALogP 3.32, HBA 6, HBD 3, PSA 112.24, QED 0.49
Compound (SMILES): N[C@H]1C[C@@H](CO)[C@H](c2ccc(-c3cc(C(=O)O)cc4cc(-c5ccc(C(F)(F)F)cc5)ccc34)cc2)C1
InChIKey: ZGUKBYAGUXPWLB-RMDSEJHCSA-N
Target: P2Y purinoceptor 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15391
Assay: Inhibition of fluorescent antagonist binding to human P2Y14R expressed in CHO cells preincubated for 30 mins followed by 6-amino-9-(2-carboxy-4-((6-(4-(4-(4-(4-(3-carboxy 6-(4-(trifluoromethyl)phenyl)naphthalen-1-yl)phenyl)piperidin-1-yl)butyl)-1H-1,2,3-triazol-1-yl)hexyl)carbamoyl)phenyl)-3-iminio-5-sulfo-3H-xanthene-4-sulfonate addition and measured after 30 mins by BD FACSCalibur flow cytometry analysis
Measurement: IC50 = 12.6 nM (pChEMBL 7.900000095367432)
Descriptors: MW 505.54, ALogP 6.7, HBA 3, HBD 3, PSA 83.55, QED 0.28
Compound (SMILES): CCc1cc(O)c(F)cc1-c1cc(NC(CO)CO)c2nc(N)ncc2c1
InChIKey: SQGLRKHUXRLUBD-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of GST-tagged recombinant human JAK2 (808 to 1132 residues) expressed in baculovirus expression system using ULight-JAK-1 Tyr1023 peptide as substrate preincubated for 30 mins followed by substrate addition and further incubated for 20 mins in presence of ATP by FRET assay
Measurement: IC50 = 1.995 nM (pChEMBL 8.699999809265137)
Descriptors: MW 372.4, ALogP 2.05, HBA 7, HBD 5, PSA 124.52, QED 0.45
Compound (SMILES): Cc1cc(-c2ccc(OC[C@@H](N)CC(C)C)c(C#N)c2)ccn1
InChIKey: BSOULHYZJJKVGA-SFHVURJKSA-N
Target: AP2-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q2M2I8
Assay: Kinase Assay: The assays were performed in U-bottom 384-well plates. The final assay volume was 30 μl prepared from 15 μl additions of enzyme and substrates (fluoresceinated peptide (5-FAM)-Aha-KEEQSQITSQVTGQIGWR-NH2 and ATP) and test compounds in assay buffer (10 mM Tris-HCL pH 7.4, 10 mM MgCl2, 0.01% Tween-20 and 1.0 mM DTT). The reactions were initiated by the combination of bacterially expressed, GST-Xa-hAAK1 with substrates and test compounds. The reactions were incubated at room temperature for 3 hours and terminated by adding 60 μl of 35 mM EDTA buffer to each sample. The reactions were analyzed on the Caliper LabChip 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product Inhibition data were calculated by comparison to EDTA quenched control reactions for 100% inhibition and vehicle-only reactions for 0% inhibition. The final concentration of reagents in the assays are ATP, 22 μM; (5-FAM)-Aha-KEEQSQITSQVTGQIGWR-NH2, 1.5 μM; GST-Xa-hAAK1, 3.5 nM; and DMSO, 1.6%. Dose response curves were generated to determine the concentration required inhibiting 50% of kinase activity (IC50). Compounds were dissolved at 10 mM in dimethylsulfoxide (DMSO) and evaluated at eleven concentrations.
Measurement: IC50 = 0.81 nM (pChEMBL 9.09000015258789)
Descriptors: MW 309.41, ALogP 3.68, HBA 4, HBD 1, PSA 71.93, QED 0.88
Compound (SMILES): NS(=O)(=O)c1cccc(Nc2cc(-c3ccccc3)nc(SCC(=O)c3ccc(Br)cc3)n2)c1
InChIKey: APYMXPCWKMOFTR-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human CA9 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 525 nM (pChEMBL 6.28000020980835)
Descriptors: MW 555.48, ALogP 5.27, HBA 7, HBD 2, PSA 115.04, QED 0.17
Compound (SMILES): Cn1cc(Nc2nccc(-c3ccc4c(c3)CN(CC(F)(F)F)CC[C@H]4NC(=O)c3cn(C(C)(C)C)nn3)n2)cn1
InChIKey: ARSHLFAGIBAPNW-JOCHJYFZSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: BTK-POLYGAT-LS ASSAY: The purpose of the BTK in vitro assay is to determine compound potency against BTK through the measurement of IC50. Compound inhibition is measured after monitoring the amount of phosphorylation of a fluorescein-labeled polyGAT peptide (Invitrogen PV3611) in the presence of active BTK enzyme (Upstate 14-552), ATP, and inhibitor. The BTK kinase reaction was done in a black 96 well plate (costar 3694). For a typical assay, a 24 μL aliquot of a ATP/peptide master mix (final concentration; ATP 10 μM, polyGAT 100 nM) in kinase buffer (10 mM Tris-HCl pH 7.5, 10 mM MgCl2, 200 μM Na3PO4, 5 mM DTT, 0.01% Triton X-100, and 0.2 mg/ml casein) is added to each well. Next, 1 pL of a 4-fold, 40× compound titration in 100% DMSO solvent is added, followed by adding 15 uL of BTK enzyme mix in 1× kinase buffer (with a final concentration of 0.25 nM). The assay is incubated for 30 minutes before being stopped with 28 pL of a 50 mM EDTA solution. Aliquots (5 uL) of the kinase reaction are transferred to a low volume white 384 well plate (Corning 3674), and 5 pL of a 2× detection buffer (Invitrogen PV3574, with 4 nM Tb-PY20 antibody, Invitrogen PV3552) is added. The plate is covered and incubated for 45 minutes at room temperature. Time resolved fluorescence (TRF) on Molecular Devices M5 (332 nm excitation; 488 nm emission; 518 nm fluorescein emission) is measured. IC50 values are calculated using a four parameter fit with 100% enzyme activity determined from the DMSO control and 0% activity from the EDTA control.
Measurement: IC50 < 1 nM (pChEMBL 9)
Descriptors: MW 568.61, ALogP 4.21, HBA 10, HBD 2, PSA 118.68, QED 0.36
Compound (SMILES): CN1CC(C(=O)NCc2ccc3c(-c4cccc(C(N)=S)c4)cn(C4CCN(S(=O)(=O)C(F)(F)F)CC4)c3c2)C1
InChIKey: VPQCHIWQHIOPQS-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase ASH1L (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR48
Assay: Affinity Biochemical interaction: (Histone methyltransferase radioactivity assay) EUB0001089a ASH1L
Measurement: IC50 = 790 nM (pChEMBL 6.099999904632568)
Descriptors: MW 593.7, ALogP 3.61, HBA 6, HBD 2, PSA 100.67, QED 0.41
Compound (SMILES): COc1cc2cc(C#N)ccc2c(OC)c1Oc1cc(N2CCC(O)C2)nc(Nc2ccc(C#N)cc2)n1
InChIKey: YLZNKJOFTVOTNJ-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of HIV1 reverse transcriptase L100I mutant using oligo(dT)16 as primer measured after 40 mins by picogreen-dye based spectrofluorimetric analysis
Measurement: IC50 = 490 nM (pChEMBL 6.309999942779541)
Descriptors: MW 508.54, ALogP 4.5, HBA 10, HBD 2, PSA 136.55, QED 0.37
Compound (SMILES): Cl.O=C(Cc1ccco1)N[C@@H]1CC[C@@]2(O)[C@H]3Cc4ccc(O)c5c4[C@@]2(CCN3CC2CC2)[C@H]1O5
InChIKey: YDQXNBRFGWNDKZ-NYOJXWEGSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Displacement of [3H]-diprenorphine from human delta opioid receptor expressed in CHO cell membranes assessed as inhibition constant incubated for 1.5 hrs by competitive binding assay
Measurement: Ki = 45.6 nM (pChEMBL 7.340000152587891)
Descriptors: MW 450.54, ALogP 2.28, HBA 6, HBD 3, PSA 95.17, QED 0.65
Compound (SMILES): Cc1cc(-c2ccc(OC[C@@](C)(N)CC(C)C)c(C#N)c2)ccn1
InChIKey: WKMRZAXLCSNZFP-FQEVSTJZSA-N
Target: AP2-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q2M2I8
Assay: AAK1 Kinase Assay: The assays were performed in U-bottom 384-well plates. The final assay volume was 30 μl prepared from 15 μl additions of enzyme and substrates (fluoresceinated peptide (5-FAM)-Aha-KEEQSQITSQVTGQIGWR-NH2 and ATP) and test compounds in assay buffer (10 mM Tris-HCL pH 7.4, 10 mM MgCl2, 0.01% Tween-20 and 1.0 mM DTT). The reactions were initiated by the combination of bacterially expressed, GST-Xa-hAAK1 with substrates and test compounds. The reactions were incubated at room temperature for 3 hours and terminated by adding 60 μl of 35 mM EDTA buffer to each sample. The reactions were analyzed on the Caliper LabChip 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison to EDTA quenched control reactions for 100% inhibition and vehicle-only reactions for 0% inhibition. The final concentration of reagents in the assays are ATP, 22 μM; (5-FAM)-Aha-KEEQSQITSQVTGQIGWR-NH2, 1.5 μM; GST-Xa-hAAK1, 3.5 nM; and DMSO, 1.6%. Dose response curves were generated to determine the concentration required inhibiting 50% of kinase activity (IC50). Compounds were dissolved at 10 mM in dimethylsulfoxide (DMSO) and evaluated at eleven concentrations. IC50 values were derived by non-linear regression analysis.
Measurement: IC50 = 4.6 nM (pChEMBL 8.34000015258789)
Descriptors: MW 323.44, ALogP 4.07, HBA 4, HBD 1, PSA 71.93, QED 0.87
Compound (SMILES): Cc1cc(C)cc(Nc2nccc(-c3c(-c4ccc(I)cc4)ncn3C3CCNCC3)n2)c1
InChIKey: GHSOTOANBWUJKM-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Binding affinity to wild-type human full length p38-alpha (M1 to S360 residues) expressed in bacterial expression system by Kinomescan method
Measurement: Kd = 100 nM (pChEMBL 7)
Descriptors: MW 550.45, ALogP 5.9, HBA 6, HBD 2, PSA 67.66, QED 0.3
Compound (SMILES): CNc1ccc2ccc(OC[C@H]3O[C@@H](n4cc(Br)c5c(N)ncnc54)[C@H](O)[C@@H]3O)cc2n1
InChIKey: AOVSRPFQYGNVRI-HAXDFEGKSA-N
Target: N6-adenosine-methyltransferase catalytic subunit (SINGLE PROTEIN), Homo sapiens
UniProt: Q86U44
Assay: Inhibition of METTL3-mediated m6A methylation in human MOLM-13 cells assessed as reduction in mRNA level measured after 24 hrs by LC-MS/MS analysis
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 501.34, ALogP 2.06, HBA 10, HBD 4, PSA 140.57, QED 0.32
Compound (SMILES): Cn1ccc(-c2cn([C@@H]3C[C@H](CCc4ccc5ccc(N6CCC6)nc5c4)[C@@H](O)C3)c3ncnc(N)c23)n1
InChIKey: PUAYFPQLLQRSKB-BKSPAHHJSA-N
Target: N6-adenosine-methyltransferase catalytic subunit (SINGLE PROTEIN), Homo sapiens
UniProt: Q86U44
Assay: Inhibition of METTL3-mediated m6A methylation in human MOLM-13 cells assessed as reduction in mRNA level measured after 24 hrs by LC-MS/MS analysis
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 508.63, ALogP 4.12, HBA 9, HBD 2, PSA 110.91, QED 0.35
Compound (SMILES): O=S(=O)(C1CCC(n2cccn2)CC1)N1Cc2cnc(C(O)c3ccccc3)cc2C1
InChIKey: SIDOVQFFGGWIMV-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 9X (SINGLE PROTEIN), Homo sapiens
UniProt: Q93008
Assay: Inhibition of USP9X (unknown origin) using Ubiquitin-Rhoadmine 110 as substrate preincubated for 30 mins followed by substrate addition and measured after 11 mins by fluorescence assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 438.55, ALogP 3.19, HBA 6, HBD 1, PSA 88.32, QED 0.66
Compound (SMILES): Cc1cc2c(NC3CCN(C)CC3)n[nH]c2cc1-c1ccnc(C)c1F
InChIKey: BBEKIKINIZAJCH-UHFFFAOYSA-N
Target: Toll-like receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYK1
Assay: Antagonist activity at human TLR7 expressed in human PBMC cells assessed as inhibition of ssRNA stimulated IFNalpha level preincubated for 30 mins followed by stimulation and measured after 20 hrs by AlphaLISA method
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 353.45, ALogP 3.89, HBA 4, HBD 2, PSA 56.84, QED 0.75
Compound (SMILES): O=C(COc1ccc2cc(/C=C3/SC(=O)NC3=O)ccc2c1)Nc1ccc([N+](=O)[O-])cc1
InChIKey: CZWQVHMBWIVBNF-VXLYETTFSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Partial agonist activity at Gal4-fused human PPARgamma LBD in HepG2 cells assessed as transactivation incubated for 20 hrs measured by luminometer
Measurement: EC50 = 1610 nM (pChEMBL 5.789999961853027)
Descriptors: MW 449.44, ALogP 4.09, HBA 7, HBD 2, PSA 127.64, QED 0.33
Compound (SMILES): O=C(CCc1cn[nH]c1)N[C@@H]1CC[C@@]2(O)[C@H]3Cc4ccc(O)c5c4[C@@]2(CCN3CC2CC2)[C@H]1O5
InChIKey: MEWWWDPCRSZRSV-HFXSLSFNSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Binding affinity to human delta opioid receptor in presence of SNC80 incubated for 1.5 hrs by competitive radioligand binding assay
Measurement: Ki = 97.8 nM (pChEMBL 7.010000228881836)
Descriptors: MW 464.57, ALogP 1.8, HBA 6, HBD 4, PSA 110.71, QED 0.52
Compound (SMILES): CC1=C(N2CCC3(CCN(C[C@H](O)c4ccc5c(c4C)COC5=O)CC3)C2=O)CCC1=O
InChIKey: PGWBLSDFIPRYII-QFIPXVFZSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in HEK-293 cells by voltage clamp electrophysiology assay
Measurement: IC50 = 22000 nM (pChEMBL 4.659999847412109)
Descriptors: MW 438.52, ALogP 2.65, HBA 6, HBD 1, PSA 87.15, QED 0.73
Compound (SMILES): C[C@@H]1CC2c3ccccc3NC2[C@@H](c2c(F)cc(/C=C/C(=O)O)cc2F)N1CC(C)(C)F
InChIKey: GGQZYDWUDLHXPZ-RCDMODNJSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin)
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 444.5, ALogP 5.52, HBA 3, HBD 2, PSA 52.57, QED 0.6
Compound (SMILES): COc1cc2c(c3c1OCOC3)C[C@H]1c3c(cc4c(c3OC)OCO4)CCN1C2
InChIKey: QJZHAQOTBKWPGS-INIZCTEOSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human recombinant AChE using acetylthiocholine chloride as substrate incubated for 5 mins by DTNB reagent based Ellman's method
Measurement: IC50 = 19900 nM (pChEMBL 4.699999809265137)
Descriptors: MW 397.43, ALogP 2.95, HBA 7, HBD 0, PSA 58.62, QED 0.77
Compound (SMILES): CC(=O)N1CCC[C@H](NS(=O)(=O)C(C)C)[C@@H]1CO[C@H]1CC[C@@H](C(C)C)CC1
InChIKey: KYMDPDRXJOEXIR-YRPNKDGESA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Measurement of Orexin Type 2 Receptor Agonist Activity: Chinese hamster ovary (CHO) dhfr-cells forcibly expressing human orexin type 2 receptor (hOX2R) were seeded in each well of Black clear bottom plate (384 wells) (Becton, Dickinson and Company) by 10,000 cells, and cultured for 16 hr in an MEM-alpha (Nikken-Bio Co., Ltd.) medium containing 100 U/ml penicillin, 100 μg/ml streptomycin, 0.5 g/ml G418 (all above Invitrogen), and 10% fetal calf serum (Thermo), under the conditions of 37° C., 5% CO2. After removal of the medium, 30 μL of assay buffer 1 (0.1% bovine serum albumin (Wako Pure Chemical Industries, Ltd.), 1.25 mM probenecid, 10% B2-Quencher, 2.5 μg/mL Fluo-4AM, 10 mM HEPES (DOJINDO)) was added, and the cells were incubated for 60 min under the conditions of 37° C., 5% CO2. A test compound was dissolved in dimethyl sulfoxide to 10 mM, and then diluted with assay buffer 2 (20 mM HEPES, Hanks' balanced salt solution (Invitrogen), 0.1% bovine serum albumin). For the reaction, a test compound solution (10 μL) was added using Fluorescent Imaging Plate Reader TETRA (FLIPR TETRA; manufactured by Molecular Devices), a fluorescence value (excitation wavelength 488 nm, measurement wavelength 570 nm) of each well was measured every one second for 1 min, and the agonist activity was determined using the area of the fluorescence value as an indicator of intracellular Ca2+ concentration. The agonist activity of the test compound was calculated assuming that the fluorescence value of the well added with only the dilution buffer was 0% and the fluorescence value of the well added with 10 nM human orexin B (PEPTIDE INSTITUTE, INC.) buffer was 100%. The agonist activity values EC50 and Emax of each compound are shown below. As used herein, Emax indicates the value at 30 uM concentration when orexin B is converted to a full agonist (maximum value of agonist activity: 100%). As is clear from the results, the compound of the present invention was shown to have an agonist activity on hOX2R.
Measurement: EC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 402.6, ALogP 2.93, HBA 4, HBD 1, PSA 75.71, QED 0.71
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@@H](CCCNC(=N)N)NC(=O)C=C(c1ccccc1)c1ccccc1)C(N)=O
InChIKey: DHCKIFBNEHPVAG-PKTZIBPZSA-N
Target: Neuropeptide FF receptor 2 (SINGLE PROTEIN), Mus musculus
UniProt: Q924H0
Assay: Displacement of [125I]-1DMeNPFF from mouse NPFF2R receptor by TopCount scintillation counting method
Measurement: Ki = 4300 nM (pChEMBL 5.369999885559082)
Descriptors: MW 492.62, ALogP 1.88, HBA 4, HBD 6, PSA 163.19, QED 0.11
Compound (SMILES): C[C@H](Cc1nncn1C)c1cccc(NC(=O)c2ccnc(C3CC3)n2)c1
InChIKey: ZXMXDDSSNLVNRJ-CYBMUJFWSA-N
Target: E3 ubiquitin-protein ligase CBL-B (SINGLE PROTEIN), Homo sapiens
UniProt: Q13191
Assay: Inhibition of N-terminal Avi-tagged human CBL-B (36 to 427 residues) incubated with 60 nM Src kinase for 1.5 hrs followed by incubation with fluorescently labeled UbcH5B-Ub for 1 hr and measured by TR-FRET assay
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 362.44, ALogP 3.08, HBA 6, HBD 1, PSA 85.59, QED 0.73
Compound (SMILES): CO[C@@H]1[C@@H](n2cc(-c3cc(F)c(F)c(F)c3)nn2)[C@@H](O)[C@@H](CO)O[C@H]1S[C@@H]1COC[C@H](n2cc(-c3cccc(F)c3)nn2)[C@H]1O
InChIKey: SUNKMJAJNZISJX-XBSVYHDWSA-N
Target: Galectin-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09382
Assay: Inhibition in human Gal-1
Measurement: IC50 = 2360 nM (pChEMBL 5.630000114440918)
Descriptors: MW 652.63, ALogP 2.13, HBA 13, HBD 3, PSA 149.8, QED 0.19
Compound (SMILES): Cc1cc(-c2ccc(OC[C@@](C)(N)CC(C)C)c(Cl)n2)ccn1
InChIKey: BHOKOGJZOVMLHI-SFHVURJKSA-N
Target: AP2-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q2M2I8
Assay: AAK1 Kinase Assay: The assays were performed in U-bottom 384-well plates. The final assay volume was 30 μl prepared from 15 μl additions of enzyme and substrates (fluoresceinated peptide (5-FAM)-Aha-KEEQSQITSQVTGQIGWR-NH2 and ATP) and test compounds in assay buffer (10 mM Tris-HCL pH 7.4, 10 mM MgCl2, 0.01% Tween-20 and 1.0 mM DTT). The reactions were initiated by the combination of bacterially expressed, GST-Xa-hAAK1 with substrates and test compounds. The reactions were incubated at room temperature for 3 hours and terminated by adding 60 μl of 35 mM EDTA buffer to each sample. The reactions were analyzed on the Caliper LabChip 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison to EDTA quenched control reactions for 100% inhibition and vehicle-only reactions for 0% inhibition. The final concentration of reagents in the assays are ATP, 22 μM; (5-FAM)-Aha-KEEQSQITSQVTGQIGWR-NH2, 1.5 μM; GST-Xa-hAAK1, 3.5 nM; and DMSO, 1.6%. Dose response curves were generated to determine the concentration required inhibiting 50% of kinase activity (IC50). Compounds were dissolved at 10 mM in dimethylsulfoxide (DMSO) and evaluated at eleven concentrations. IC50 values were derived by non-linear regression analysis.
Measurement: IC50 = 4.7 nM (pChEMBL 8.329999923706055)
Descriptors: MW 333.86, ALogP 4.25, HBA 4, HBD 1, PSA 61.03, QED 0.8
Compound (SMILES): C[C@H]1C[C@H](NS(=O)(=O)c2ccc3cc(Cl)ccc3c2)CN1CCCc1noc2cc(F)ccc12
InChIKey: JMQUTFMPAXQIBI-KKSFZXQISA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Displacement of [3H]-LSD from human 5-HT7 receptor transfected in CHO-K1 cells measured after 120 mins by scintillation counting method
Measurement: Ki = 158.49 nM (pChEMBL 6.800000190734863)
Descriptors: MW 502.01, ALogP 5.15, HBA 5, HBD 1, PSA 75.44, QED 0.38
Compound (SMILES): COc1cccc(-c2nccc3c2CN(c2ccccc2)C3=O)c1
InChIKey: CECLXQDMAJQBCR-UHFFFAOYSA-N
Target: Ceramide glucosyltransferase (SINGLE PROTEIN), Mus musculus
UniProt: O88693
Assay: Mouse GCS enzymatic assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 316.36, ALogP 3.92, HBA 3, HBD 0, PSA 42.43, QED 0.74
Compound (SMILES): C[C@@]1(c2cc(NC(=O)c3ccc(F)cn3)ccc2F)Cn2nc(C#N)cc2C(N)=N1
InChIKey: AMWCDMOOTAVMSV-FQEVSTJZSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Inhibition of human amyloid beta (1 to 42) in human SKNBE2 cells expressing wild-type amyloid precursor protein hAPP695 incubated for 18 hrs by sandwich ELISA
Measurement: IC50 = 2.6 nM (pChEMBL 8.59000015258789)
Descriptors: MW 407.38, ALogP 2.31, HBA 7, HBD 2, PSA 121.98, QED 0.69
Compound (SMILES): CCN(CC)S(=O)(=O)/N=C(/N=C(\N)C(C)(C)C)N1CC(c2ccccc2)C(c2ccc(Cl)cc2)=N1
InChIKey: YVKYBZPIZUWLTD-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Antagonist activity at human CB1R expressed in CHO-K1 cell membranes assessed as stimulation of [35S]-GTPgammaS binding by liquid scintillation counting method
Measurement: IC50 = 375 nM (pChEMBL 6.429999828338623)
Descriptors: MW 517.1, ALogP 4.49, HBA 3, HBD 1, PSA 103.72, QED 0.45
Compound (SMILES): N#Cc1cc(C2=Nc3ccc(Br)cc3NC(=O)C2)ccn1
InChIKey: KMKZCMKOSAKVGY-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14416
Assay: Negative allosteric modulator activity at human recombinant mGlur2 expressed in HEK293 cells by calcium assay
Measurement: IC50 = 8.3 nM (pChEMBL 8.079999923706055)
Descriptors: MW 341.17, ALogP 3.18, HBA 4, HBD 1, PSA 78.14, QED 0.87
Compound (SMILES): CC(C)(CCCCCCN=C=S)c1cc(O)c2c(c1)OC(C)(C)[C@@H]1CC[C@@H](CO)C[C@@H]21
InChIKey: JCIYJYHFBBXSBF-HMXCVIKNSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]CP55940 from human CB2 expressed in HEK293 cell membrane assessed as inhibition constant incubated for 1 hr by TopCount scintillation counting method
Measurement: Ki = 3.15 nM (pChEMBL 8.5)
Descriptors: MW 445.67, ALogP 6.39, HBA 5, HBD 2, PSA 62.05, QED 0.26
Compound (SMILES): CNCCNc1nc(N2CCOCC2)nc(-n2c(C(F)F)nc3ccccc32)n1
InChIKey: QKGDICWSMXXAKY-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of human PI3Kgamma by TR-FRET based Adapta assay
Measurement: IC50 = 681 nM (pChEMBL 6.170000076293945)
Descriptors: MW 404.43, ALogP 1.62, HBA 9, HBD 2, PSA 93.02, QED 0.57
Compound (SMILES): O=C(NCCCNc1nc(Nc2cccc(NC(=O)N3CCCC3)c2)ncc1Br)C1CCC1
InChIKey: ZSZOBRBJIJWWHH-UHFFFAOYSA-N
Target: MAP/microtubule affinity-regulating kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96L34
Assay: Displacement of tracer K5 from NLuc fused MARK4 (unknown origin) expressed in HEK293 cells by NanoBRET assay
Measurement: IC50 = 72 nM (pChEMBL 7.139999866485596)
Descriptors: MW 516.44, ALogP 4.33, HBA 6, HBD 4, PSA 111.28, QED 0.37
Compound (SMILES): COc1ccc2c(c1)N(CCC/C=C\c1cccc3c1N[C@H](C)CC(=O)N3)CCC2
InChIKey: VBTDHMQUNCGCSZ-MPYGFJLXSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to human BRD4 bromodomain 1 assessed as dissociation constant by ITC assay
Measurement: Kd = 1170 nM (pChEMBL 5.929999828338623)
Descriptors: MW 405.54, ALogP 5.08, HBA 4, HBD 2, PSA 53.6, QED 0.66
Compound (SMILES): CN1C(=O)CNC(=O)[C@H](NC(=O)[C@@H](N)Cc2ccc(O)cc2)CCCCNC(=O)C[C@@H](C(=O)N2CCC[C@H]2C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc2ccccc2)C(N)=O)NC(=O)[C@@H]1Cc1ccccc1
InChIKey: GSGQKVJVZLVGIE-MQRRDULVSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Agonist activity at KOR (unknown origin) expressed in HEK293-A cells assessed as inhibition of forskolin-induced cAMP accumulation preincubated for 30 mins in presence of 3-isobutyl-1-methylxanthine followed by forskolin and compound addition by competitive PKA binding assay
Measurement: EC50 = 39 nM (pChEMBL 7.409999847412109)
Descriptors: MW 1152.32
Compound (SMILES): COc1cc2c(NC3CCN(C)CC3)n[nH]c2cc1-c1ccnc(C)c1F
InChIKey: JDWWBWZTNILPQF-UHFFFAOYSA-N
Target: Toll-like receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYK1
Assay: Antagonist activity at human TLR7 expressed in human PBMC cells assessed as inhibition of ssRNA stimulated IFNalpha level preincubated for 30 mins followed by stimulation and measured after 20 hrs by AlphaLISA method
Measurement: IC50 = 0.67 nM (pChEMBL 9.170000076293945)
Descriptors: MW 369.44, ALogP 3.59, HBA 5, HBD 2, PSA 66.07, QED 0.74
Compound (SMILES): Cc1n[nH]c2nc(-c3ccc(NS(=O)(=O)c4cc(Cl)ccc4F)cc3)nc(OC3CCNCC3(F)F)c12
InChIKey: GGGNEMNJKLCCLN-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase Sgk1 (SINGLE PROTEIN), Homo sapiens
UniProt: O00141
Assay: Enzymatic Activity Assay: The compounds were tested for serum and glucocorticoid-regulated kinase 1 (SGK-1) inhibitory activity in a substrate phosphorylation assay designed to measure the ability of the isolated enzyme to catalyze the transfer of phosphate from ATP to serine/threonine residues in a fluorescein-labeled substrate peptide, using recombinant human SGK-1 enzyme produced in a baculovirus system (Biomol, Hamburg, Germany, Cat. No. 4-331). The synthesized fluorescent labeled peptide substrate contained (5(6)-Carboxyfluorescein)-RPRAATF-NH2. The phosphorylated substrate peptide and non-phosphorylated substrate peptide were separated with caliper life science's lab-chip technology based on a micro fluidics method. All fluid flow was established on the chip by applying a vacuum of a few psi to the waste well transporting fluid from various sources through interconnecting channels. Because the phosphoryl group is doubly negatively charged, under the pressure-driven hydrodynamic flow and the voltage-driven flow within the electric field, the fluorescent labeled peptide substrate and its phosphorylation product appear at different times in the detection window to the detection point. Substrate turnover can thus be determined as the ratio of the product peak area and the sum of substrate peak area and product peak area.The enzyme reaction was carried out in a buffer containing 25 mM Tris-HCl (pH 7.4), 5 mM MgCl2, 2 mM MnCl2, 2 mM DTT, and 0.03% bovine serum albumine. The enzyme was pre-incubated with the test compound for 30 min at 24° C. The kinase reaction was initiated by addition of the substrate mixture containing the peptide substrate (final concentration 1 μM) and ATP (final concentration 10 μM). After 60 min incubation at 37° C., the enzyme reaction was terminated by adding a buffer containing 100 mM Hepes (pH 7.4) and 35 mM EDTA.
Measurement: IC50 = 1.9 nM (pChEMBL 8.720000267028809)
Descriptors: MW 552.97, ALogP 4.3, HBA 7, HBD 3, PSA 121.89, QED 0.33
Compound (SMILES): Cc1cc(Cn2ncn(-c3ccc(Cl)cc3)c2=O)cc(C)c1OC(C)(C)C(=O)O
InChIKey: YXMAYPGGKODTGP-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Agonist activity at PPARgamma (unknown origin)
Measurement: EC50 = 1831.6 nM (pChEMBL 5.739999771118164)
Descriptors: MW 415.88, ALogP 3.59, HBA 6, HBD 1, PSA 86.35, QED 0.66
Compound (SMILES): CCCO[C@@H]1O[C@H](CNC(=O)c2ccc(S(N)(=O)=O)cc2)[C@@H](O)[C@H](O)[C@H]1O
InChIKey: YOJAMANFZBEUHY-XYFZXANASA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human CA9 using 4-nitrophenylacetate as substrate by esterase assay
Measurement: IC50 = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 404.44, ALogP -1.7, HBA 8, HBD 5, PSA 168.41, QED 0.36
Compound (SMILES): CC(C)(O)c1ccc(NC(=O)c2ccnn(-c3ccccc3OCC(F)(F)F)c2=O)cc1
InChIKey: CQAPXPSWLDAVEG-UHFFFAOYSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P31645
Assay: Inhibition of human SERT
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 447.41, ALogP 3.65, HBA 6, HBD 2, PSA 93.45, QED 0.6
Compound (SMILES): N#Cc1cccc(C(=O)c2cnc(NCc3ccccc3)nc2)c1
InChIKey: RXWGCAHYHQFVJH-UHFFFAOYSA-N
Target: Pantetheinase (SINGLE PROTEIN), Homo sapiens
UniProt: O95497
Assay: Human Vanin-1 Enzyme Assay 3: The vanin-1 protein was prepared in-house from a construct expressing the extracellular domain of human vanin-1 (GenBank ID NM_004666) preceded N-terminally by the honey bee melittin signal peptide, a GSG linker sequence, a His6X tag and a FLAG tag. The secreted, soluble enzyme was purified from the conditioned medium from a CHO cell line stably expressing the resulting protein. Enzyme purification was performed through sequential Ni NTA and size-exclusion chromatography steps.On the day of the assay, dose response plates were prepared by diluting the inhibitors in DMSO at compound concentration 100-fold the final in-assay concentration. Concentration series were prepared by serially diluting in DMSO in a two-fold series for a total of 11 data points. Intermediate compound plates containing compound in 10% DMSO were then created by diluting the compounds 10-fold in assay buffer consisting of 50 mM Tris-HCl pH=8.0, 50 mM KCl, 0.005% Brij-35 and 1.5 mM cysteamine. To begin the assay 3 μL were transferred from the intermediate compound plate to the assay plate.A working solution of human vanin-1 was prepared by diluting the enzyme stock to 2.5 nM in assay buffer. Next, 24 μL of the vanin-1 working solution were transferred to the assay plate. The enzyme reaction was then initiated by the addition of 3 μL of 100 μM pantetheine 7-amino-4-trifluoromethylcoumarin prepared in 5 uM acetic acid. The final concentrations in the assay were 2 nM human vanin-1 and 10 uM substrate. The final concentration of DMSO was 1%. The assay plates were incubated at room temperature for 15 minutes and before they were read on a Tecan Safire using a 405 nm excitation wavelength and a 505 nm emission wavelength for detection.
Measurement: IC50 = 52.2 nM (pChEMBL 7.28000020980835)
Descriptors: MW 314.35, ALogP 3.19, HBA 5, HBD 1, PSA 78.67, QED 0.73
Compound (SMILES): c1cnc2c(c1)CN[C@@H](CN(CCCCNC1CCOCC1)[C@H]1CCCc3cccnc31)C2
InChIKey: POWOJVYGOJPOQL-RSXGOPAZSA-N
Target: Alpha-2C adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P18825
Assay: Inhibition of alpha 2C adrenergic receptor (unknown origin)
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 449.64, ALogP 3.42, HBA 6, HBD 2, PSA 62.31, QED 0.57
Compound (SMILES): C[C@@]1(c2cc(NC(=O)c3ccc(C#N)cn3)ccc2F)Cn2cc(C#N)nc2C(N)=N1
InChIKey: SMKLPOGYVJHNSP-NRFANRHFSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Inhibition of human amyloid beta (1 to 42) in human SKNBE2 cells expressing wild-type amyloid precursor protein hAPP695 incubated for 18 hrs by sandwich ELISA
Measurement: IC50 = 8.5 nM (pChEMBL 8.069999694824219)
Descriptors: MW 414.4, ALogP 2.05, HBA 8, HBD 2, PSA 145.77, QED 0.67
Compound (SMILES): COc1cc2nc(C)nc(N[C@H](C)c3cccc(S(N)(=O)=O)c3)c2cc1OC
InChIKey: ZMRIZYACHXKNRP-LLVKDONJSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin)
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 402.48, ALogP 2.78, HBA 7, HBD 2, PSA 116.43, QED 0.65
Compound (SMILES): Cc1nc(N)sc1CCCN/C(N)=N/C(=O)NCCCCCCCC[n+]1c(C)cc(/C=C/C=C/c2ccc(N(C)C)cc2)cc1C
InChIKey: UFVWKCMLJZPNQW-UHFFFAOYSA-O
Target: Histamine H2 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P25021
Assay: Agonist activity at NlucN/mini-Gi protein-fused human H2R stably expressed in HEK293T cells assessed as induction of mini-Gi protein recruitment using furimazine as substrate measured for 45 mins by luminescence assay
Measurement: EC50 = 1380.38 nM (pChEMBL 5.860000133514404)
Descriptors: MW 645.94, ALogP 6.32, HBA 5, HBD 4, PSA 125.54, QED 0.04
Compound (SMILES): O=C(COc1ccc2cc(/C=C3/SC(=O)NC3=O)ccc2c1)Nc1c(F)cc(F)cc1Br
InChIKey: VBAPRGNDRKQXHC-NGYBGAFCSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Partial agonist activity at Gal4-fused human PPARgamma LBD in HepG2 cells assessed as transactivation incubated for 20 hrs measured by luminometer
Measurement: EC50 = 245 nM (pChEMBL 6.610000133514404)
Descriptors: MW 519.32, ALogP 5.22, HBA 5, HBD 2, PSA 84.5, QED 0.45
Compound (SMILES): CN(c1ncccc1CNc1ccnc(-c2nc3c(F)c(Cl)ccc3[nH]2)n1)S(C)(=O)=O
InChIKey: WBFJDKLBAAHKIL-UHFFFAOYSA-N
Target: SRSF protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96SB4
Assay: Cellular target engagement assay with: SRPK1
Measurement: IC50 = 44 nM (pChEMBL 7.360000133514404)
Descriptors: MW 461.91, ALogP 3.22, HBA 7, HBD 2, PSA 116.76, QED 0.45
Compound (SMILES): Cc1cccc(-c2ccc(/C=C/[C@@H]3[C@@H]4[C@@H](C)OC(=O)[C@]4(O)CC(F)(F)[C@H]3C)nc2)c1C#N
InChIKey: HYZZUHLFTHINHG-LPMNVVFPSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of [35S]MK-499 binding to hERG expressed in HEK293 cells at 60 uM
Measurement: IC50 = 9000 nM (pChEMBL 5.050000190734863)
Descriptors: MW 438.47, ALogP 4.53, HBA 5, HBD 1, PSA 83.21, QED 0.71
Compound (SMILES): O=C(NO)c1ccc(CN(Cc2ccc(C(F)(F)F)cc2)S(=O)(=O)c2c(F)c(F)c(F)c(F)c2F)cc1
InChIKey: YUGONRLLAWHKIA-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of full length human HDAC6 using FAM-labeled acetylated peptide as substrate by electrophoretic mobility shift assay
Measurement: IC50 = 45 nM (pChEMBL 7.349999904632568)
Descriptors: MW 554.42, ALogP 4.91, HBA 4, HBD 2, PSA 86.71, QED 0.14
Compound (SMILES): CC(O)c1cn(CCNc2nonc2/C(=N/O)Nc2ccc(F)c(Br)c2)nn1
InChIKey: HCRPFHXLEWDMOC-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 455.25, ALogP 1.98, HBA 10, HBD 4, PSA 146.51, QED 0.18
Compound (SMILES): Cc1ccccc1-c1ccc(C(=O)NC[C@@H](N)C(=O)O)o1
InChIKey: LXFUTMOKRNGXDZ-LLVKDONJSA-N
Target: Ionotropic glutamate receptor NMDA 1/2D (PROTEIN COMPLEX), Rattus norvegicus
UniProt: Q62645
Assay: Agonist activity at rat GluN1/GluN2D NMDA receptor expressed in Xenopus oocytes measured after 4 days in presence of L-glutamte by two-electrode voltage-clamp recording assay
Measurement: EC50 = 260 nM (pChEMBL 6.579999923706055)
Descriptors: MW 288.3, ALogP 1.4, HBA 4, HBD 3, PSA 105.56, QED 0.77