lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cc1ccc(CNC(=O)C(CCN)N(C)CCC=C(c2sccc2C)c2sccc2C)cc1
InChIKey: JIQVQICEOCLXMK-UHFFFAOYSA-N
Target: GABA transporter 4 (SINGLE PROTEIN), Mus musculus
UniProt: P31650
Assay: Inhibition of mouse GAT4 expressed in HEK293 cell line assessed as inhibition of [3H]GABA uptake measured after 35 mins by liquid scintillation method
Measurement: IC50 = 6918.31 nM (pChEMBL 5.159999847412109)
Descriptors: MW 481.73, ALogP 5.52, HBA 5, HBD 2, PSA 58.36, QED 0.38
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)C1CCOCC1)c1[nH]c(-c2ccc(F)cc2)nc1C(N)=O
InChIKey: UNZNVKKXXYZTJE-FQEVSTJZSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of HDAC1 (unknown origin)
Measurement: IC50 = 12.3 nM (pChEMBL 7.909999847412109)
Descriptors: MW 472.56, ALogP 3.83, HBA 5, HBD 3, PSA 127.17, QED 0.4
Compound (SMILES): C[C@H]1COC[C@H](C)N1c1c(NC(=O)Nc2ccnc(C(F)(F)F)c2)cnc2cc(Cl)nn12
InChIKey: BFPCFGGFGQMJQG-QWRGUYRKSA-N
Target: Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UDY8
Assay: Allosteric inhibition of MALT1-mediated T cell activation in human Jurkat cells assessed as decrease in PMA induced IL2 activation preincubated for 1 hr followed by addition of PMA measured after 5.5 hrs by luciferase reporter gene assay
Measurement: IC50 = 180 nM (pChEMBL 6.75)
Descriptors: MW 469.86, ALogP 4.05, HBA 7, HBD 2, PSA 96.68, QED 0.6
Compound (SMILES): CNc1cccc(OCCNCC2(F)CCN(C(=O)c3ccc(F)c(Cl)c3)CC2)c1
InChIKey: PHEGDBVVFIATGX-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Biased agonist activity at Gal4-VP16 transcription factor linked human 5-HT1A receptor expressed in human U2OS cells assessed as induction of beta-arrestin2 recruitment measured after 5 hrs by Tango assay
Measurement: EC50 = 0.08913 nM (pChEMBL 10.050000190734863)
Descriptors: MW 437.92, ALogP 4.13, HBA 4, HBD 2, PSA 53.6, QED 0.61
Compound (SMILES): Cn1nc(-c2ccc(OCC3C[C@H]4CC[C@@H](C3)N4)c(F)c2)c2cnc(N)nc21
InChIKey: DSWZHRVQJSIDFD-QXMXGUDHSA-N
Target: Toll-like receptor 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR96
Assay: Antagonist activity at TLR9 in human PBMC assessed as inhibition of ODN2216-induced IFNalpha production
Measurement: IC50 = 1200 nM (pChEMBL 5.920000076293945)
Descriptors: MW 382.44, ALogP 2.66, HBA 7, HBD 2, PSA 90.88, QED 0.72
Compound (SMILES): O=C(CCN1CCCc2ccccc21)NCc1cccs1
InChIKey: WELWVDXGWKTSSU-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Antagonist activity at human muscarinic M2 receptor expressed in CHO cells co-expressing Galpha15 assessed as inhibition of acetylcholine-induced calcium mobilization relative to acetylcholine
Measurement: IC50 = 1023.29 nM (pChEMBL 5.989999771118164)
Descriptors: MW 300.43, ALogP 3.21, HBA 3, HBD 1, PSA 32.34, QED 0.92
Compound (SMILES): CC(=O)N[C@@H]1CCC[C@H](C(=O)Nc2cc(-c3cnn4c3OCCC4)c(Cl)cn2)C1
InChIKey: IIFJRNNBNQWDLA-UONOGXRCSA-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 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 417.9, ALogP 3.01, HBA 6, HBD 2, PSA 98.14, QED 0.8
Compound (SMILES): CS(=O)(=O)N1CCC(Nc2ncc3cc(Cl)c(=O)n(C4CCCC4)c3n2)CC1
InChIKey: YEMOJJTZJLWRNY-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 4/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24385
Assay: Inhibition of CDK4/cyclin D1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay
Measurement: Ki = 0.3 nM (pChEMBL 9.520000457763672)
Descriptors: MW 425.94, ALogP 2.4, HBA 7, HBD 1, PSA 97.19, QED 0.81
Compound (SMILES): N#Cc1c(N2CCOCC2)sc(-c2nc[nH]n2)c1-c1ccc(NC(=O)Nc2ccccc2Cl)cc1
InChIKey: OHHJTGRTQJGKLY-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of GST-tagged human recombinant PI3Kgamma catalytic domain (468 to 1203 residues) expressed in insect cells using PIP2 peptide as substrate incubated for 1 hr in presence ATP by ADP-Glo Kinase Assay
Measurement: IC50 = 258 nM (pChEMBL 6.590000152587891)
Descriptors: MW 505.99, ALogP 5.21, HBA 7, HBD 3, PSA 118.96, QED 0.34
Compound (SMILES): C[C@@H](NC(=O)[C@@H](N)Cc1ccc(O)cc1)C(=O)NCC(=O)N(C)[C@@H](Cc1ccccc1)C(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccccc1)C(N)=O
InChIKey: NMKYKQNZEVJKQC-WJYGCBBBSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at delta opioid receptor (unknown origin) expressed in HEK293-A cells assessed as reduction in forskolin-induced cAMP accumulation incubated for 30 mins by competition PKA binding assay
Measurement: EC50 = 574.7 nM (pChEMBL 6.239999771118164)
Descriptors: MW 1055.21
Compound (SMILES): CCCCNc1nc2cc([N+](=O)[O-])ccc2s1
InChIKey: KGMPZRJHVILPMZ-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of human recombinant CDK9/cyclin T expressed in baculovirus infected Sf9 insect cells using YSPTSPSYSPTSPSYSPTSPSKKKK as substrate by ADP-glo assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 251.31, ALogP 3.42, HBA 5, HBD 1, PSA 68.06, QED 0.5
Compound (SMILES): CCCCN(CCCC)C(=O)CN1C[C@@H](c2cc(OC)c3c(c2)OCO3)[C@H](C(=O)O)[C@H]1CC(C)(C)CCC.Cl
InChIKey: KMKKFZCVBRAWNX-GSAMTNRBSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Selectivity interaction (GPCR panel (PDSP screen)) EUB0000289bCl OPRK1
Measurement: Ki = 2785 nM (pChEMBL 5.550000190734863)
Descriptors: MW 532.72, ALogP 5.54, HBA 6, HBD 1, PSA 88.54, QED 0.32
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccc(OC)cc4n3)C2)cc1
InChIKey: ADHABGMDGASWTO-GOSISDBHSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51948
Assay: Inhibition of CDK7/cyclin H/MAT1 (unknown origin) assessed as incoporation of [33]Pi using RBER-IRStide as substrate and in presence of [gamma-33P]-ATP measured after 60 mins by microplate scintillation counter
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 417.47, ALogP 3.09, HBA 6, HBD 2, PSA 96.45, QED 0.6
Compound (SMILES): C[C@H](CO)n1cnnc1-c1cccc(NC(=O)Nc2cc3ccccn3n2)n1
InChIKey: GSYUZRLLPWNNAL-GFCCVEGCSA-N
Target: CDK2/Cyclin A2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P20248
Assay: Inhibition of full length human recombinant CDK2/Cyclin A using histone H1 as substrate incubated for 40 mins in presence of [gamma-33ATP] by radiometric scintillation counting analysis
Measurement: IC50 = 351.7 nM (pChEMBL 6.449999809265137)
Descriptors: MW 378.4, ALogP 2.19, HBA 8, HBD 3, PSA 122.26, QED 0.49
Compound (SMILES): O=C[C@H](C[C@@H]1CCNC1=O)NC(=O)[C@H](CC1CCCCC1)NC(=O)c1cc2ccccc2[nH]1
InChIKey: HPKJGHVHQWJOOT-ZJOUEHCJSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of SARS CoV-2 Main protease incubated for 10 min by FRET assay
Measurement: IC50 = 53 nM (pChEMBL 7.28000020980835)
Descriptors: MW 452.56, ALogP 2.45, HBA 4, HBD 4, PSA 120.16, QED 0.44
Compound (SMILES): CN1CCN(CCCN2C(=O)c3ccccc3/C=C\c3ccccc32)CC1
InChIKey: GRZVXITWIIKNCX-QXMHVHEDSA-N
Target: Histamine H1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35367
Assay: Binding affinity to H1 receptor (unknown origin)
Measurement: Ki > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 361.49, ALogP 3.45, HBA 3, HBD 0, PSA 26.79, QED 0.83
Compound (SMILES): Nc1nc(-c2ccc(NC(=O)c3ccc(S(N)(=O)=O)cc3)cc2)cn2c(=O)n(-c3ccccc3)nc12
InChIKey: ZYILDTWBSDDXCD-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human CA2 incubated for 15 mins by stopped- flow CO2 hydrase assay method
Measurement: Ki = 46 nM (pChEMBL 7.340000152587891)
Descriptors: MW 501.53, ALogP 2.03, HBA 9, HBD 3, PSA 167.47, QED 0.33
Compound (SMILES): CC1CCN(C(=O)c2ccc3occc3c2)CC1c1cc(C(F)F)nc2ncnn12
InChIKey: LYEXNMDIPNPRIQ-UHFFFAOYSA-N
Target: High affinity 3',5'-cyclic-AMP phosphodiesterase 7A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13946
Assay: Inhibition of 6xHis-tagged human recombinant PDE7A1 expressed in Sf9 cells by scintillation counting method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 411.41, ALogP 4.07, HBA 6, HBD 0, PSA 76.53, QED 0.51
Compound (SMILES): CC#C[C@@H](CC(=O)O)c1ccc(OCc2cc(C)c(CN3CCC4(C=Cc5ccccc54)CC3)s2)cc1
InChIKey: WZOVXNKWRTVWKI-SANMLTNESA-N
Target: Free fatty acid receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q8K3T4
Assay: Agonist activity at Prolink-tagged rat GPR40 fused with EA-tagged beta-arrestin expressed in human U2OS cells assessed as induction of beta-arrestin recruitment measured after 90 mins by beta-galactosidase based PathHunter assay
Measurement: EC50 = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 511.69, ALogP 6.78, HBA 4, HBD 1, PSA 49.77, QED 0.34
Compound (SMILES): FC(F)(F)c1nccc2cc(Nc3n[nH]c4ncccc34)ccc12
InChIKey: RUEXKBWCUUFJMY-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes using midazolam as substrate preincubated for 15 mins followed by NADPH addition and measured after 8 mins by LC/MS/MS analysis
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 329.29, ALogP 4.27, HBA 4, HBD 2, PSA 66.49, QED 0.58
Compound (SMILES): COc1ccc(C(=O)Nc2nc(-c3ccccc3)c(C(=O)c3ccc(C)cc3)s2)cc1
InChIKey: QWYBNZBBHWLLPB-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Displacement of [3H]PSB-603 from human adenosine receptor A2B expressed in CHO cell membranes incubated for 75 mins by radioligand competition assay
Measurement: Ki > 100 nM (pChEMBL 7)
Descriptors: MW 428.51, ALogP 5.61, HBA 5, HBD 1, PSA 68.29, QED 0.41
Compound (SMILES): Cn1ncc(-c2ccc3cnc(NC(=O)c4ccc(OC(F)F)cc4)cc3c2)c1CO
InChIKey: VGSIIVYVVBWFFZ-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Kinase Assay: The DYRKIA kinase assay was run using the Ser/Thr 18 peptide Z-lyte assay kit according to manufacturer's instructions (Life Technologies-a Division of Thermo-Fisher). This is a non-radioactive assay using fluorescence resonance energy transfer (FRET) between coumarin and fluorescein to detect kinase activity which is represented as a ratio of coumarin emission/fluorescein emission. Briefly, recombinant DYRKIA kinase, ATP and Ser/Thr peptide 18 were prepared in 1× Kinase buffer to final concentrations of 0.19 μg/mL, 30 μM, and 4 μM respectively. The mixture was 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 served as control reactions. Additionally, an 11-point dose-response curve of Staurosporine (1 uM top) was run to serve as a positive compound control. After incubation, Development Reagent A was diluted in Development Buffer then added to the reaction and allowed to further incubate for one hour at room temperature. The plate was 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 = 4.3 nM (pChEMBL 8.369999885559082)
Descriptors: MW 424.41, ALogP 3.98, HBA 6, HBD 2, PSA 89.27, QED 0.49
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(C)CC2)c1[nH]c(-c2ccc(F)cc2F)nc1C#N
InChIKey: ODGPDTHYRQCSNH-GGAORHGYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of HDAC1 (unknown origin)
Measurement: IC50 = 35.2 nM (pChEMBL 7.449999809265137)
Descriptors: MW 511.62, ALogP 5.05, HBA 5, HBD 2, PSA 101.88, QED 0.41
Compound (SMILES): O=C(c1ccc(F)c(Cl)c1)N1CCC(F)(CNCCOc2cccc(Cl)c2)CC1
InChIKey: NPVINTHTFSBGKQ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Biased agonist activity at Gal4-VP16 transcription factor linked human 5-HT1A receptor expressed in human U2OS cells assessed as induction of beta-arrestin2 recruitment measured after 5 hrs by Tango assay
Measurement: EC50 = 223.87 nM (pChEMBL 6.650000095367432)
Descriptors: MW 443.32, ALogP 4.75, HBA 3, HBD 1, PSA 41.57, QED 0.63
Compound (SMILES): CN1COc2ccc(OCCCN3CCC(c4noc5cc(F)ccc45)CC3)cc2C1=O
InChIKey: KDMVVQOQEKIXTC-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P19327
Assay: Receptor Binding Assay: 5-HT1A: (1) The prepared membrane was applied with appropriate amount of buffer, and homogenizer was used for evenly dispersing. 15 tubes were mixed into a 100 ml container, and appropriate amount of buffer was added to give 50 ml of membrane suspension, which was reserved for future use. (2) 100 μL of membrane preparation and 100 μL of buffer were added into each reaction tube. (3) 100 μL of buffer was added into the total binding tube (TB), 100 μL of 5-HT (final concentration 10-5M) was added into the nonspecific binding tube (NB), 100 μL of the test compound (final concentration 10-5M) was added into the specific binding tube (SB) of each test compound. (4) 10 μL of radioactive ligand 3H-8-OH-DPAT was respectively added into each reaction tube (2 parallel tubes were used for each reaction tube, and each of them was placed on ice when adding sample). (5) Each reaction tube was incubated at 37° C. for 10 min; after the reaction was completed, the bound ligands were rapidly filtered under reduced pressure, and sufficiently washed with ice-chilled assay buffer. The filter was taken out and put into a 3 ml scintillation vial, and 2 ml of toluene scintillation cocktail was added and blended.
Measurement: Ki = 24.6 nM (pChEMBL 7.610000133514404)
Descriptors: MW 439.49, ALogP 4.04, HBA 6, HBD 0, PSA 68.04, QED 0.54
Compound (SMILES): CC[C@H](N[C@H]1CC[C@@]2(OC)[C@H]3Cc4ccc(O)c5c4[C@@]2(CCN3C)[C@H]1O5)C(=O)O
InChIKey: FGPMICJYDSZBIT-YRBIGKLASA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at human DOR expressed in CHO cell membranes incubated for 60 mins scintillation counting assay
Measurement: EC50 = 98.2 nM (pChEMBL 7.010000228881836)
Descriptors: MW 402.49, ALogP 1.65, HBA 6, HBD 3, PSA 91.26, QED 0.69
Compound (SMILES): O=C(Nc1nc(-c2ccccc2)c(C(=O)c2ccc(F)cc2F)s1)c1ccco1
InChIKey: RVXUCDYZOPPLSL-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Displacement of [3H]PSB-603 from human adenosine receptor A2B expressed in CHO cell membranes incubated for 75 mins by radioligand competition assay
Measurement: Ki > 100 nM (pChEMBL 7)
Descriptors: MW 410.4, ALogP 5.16, HBA 5, HBD 1, PSA 72.2, QED 0.46
Compound (SMILES): O=c1c2ccccc2oc2ccc(OCCCCCN3CCCCCC3)cc12
InChIKey: KNIPHGXUVWAHCN-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of recombinant human AChE using ATCI as substrate incubated for 5 mins followed by substrate addition and measured after 5 mins by spectrophotometric based Ellman's method
Measurement: IC50 = 392 nM (pChEMBL 6.409999847412109)
Descriptors: MW 379.5, ALogP 5.37, HBA 4, HBD 0, PSA 42.68, QED 0.41
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](CCCNC(=N)N)C(=O)N[C@@H](Cc2ccccc2)C(N)=O)C1=O
InChIKey: GQODKPDOYBQBRL-GJOOVXBSSA-N
Target: Nociceptin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41146
Assay: Agonist activity at human nociceptin receptor expressed in HEK293 cells assessed as inhibition of forskolin-induced cAMP accumulation incubated for 15 mins followed by forskolin addition in presence of IBMX by Glo-sensor cAMP assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 898.08, ALogP -0.95, HBA 10, HBD 13, PSA 349.85, QED 0.03
Compound (SMILES): Cc1c(N2CCC3(CC2)Cc2ccccc2[C@H]3N)nc(C)n(-c2cccc(Cl)c2Cl)c1=O
InChIKey: MFHWVKLJXFEKJX-JOCHJYFZSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: In-Vitro Safety Profile-Testing the Selectivity Over hErg: Inhibition of the ion channel hErg (or Kv11.1) current causes QT interval prolongation resulting in potentially fatal ventricular tachyarrhythmia called Torsade de Pointes. This is one of the major causes of cardiotoxicity and hErg channel activity is usually evaluated early in the drug development process to mitigate cardiotoxicity risk.hERG ion channel activity was assessed using a patch clamp technique in stable Kv11.1 (hERG) transfected human embryonic kidney cell line (HEK293). Whole cell recordings were carried out with an automated patch clamp device Patchliner™ from Nanion Technologies, Munich following manufacturer recommendation. Different concentrations of the test compound or reference, quinidine, were applied to whole cells suspension and current was measured using a pulse pattern with fixed amplitudes. The effect on Kv11.1 (hERG) ion channel activity was judged from the tail current amplitude and Changes in Kv11.1 (hERG) ion channel activity between control value (defined as 100%) and test compound and reported as percent change of control value of COI.
Measurement: Ki = 1200 nM (pChEMBL 5.920000076293945)
Descriptors: MW 469.42, ALogP 5, HBA 5, HBD 1, PSA 64.15, QED 0.57
Compound (SMILES): COc1ccc2c(c1)C(/C=C/c1n[nH]c(=O)o1)=CCC2
InChIKey: DTZLGFSNOPDVSN-SOFGYWHQSA-N
Target: Polyunsaturated fatty acid 5-lipoxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P09917
Assay: Inhibition of human 5-Lipoxygenase using H2DCFDA as substrate preincubated for 5 mins and measured by Spectrophotometric assay
Measurement: IC50 = 12500 nM (pChEMBL 4.900000095367432)
Descriptors: MW 270.29, ALogP 2.41, HBA 4, HBD 1, PSA 68.12, QED 0.93
Compound (SMILES): Cn1cc(-c2cccc(-c3coc4ccc(-c5cnn(C)c5)nc34)c2)cn1
InChIKey: XQQYRDDJENLAME-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of human full length recombinant DYRK1A using RRRFRPASPLRGPP substrate by radiometric scintillation assay
Measurement: IC50 = 147 nM (pChEMBL 6.829999923706055)
Descriptors: MW 355.4, ALogP 4.3, HBA 6, HBD 0, PSA 61.67, QED 0.48
Compound (SMILES): Nc1nc(-c2ccc(NC(=O)CCNCc3ccc(S(N)(=O)=O)cc3)cc2)cn2c(=O)n(-c3ccccc3)nc12
InChIKey: YKNBYIQXICDOOY-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human CA2 incubated for 15 mins by stopped- flow CO2 hydrase assay method
Measurement: Ki = 6763 nM (pChEMBL 5.170000076293945)
Descriptors: MW 558.62, ALogP 1.9, HBA 10, HBD 4, PSA 179.5, QED 0.2
Compound (SMILES): C/C(=N\Nc1nc(-c2ccc(Cl)cc2)cs1)c1nnn(-c2ccc(C(=O)O)cc2)c1C
InChIKey: TWOUDRJRIGZZPR-WYMPLXKRSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human CA9 by stopped-flow carbon dioxide hydration assay
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 452.93, ALogP 4.89, HBA 8, HBD 2, PSA 105.29, QED 0.32
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-c2ccc(C(C)(C)C)cc2)[nH]1)C(C)C.Cl.Cl.Cl.Cl
InChIKey: FXKYRSFCODUPSI-LLKZCWBVSA-N
Target: Nonstructural protein 5A (SINGLE PROTEIN), Hepatitis C virus
UniProt: Q5L478
Assay: Inhibition of HCV genotype 2a 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 = 1.684 nM (pChEMBL 8.770000457763672)
Descriptors: MW 843.04, ALogP 7.26, HBA 8, HBD 4, PSA 174.64, QED 0.12
Compound (SMILES): CNc1nc(NCc2ncccn2)c2c(-c3ccc4ncccc4c3)c[nH]c2n1
InChIKey: PMWVYONICYRLNY-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P49759
Assay: Binding affinity to CLK1 (unknown origin) assessed as dissociation constant
Measurement: Kd = 4.8 nM (pChEMBL 8.319999694824219)
Descriptors: MW 382.43, ALogP 3.62, HBA 7, HBD 3, PSA 104.3, QED 0.43
Compound (SMILES): CC1(C)Cc2c(ccc3[nH]ncc23)[C@@H](c2ccc(NC3CN(CCCF)C3)cn2)N1CC(F)F
InChIKey: NNKIFQRRDDJHKS-DEOSSOPVSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Binding Assay: ER: The ability of compounds to bind to isolated Estrogen Receptor Alpha Ligand binding domain (ER alpha-LBD (GST)) was assessed in competition assays using a LanthaScreen Time-Resolved Fluorescence Resonance Energy Transfer (TR-FRET) detection end-point. For the LanthaScreen TR-FRET endpoint, a suitable fluorophore (Fluormone ES2, ThermoFisher, Product code P2645) and recombinant human Estrogen Receptor alpha ligand binding domain, residues 307-554 (expressed and purified in-house) were used to measure compound binding. The assay principle is that ER alpha-LBD (GST) is added to a fluorescent ligand to form a receptor/fluorophore complex. A terbium-labelled anti-GST antibody (Product code PV3551) is used to indirectly label the receptor by binding to its GST tag, and competitive binding is detected by a test compound's ability to displace the fluorescent ligand, resulting in a loss of TR-FRET signal between the Tb-anti-GST antibody and the tracer. The assay was performed as follows with all reagent additions carried out using the Beckman Coulter BioRAPTR FRD microfluidic workstation:    1. Acoustic dispense 120 nL of the test compound into a black low volume 384 well assay plates.    2. Prepare 1×ER alpha-LBD/Tb-antiGST Ab in ES2 screening buffer and incubate for 15 minutes.    3. Dispense 6 μL of the 1×AR-LBD/Tb-anti-GST Ab reagent into each well of the assay plate followed by 6 μL of Fluorophore reagent into each well of the assay plate    4. Cover the assay plate to protect the reagents from light and evaporation, and incubate at room temperature for 4 hours.    5. Excite at 337 nm and measure the fluorescent emission signal of each well at 490 nm and 520 nm using the BMG PheraSTAR.Compounds were dosed directly from a compound source microplate containing serially diluted compound (4 wells containing 10 mM, 0.1 mM, 1 mM and 10 nM final compound respectively) to an assay microplate using the Labcyte Echo 550. The Echo 550 is a liquid handler that uses acoustic technology to perform direct microplate-to-microplate transfers of DMSO compound solutions and the system can be programmed to transfer multiple small nL volumes of compound from the different source plate wells to give the desired serial dilution of compound in the assay which is then back-filled to normalise the DMSO concentration across the dilution range.
Measurement: IC50 = 12000 nM (pChEMBL 4.920000076293945)
Descriptors: MW 472.56, ALogP 4.4, HBA 5, HBD 2, PSA 60.08, QED 0.51
Compound (SMILES): O=C(c1ccc(F)c(Cl)c1)N1CCC(F)(CNCCOc2ccc(Cl)cc2)CC1
InChIKey: HDFGGNSQPFXQRL-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Biased agonist activity at Gal4-VP16 transcription factor linked human 5-HT1A receptor expressed in human U2OS cells assessed as induction of beta-arrestin2 recruitment measured after 5 hrs by Tango assay
Measurement: EC50 = 977.24 nM (pChEMBL 6.010000228881836)
Descriptors: MW 443.32, ALogP 4.75, HBA 3, HBD 1, PSA 41.57, QED 0.63
Compound (SMILES): NCc1ccc(NC(=O)N2C(=O)CC2CC(=O)NCCC(=O)O)cc1.O=C(O)C(F)(F)F
InChIKey: WNJSILFLYVIFJS-UHFFFAOYSA-N
Target: Integrin alpha-V/beta-5 (PROTEIN COMPLEX), Homo sapiens
UniProt: P18084
Assay: Agonist activity at alphaVbeta5 in human MCF7 cells assessed as increase in cell adhesion to fibrinogen pre-incubated for 30 mins before fibrinogen and further incubated for 1 hr by nitrophenyl-N-acetyl-beta-D-glucosaminide substrate based chromogenic assay
Measurement: EC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 348.36, ALogP 0.26, HBA 5, HBD 4, PSA 141.83, QED 0.52
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H]1CCCN1C(=O)CNC(=O)[C@@H](N)Cc1ccc(O)cc1)C(=O)N[C@@H](CCCNC(=N)N)C(N)=O
InChIKey: BKBCMJYQMWAFCX-KWIWMOKLSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Antagonist activity at human KOR expressed in CHO cell membranes assessed as reduction in U50,488 induced response incubated for 1 hr by liquid scintillation counting based [35S]GTP-gamma-S assay
Measurement: IC50 > 2500 nM (pChEMBL 5.6020002365112305)
Descriptors: MW 1020.25
Compound (SMILES): C[C@@H]1NC(=O)[C@H](CN)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)CN(CCCNC(=N)N)C(=O)[C@@H]2CCCN2C(=O)[C@H]2CCCN2C(=O)[C@H](Cc2ccccc2)NC1=O
InChIKey: FGTXJLSBIKUVQB-NETOACFBSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Mus musculus
UniProt: P56450
Assay: Antagonist activity at mouse MC4R assessed as antagonist potency by alphascreen cAMP assay
Measurement: Kd > 3162.28 nM (pChEMBL 5.5)
Descriptors: MW 949.13, ALogP -1.19, HBA 10, HBD 9, PSA 294.35, QED 0.06
Compound (SMILES): CC#C[C@@H](CC(=O)O)c1ccc(OCc2ccc(CN3CCC4(CC3)CN(c3ccccc3)c3ccccc34)cc2)cc1
InChIKey: YPPVVNXEJUDPRL-YTTGMZPUSA-N
Target: Free fatty acid receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q8K3T4
Assay: Agonist activity at Prolink-tagged rat GPR40 fused with EA-tagged beta-arrestin expressed in human U2OS cells assessed as induction of beta-arrestin recruitment measured after 90 mins by beta-galactosidase based PathHunter assay
Measurement: EC50 = 0.83 nM (pChEMBL 9.079999923706055)
Descriptors: MW 570.73, ALogP 7.53, HBA 4, HBD 1, PSA 53.01, QED 0.21
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(C)CC2)c1[nH]c(-c2ccc(C(F)(F)F)cc2)nc1C#N
InChIKey: QSAPXBCUKYHAFP-PKTZIBPZSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of HDAC1 (unknown origin)
Measurement: IC50 = 3.7 nM (pChEMBL 8.430000305175781)
Descriptors: MW 543.63, ALogP 5.79, HBA 5, HBD 2, PSA 101.88, QED 0.35
Compound (SMILES): COc1nc(-c2csc(Nc3c4c(nn3C3CCC3)CCCC4)n2)ccc1-n1cnc(C)c1
InChIKey: OPBCSQTYQHKIFO-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of recombinant CYP2D6 (unknown origin) by fluorescence-based assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 461.6, ALogP 5.25, HBA 9, HBD 1, PSA 82.68, QED 0.42
Compound (SMILES): Cc1nc(NC(=O)NCCc2cn(CC(F)F)cn2)sc1C#Cc1cccnc1
InChIKey: FUKVQYDAJUEJHW-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by planar patch clamp method
Measurement: IC50 = 13000 nM (pChEMBL 4.889999866485596)
Descriptors: MW 416.46, ALogP 3.07, HBA 6, HBD 2, PSA 84.73, QED 0.61
Compound (SMILES): CCc1ccccc1NC(=O)NCCS(=O)(=O)Nc1ccc(S(N)(=O)=O)cc1
InChIKey: RNBCGDGLONSUIF-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 incubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 7.9 nM (pChEMBL 8.100000381469727)
Descriptors: MW 426.52, ALogP 1.46, HBA 5, HBD 4, PSA 147.46, QED 0.5
Compound (SMILES): O=C(NO)c1ccc(Nc2c3ccccc3nc3ccc(Br)cc23)cc1
InChIKey: PESSDQDERPAVNH-UHFFFAOYSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Inhibition of amyloid beta (1 to 42) (unknown origin) self aggregation after 24 hrs by thioflavin-T fluorescence method
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 408.26, ALogP 5.01, HBA 4, HBD 3, PSA 74.25, QED 0.25
Compound (SMILES): Cc1ccc(C(=O)c2sc(NC(=O)c3ccco3)nc2-c2ccccc2)cc1
InChIKey: NSGJWVVFFNBRGB-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Rattus norvegicus
UniProt: P29276
Assay: Displacement of [3H]PSB-603 from rat adenosine receptor A2B expressed in CHO cell membranes incubated for 75 mins by radioligand competition assay
Measurement: Ki > 100 nM (pChEMBL 7)
Descriptors: MW 388.45, ALogP 5.19, HBA 5, HBD 1, PSA 72.2, QED 0.48
Compound (SMILES): O=C(N[C@@H]1CC[C@@]2(S(=O)(=O)c3ccc(F)cc3)c3ccc(C(F)(C(F)(F)F)C(F)(F)F)cc3CC[C@@H]12)C1CCS(=O)(=O)CC1
InChIKey: LOOWXSUDJJEUCC-JBRSBNLGSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 = 5800 nM (pChEMBL 5.239999771118164)
Descriptors: MW 673.64, ALogP 5.45, HBA 5, HBD 1, PSA 97.38, QED 0.34
Compound (SMILES): CNc1cccc(OCCNCC2(F)CCN(C(=O)c3ccc(F)c(Cl)c3)CC2)c1
InChIKey: PHEGDBVVFIATGX-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 co-expressing Galpha16/GPCR assessed as increase in calcium mobilization measured for 30 secs in presence of coelenterazine by aequorin-reporter gene based luminescence assay
Measurement: EC50 = 32.36 nM (pChEMBL 7.489999771118164)
Descriptors: MW 437.92, ALogP 4.13, HBA 4, HBD 2, PSA 53.6, QED 0.61
Compound (SMILES): CS(=O)(=O)N1CCC(Nc2ncc3cc(Cl)c(=O)n(C4CCCC4)c3n2)CC1
InChIKey: YEMOJJTZJLWRNY-UHFFFAOYSA-N
Target: CDK6/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24385
Assay: Inhibition of CDK6/cyclin D1 (unknown origin) assessed as reduction in substrate peptide phosphorylation using DYRKtide peptide as substrate preincubated for 12 mins followed by ATP addition and measured for 45 mins by mobility shift assay
Measurement: Ki = 0.36 nM (pChEMBL 9.4399995803833)
Descriptors: MW 425.94, ALogP 2.4, HBA 7, HBD 1, PSA 97.19, QED 0.81
Compound (SMILES): N#Cc1c(N2CCOCC2)sc(-c2nc[nH]n2)c1-c1ccc(NC(=O)Nc2ccccc2Cl)cc1
InChIKey: OHHJTGRTQJGKLY-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of GST-tagged human recombinant PI3Kgamma catalytic domain (468 to 1203 residues) expressed in insect cells using PIP2 peptide as substrate incubated for 1 hr in presence ATP by ADP-Glo Kinase Assay
Measurement: Ki = 193 nM (pChEMBL 6.710000038146973)
Descriptors: MW 505.99, ALogP 5.21, HBA 7, HBD 3, PSA 118.96, QED 0.34
Compound (SMILES): C[C@@H](NC(=O)[C@@H](N)Cc1ccc(O)cc1)C(=O)NCC(=O)N(C)[C@@H](Cc1ccccc1)C(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccccc1)C(N)=O
InChIKey: NMKYKQNZEVJKQC-WJYGCBBBSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at delta opioid receptor (unknown origin) expressed in HEK293-A cells assessed as reduction in forskolin-induced cAMP accumulation incubated for 30 mins by competition PKA binding assay
Measurement: EC50 = 575.44 nM (pChEMBL 6.239999771118164)
Descriptors: MW 1055.21
Compound (SMILES): CCCCNc1nc2cc([N+](=O)[O-])ccc2s1
InChIKey: KGMPZRJHVILPMZ-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK1 (SINGLE PROTEIN), Mus musculus
UniProt: P22518
Assay: Inhibition of mouse recombinant CLK1 expressed in bacterial expression system using GRSRSRSRSRSR as substrate by ADP-glo assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 251.31, ALogP 3.42, HBA 5, HBD 1, PSA 68.06, QED 0.5
Compound (SMILES): CCCCN(CCCC)C(=O)CN1C[C@@H](c2cc(OC)c3c(c2)OCO3)[C@H](C(=O)O)[C@H]1CC(C)(C)CCC.Cl
InChIKey: KMKKFZCVBRAWNX-GSAMTNRBSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Selectivity interaction (GPCR panel (PDSP screen)) EUB0000289bCl OPRM1
Measurement: Ki = 2781 nM (pChEMBL 5.559999942779541)
Descriptors: MW 532.72, ALogP 5.54, HBA 6, HBD 1, PSA 88.54, QED 0.32
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3ncc4ccc(OC)cc4n3)C2)cc1
InChIKey: ADHABGMDGASWTO-GOSISDBHSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51948
Assay: Inhibition of CDK7/cyclin H/MAT1 (unknown origin) assessed as incoporation of [33]Pi using RBER-IRStide as substrate and in presence of [gamma-33P]-ATP measured after 60 mins under thiol free condition by microplate scintillation counter
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 417.47, ALogP 3.09, HBA 6, HBD 2, PSA 96.45, QED 0.6
Compound (SMILES): C[C@H](CO)n1cnnc1-c1cccc(NC(=O)Nc2cc3ccccn3n2)n1
InChIKey: GSYUZRLLPWNNAL-GFCCVEGCSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of human recombinant GSK3 beta H350L mutant using YRRAAVPPSPSLSR as substrate incubated for 40 mins in presence of [gamma-33ATP] by radiometric scintillation counting analysis
Measurement: IC50 = 282.9 nM (pChEMBL 6.550000190734863)
Descriptors: MW 378.4, ALogP 2.19, HBA 8, HBD 3, PSA 122.26, QED 0.49
Compound (SMILES): O=C[C@H](C[C@@H]1CCNC1=O)NC(=O)[C@H](CC1CCCCC1)NC(=O)c1cc2ccccc2[nH]1
InChIKey: HPKJGHVHQWJOOT-ZJOUEHCJSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of SARS-CoV-2 main protease expressed in Escherichia coli using MCA-AVLQSGFR-Lys(Dnp)-Lys-NH2 as substrate by FRET based assay
Measurement: IC50 = 530 nM (pChEMBL 6.28000020980835)
Descriptors: MW 452.56, ALogP 2.45, HBA 4, HBD 4, PSA 120.16, QED 0.44
Compound (SMILES): CN1CCN(CCCN2C(=O)c3ccccc3/C=C\c3ccccc32)CC1
InChIKey: GRZVXITWIIKNCX-QXMHVHEDSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Binding affinity to D2 receptor (unknown origin)
Measurement: Ki = 7500 nM (pChEMBL 5.119999885559082)
Descriptors: MW 361.49, ALogP 3.45, HBA 3, HBD 0, PSA 26.79, QED 0.83
Compound (SMILES): Nc1nc(-c2ccc(NC(=O)c3ccc(S(N)(=O)=O)cc3)cc2)cn2c(=O)n(-c3ccccc3)nc12
InChIKey: ZYILDTWBSDDXCD-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human CA9 incubated for 15 mins by stopped- flow CO2 hydrase assay method
Measurement: Ki = 466 nM (pChEMBL 6.329999923706055)
Descriptors: MW 501.53, ALogP 2.03, HBA 9, HBD 3, PSA 167.47, QED 0.33
Compound (SMILES): CC1CCN(C(=O)c2ccc3occc3c2)CC1c1cc(C(F)F)nc2ncnn12
InChIKey: LYEXNMDIPNPRIQ-UHFFFAOYSA-N
Target: Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HCR9
Assay: Inhibition of 6xHis-tagged human recombinant PDE11A4 expressed in HEK cells by scintillation counting method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 411.41, ALogP 4.07, HBA 6, HBD 0, PSA 76.53, QED 0.51
Compound (SMILES): CC#C[C@@H](CC(=O)O)c1ccc(OCc2cc(C)c(CN3CCC4(C=Cc5ccccc54)CC3)s2)cc1
InChIKey: WZOVXNKWRTVWKI-SANMLTNESA-N
Target: Free fatty acid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O14842
Assay: Agonist activity at human recombinant full length GPR40 overexpressed in human HEK293 cells assessed as increase in inositol phosphate accumulation in presence of terbium cryptate-labeled anti IP1/d2-labelled IP1 measured after 120 mins by HTRF assay
Measurement: EC50 = 0.98 nM (pChEMBL 9.010000228881836)
Descriptors: MW 511.69, ALogP 6.78, HBA 4, HBD 1, PSA 49.77, QED 0.34
Compound (SMILES): FC(F)(F)c1nccc2cc(Nc3n[nH]c4ncccc34)ccc12
InChIKey: RUEXKBWCUUFJMY-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes using midazolam as substrate preincubated for 15 mins followed by NADPH addition and measured after 8 mins by LC/MS/MS analysis
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 329.29, ALogP 4.27, HBA 4, HBD 2, PSA 66.49, QED 0.58
Compound (SMILES): COc1ccc(C(=O)Nc2nc(-c3ccccc3)c(C(=O)c3ccc(C)cc3)s2)cc1
InChIKey: QWYBNZBBHWLLPB-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Rattus norvegicus
UniProt: P29276
Assay: Displacement of [3H]PSB-603 from rat adenosine receptor A2B expressed in CHO cell membranes incubated for 75 mins by radioligand competition assay
Measurement: Ki > 100 nM (pChEMBL 7)
Descriptors: MW 428.51, ALogP 5.61, HBA 5, HBD 1, PSA 68.29, QED 0.41
Compound (SMILES): Cn1ncc(-c2ccc3cnc(NC(=O)c4ccc(OC(F)F)cc4)cc3c2)c1CO
InChIKey: VGSIIVYVVBWFFZ-UHFFFAOYSA-N
Target: Proto-oncogene Wnt-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P04628
Assay: The screening assay for Wnt activity: The screening assay for Wnt activity is described as follows. 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. Each compound was dissolved in DMSO as a 10 mM stock and used to prepare compound source plates. Serial dilution (1:3, 10-point dose-response curves starting from 10 μM) and compound transfer was performed using the ECHO 550 (Labcyte, Sunnyvale, Calif.) into 384-well white solid bottom assay plates (Greiner Bio-One) with appropriate DMSO backfill for a final DMSO concentration of 0.1%. For Sp5-Luc reporter gene assays, the cells were plated at 4,000 cells/well in 384-well plates with a DMEM medium containing 1% fetal bovine serum, and 1% Penicillin-Streptomycin and incubated for 36 to 48 hours at 37° C. and 5% CO2. Following incubation, 15 μl of BriteLite Plus luminescence reagent (Perkin Elmer) was added to each well of the 384-well assay plates. The plates were placed on an orbital shaker for 2 min and then luminescence was quantified using the Envision (Perkin Elmer) plate reader. Readings were normalized to DMSO only treated cells, and normalized activities were utilized for EC50 calculations using the dose-response log (inhibitor) vs. responsevariable slope (four parameters) nonlinear regression feature available in GraphPad Prism 5.0 (or Dotmatics).
Measurement: EC50 = 265 nM (pChEMBL 6.579999923706055)
Descriptors: MW 424.41, ALogP 3.98, HBA 6, HBD 2, PSA 89.27, QED 0.49
Compound (SMILES): O=C(c1ccc(F)c(Cl)c1)N1CCC(F)(CNCCOc2cccc(Cl)c2)CC1
InChIKey: NPVINTHTFSBGKQ-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 co-expressing Galpha16/GPCR assessed as increase in calcium mobilization measured for 30 secs in presence of coelenterazine by aequorin-reporter gene based luminescence assay
Measurement: EC50 = 251.19 nM (pChEMBL 6.599999904632568)
Descriptors: MW 443.32, ALogP 4.75, HBA 3, HBD 1, PSA 41.57, QED 0.63
Compound (SMILES): CN1COc2ccc(OCCCN3CCC(c4noc5cc(F)ccc45)CC3)cc2C1=O
InChIKey: KDMVVQOQEKIXTC-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P14842
Assay: Receptor Binding Assay: 5-HT2A:(1) The prepared membrane was applied with buffer, and homogenizer was used for evenly dispersing. 15 tubes were mixed into a 100 ml container, and appropriate amount of buffer was added to give 50 ml of membrane suspension, which was reserved for future use.(2) 100 μL of membrane preparation and 100 μL of buffer were added into each reaction tube.(3) 100 μL of buffer was added into the total binding tube (TB), 100 μL of Methysergide (final concentration 10−5M) was added into the nonspecific binding tube (NB), 100 μL of the test compound (final concentration 10−5M) was added into the specific binding tube (SB) of each test compound.(4) 10 μL of radioactive ligand 3H-Ketanserin was respectively added into each reaction tube (2 parallel tubes were used for each reaction tube, and each of them was placed on ice when adding sample).(5) Each of the reaction tubes was incubated at 37° C. for 15 min. After the reaction was completed, the bound ligands were rapidly filtered under reduced pressure, and sufficiently washed with ice-chilled assay buffer. The filter was taken out and put into a 3 ml scintillation vial, and 2 ml of toluene scintillation cocktail was added and blended.(6) The scintillation vial were put into Liquid Scintillation Counter for counting.Inhibition rate(I%)=(Total binding tube cpm−compound cpm)/(Total binding tube cpm−nonspecific binding tube cpm)×100% .
Measurement: Ki = 3.6 nM (pChEMBL 8.4399995803833)
Descriptors: MW 439.49, ALogP 4.04, HBA 6, HBD 0, PSA 68.04, QED 0.54
Compound (SMILES): CC[C@H](N[C@H]1CC[C@@]2(OC)[C@H]3Cc4ccc(O)c5c4[C@@]2(CCN3C)[C@H]1O5)C(=O)O
InChIKey: FGPMICJYDSZBIT-YRBIGKLASA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Agonist activity at human KOR expressed in CHO cell membranes incubated for 60 mins scintillation counting assay
Measurement: EC50 = 942 nM (pChEMBL 6.03000020980835)
Descriptors: MW 402.49, ALogP 1.65, HBA 6, HBD 3, PSA 91.26, QED 0.69
Compound (SMILES): O=C(Nc1nc(-c2ccccc2)c(C(=O)c2ccc(F)cc2F)s1)c1ccco1
InChIKey: RVXUCDYZOPPLSL-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Rattus norvegicus
UniProt: P29276
Assay: Displacement of [3H]PSB-603 from rat adenosine receptor A2B expressed in CHO cell membranes incubated for 75 mins by radioligand competition assay
Measurement: Ki > 100 nM (pChEMBL 7)
Descriptors: MW 410.4, ALogP 5.16, HBA 5, HBD 1, PSA 72.2, QED 0.46
Compound (SMILES): O=c1c2ccccc2oc2ccc(OCCCCCN3CCCCCC3)cc12
InChIKey: KNIPHGXUVWAHCN-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human BuChE by spectrophotometric based Ellman's method
Measurement: IC50 = 1278 nM (pChEMBL 5.889999866485596)
Descriptors: MW 379.5, ALogP 5.37, HBA 4, HBD 0, PSA 42.68, QED 0.41
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](CCCNC(=N)N)C(=O)N[C@@H](Cc2ccccc2)C(N)=O)C1=O
InChIKey: GQODKPDOYBQBRL-GJOOVXBSSA-N
Target: Neuropeptide FF receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X5
Assay: Agonist activity at human NPFFR2 expressed in CHO cells by [35S]-GTP S binding assay
Measurement: EC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 898.08, ALogP -0.95, HBA 10, HBD 13, PSA 349.85, QED 0.03
Compound (SMILES): Cc1c(N2CCC3(CC2)Cc2ccccc2[C@H]3N)nc(C)n(-c2cccc(Cl)c2Cl)c1=O
InChIKey: MFHWVKLJXFEKJX-JOCHJYFZSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: SHP2 Biochemical Assay (with IRSI_2pY): The inhibition of SHP2 by compounds of the invention was monitored using the surrogate substrate DiFMUP after protein activation by a peptide bearing two appropriately spaced phosphotyrosine. Full length SHP2 protein (Recombinant HumanSHP-2,E. coli derived Ser2Arg593, N-terminal 6His tag from R&D systems; 0.0.24 nM) was incubated with activating peptide, IRSI_2pY (New England Peptide, 140 nM) and DiFMUP (molecular probes, 80 uM) at RT in buffer (HEPES pH 7.2 60 mM, DDT 5 mM, KCl 75 mM, NaCl 75 mM, EDTA 1 mM, Tween 20 0.05%) in presence of compound (10 concentrations range, top concentration 50 μM) for 60 min with activating IRSI_2pY. The generation of the DiFMU product by activated SHP2 was monitored through Fluorescence measurement with a PerkinElmer Envision reader. The inhibitor dose response curves were analyzed with Genedata Screener.
Measurement: IC50 = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 469.42, ALogP 5, HBA 5, HBD 1, PSA 64.15, QED 0.57
Compound (SMILES): Cn1cc(-c2cccc(-c3coc4ccc(-c5cnn(C)c5)nc34)c2)cn1
InChIKey: XQQYRDDJENLAME-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y463
Assay: Inhibition of human full length recombinant DYRK1B using RRRFRPASPLRGPP substrate by radiometric scintillation assay
Measurement: IC50 = 2418 nM (pChEMBL 5.619999885559082)
Descriptors: MW 355.4, ALogP 4.3, HBA 6, HBD 0, PSA 61.67, QED 0.48
Compound (SMILES): Nc1nc(-c2ccc(NC(=O)CCNCc3ccc(S(N)(=O)=O)cc3)cc2)cn2c(=O)n(-c3ccccc3)nc12
InChIKey: YKNBYIQXICDOOY-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human CA9 incubated for 15 mins by stopped- flow CO2 hydrase assay method
Measurement: Ki = 318.7 nM (pChEMBL 6.5)
Descriptors: MW 558.62, ALogP 1.9, HBA 10, HBD 4, PSA 179.5, QED 0.2
Compound (SMILES): C/C(=N\Nc1nc(-c2ccc(Cl)cc2)cs1)c1nnn(-c2ccc(C(=O)O)cc2)c1C
InChIKey: TWOUDRJRIGZZPR-WYMPLXKRSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human CA12 by stopped-flow carbon dioxide hydration assay
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 452.93, ALogP 4.89, HBA 8, HBD 2, PSA 105.29, QED 0.32
Compound (SMILES): CNc1nc(NCc2ncccn2)c2c(-c3ccc4ncccc4c3)c[nH]c2n1
InChIKey: PMWVYONICYRLNY-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Binding affinity to CLK3 (unknown origin) assessed as dissociation constant
Measurement: Kd = 6.5 nM (pChEMBL 8.1899995803833)
Descriptors: MW 382.43, ALogP 3.62, HBA 7, HBD 3, PSA 104.3, QED 0.43
Compound (SMILES): CC1(C)Cc2c(ccc3[nH]ncc23)[C@@H](c2ccc(NC3CN(CCCF)C3)cn2)N1CC(F)F
InChIKey: NNKIFQRRDDJHKS-DEOSSOPVSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Displacement of fluormone ES2 green reagent from human GST-tagged ERalpha LBD (282 to 595 residues) expressed in baculovirus infected insect cells incubated for 1 hrs by TR-FRET Lanthascreen assay
Measurement: IC50 = 3.162 nM (pChEMBL 8.5)
Descriptors: MW 472.56, ALogP 4.4, HBA 5, HBD 2, PSA 60.08, QED 0.51
Compound (SMILES): O=C(c1ccc(F)c(Cl)c1)N1CCC(F)(CNCCOc2ccc(Cl)cc2)CC1
InChIKey: HDFGGNSQPFXQRL-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 co-expressing Galpha16/GPCR assessed as increase in calcium mobilization measured for 30 secs in presence of coelenterazine by aequorin-reporter gene based luminescence assay
Measurement: EC50 = 5248.07 nM (pChEMBL 5.28000020980835)
Descriptors: MW 443.32, ALogP 4.75, HBA 3, HBD 1, PSA 41.57, QED 0.63
Compound (SMILES): NCc1ccc(NC(=O)N2C(=O)CC2CC(=O)NCCC(=O)O)cc1.O=C(O)C(F)(F)F
InChIKey: WNJSILFLYVIFJS-UHFFFAOYSA-N
Target: Integrin alpha-V/beta-5 (PROTEIN COMPLEX), Homo sapiens
UniProt: P18084
Assay: Antagonist activity at alphaVbeta5 in human MCF7 cells assessed as reduction in cell adhesion to fibrinogen pre-incubated for 30 mins before fibrinogen and further incubated for 1 hr by nitrophenyl-N-acetyl-beta-D-glucosaminide substrate based chromogenic assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 348.36, ALogP 0.26, HBA 5, HBD 4, PSA 141.83, QED 0.52