lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC(=O)Nc1cn2cc(-c3cc(NC(=O)c4cccc(C(F)(F)F)c4)ccc3C)ccc2n1
InChIKey: MRTHXFZEQBERDI-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of B-Raf V600E mutant in human A375 cells assessed as reduction in ERK phosphorylation
Measurement: EC50 = 230 nM (pChEMBL 6.639999866485596)
Descriptors: MW 452.44, ALogP 5.54, HBA 4, HBD 2, PSA 75.5, QED 0.43
Compound (SMILES): CC(=O)N1c2ccccc2N(Cc2cccc(O)c2)CC1C1CC1
InChIKey: YRXSGADWHOCKQV-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of (+)-JQ1 from 6H-Thr BRD4 Y97A mutant BD2 (unknown origin) after 30 mins by TR-FRET assay
Measurement: IC50 = 630.96 nM (pChEMBL 6.199999809265137)
Descriptors: MW 322.41, ALogP 3.54, HBA 3, HBD 1, PSA 43.78, QED 0.94
Compound (SMILES): CCCCC/C=C\[C@H](C)/C=C\C/C=C\C/C=C\CCCC(=O)NCCO
InChIKey: HPZWGIGIINAFKI-VVFVXTANSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P20272
Assay: Displacement of [3H]CP-55,940 from CB1 receptor in rat brain membranes in presence of FAAH inhibitor PMSF by radioligand binding assay
Measurement: Ki = 4.8 nM (pChEMBL 8.319999694824219)
Descriptors: MW 361.57, ALogP 5.49, HBA 2, HBD 2, PSA 49.33, QED 0.28
Compound (SMILES): O=C(CN(Cc1cccc(C(=O)O)c1)Cc1cccc(C(=O)O)c1)NO
InChIKey: KHSBLMDTVROJFV-UHFFFAOYSA-N
Target: Meprin A subunit beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q16820
Assay: Inhibition of recombinant human meprin beta expressed in yeast using Abz-YVAEAPK(Dnp)G-OH as substrate by fluorescence assay
Measurement: IC50 = 49 nM (pChEMBL 7.309999942779541)
Descriptors: MW 358.35, ALogP 1.59, HBA 5, HBD 4, PSA 127.17, QED 0.42
Compound (SMILES): CN1CCN(c2nc(NCc3nc4cc(F)c(F)cc4[nH]3)c3ncn(-c4cccnc4)c3n2)CC1
InChIKey: HTHDTOPDKQYAIA-UHFFFAOYSA-N
Target: Casein kinase I isoform epsilon (SINGLE PROTEIN), Homo sapiens
UniProt: P49674
Assay: Inhibition of recombinant human full length N-terminal GST-tagged CK1epsilon expressed in baculovirus in Sf9 insect cells using ULight-Topo-IIa(Thr1342) peptide as substrate after 10 mins by TR-FRET assay
Measurement: IC50 = 660 nM (pChEMBL 6.179999828338623)
Descriptors: MW 476.5, ALogP 2.73, HBA 9, HBD 2, PSA 103.68, QED 0.4
Compound (SMILES): CN1CCN(C(=O)c2ccc(-c3cn4c(-c5cccc(O)c5)cnc4cn3)cc2)CC1
InChIKey: NTKMBZXHYFBSOK-UHFFFAOYSA-N
Target: MAP kinase-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BUB5
Assay: Inhibition of GST-tagged MNK1 (37 to 341 residues) (unknown origin) expressed in Escherichia coli BL21(DE3) using JH3 peptide as substrate preincubated for 10 mins followed by substrate and ATP addition measured after 60 mins
Measurement: IC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 413.48, ALogP 3.16, HBA 6, HBD 1, PSA 73.97, QED 0.56
Compound (SMILES): CCC1(OC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C[C@@H]2CCNC2=O)C(O)S(=O)(=O)[O-])CCN(C(=O)OC(C)(C)C)CC1.[Na+]
InChIKey: LSFQRCABQFHJEZ-FIGVUBRSSA-M
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome-related coronavirus
UniProt: P0C6X7
Assay: Inhibition of SARS coronavirus 3CL protease using Dabcyl-KTSAVLQ/SGFRKME-Edans as substrate incubated for 30 mins followed by substrate addition measured after 1 hr by FRET assay
Measurement: IC50 = 4100 nM (pChEMBL 5.389999866485596)
Descriptors: MW 606.74, ALogP 1.52, HBA 9, HBD 5, PSA 200.67, QED 0.21
Compound (SMILES): CN(C)C1CCN(C(=O)c2ccc(-c3ccc4ncc(-c5ccc(C#N)cc5)n4n3)cc2)CC1
InChIKey: KTBKRHUBYKAUFQ-UHFFFAOYSA-N
Target: MAP kinase-interacting serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HBH9
Assay: In Vitro Kinase Assay: MNK1 and MNK2 inhibitor activity was determined using recombinant kinase domains expressed in E. coli. MNK1 and MNK2 were expressed as GST fusion proteins and the GST tag was removed using PreScission protease. After concentration to 10-15 mg/ml the proteins were flash frozen in liquid nitrogen and stored at −80° C. MNK1 and MNK2 were activated using recombinant ERK2 which was activated using a constitutively active mutant of MEK1, both ERK2 and MEK1 were expressed in E. coli as N-terminally his tagged proteins. Recombinant ERK2 was activated by incubating 11.3 μM of the kinase with 1 μM MEK1 and 100 μM ATP. This reaction mixture was then used immediately for the activation of the MNKs. The activation of the MNK1 was performed by incubating 5.0 μM of MNK1 with 0.3 μM of activated ERK2 and 500 μM ATP at 30° C. for 6 hours. The activation of MNK2 was performed by incubating 50 μM of MNK2 with 3.0 μM of activated ERK2 and 500 μM ATP at 30° C. for 2 hours. The activated MNKs were stored at −20° C. until required for assay.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 450.55, ALogP 4.1, HBA 6, HBD 0, PSA 77.53, QED 0.47
Compound (SMILES): CC(C)n1cc(NC(=O)c2ccc(Nc3cnc4ccccc4n3)cc2)c(=O)n(C2(C(=O)N[C@H]3CC(=O)OC3O)CC2)c1=O
InChIKey: VCLBBDAIKKHTIS-LWAJAQLZSA-N
Target: Caspase-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P29466
Assay: Inhibition of caspase-1 in human THP1 cells assessed as decrease in LPS-induced IL-1beta secretion after overnight incubation by sandwich immunoassay
Measurement: IC50 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 599.6, ALogP 1.77, HBA 12, HBD 4, PSA 186.54, QED 0.22
Compound (SMILES): CCOC(=O)[C@@H]1CN(CCn2c(=O)[nH]c3ccccc3c2=O)CC[C@@H]1c1ccc(C)cc1
InChIKey: MQIXEEQLFJEKSG-TZIWHRDSSA-N
Target: Synaptic vesicular amine transporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q05940
Assay: Displacement of [3H]DHTB from human VMAT2 expressed in HEK293 cell membranes incubated for 90 mins by microbeta scintillation counting method
Measurement: Ki > 9100 nM (pChEMBL 5.040999889373779)
Descriptors: MW 435.52, ALogP 2.67, HBA 6, HBD 1, PSA 84.4, QED 0.6
Compound (SMILES): Cc1cc(C)nc(NS(=O)(=O)c2ccc(NCNc3n[nH]c(=S)s3)cc2)n1
InChIKey: LFDDGWWNWANBSX-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Ovis aries
UniProt: P79208
Assay: Inhibition of ovine COX2 using arachidonic acid as substrate incubated for 5 mins followed by substrate addition measured after 2 mins by enzyme immunoassay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 423.55, ALogP 2.89, HBA 9, HBD 4, PSA 124.69, QED 0.34
Compound (SMILES): NS(=O)(=O)c1ccc(/N=C2\NC(=O)/C(=C3/C(=O)N(Cc4ccccc4)c4ccccc43)S2)cc1
InChIKey: BRLCVKYPAQNQIC-MRCUWXFGSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human cytosolic carbonic anhydrase 2 by stopped-flow CO2 hydrase assay
Measurement: Ki = 8.3 nM (pChEMBL 8.079999923706055)
Descriptors: MW 490.57, ALogP 3.14, HBA 6, HBD 2, PSA 121.93, QED 0.54
Compound (SMILES): CC(C)c1ccccc1OCCCN1CCC(NS(=O)(=O)c2ccc(F)cc2)CC1
InChIKey: VSRQIONFRPRLGS-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]-8-OH-DPAT from human 5-HT1A receptor expressed in HEK293 or CHO-K1 cells after 1 hr by microbeta counting analysis
Measurement: Ki = 2081 nM (pChEMBL 5.679999828338623)
Descriptors: MW 434.58, ALogP 4.16, HBA 4, HBD 1, PSA 58.64, QED 0.6
Compound (SMILES): O=C1COC2CN(C(=O)Cc3ccc(Cl)c(Cl)c3)CC(N3CCCC3)C2N1
InChIKey: NRIIKTBFHPWWEY-UHFFFAOYSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Cavia porcellus
UniProt: P97266
Assay: Displacement of [3H]DAMGO from mu opioid receptor in guinea pig brain membranes after 120 mins by scintillation counting analysis
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 412.32, ALogP 1.73, HBA 4, HBD 1, PSA 61.88, QED 0.82
Compound (SMILES): O=C1C(c2cccc3ccccc23)Oc2ccccc2N1Cc1ccc(F)cc1
InChIKey: ZJLYKSWVZKNQMT-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of recombinant human His-tagged GSK3beta using GS-2 peptide as substrate in presence of [33P]gamma-ATP after 15 mins by microbeta counting method
Measurement: IC50 = 5400 nM (pChEMBL 5.269999980926514)
Descriptors: MW 383.42, ALogP 5.65, HBA 2, HBD 0, PSA 29.54, QED 0.46
Compound (SMILES): COc1cc2c(NC3CC4(CCN(C)C4)C3)cc(-c3ccc(C)o3)nc2cc1OCCCN1CCCC1
InChIKey: RDPYODVIYQQQFZ-UHFFFAOYSA-N
Target: DNA (cytosine-5)-methyltransferase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P26358
Assay: Inhibition of human DNMT1 using polydeoxyinosine polydeoxycytosine DNA as substrate after 15 mins in presence of SAM by TR-FRET assay
Measurement: IC50 = 201 nM (pChEMBL 6.699999809265137)
Descriptors: MW 504.68, ALogP 5.57, HBA 7, HBD 1, PSA 63, QED 0.38
Compound (SMILES): Cl.NCc1ccc(OCc2ccc(C(F)(F)F)cc2)cc1
InChIKey: OQPRLHHTEJYUSU-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of recombinant human MAO-B using benzylamine as substrate preincubated for 15 mins followed by substrate addition measured after 20 mins by amplex red reagent based spectrophotometric assay
Measurement: IC50 = 136 nM (pChEMBL 6.869999885559082)
Descriptors: MW 281.28, ALogP 3.74, HBA 2, HBD 1, PSA 35.25, QED 0.93
Compound (SMILES): C#CCN(CCOc1ccc2ccc(=O)oc2c1)Cc1ccc(OC)cc1
InChIKey: YUBVIFPCNJUNOC-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of recombinant human MAO-B using p-tyramine as substrate preincubated for 15 mins followed by substrate addition measured after 20 mins by amplex red reagent based fluorescence assay
Measurement: IC50 = 3513 nM (pChEMBL 5.449999809265137)
Descriptors: MW 363.41, ALogP 3.32, HBA 5, HBD 0, PSA 51.91, QED 0.45
Compound (SMILES): O=C(O)Cn1c2c(c3ccccc31)CN(C(=O)C1CC1)CC2
InChIKey: QJMWONYCPYAZIZ-UHFFFAOYSA-N
Target: Aldo-keto reductase family 1 member B1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P07943
Assay: Inhibition of ALR1 in Wistar rat kidney assessed as reduction in NADPH consumption preincubated for 1 min followed by substrate addition measured after 4 mins by spectrophotometric analysis
Measurement: IC50 = 7540 nM (pChEMBL 5.119999885559082)
Descriptors: MW 298.34, ALogP 2.02, HBA 3, HBD 1, PSA 62.54, QED 0.94
Compound (SMILES): Cc1ccccc1NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@]1(C)CCC[C@]2(C)c3cc(S(=O)(=O)N[C@@H](Cc4ccccc4)C(=O)Nc4ccccc4C)c(C(C)C)cc3CC[C@@H]12
InChIKey: GZXCOTIIWVSSDZ-ULBMYSQZSA-N
Target: Neutrophil collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P22894
Assay: Inhibition of recombinant human MMP8 (Phe21 to Gly467 residues) expressed in mouse myeloma cells using Mca-Pro-LeuGly-Leu-Dpa-Ala-Arg-NH2 as substrate preincubated for 30 mins followed by substrate addition by fluorescence assay
Measurement: IC50 = 24300 nM (pChEMBL 4.610000133514404)
Descriptors: MW 853.14, ALogP 9.33, HBA 5, HBD 4, PSA 133.47, QED 0.09
Compound (SMILES): O=C(Nc1ccc(-c2nn(C3CCC(C(=O)O)CC3)c3ccncc23)cc1)c1ccccc1
InChIKey: POONEVBKDCETSH-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of BTK (unknown origin) using peptide substrate after 1 hr by HTRF assay
Measurement: IC50 >= 10000 nM (pChEMBL 5)
Descriptors: MW 440.5, ALogP 5.17, HBA 5, HBD 2, PSA 97.11, QED 0.45
Compound (SMILES): Nc1ncnc2c1c(-c1ccc(Oc3ccccc3)cc1)cn2[C@H]1CC[C@H](N[C@@H](Cc2ccccc2)C(=O)O)CC1
InChIKey: XLRGWOQAKMIFSL-QEMZJVQQSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of recombinant human C-terminal FLT3 ITD mutant (571 to 993 residues) after 90 mins by mobility shift assay
Measurement: IC50 = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 547.66, ALogP 6.24, HBA 7, HBD 3, PSA 115.29, QED 0.2
Compound (SMILES): CC(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)N[C@@H](CN)C(=O)N[C@@H](CC1CCCC1)C(=O)N1CCC[C@H]1c1nc(-c2ccccc2)cn1C(C)C)C(C)C
InChIKey: KQZVAZQBTCAOFN-NCDLOLNQSA-N
Target: Protein ENL (SINGLE PROTEIN), Homo sapiens
UniProt: Q03111
Assay: Displacement of N-Flu-DOT1L from MBP-tagged ENL (unknown origin) (489 to 559 residues) expressed in Escherichia coli BL21(DE3) measured after 3 hrs by fluorescence polarization assay
Measurement: IC50 = 1220 nM (pChEMBL 5.909999847412109)
Descriptors: MW 832.1, ALogP 3.99, HBA 9, HBD 5, PSA 200.86, QED 0.15
Compound (SMILES): Cc1cc(C(=O)N2Cc3cnn(C)c3Nc3ccccc32)ccc1CNC(=O)N1CCC[C@H]1C(=O)N(C)C
InChIKey: ZBEAQAWGAOVDQA-DEOSSOPVSA-N
Target: Vasopressin V1a receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P37288
Assay: Antagonist activity at human V1A receptor expressed in HEK cells assessed as inhibition of AVP-induced intracellular calcium flux incubated for 45 mins by Indo1-AM dye based fluorescence assay relative to AVP
Measurement: IC50 = 95 nM (pChEMBL 7.019999980926514)
Descriptors: MW 515.62, ALogP 3.39, HBA 6, HBD 2, PSA 102.81, QED 0.55
Compound (SMILES): CC(=O)Nc1ccccc1C(F)(F)C(=O)NNc1ccccc1
InChIKey: HRAVXIQFJGVSTR-UHFFFAOYSA-N
Target: Arginase (SINGLE PROTEIN), Leishmania amazonensis
UniProt: O96394
Assay: Inhibition of recombinant Leishmania amazonensis arginase expressed in Escherichia coli assessed as reduction in urea production using L-arginine as substrate by Berthelot colorimetric method relative to control
Measurement: IC50 = 12000 nM (pChEMBL 4.920000076293945)
Descriptors: MW 319.31, ALogP 2.88, HBA 3, HBD 3, PSA 70.23, QED 0.74
Compound (SMILES): CCCCC[C@@](C)(O)C/C=C/[C@H]1CCC(=O)[C@@H]1CCSc1nc(C(=O)O)cs1
InChIKey: XSQHRDAGSMEMIV-NHGZPOSLSA-N
Target: Prostaglandin E2 receptor EP3 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P43115
Assay: Agonist activity at recombinant human EP3 receptor expressed in CHO cells assessed as increase in intracellular calcium level measured at 3 secs time interval by fura-2-AM dye based fluorescence assay
Measurement: EC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 425.62, ALogP 5.2, HBA 6, HBD 2, PSA 87.49, QED 0.27
Compound (SMILES): C=CC(=O)N1CC[C@]2(C1)C[C@H](n1c(NC(=O)c3ccc(-c4cnco4)s3)nc3cc(NC)ccc31)C2
InChIKey: QRYWETQFXDSLKP-PJCCXEONSA-N
Target: Tyrosine-protein kinase TXK (SINGLE PROTEIN), Homo sapiens
UniProt: P42681
Assay: Inhibition of TXK (unknown origin) using fluorescently labeled peptide as substrate after 3 hrs by microfluidic mobility shift assay
Measurement: IC50 = 0.25 nM (pChEMBL 9.600000381469727)
Descriptors: MW 502.6, ALogP 4.79, HBA 8, HBD 2, PSA 105.29, QED 0.37
Compound (SMILES): CC(C)[C@H]1COC(=O)N1c1ccnc(N[C@@H](C)c2ncc(Oc3ccc(F)cc3)cn2)n1
InChIKey: QZSFGXVFAIYNNF-KBXCAEBGSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of human N-terminal 6His-tagged IDH1 R132H mutant expressed in Escherichia coli Rosetta2 (DE3) assessed as effect on intracellular 2-HG level incubated for 60 mins in presence of alpha-ketoglutarate and NADPH by LC/MS/MS analysis
Measurement: IC50 = 81 nM (pChEMBL 7.090000152587891)
Descriptors: MW 438.46, ALogP 4.35, HBA 8, HBD 1, PSA 102.36, QED 0.58
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(C)C)NC(C)=O)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N(C)C)[C@@H](C)CC
InChIKey: UVVWKHNVNZMJPK-RYWOMTJGSA-N
Target: Protein ENL (SINGLE PROTEIN), Homo sapiens
UniProt: Q03111
Assay: Displacement of N-Flu-DOT1L from MBP-tagged ENL (unknown origin) (489 to 559 residues) expressed in Escherichia coli BL21(DE3) measured after 3 hrs by fluorescence polarization assay
Measurement: IC50 = 6830 nM (pChEMBL 5.170000076293945)
Descriptors: MW 821.07, ALogP 0.68, HBA 9, HBD 6, PSA 226.66, QED 0.1
Compound (SMILES): c1cncc(-n2cnc3c(NCc4nc5ccccc5[nH]4)nc(N4CCNCC4)nc32)c1
InChIKey: QNOGOWQWDXIZSG-UHFFFAOYSA-N
Target: Casein kinase I isoform epsilon (SINGLE PROTEIN), Homo sapiens
UniProt: P49674
Assay: Inhibition of recombinant human full length N-terminal GST-tagged CK1epsilon expressed in baculovirus in Sf9 insect cells using ULight-Topo-IIa(Thr1342) peptide as substrate after 10 mins by TR-FRET assay
Measurement: IC50 = 1840 nM (pChEMBL 5.739999771118164)
Descriptors: MW 426.49, ALogP 2.11, HBA 9, HBD 3, PSA 112.47, QED 0.39
Compound (SMILES): Cc1nnc2sc(C(=O)N3CC(c4cccc(F)c4)C3)c(N)c2c1C
InChIKey: CHOSNVWZSYIWJH-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Positive allosteric modulation of human M2 receptor assessed as increase in acetylcholine-induced response
Measurement: EC50 = 2100 nM (pChEMBL 5.679999828338623)
Descriptors: MW 356.43, ALogP 3.27, HBA 5, HBD 1, PSA 72.11, QED 0.76
Compound (SMILES): C[C@H](Nc1nn(C)c(=O)c2cccnc12)[C@H](c1ccccc1)N(C)C
InChIKey: OFKKYVMUDLMESU-SUMWQHHRSA-N
Target: Histone acetyltransferase KAT2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q92831
Assay: PCAF AlphaLisa Binding Assay: His/Flag epitope tagged PCAF719-832 bromodomain was cloned, expressed and purified to homogeneity in-house. PCAF bromodomain binding and inhibition of the compounds disclosed herein was assessed by monitoring the engagement of biotinylated small molecule ligand (known to bind to the PCAF bromodomain) with the target using the AlphaLisa technology (Perkin-Elmer). Specifically, in a 384 well ProxiPlate PCAF bromodomain (225 nM final) was combined with the biotinylated small molecule ligand (6 nM final) in 50 mM HEPES (pH 7.5), 75 mM NaCl, 1 mM TCEP, 0.01% (w/v) BSA, and 0.008% (w/v) Brij-35 either in the presence of DMSO (final 0.2% DMSO) or compound dilution series in DMSO. After 15 minute incubation at room temperature AlphaLisa streptavidin acceptor beads and AlphaLisa anti-histidine donor beads were added to a final concentration of 12.5 μg/mL each. After 90 minutes of equilibration plates were read on an Envision instrument and IC50s calculated using a four parameter non-linear curve fit.
Measurement: IC50 = 1900 nM (pChEMBL 5.71999979019165)
Descriptors: MW 337.43, ALogP 2.43, HBA 6, HBD 1, PSA 63.05, QED 0.77
Compound (SMILES): CC(C)c1cc2c(cc1S(=O)(=O)N[C@@H](Cc1ccccc1)C(=O)Nc1ccccc1)[C@@]1(C)CCC[C@@](C)(C(=O)N[C@@H](Cc3ccccc3)C(=O)Nc3ccccc3)[C@@H]1CC2
InChIKey: KDSZBJVBHXTOGE-HNLKLKQNSA-N
Target: Neutrophil collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P22894
Assay: Inhibition of recombinant human MMP8 (Phe21 to Gly467 residues) expressed in mouse myeloma cells using Mca-Pro-LeuGly-Leu-Dpa-Ala-Arg-NH2 as substrate preincubated for 30 mins followed by substrate addition by fluorescence assay
Measurement: IC50 = 28200 nM (pChEMBL 4.550000190734863)
Descriptors: MW 825.09, ALogP 8.71, HBA 5, HBD 4, PSA 133.47, QED 0.09
Compound (SMILES): O=C(N[C@@H](Cc1ccccc1)C(=O)NCc1cc(=O)[nH]c2ccc(Cl)cc12)c1ccc2[nH]c(=O)cc(O)c2c1
InChIKey: DNDMLXSODUEUMP-DEOSSOPVSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: Inhibition of human factor 11a assessed as reduction in para-nitroanilide releasee using pyroGlu-Pro-Arg-pNA.HCl substrate by by chromogenic assay
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 542.98, ALogP 3.39, HBA 5, HBD 5, PSA 144.15, QED 0.21
Compound (SMILES): CCC1(C#N)CCN(c2c(C(=O)N3CCN(S(C)(=O)=O)CC3)cnc3ccc(F)cc23)CC1
InChIKey: DJKKOMSKDDIVHL-UHFFFAOYSA-N
Target: Aldehyde dehydrogenase 1A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00352
Assay: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 473.57, ALogP 2.61, HBA 6, HBD 0, PSA 97.61, QED 0.68
Compound (SMILES): C[C@]12C=CC(=O)C=C1[C@@H](F)C[C@H]1[C@@H]3C[C@H]4CN(c5cccc(Cl)c5)C[C@@]4(C(=O)CO)[C@@]3(C)C[C@H](O)[C@@]12F
InChIKey: DXCRAIDZTZWAOF-QFZGVMIISA-N
Target: Glucocorticoid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04150
Assay: Induction of nuclear translocation of human recombinant ProLabel-tagged glucocorticoid receptor expressed in CHO-K1 cells after 3 hrs by luminescence method
Measurement: EC50 = 5.8 nM (pChEMBL 8.239999771118164)
Descriptors: MW 532.03, ALogP 4.25, HBA 5, HBD 2, PSA 77.84, QED 0.61
Compound (SMILES): O=C(CCCCNCc1ccccc1)NO
InChIKey: QJUZUPMAKNUHRU-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of recombinant human full-length C-terminal His-tagged HDAC2 expressed in baculovirus infected Sf9 insect cells using Boc-L-Lys(Ac)-AMC as substrate preincubated for 5 mins followed by substrate addition measured after 35 mins by fluorescence assay
Measurement: IC50 = 58000 nM (pChEMBL 4.239999771118164)
Descriptors: MW 222.29, ALogP 1.45, HBA 3, HBD 3, PSA 61.36, QED 0.37
Compound (SMILES): CNC(=O)c1c(-c2ccc(F)cc2)oc2cc3c(cc12)[C@@H](C)O[C@H](CO)CN3S(C)(=O)=O
InChIKey: LEGFVEQZPWXYTI-DOMZBBRYSA-N
Target: RNA-directed RNA polymerase (SINGLE PROTEIN), Hepacivirus hominis
UniProt: O39930
Assay: Inhibition of HCV genotype 1b NS5B polymerase infected in human HuH7 replicon cells by luciferase reporter gene assay
Measurement: EC50 = 69 nM (pChEMBL 7.159999847412109)
Descriptors: MW 462.5, ALogP 2.82, HBA 6, HBD 2, PSA 109.08, QED 0.62
Compound (SMILES): O=C(Nc1ccc(CP(=O)(O)O)cc1)C1CCN(C(=O)OCc2ccccc2Cl)CC1
InChIKey: NWCKCFQKRUTVDO-UHFFFAOYSA-N
Target: Autotaxin (SINGLE PROTEIN), Homo sapiens
UniProt: Q13822
Assay: Inhibition of human ENPP2 using FS3 as substrate measured every 5 mins for 30 mins by fluorescence assay
Measurement: IC50 = 3.29 nM (pChEMBL 8.479999542236328)
Descriptors: MW 466.86, ALogP 4.01, HBA 4, HBD 3, PSA 116.17, QED 0.55
Compound (SMILES): N=C(N)NCCC[C@@H]1NC(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](Cc2c[nH]cn2)NC(=O)C2(CCC2)NC(=O)CC[C@@H](C(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC1=O
InChIKey: HUGYDNYMMALPAG-SYJCBOMESA-N
Target: Melanocyte-stimulating hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q01726
Assay: Displacement of [125I]-NDP-alpha-MSH from human MC1R expressed in HEK293 cells after 40 mins by gamma counting method
Measurement: IC50 = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 851.97, ALogP -1.08, HBA 9, HBD 12, PSA 324.06, QED 0.05
Compound (SMILES): O=S(=O)(NC1CCN(CCOc2ccccc2)CC1)c1cccc(Cl)c1
InChIKey: ZQXHQNMVUKVOKI-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]-8-OH-DPAT from human serotonin 5-HT1A receptor expressed in HEK293 cells incubated for 1 hr by radioligand binding assay
Measurement: Ki = 1428 nM (pChEMBL 5.840000152587891)
Descriptors: MW 394.92, ALogP 3.16, HBA 4, HBD 1, PSA 58.64, QED 0.78
Compound (SMILES): CCCCCCCCOc1ccc(C2=N[C@@H](CO)[C@H](C)S2)cc1
InChIKey: IIEWAJHEHBGVAH-YJBOKZPZSA-N
Target: 5-hydroxytryptamine receptor 1D (SINGLE PROTEIN), Homo sapiens
UniProt: P28221
Assay: Displacement of [3H]5-CT from human 5-HT1D receptor expressed in HEKT cells after 90 mins by microbeta scintillation counting analysis
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 335.51, ALogP 4.67, HBA 4, HBD 1, PSA 41.82, QED 0.63
Compound (SMILES): CCn1c2ccccc2c2cc(/C=N/Nc3cc(C)nc4cc5c(cc34)OCO5)ccc21
InChIKey: ZXPGMLVLRGBYBF-MZJWZYIUSA-N
Target: DNA repair nuclease/redox regulator APEX1 (SINGLE PROTEIN), Homo sapiens
UniProt: P27695
Assay: Inhibition Assay: The initial screen was designed to look at the effect of potential inhibitors on APE1 repair kinetics. The approach can be used as a high throughput screen by choosing a specific timepoint to monitor. The screen utilizes a molecular beacon with a tetrahydrofuran (THF) abasic site within the stem region of a DNA hairpin that has a fluorophore on the 5′-terminus and a quencher on the 3′-terminus (FIG. 2a ). Compounds that had good inhibitory activity in this screen were then retested using a gel based assay to directly measure DNA excision as a function of inhibitor concentration. An example of the molecular beacon screen and the excision assay are shown in FIGS. 2b,c and 2d , respectively.Evidence that Inhibitor Binds Directly to APE1 Evidence that the inhibitors directly bound to APE1 was established using isothermal titration calorimetry (ITC). This method provides thermodynamic information on the binding affinity, stoichiometry and the thermodynamic parameters, i.e., ΔG, ΔH and TΔS. In addition to the studies on the binding of the inhibitor to APE1, it was also confirmed that the inhibitor did not block enzymatic activity by binding to the DNA.
Measurement: Ki = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 422.49, ALogP 5.85, HBA 6, HBD 1, PSA 60.67, QED 0.29
Compound (SMILES): COC(=O)CNP(=O)(CC/C=C(\C)CO)Oc1cccc2ccccc12
InChIKey: RYDVADCXLXGVTP-VIZOYTHASA-N
Target: Butyrophilin subfamily 3 member A1 (SINGLE PROTEIN), Homo sapiens
UniProt: O00481
Assay: Binding affinity to BTN3A1 in human Vgamma9 Vdelta2 T cells mixed with human K562 cells pretreated with compound for 4 hrs assessed as INF-gamma production measured after 20 hrs by ELISA
Measurement: EC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 377.38, ALogP 3.5, HBA 5, HBD 2, PSA 84.86, QED 0.4
Compound (SMILES): O=S(=O)(Nc1cc(-c2cnc3[nH]nc(-c4ccccc4)c3c2)cnc1Cl)c1ccccc1
InChIKey: JBCFMJUKWOMHEO-UHFFFAOYSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P42336
Assay: Inhibition of recombinant full length N-terminal His-tagged human PI3K p110alpha/p85alpha expressed in baculovirus expression system using PIP2/PS as substrate after 1 hr by ADP-Glo luminescence assay
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 461.93, ALogP 5.14, HBA 5, HBD 2, PSA 100.63, QED 0.35
Compound (SMILES): Clc1ccc(CN2CCN(Cc3c[nH]c4ccccc34)CC2)cc1Cl
InChIKey: GBYXTIZDOIKXPZ-UHFFFAOYSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Cavia porcellus
UniProt: Q60492
Assay: Displacement of [3H]-(+)-pentazocine from sigma-1 receptor in guinea pig brain membranes after 180 mins by scintillation counting method
Measurement: Ki <= 130 nM (pChEMBL 6.886000156402588)
Descriptors: MW 374.31, ALogP 4.79, HBA 2, HBD 1, PSA 22.27, QED 0.71
Compound (SMILES): C#CCN(CCCCOc1ccc2ccc(=O)oc2c1)Cc1ccc(C)cc1
InChIKey: PTGNYSYUDVJEBF-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of recombinant human MAO-B using p-tyramine as substrate preincubated for 15 mins followed by substrate addition measured after 20 mins by amplex red reagent based fluorescence assay
Measurement: IC50 = 1676 nM (pChEMBL 5.78000020980835)
Descriptors: MW 375.47, ALogP 4.4, HBA 4, HBD 0, PSA 42.68, QED 0.32
Compound (SMILES): CCn1cncc1-c1c[nH]c2ccc(I)cc12
InChIKey: JLCILCCDUVFIRF-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Displacement of [3H]-5-CT from recombinant human 5HT7b receptor expressed in HEK293 cells measured after 1 hr by microbeta counting method
Measurement: Ki = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 337.16, ALogP 3.66, HBA 2, HBD 1, PSA 33.61, QED 0.71
Compound (SMILES): COc1cc(N2CCN(C)CC2)ccc1Nc1ncc(Cl)c(Oc2ccccc2NC(C)=O)n1
InChIKey: PEJUBMHYQKMFOZ-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR E746_A750 deletion/T790M mutant in human growth-resistant PC9 cells assessed as reduction in cell viability after 72 hrs by MTT assay
Measurement: IC50 = 5640 nM (pChEMBL 5.25)
Descriptors: MW 482.97, ALogP 4.38, HBA 8, HBD 2, PSA 91.85, QED 0.51
Compound (SMILES): Cn1cnc(-c2cnc(O[C@H]3CCN(C(=O)Cc4ccc(OC(F)(F)F)cc4)C[C@@H]3F)c(C(N)=O)c2)c1
InChIKey: XJIIVPVOGYFVME-ICSRJNTNSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by fluorescence polarization assay
Measurement: IC50 = 24000 nM (pChEMBL 4.619999885559082)
Descriptors: MW 521.47, ALogP 3.04, HBA 7, HBD 1, PSA 112.57, QED 0.48
Compound (SMILES): COc1ccc(Cn2ccc(NC(=O)Cc3ccc(N(C)C)cc3)n2)cc1
InChIKey: OZPRELOEKQERJE-UHFFFAOYSA-N
Target: Voltage-dependent T-type calcium channel subunit alpha-1H (SINGLE PROTEIN), Homo sapiens
UniProt: O95180
Assay: Inhibition of recombinant Cav3.2 (unknown origin) expressed in HEK293 cells assessed as decrease in calcium flux preincubated for 3 mins followed by CaCl2 addition by Fluo-4-AM dye-based FLIPR assay
Measurement: IC50 = 47 nM (pChEMBL 7.329999923706055)
Descriptors: MW 364.45, ALogP 3.19, HBA 5, HBD 1, PSA 59.39, QED 0.7
Compound (SMILES): COc1ccc(-c2c3c4cc(OC)c(OCCNC(=N)N)cc4oc(=O)c3n3ccc4cc(O)c(OC)cc4c23)cc1O.O=C(O)C(F)(F)F
InChIKey: RVZGHQNYPQHPAY-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of recombinant wild type EGFR (696 to C-terminal residues) (unknown origin) preincubated for 30 mins followed by poly (Glu-Tyr) biotinylated peptide substrate addition measured after 30 mins in presence of ATP by ELISA
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 584.59, ALogP 4.32, HBA 10, HBD 5, PSA 173.9, QED 0.08
Compound (SMILES): FC(F)(F)c1cccc2c1nc1n2C[C@@]2(CN3CCC2CC3)O1
InChIKey: GZGMORZIUKXWJK-OAHLLOKOSA-N
Target: 5-hydroxytryptamine receptor 3A (SINGLE PROTEIN), Homo sapiens
UniProt: P46098
Assay: Antagonist activity at human 5-HT3A receptor expressed in HEK293 cells assessed as inhibition of 5-HT-induced calcium flux preincubated for 30 mins prior to 5-HT addition by Fluo-4 AM dye based FLIPR assay
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 323.32, ALogP 2.91, HBA 4, HBD 0, PSA 30.29, QED 0.75
Compound (SMILES): CN1CC[C@@](O)(C#Cc2cccc(-c3ccc(N)c(C(N)=O)n3)c2)C1=O
InChIKey: LQQYQPONDYAXFT-IBGZPJMESA-N
Target: Mitogen-activated protein kinase kinase kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99558
Assay: Inhibition of NIK (unknown origin) expressed in HEK293 cells harboring NFkB-Luc assessed as reduction in NFkB signal after 24 hrs by luciferase reporter gene assay
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 350.38, ALogP 0.37, HBA 5, HBD 3, PSA 122.54, QED 0.68
Compound (SMILES): O=C(Nc1c(-c2cccs2)nc2c(Br)cc(Br)cn12)c1ccc(F)cc1
InChIKey: IRXNDWVQEQWQIM-UHFFFAOYSA-N
Target: Gamma-aminobutyric acid receptor subunit alpha-6/beta-3/gamma-2 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P18508
Assay: Displacement of [3H]EBOB from rat GABA-A receptor alpha6beta3gamma2 expressed in HEK293 cell membranes after 90 mins by liquid scintillation counting analysis
Measurement: IC50 = 3390 nM (pChEMBL 5.46999979019165)
Descriptors: MW 495.17, ALogP 5.98, HBA 4, HBD 1, PSA 46.4, QED 0.38
Compound (SMILES): COc1ccc(NC(=O)N2CCN(c3nc(N)nc4scnc34)CC2)c(C)n1
InChIKey: FXHQAAGCIBZXGI-UHFFFAOYSA-N
Target: Phosphatidylinositol 4-kinase beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBF8
Assay: Inhibition of PI4K3beta in human PBMC assessed as reduction in mitomycin-C treated human RPMI1788 cells-stimulated lymphocyte proliferation by measuring reduction in [3H]thymidine incorporation preincubated for 5 days followed by [3H]thymidine addition measured after 18 hrs by liquid scintillation counting method
Measurement: IC50 = 195 nM (pChEMBL 6.710000038146973)
Descriptors: MW 400.47, ALogP 1.73, HBA 9, HBD 2, PSA 122.39, QED 0.68
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H]1Cc2ccc(O)c(c2)CC=CCNCCC[C@@H](N)C(=O)N[C@@H](CCCCN)C(=O)N2CCC[C@H]2C(=O)N1)C(=O)N[C@@H](CC(C)C)C(=O)O
InChIKey: ZERHMVNHOAJQDO-JXDRVDKESA-N
Target: Neurotensin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30989
Assay: Agonist activity at GFP10/beta-arrestin2-Rluc2 fused human NTS1 expressed in CHO-K1 cell membranes assessed as beta-arrestin2 recruitment after 20 mins by BRET assay
Measurement: EC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 799.03, ALogP 0.98, HBA 10, HBD 9, PSA 258.31, QED 0.1
Compound (SMILES): Cc1ccc(Cn2nc(-c3ccc(C)cc3)cc(SNC3CCCCCC3)c2=O)cc1
InChIKey: FUWSOLKXJYIMMV-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]CP,55-940 from recombinant human CB2 receptor expressed in HEK293 EBNA cell membranes after 90 mins by microbeta scintillation counting method
Measurement: Ki > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 433.62, ALogP 5.89, HBA 5, HBD 1, PSA 46.92, QED 0.39
Compound (SMILES): COCc1ccc(-c2ccc3nnc(C(N)=O)c(N[C@@H](C)c4nn(C)cc4C)c3c2)cn1
InChIKey: XSVCEXJOBQYTNH-AWEZNQCLSA-N
Target: Serine/threonine-protein kinase ATR (SINGLE PROTEIN), Homo sapiens
UniProt: Q13535
Assay: Inhibition of ATR in human HT-29 cells measured after 1 hr by Hoechst 33258 staining based fluorescence assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 431.5, ALogP 3.15, HBA 8, HBD 2, PSA 120.84, QED 0.46
Compound (SMILES): COc1cc(OCc2cccc(-c3ccccc3)c2C)cc(OC)c1CNCC1CC(=O)N1
InChIKey: YLXAVKAGODUILD-UHFFFAOYSA-N
Target: Programmed cell death 1 ligand 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NZQ7
Assay: Homogenous Time-Resolved Fluorescence (HTRF) Binding Assay: All binding studies were performed in an HTRF assay buffer consisting of dPBS supplemented with 0.1% (withv) bovine serum albumin and 0.05% (v/v) Tween-20. For the PD-1-Ig/PD-L1-His binding assay, inhibitors were pre-incubated with PD-L1-His (10 nM final) for 15 m in 4 μl of assay buffer, followed by addition of PD-1-Ig (20 nM final) in 1 μl of assay buffer and further incubation for 15 m. PD-L1 from either human, cyno, or mouse were used. HTRF detection was achieved using europium crypate-labeled anti-Ig (1 nM final) and allophycocyanin (APC) labeled anti-His (20 nM final). Antibodies were diluted in HTRF detection buffer and 5 μl was dispensed on top of binding reaction. The reaction mixture was allowed to equilibrate for 30 minutes and signal (665 nm/620 nm ratio) was obtained using an EnVision fluorometer. Additional binding assays were established between PD-1-Ig/PD-L2-His (20 & 5 nM, respectively), CD80-His/PD-L1-Ig (100 & 10 nM, respectively) and CD80-His/CTLA4-Ig (10 & 5 nM, respectively). Competition studies between biotinylated SEQ ID NO:71 and human PD-L1-His were performed as follows. Inhibitors were pre-incubated with PD-L1-His (10 nM final) for 60 m in 4 μl of assay buffer followed by addition of biotinylated SEQ ID NO:71 (0.5 nM final) in 1 μl of assay buffer. Binding was allowed to equilibrate for 30 m followed by addition of europium crypated labeled Strepatavidin (2.5 pM final) and APC-labeled anti-His (20 nM final) in 5 μl of HTRF buffer. The reaction was allowed to equilibrate for 30 m and signal (665 nm/620 nm ratio) was obtained using an EnVision fluorometer.
Measurement: IC50 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 446.55, ALogP 4.24, HBA 5, HBD 2, PSA 68.82, QED 0.46
Compound (SMILES): NCC(CCN1CC=C(c2ccc(Cl)cc2)CC1)(c1ccccc1)C1CCCC1
InChIKey: ROBJDFLYWHJESD-UHFFFAOYSA-N
Target: Menin (SINGLE PROTEIN), Homo sapiens
UniProt: O00255
Assay: Displacement of FITC-MBM1 from full length human menin measured after 2 hrs by fluorescence polarization assay
Measurement: IC50 = 830 nM (pChEMBL 6.079999923706055)
Descriptors: MW 409.02, ALogP 5.91, HBA 2, HBD 1, PSA 29.26, QED 0.62
Compound (SMILES): O=Cc1csc(-c2ccccc2O)n1
InChIKey: KQXPEMHRIDDMQC-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Displacement of [3H]-LSD from human 5-HT2B receptor expressed in baculovirus infected Sf9 cells
Measurement: Ki = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 205.24, ALogP 2.33, HBA 4, HBD 1, PSA 50.19, QED 0.77
Compound (SMILES): CCn1cc(Nc2nc(N)nc(-c3cccc(-n4ccc5cc(C6CC6)cc(F)c5c4=O)c3CO)n2)cc1C#N
InChIKey: YRDMGLSTJWMOGG-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of N-terminal DYKDDDDK tagged biotinylated unactivated human recombinant BTK using FITC-labeled Srctide peptide substrate by by mobility shift assay
Measurement: IC50 = 0.58 nM (pChEMBL 9.239999771118164)
Descriptors: MW 536.57, ALogP 4.37, HBA 10, HBD 3, PSA 147.67, QED 0.28
Compound (SMILES): COc1cc(/C=C/C(=O)NCCCNc2c3c(nc4ccccc24)CCCC3)cc(OC)c1OCc1nc(C)c(C)nc1C
InChIKey: IGJKPBYXHLKLFB-FOCLMDBBSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of electric eel AChE using acetylthiocholine iodide as substrate preincubated for 5 mins followed by DTNB addition for 5 mins and subsequent addition of substrate measured after 3 mins by Ellman's method
Measurement: IC50 = 115.7 nM (pChEMBL 6.940000057220459)
Descriptors: MW 595.74, ALogP 6.06, HBA 8, HBD 2, PSA 107.49, QED 0.15
Compound (SMILES): COc1ccc(C2CC(=O)c3c(O)cc(O)cc3O2)cc1-c1c(O)cc2c(c1O)C(=O)CC(c1ccc(O)cc1)O2
InChIKey: CDWSDIACYSFCGJ-UHFFFAOYSA-N
Target: Matrix metalloproteinase-9 (SINGLE PROTEIN), Homo sapiens
UniProt: P14780
Assay: Inhibition of recombinant human MMP9 preincubated for 30 mins followed by McaPro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 substrate addition measured by fluorescence assay
Measurement: IC50 = 25430 nM (pChEMBL 4.590000152587891)
Descriptors: MW 556.52, ALogP 5.3, HBA 10, HBD 5, PSA 162.98, QED 0.22
Compound (SMILES): O=C1CSC2SC(/N=C/c3ccc(Cl)cc3)=NN12
InChIKey: OOFRSUYAYOHFRF-WLRTZDKTSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Ovis aries
UniProt: P79208
Assay: Inhibition of ovine COX2 using arachidonic acid as substrate incubated for 5 mins followed by substrate addition measured after 2 mins by enzyme immunoassay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 297.79, ALogP 2.64, HBA 5, HBD 0, PSA 45.03, QED 0.75
Compound (SMILES): CCCc1nn(C)c2c(=O)[nH]c(-c3cc(Cc4ccc(C(=O)NO)cc4OC)ccc3OCC)nc12
InChIKey: AJYPACHRWFLJSI-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of full length human recombinant C-terminal His-tagged HDAC2 expressed in baculovirus infected sf9 cells using fluorogenic HDAC substrate 3 after 30 mins by fluorescence assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 491.55, ALogP 3.39, HBA 8, HBD 3, PSA 131.36, QED 0.24
Compound (SMILES): C=C[C@@H]1C[C@]1(NC(=O)[C@@H]1C[C@]2(OC)CN1C(=O)[C@H](C(C)(C)C)NC(=O)OCCCCCCCCc1cc3cc2ccc3cc1OC)C(=O)NS(=O)(=O)C1CC1
InChIKey: OONRICXKFMZCSN-WCPAEXBBSA-N
Target: NS3 (SINGLE PROTEIN), Hepatitis C virus
UniProt: A3EZJ3
Assay: Inhibition of HCV genotype 1a H77 NS3 protease infected in human HuH7 replicon cells assessed as reduction in viral replication after 4 days by luciferase reporter gene assay
Measurement: EC50 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 780.98, ALogP 5, HBA 9, HBD 3, PSA 169.44, QED 0.31
Compound (SMILES): C[C@H](Oc1ccc(F)c(F)c1F)C(=O)Nc1ccc2oc(-c3ccc(C#N)cc3)nc2c1
InChIKey: HXEVVVKRKUTSHY-LBPRGKRZSA-N
Target: GMP reductase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P2T1
Assay: Inhibition of human GMPR2 using GMP as substrate by spectrophotometric method
Measurement: Ki > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 437.38, ALogP 5.19, HBA 5, HBD 1, PSA 88.15, QED 0.43
Compound (SMILES): O=C(NC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO)c1ccn(Cc2cc(Cl)c(CN3CSC[C@H]3C(=O)N3CCN(C4CC4)c4ccccc43)cc2Cl)n1
InChIKey: WHXVSGSTNQQYPW-OXMBMXHISA-N
Target: G-protein coupled bile acid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TDU6
Assay: Agonist activity at human TGR5 expressed in HEK293 cells assessed as increase in intracellular cAMP level by HTRF assay
Measurement: EC50 = 100 nM (pChEMBL 7)
Descriptors: MW 735.69, ALogP 1.29, HBA 12, HBD 6, PSA 174.86, QED 0.15
Compound (SMILES): O=C(Nc1ccc(OC(F)(F)F)cc1)N[C@H]1CC[C@H](Oc2ccc(O)cc2)CC1
InChIKey: FTVGDRKKJVKLHA-SAZUREKKSA-N
Target: Fatty-acid amide hydrolase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O00519
Assay: Inhibition of human FAAH expressed in baculovirus-infected High Five cells S9 fraction using OMP substrate by fluorescence based assay
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 410.39, ALogP 4.8, HBA 4, HBD 3, PSA 79.82, QED 0.66
Compound (SMILES): CC1(C#N)CCN(c2c(C(=O)N3CCN(S(C)(=O)=O)CC3)cnc3ccc(F)cc23)CC1
InChIKey: SIGXVLVHXOJBCM-UHFFFAOYSA-N
Target: Aldehyde dehydrogenase 1A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00352
Assay: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay
Measurement: IC50 = 94 nM (pChEMBL 7.03000020980835)
Descriptors: MW 459.55, ALogP 2.22, HBA 6, HBD 0, PSA 97.61, QED 0.7
Compound (SMILES): CCNC(=O)c1cnc(N)c(O[C@H]2CN(C(=O)Cc3ccc(OC(F)(F)F)cc3)CC2(F)F)c1
InChIKey: HHWLDERRTIKZLN-INIZCTEOSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by fluorescence polarization assay
Measurement: IC50 = 43000 nM (pChEMBL 4.369999885559082)
Descriptors: MW 488.41, ALogP 2.78, HBA 6, HBD 2, PSA 106.78, QED 0.58
Compound (SMILES): COc1nc2ccc(C(O)(c3cnc(C)n3C)c3cnc(C)n3C)cc2c(Cl)c1Cc1ccc(-n2cccn2)cc1
InChIKey: STCBIFUVWBDNPX-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at GAL4 DBD-fused wild type human RORgammat LBD (850 to 1635 residues) expressed in HEK293T cells assessed as inhibition of transcriptional activity after 24 hrs by dual-glo luciferase reporter gene assay
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 568.08, ALogP 5.04, HBA 9, HBD 1, PSA 95.81, QED 0.29
Compound (SMILES): CC(c1ccc(OC(F)(F)F)cc1)N1CCC(n2c(=O)[nH]c3ccccc32)CC1
InChIKey: ZDEKHWFIPZPOBM-UHFFFAOYSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Agonist activity at human mu opioid receptor expressed in human USOS-beta-arrestin-hMOR-PathHunter cells incubated for 90 mins by beta-arrestin-2 enzyme fragment complementation assay
Measurement: EC50 = 1678 nM (pChEMBL 5.78000020980835)
Descriptors: MW 405.42, ALogP 4.63, HBA 4, HBD 1, PSA 50.26, QED 0.69
Compound (SMILES): CC1(C)CCC(c2ccc(Cl)cc2)=C(CN2CCc3nc(C(=O)NS(=O)(=O)c4ccc(N[C@H](CCN5CCOCC5)CSc5ccccc5)c(S(=O)(=O)C(F)(F)F)c4)sc3C2)C1
InChIKey: LVBGCCULSLDQKD-JGCGQSQUSA-N
Target: Bcl-2-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07817
Assay: Displacement of Bad-derived peptide from Bcl-XL (unknown origin) by fluorescence polarization assay
Measurement: IC50 = 13.2 nM (pChEMBL 7.880000114440918)
Descriptors: MW 952.61, ALogP 8.53, HBA 12, HBD 2, PSA 138.01, QED 0.11
Compound (SMILES): CC(C)(C)c1ccc(C(=O)/C(C#N)=N/Nc2cc(Cl)c(Cl)c(Cl)c2)cc1
InChIKey: ZGLGANBSTZWTSE-PCLIKHOPSA-N
Target: Rap guanine nucleotide exchange factor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O95398
Assay: Antagonist activity at recombinant full length EPAC1 (unknown origin) assessed as inhibition of cAMP-mediated Rap1b-BODIPY GDP nucleotide exchange activity
Measurement: IC50 = 13900 nM (pChEMBL 4.860000133514404)
Descriptors: MW 408.72, ALogP 6.12, HBA 4, HBD 1, PSA 65.25, QED 0.29
Compound (SMILES): CC(=O)Nc1cn2cc(-c3cc(NC(=O)c4cccc(Cl)c4)ccc3C)ccc2n1
InChIKey: SRQFAPOIRHMKQI-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of B-Raf V600E mutant in human A375 cells assessed as reduction in ERK phosphorylation
Measurement: EC50 = 480 nM (pChEMBL 6.320000171661377)
Descriptors: MW 418.88, ALogP 5.17, HBA 4, HBD 2, PSA 75.5, QED 0.48
Compound (SMILES): CC(C)(C)Oc1ccc(S(C)(=O)=O)cc1C(=O)N1Cc2cn(-c3ccccc3F)nc2C1
InChIKey: QQHKFFYXYXEBIW-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in CHO cells at 10 nM to 10 uM at holding potential of -80 mV measured after 5 mins by QPatch automated patch clamp electrophysiology method
Measurement: IC50 = 8100 nM (pChEMBL 5.090000152587891)
Descriptors: MW 457.53, ALogP 3.75, HBA 6, HBD 0, PSA 81.5, QED 0.6
Compound (SMILES): COc1ccc2nc(CNc3nc(N4CCN(C)CC4)nc4c3ncn4-c3cccnc3)[nH]c2c1
InChIKey: DWZNVSPLYSTTQB-UHFFFAOYSA-N
Target: Casein kinase I isoform epsilon (SINGLE PROTEIN), Homo sapiens
UniProt: P49674
Assay: Inhibition of recombinant human full length N-terminal GST-tagged CK1epsilon expressed in baculovirus in Sf9 insect cells using ULight-Topo-IIa(Thr1342) peptide as substrate after 10 mins by TR-FRET assay
Measurement: IC50 = 335 nM (pChEMBL 6.46999979019165)
Descriptors: MW 470.54, ALogP 2.46, HBA 10, HBD 2, PSA 112.91, QED 0.39
Compound (SMILES): CC(=O)N[C@@H]1C[C@H](n2c3ccccc3c3c4c(c5c6ccccc6[nH]c5c32)CNC4=O)O[C@@H](C)[C@@H]1O
InChIKey: QOGRCYLUNKUCSL-PAFZLBRNSA-N
Target: Rho-associated protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75116
Assay: Inhibition of N-terminal His10-StrepII tagged human ROCK2 catalytic domain (1 to 553 residues) expressed in Sf9 insect cells by HTRF assay
Measurement: IC50 = 2700 nM (pChEMBL 5.570000171661377)
Descriptors: MW 482.54, ALogP 3.85, HBA 5, HBD 4, PSA 108.38, QED 0.31
Compound (SMILES): O=C(O)c1ccncc1NC[C@@H]1CCCc2cc(Sc3ccccc3)ccc21
InChIKey: DZVIPXUKOHSZJK-KRWDZBQOSA-N
Target: Lysine-specific demethylase 4C (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H3R0
Assay: Inhibition of KDM4C (unknown origin) using biotinylated H3K9me3 peptide and alpha-ketoglutarate as substrate pretreated for 1 hr followed by substrate addition measured after 20 mins in presence of 0.2 mg/ml BSA by LANCE TR-FRET assay
Measurement: IC50 = 48 nM (pChEMBL 7.320000171661377)
Descriptors: MW 390.51, ALogP 5.46, HBA 4, HBD 2, PSA 62.22, QED 0.58
Compound (SMILES): N[C@H]1CC[C@H](Nc2nc(Nc3ccc(Br)cc3)c3ncn(C4CCCC4)c3n2)CC1
InChIKey: BUBIRDGMXHNBKV-JCNLHEQBSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of N-terminal GST/His6-fused recombinant wild type human FLT3 (R571 to S993 residues) expressed in Sf9 insect cells using poly (Ala,Glu,Lys,Tyr) 6:2:5:1 hydrobromide as substrate in presence of [gamma-33P]ATP
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 470.42, ALogP 5.13, HBA 7, HBD 3, PSA 93.68, QED 0.48
Compound (SMILES): COc1ccc2ncc(C(=O)N3CCN(C(=O)C4CC4)CC3)c(N3CCC4(CC3)OCCO4)c2c1
InChIKey: MVRZYUFICDYWBI-UHFFFAOYSA-N
Target: Aldehyde dehydrogenase 1A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00352
Assay: Inhibition of human ALDH1A1 using NAD+/propionaldehyde as substrate/cofactor preincubated for 15 mins followed by substrate/cofactor addition measured for 30 mins by fluorescence assay
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 480.57, ALogP 2.28, HBA 7, HBD 0, PSA 84.44, QED 0.66
Compound (SMILES): CC(C)[C@H](CO)NC(=O)N[C@H]1CC[C@@H](Nc2nc(N[C@H](C)CO)nc3cnc(-c4cccc(F)c4)cc23)CC1
InChIKey: OACSQNNUFUFSOV-DUHPJZPXSA-N
Target: Atrial natriuretic peptide receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P16066
Assay: Agonist activity at human NPR-A expressed in CHO cells assessed as increase in cGMP accumulation after 30 mins by radioimmunoassay
Measurement: EC50 = 620 nM (pChEMBL 6.210000038146973)
Descriptors: MW 539.66, ALogP 3.66, HBA 8, HBD 6, PSA 144.32, QED 0.23
Compound (SMILES): C[C@@](Cc1ccccc1)(NC(=O)[C@H](Cc1ccccc1)CP(=O)(O)C(N)Cc1ccccc1)C(=O)O
InChIKey: AQKFQKJKRAJFTH-CTGOOGPZSA-N
Target: Glutamyl aminopeptidase (SINGLE PROTEIN), Homo sapiens
UniProt: Q07075
Assay: Inhibition of APA (unknown origin) using GluNA as substrate
Measurement: Ki = 40000 nM (pChEMBL 4.400000095367432)
Descriptors: MW 508.56, ALogP 3.85, HBA 4, HBD 4, PSA 129.72, QED 0.28
Compound (SMILES): NS(=O)(=O)c1ccc(CCNC(=[Se])Nc2cccc(C(F)(F)F)c2)cc1
InChIKey: QXZHBTKZNJXXJP-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of recombinant human carbonic anhydrase 4 preincubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 928.9 nM (pChEMBL 6.03000020980835)
Descriptors: MW 450.34
Compound (SMILES): Cc1cc(C#N)cnc1C(=O)Nc1ccc(F)c([C@]2(C)C=C(C(F)F)OC(N)=N2)c1
InChIKey: DSZGYBZHOVZDKX-FQEVSTJZSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of BACE1 in human SH-SY5Y cells transfected with human wild type beta-APP assessed as reduction in amyloid beta (1 to 40) levels after 24 hrs by HTRF assay
Measurement: IC50 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 415.38, ALogP 3.36, HBA 6, HBD 2, PSA 113.39, QED 0.79
Compound (SMILES): CCc1cccc(-c2c(F)cccc2C(O)(CCCNC(=O)OC)[C@@H]2CCCN(C(=O)CC(O)CN)C2)c1
InChIKey: IIIBTAZKWKWKNG-HFSRXPFLSA-N
Target: Renin (SINGLE PROTEIN), Homo sapiens
UniProt: P00797
Assay: Inhibition of renin in human plasma using angiotensinogen as substrate measured for 90 mins by [125I]-angiotensin based radioimmunoassay
Measurement: IC50 = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 529.65, ALogP 3.33, HBA 6, HBD 4, PSA 125.12, QED 0.33