lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): C/C=C/Cn1cc(-c2cccc(C(=O)N(C)C)c2)c2cc[nH]c2c1=O
InChIKey: RJEMCUZKQLRUIS-SNAWJCMRSA-N
Target: Transcription initiation factor TFIID subunit 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21675
Assay: Inhibition of recombinant His-tagged TAF1 isoform-2 (unknown origin) using biotinylated ligand incubated for 10 mins by TR-FRET assay
Measurement: IC50 = 410 nM (pChEMBL 6.389999866485596)
Descriptors: MW 335.41, ALogP 3.27, HBA 3, HBD 1, PSA 58.1, QED 0.74
Compound (SMILES): C[C@H](Nc1cc(F)c(S(=O)(=O)Nc2nccs2)cc1Cl)c1ccc(F)cc1
InChIKey: NNOURUCQGKSLJV-JTQLQIEISA-N
Target: Sodium channel protein type 8 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQD0
Assay: Sodium Influx Assay (In Vitro Assay): This sodium influx assay employs the use of the cell permeable, sodium sensitive dye ANG2 to quantify sodium ion influx through sodium channels which are maintained in an open state by use of sodium channel modulators. This high throughput sodium influx assay allows for rapid profiling and characterization of sodium channel blockers.In general, Trex HEK293 cells were stably transfected with an inducible expression vector containing the full-length cDNA coding for the desired human sodium channel α-subunit and with an expression vector containing full length cDNA coding for the β1-subunit. Sodium channel expressing cell lines were induced with tetracycline (1 μg/mL) and plated on 384-well PDL-coated plates at a density of 25K-30K cells/well in culture media (DMEM, containing 10% FBS and 1% L-glutamine). After overnight incubation (37° C., 5% CO2), culture media was removed and cells were loaded with 5 uM ANG2 dye for 1-1.5 h in Buffer 1 (155 mM NMDG, 5 mM KCl, 2 mM CaCl2, 1 mM MgCl2, 10 mM HEPES, 10 mM glucose, adjusted with Tris to pH 7.4). Access dye was removed and cells were incubated with test compounds for 1 hr in buffer 1 containing sodium channel modulator(s) at room temperature. Hamamatsu FDSS μCell was used to perform a 1:1 addition of Na/K challenge buffer (140 mM NaCl, 20 mM HEPES, 1 mM CaCl2, 15 mM KCl, 1 mM MgCl2, 10 mM glucose, adjusted with Tris to pH 7.4) and simultaneously read plates at excitation wavelength of 530 nm and emission wavelength set at 558 nm. Percent inhibition of sodium ion influx was calculated for each test compound at each test concentration to determine the IC50 values.
Measurement: IC50 = 716 nM (pChEMBL 6.139999866485596)
Descriptors: MW 429.9, ALogP 5.05, HBA 5, HBD 2, PSA 71.09, QED 0.57
Compound (SMILES): COC(=O)N[C@H](C(=O)N1CCC[C@H]1c1ncc(-c2ccc3c(c2)COc2cc4c(ccc5nc([C@@H]6CC[C@H](C)N6C(=O)[C@@H](NC(=O)OC)C(C)C)[nH]c54)cc2-3)[nH]1)C(C)C
InChIKey: CBGSDAZMMLBVTP-NZOYNQROSA-N
Target: Nonstructural protein 5A (SINGLE PROTEIN), Hepatitis C virus
UniProt: Q5L478
Assay: Inhibition of NS5A in HCV genotype 1b Con1 infected in human HuH7 replicon cells assessed as reduction in viral replication after 3 days by luciferase reporter gene assay
Measurement: EC50 = 0.018 nM (pChEMBL 10.739999771118164)
Descriptors: MW 804.95, ALogP 7.14, HBA 9, HBD 4, PSA 183.87, QED 0.12
Compound (SMILES): Nc1ncc(N2CCN(c3cccc(-c4ccccn4)c3)CC2)c(N)n1
InChIKey: PHMAETGQIBUYHS-UHFFFAOYSA-N
Target: Bifunctional dihydrofolate reductase-thymidylate synthase (SINGLE PROTEIN), Toxoplasma gondii
UniProt: Q07422
Assay: Inhibition of Toxoplasma gondii DHFR-TS expressed in Escherichia coli BL21 competent cells using DHF as substrate preincubated for 15 mins followed by substrate and NADPH addition and measured after 60 mins by resazurin dye based diaphorase-coupled assay
Measurement: IC50 = 10.3 nM (pChEMBL 7.989999771118164)
Descriptors: MW 347.43, ALogP 2.03, HBA 7, HBD 2, PSA 97.19, QED 0.75
Compound (SMILES): O=C(NCC1CCC(F)(F)CC1)c1c(Cl)ccc2ncccc12
InChIKey: QIFLEBFQNFAPSK-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99572
Assay: Antagonist activity at P2X7R in LPS-stimulated human THP1 cells assessed as inhibition of BzATP-induced IL-1beta release preincubated for 30 mins followed by BzATP stimulation and measured after 30 mins by sandwich ELISA
Measurement: IC50 = 220 nM (pChEMBL 6.659999847412109)
Descriptors: MW 338.79, ALogP 4.44, HBA 2, HBD 1, PSA 41.99, QED 0.9
Compound (SMILES): COc1ccccc1NC(=O)C(Sc1cccc[n+]1[O-])c1ccccc1
InChIKey: HRNOJRMDEAFOQH-UHFFFAOYSA-N
Target: START domain-containing protein 10 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y365
Assay: Inhibition of StarD10 (unknown origin) using NBD-PC and donor and acceptor small unilamellar vesicles by fluorescence quench assay
Measurement: IC50 = 15000 nM (pChEMBL 4.820000171661377)
Descriptors: MW 366.44, ALogP 3.8, HBA 4, HBD 1, PSA 65.27, QED 0.41
Compound (SMILES): Nc1nc(-c2ccc3c(c2)OCO3)cn2c(=O)n(-c3ccccc3)nc12
InChIKey: QBFYXESNHIORPZ-UHFFFAOYSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30542
Assay: Displacement of [3H]CCPA from human adenosine A1 receptor expressed in CHO cell membranes by radioligand competition assay
Measurement: Ki = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 347.33, ALogP 1.86, HBA 8, HBD 1, PSA 96.67, QED 0.59
Compound (SMILES): CC(C)(C)c1ccc(S(=O)(=O)N2CCN(Cn3cc4c(=O)oc5ccccc5c4n3)CC2)cc1
InChIKey: GBPGUKZYQBSJJH-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Inhibition of PI3Kbeta (unknown origin) using diC8-PI(4,5)P2 as substrate incubated for 3 hrs in presence of ATP by fluorescence polarization assay
Measurement: IC50 = 2650 nM (pChEMBL 5.579999923706055)
Descriptors: MW 480.59, ALogP 3.4, HBA 7, HBD 0, PSA 88.65, QED 0.42
Compound (SMILES): CCC(CC)CNc1c(C(N)=O)cnc2ccc(-c3ccc(CS(C)(=O)=O)cc3)cc12
InChIKey: ATUPPYCMPHBNGW-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase ATR (SINGLE PROTEIN), Homo sapiens
UniProt: Q13535
Assay: Inhibition of ATR in human HT-29 cells assessed as reduction in Chk1 phosphorylation at Ser-345 residue after 60 mins in presence of 4-nitroquinoline-1-oxide by Hoechst 33258 staining based plate reader analysis
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 439.58, ALogP 4.39, HBA 5, HBD 2, PSA 102.15, QED 0.51
Compound (SMILES): COc1cccc2c1nc(C(F)F)n2-c1nc(N2CCOCC2)nc(N2CCN(S(=O)(=O)CCCN(C)C)CC2)n1
InChIKey: RMJFKPZURQNXIZ-UHFFFAOYSA-N
Target: PI3K p110 beta/p85 alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of recombinant human N-terminal p110beta/p85alpha expressed in baculovirus infected Sf9 insect cells using PIP2 as substrate by HTRF assay
Measurement: IC50 = 1165 nM (pChEMBL 5.929999828338623)
Descriptors: MW 595.68, ALogP 1.4, HBA 12, HBD 0, PSA 122.05, QED 0.34
Compound (SMILES): O=C1COc2ccc(-c3cnc(Cl)c(NS(=O)(=O)c4ccc(F)cc4)c3)cc2N1c1ccc(Cl)cc1
InChIKey: KPIDGWGWXJVEHJ-UHFFFAOYSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: O00329
Assay: Inhibition of recombinant human full length N-terminal GST-tagged PI3Kdelta (1 to 1044 residues)/PIK3R1 (1 to 724 residues) expressed in baculovirus expression system using PIP2 as substrate incubated for 2 hrs by ADP-Glo assay
Measurement: IC50 = 3.2 nM (pChEMBL 8.489999771118164)
Descriptors: MW 544.39, ALogP 6.05, HBA 5, HBD 1, PSA 88.6, QED 0.31
Compound (SMILES): NS(=O)(=O)c1ccc(CNC(=O)CN2C(=O)NC3(CCCCCC3)C2=O)cc1
InChIKey: QUAFYIJGNASVBL-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human carbonic anhydrase 2 incubated for 15 mins prior to testing by stopped-flow CO2 hydration assay
Measurement: Ki = 47.1 nM (pChEMBL 7.329999923706055)
Descriptors: MW 408.48, ALogP 0.6, HBA 5, HBD 3, PSA 138.67, QED 0.61
Compound (SMILES): CCCCNC(=O)C#Cc1cc(C2=NN(C3CCCCCC3)C(=O)[C@@H]3CC=CC[C@H]23)ccc1OC
InChIKey: QBSSMBQSBXGATC-LOSJGSFVSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4B (SINGLE PROTEIN), Homo sapiens
UniProt: Q07343
Assay: Inhibition of human PDE4B catalytic domain incubated for 20 mins using cAMP as substrate by PDELight HTS cAMP phosphodiesterase Kit based luminometry
Measurement: Ki = 630.96 nM (pChEMBL 6.199999809265137)
Descriptors: MW 475.63, ALogP 4.81, HBA 4, HBD 1, PSA 71, QED 0.28
Compound (SMILES): CSCC[C@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CS)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CS)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CS)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(=O)O)C(=O)NCC(=O)N[C@@H](Cc1ccccc1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CS)C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)O)[C@@H](C)O)C(C)C
InChIKey: BMPHBWORAPRSPM-HJNMRNCJSA-N
Target: Dickkopf-related protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O94907
Assay: Inhibition of biotin-labeled human recombinant DKK1 assessed as reduction in DKK1 interaction with LRP-6/Fc incubated overnight by chemiluminescence based Alpha-screen assay
Measurement: IC50 <= 1 nM (pChEMBL 9)
Descriptors: MW 4879.42
Compound (SMILES): Cc1c(C(=O)N2CCC(C(F)(F)F)CC2)c(C(N)=O)nn1-c1nc2c(c(=O)[nH]1)CCC2
InChIKey: GLMMFDNBWVECMO-UHFFFAOYSA-N
Target: Sepiapterin reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P35270
Assay: Inhibition of SPR in human PBMC cells assessed as reduction in BH4 production incubated for 12 to 48 hrs by LCMS analysis
Measurement: IC50 = 84 nM (pChEMBL 7.079999923706055)
Descriptors: MW 438.41, ALogP 1.27, HBA 6, HBD 2, PSA 126.97, QED 0.75
Compound (SMILES): O=C(N[C@@H]1C2CCN(CC2)C1Cc1cccnc1)c1cc2ccccc2o1
InChIKey: OXKRFEWMSWPKKV-BDPMCISCSA-N
Target: Neuronal acetylcholine receptor subunit alpha-7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q05941
Assay: Displacement of [3H]MLA from alpha7 nAChR in rat hippocampal membranes
Measurement: Ki = 1 nM (pChEMBL 9)
Descriptors: MW 361.45, ALogP 3.26, HBA 4, HBD 1, PSA 58.37, QED 0.77
Compound (SMILES): CC(C)(C)c1cc(NC(=O)Nc2ccc(Oc3ncnc4[nH]ncc34)c(F)c2)no1
InChIKey: HYYTZUUXIPJLRY-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of human partial length FLT3 ITD mutant expressed in bacterial expression system by Kinomescan method
Measurement: IC50 = 1.3 nM (pChEMBL 8.890000343322754)
Descriptors: MW 411.4, ALogP 4.21, HBA 7, HBD 3, PSA 130.85, QED 0.46
Compound (SMILES): C[C@@H]1C[C@H]1N(C)S(=O)(=O)c1ccc(-c2cnc(N)c(-c3ccc4c(c3)CCNC4=O)n2)cc1
InChIKey: BMVVPIFLRAMCIO-SPLOXXLWSA-N
Target: Serine/threonine-protein kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13043
Assay: Inhibition of MST1 (unknown origin) pre-incubated for 10 mins before addition of 50 uM ATP and Z'-Lyte S/T Pep7 and further incubated for 1 hr
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 463.56, ALogP 2.71, HBA 6, HBD 2, PSA 118.28, QED 0.6
Compound (SMILES): CNS(=O)(=O)c1ccc(-c2cncc(/C=C3\SC(=N)NC3=O)c2)cc1
InChIKey: WYQFLYFUQOJPHD-AUWJEWJLSA-N
Target: Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P48426
Assay: Inhibition of GST-tagged recombinant PI5P4Kalpha (unknown origin) incubated for 1 hr in presence of DPPS and PI5P by ADP-Glo assay
Measurement: IC50 = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 374.45, ALogP 1.8, HBA 6, HBD 3, PSA 112.01, QED 0.71
Compound (SMILES): Cc1ccc(-c2ccc(/C=C3/NC(=S)NC3=O)o2)cc1Cl
InChIKey: VDDXLYMOOLIYRX-KPKJPENVSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of human GSK-3beta H350L mutant (2 to end residues) at 10 uM using phospho GS2 peptide as substrate after 40 mins by [gamma-33ATP] radiometric assay
Measurement: IC50 = 1291 nM (pChEMBL 5.889999866485596)
Descriptors: MW 318.79, ALogP 3.25, HBA 3, HBD 2, PSA 54.27, QED 0.66
Compound (SMILES): N#Cc1cccc(OC(=O)N2CCN(C(c3ccccc3)c3cccnc3)CC2)c1
InChIKey: YFPDNRFKGHAKAQ-UHFFFAOYSA-N
Target: Monoglyceride lipase (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q8R431
Assay: Inhibition of purified rat MGL using AHMMCE as fluorogenic substrate preincubated for 15 mins followed by substrate addition measured at 15 mins interval for 3 hrs by fluorescence assay
Measurement: IC50 = 360 nM (pChEMBL 6.440000057220459)
Descriptors: MW 398.47, ALogP 3.86, HBA 5, HBD 0, PSA 69.46, QED 0.67
Compound (SMILES): Cc1c(C(=O)N2CCN(c3nnc(-c4cccc(F)c4)o3)CC2)cnn1-c1nn2cccc2c(=O)[nH]1
InChIKey: FQLQQRAKJQVWPF-UHFFFAOYSA-N
Target: Sepiapterin reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P35270
Assay: Inhibition of SPR in human PBMC cells assessed as reduction in BH4 production incubated for 12 to 48 hrs by LCMS analysis
Measurement: IC50 = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 489.47, ALogP 1.67, HBA 10, HBD 1, PSA 130.45, QED 0.4
Compound (SMILES): N#CN1CC[C@@H](NC(=O)c2ccc(-c3ccncn3)cc2F)C1
InChIKey: DPENKAMUFPTBEJ-GFCCVEGCSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 30 (SINGLE PROTEIN), Homo sapiens
UniProt: Q70CQ3
Assay: Inhibition of human USP30 catalytic domain (57 to 517 residues) using ubiquitin-rhodamine 110 as substrate preincubated for 30 min followed by substrate addition and measured after 2 hrs by fluorescence intensity kinetic assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 311.32, ALogP 1.57, HBA 5, HBD 1, PSA 81.91, QED 0.87
Compound (SMILES): N=C(N)c1ccc(CNC(=O)[C@@H]2Cc3ccc(cc3)NC(=O)CCN3CCN(CCC(=O)Nc4ccc(cc4)C[C@@H](NC(=O)Cc4ccccc4)C(=O)N2)CC3)cc1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: KSEAMKRYDHJDFB-BYQQZPSGSA-N
Target: Plasminogen (SINGLE PROTEIN), Homo sapiens
UniProt: P00747
Assay: Inhibition of human plasmin using Mes-DSer(Bzl)-Phe-Arg-AMC as substrate by Dixon plot analysis
Measurement: Ki = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 785.95, ALogP 2.57, HBA 8, HBD 7, PSA 201.85, QED 0.11
Compound (SMILES): O=C1CCC(N2C(=O)c3cccc(OCCCCCOc4ccc(CC(=O)Nc5cc(C6CCC6)[nH]n5)cc4)c3C2=O)C(=O)N1
InChIKey: WCEHIDWONYOKOJ-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00535
Assay: Binding affinity to CDK5 (unknown origin) assessed as dissociation constant
Measurement: Kd = 230 nM (pChEMBL 6.639999866485596)
Descriptors: MW 613.67, ALogP 3.89, HBA 8, HBD 3, PSA 159.79, QED 0.19
Compound (SMILES): CN(Cc1ccccc1)c1ccc(C(=O)NC2CCN(C#N)C2)cn1
InChIKey: GSSYGNRWGKCRDC-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 30 (SINGLE PROTEIN), Homo sapiens
UniProt: Q70CQ3
Assay: Inhibition of untagged human USP30 catalytic domain (57 to 517 residues) expressed in Escherichia coli using TAMRA labeled ubiquitin peptide as substrate preincubated for 30 min followed by substrate addition and measured after 2 hrs by fluorescence polarization assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 335.41, ALogP 2, HBA 5, HBD 1, PSA 72.26, QED 0.85
Compound (SMILES): CC(C)c1cc2c(c(O)c1O)[C@@]1(C(=O)NN)CCCC(C)(C)[C@@H]1CC2
InChIKey: ONFMISOYJGYDNT-VBKZILBWSA-N
Target: Geranylgeranyl pyrophosphate synthase (SINGLE PROTEIN), Homo sapiens
UniProt: O95749
Assay: Inhibition of human N-terminal TEV protease cleavage site-fused-His6-tagged GGPPS expressed in Escherichia coli BL21 (DE3) using FPP and [14C] IPP as substrate preincubated for 15 mins with FPP followed by [14C] IPP addition and further incubated for 20 mins by scintillation counting method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 346.47, ALogP 3.22, HBA 4, HBD 4, PSA 95.58, QED 0.29
Compound (SMILES): CCc1nc(C(N)=O)c(Nc2ccc3c(c2)CCN(C2CCN(C)CC2)CC3)nc1NC1CCOCC1
InChIKey: FACYQMLOTXHWDQ-UHFFFAOYSA-N
Target: TEL/AXL (CHIMERIC PROTEIN), Homo sapiens
UniProt: P30530
Assay: Inhibition of TEL/AXL (unknown origin) expressed in mouse BA/F3 cells assessed as growth inhibition after 72 hrs by SRB assay
Measurement: IC50 = 213.9 nM (pChEMBL 6.670000076293945)
Descriptors: MW 507.68, ALogP 2.97, HBA 8, HBD 3, PSA 108.64, QED 0.52
Compound (SMILES): O=C(/C=C/c1cccnc1)NCc1ccc(C(=O)Nc2ccc(F)cc2)cc1
InChIKey: HENVWEPBVVKURY-LFYBBSHMSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of recombinant full length human HDAC1 (1 to 482 residues) expressed in baculovirus expression system using Ac-Leu-Gly-Lys(Ac)-AMC as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by fluorometric method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 375.4, ALogP 3.8, HBA 3, HBD 2, PSA 71.09, QED 0.64
Compound (SMILES): CCCNS(=O)(=O)Nc1ncnc(OCCOc2ncc(SC)cn2)c1Oc1cccc(OC)c1
InChIKey: VNLAEVZRIYGZCY-UHFFFAOYSA-N
Target: Endothelin receptor type B (SINGLE PROTEIN), Homo sapiens
UniProt: P24530
Assay: Displacement of [125I]-ET-1 from human ETB receptor expressed in CHO cell membranes after 2 hrs by scintillation counting
Measurement: IC50 = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 522.61, ALogP 2.9, HBA 11, HBD 2, PSA 146.68, QED 0.24
Compound (SMILES): O=C(O)Cc1ccc(COc2ccc3c(c2)CCC3)cc1
InChIKey: FKDVOUNKBZEBLY-UHFFFAOYSA-N
Target: Retinoic acid receptor RXR-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P19793
Assay: Agonist activity at human Gal4-DBD fused RXRalpha LBD expressed in HEK293T cells after 12 to 14 hrs by luciferase reporter gene assay
Measurement: EC50 = 13000 nM (pChEMBL 4.889999866485596)
Descriptors: MW 282.34, ALogP 3.38, HBA 2, HBD 1, PSA 46.53, QED 0.91
Compound (SMILES): C[C@H](NC(=O)[C@@H]1CCN1C(=O)[C@@H](N)CCCCNC(=O)[C@@H](N)CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)O
InChIKey: NZNPXVVKQSZIFF-ATIWLJMLSA-N
Target: Neuropilin-1 (SINGLE PROTEIN), Homo sapiens
UniProt: O14786
Assay: Inhibition of human biotinylated VEGF-A165 binding to recombinant human NRP1 receptor after 2 hrs by chemiluminescence analysis
Measurement: IC50 = 15848.93 nM (pChEMBL 4.800000190734863)
Descriptors: MW 612.74, ALogP -3.87, HBA 9, HBD 12, PSA 320.75, QED 0.04
Compound (SMILES): CC(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](Cc1ccc(Cl)cc1)C(=O)N1Cc2ccccc2C[C@H]1C(N)=O)C(C)C
InChIKey: RFBVPLQWBKNMQV-XUJYPJAKSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Mus musculus
UniProt: P56450
Assay: Agonist activity at mouse MC4R expressed in HEK293 cells co-expressing CRE/beta-galactosidase reporter gene after 6 hrs by beta-galactosidase cAMP assay
Measurement: EC50 = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 655.2, ALogP 0.71, HBA 6, HBD 7, PSA 212.6, QED 0.09
Compound (SMILES): CCNC(=O)c1ccc(Nc2nccc(N3C[C@@H]4C[C@H]3CN4C(=O)CC#N)n2)cc1
InChIKey: YUJXKTRZTBIDCL-IRXDYDNUSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of human JAK1 using fluorescence labeled peptide as substrate and using ATP at its Km level by microfluidic based mobility shift assay
Measurement: IC50 = 358 nM (pChEMBL 6.449999809265137)
Descriptors: MW 405.46, ALogP 1.67, HBA 7, HBD 2, PSA 114.25, QED 0.75
Compound (SMILES): NS(=O)(=O)c1ccc(CCNC(=O)/C(Cc2ccccc2)=N/OCc2ccccc2)cc1
InChIKey: CCSKONFHLPPKTA-SLEBQGDGSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human carbonic anhydrase 2 expressed in Escherichia coli BL21 (DE3) by stopped-flow CO2 hydration assay
Measurement: Ki = 3780 nM (pChEMBL 5.420000076293945)
Descriptors: MW 451.55, ALogP 2.81, HBA 5, HBD 2, PSA 110.85, QED 0.36
Compound (SMILES): CCCCCn1cc(C(=O)c2cccc3ccccc23)c2cc(F)ccc21
InChIKey: UGSBUBYCSSIFIU-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]-CP55940 from human CB2 receptor
Measurement: Ki = 65 nM (pChEMBL 7.190000057220459)
Descriptors: MW 359.44, ALogP 6.35, HBA 2, HBD 0, PSA 22, QED 0.29
Compound (SMILES): CN(C1CC1)S(=O)(=O)c1ccc(-c2cnc(N)c(-c3ccc4c(c3)CCNC4=O)n2)nc1
InChIKey: SFEZDWNBDZADKG-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13043
Assay: Inhibition of MST1 (unknown origin) pre-incubated for 10 mins before addition of 50 uM ATP and Z'-Lyte S/T Pep7 and further incubated for 1 hr
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 450.52, ALogP 1.86, HBA 7, HBD 2, PSA 131.17, QED 0.61
Compound (SMILES): CC(C)c1cnn2c(NCc3ccccc3)cc(NCC3CCNCC3)nc12
InChIKey: JKCBZAYPKOXUKH-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P06493
Assay: Inhibition of CDK1 (unknown origin) by luciferase reporter gene assay
Measurement: IC50 = 1660 nM (pChEMBL 5.78000020980835)
Descriptors: MW 378.52, ALogP 3.88, HBA 6, HBD 3, PSA 66.28, QED 0.58
Compound (SMILES): CCOc1cc(CCNC(=O)c2sc3nc(C)ccc3c2N)ccc1N1CCNCC1.O=C(O)C(F)(F)F
InChIKey: OCPVNAJFFYOBIR-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 25 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHP3
Assay: Inhibition of recombinant C-terminal 6-His tagged human USP25 using ubiquitin-rhodamine 110 as substrate preincubated for 30 mins followed by substrate addition and measured after 45 mins by fluorescence based assay
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 439.59, ALogP 2.97, HBA 7, HBD 3, PSA 92.51, QED 0.52
Compound (SMILES): O=C(c1ccccn1)N1N=CCC1c1ccccc1
InChIKey: LMNCSUFKJVEMIV-UHFFFAOYSA-N
Target: Receptor-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13546
Assay: Inhibition of human GST/His-tagged RIP1 (1 to 375 residues) expressed in baculovirus expression system assessed as reduction in autophosphorylation measured after 4 hrs in presence of ATP by ADP-Glo luminescence assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 251.29, ALogP 2.65, HBA 3, HBD 0, PSA 45.56, QED 0.82
Compound (SMILES): O=C(c1ccc(Cl)c(O)c1)c1ccc(-c2cccc(NS(=O)(=O)c3ccccc3)c2)s1
InChIKey: PJWQHMPSYVIIQW-UHFFFAOYSA-N
Target: 17-beta-hydroxysteroid dehydrogenase type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14061
Assay: Inhibition of human placental cytosolic fraction 17beta-HSD1 using [3H]-E1 as substrate in presence of NAD+ by radio-HPLC analysis
Measurement: IC50 = 8.2 nM (pChEMBL 8.09000015258789)
Descriptors: MW 469.97, ALogP 5.81, HBA 5, HBD 2, PSA 83.47, QED 0.35
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCc1ccccc1)NC(=O)[C@H](Cc1ccccc1)N=[N+]=[N-])C(=O)[C@@]1(C)CO1
InChIKey: RLXBGXKBAJCDFA-ICQXYBJGSA-N
Target: Proteasome Macropain subunit MB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28074
Assay: Inhibition of catalytic activity of immunoproteasome 20s subunit beta5 in human Raji cells incubated for 1 hr by BODIPY(TMR)-NC-005-VS probe based competitive activity based protein profiling assay
Measurement: IC50 = 5.1 nM (pChEMBL 8.289999961853027)
Descriptors: MW 652.8, ALogP 4.64, HBA 6, HBD 3, PSA 165.66, QED 0.08
Compound (SMILES): CN(C1CC1)S(=O)(=O)c1ccc(-c2cnc(N)c(-c3ccc4c(c3)CCNC4=O)c2)cn1
InChIKey: HROMQVCPMDSQOR-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13043
Assay: Inhibition of MST1 (unknown origin) pre-incubated for 10 mins before addition of 50 uM ATP and Z'-Lyte S/T Pep7 and further incubated for 1 hr
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 449.54, ALogP 2.46, HBA 6, HBD 2, PSA 118.28, QED 0.62
Compound (SMILES): O=C(Nc1ccccc1F)NC1CCN(c2ncnc3c2nc(-c2ccccc2Cl)n3-c2ccc(Cl)cc2)CC1
InChIKey: SZCHRMFBGGBWMN-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]CP55940 from human CB2 receptor expressed in HEK293 cell membranes
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 576.46, ALogP 6.72, HBA 6, HBD 2, PSA 87.97, QED 0.24
Compound (SMILES): CCCN1CCN(c2ccc3c(c2)CCN3S(=O)(=O)c2ccccc2)CC1
InChIKey: FROJMJFJUZFRPE-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]raclopride from human recombinant dopamine D2 long receptor expressed in CHO-K1 cells incubated for 120 mins by scintillation counting analysis
Measurement: Ki = 245 nM (pChEMBL 6.610000133514404)
Descriptors: MW 385.53, ALogP 2.97, HBA 4, HBD 0, PSA 43.86, QED 0.79
Compound (SMILES): O=C(O)c1cccc(N2CCN(C(=O)COc3cc(Cl)cc(Cl)c3)CC2)c1
InChIKey: WOZCYXSWTTYEKQ-UHFFFAOYSA-N
Target: Autotaxin (SINGLE PROTEIN), Homo sapiens
UniProt: Q13822
Assay: Inhibition of C-terminal FLAG tagged human recombinant ATX expressed in insect sf9 cells using pNP-TMP as substrate measured every 2 mins for 60 mins by fluorescence analysis
Measurement: IC50 = 5200 nM (pChEMBL 5.28000020980835)
Descriptors: MW 409.27, ALogP 3.42, HBA 4, HBD 1, PSA 70.08, QED 0.82
Compound (SMILES): CCCCc1cc(-c2ccc(OC)cc2)nc(N)n1
InChIKey: NGUDUTAVPODMJD-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Antagonist activity at recombinant human Gi-coupled H3 receptor expressed in HEK293T cells assessed as reduction in histamine-induced inhibition of forskolin-stimulated cAMP accumulation preincubated for 10 to 15 followed by histamine addition for 10 mins and subsequent forskolin-stimulation by Glo-sensor assay
Measurement: IC50 = 4450 nM (pChEMBL 5.349999904632568)
Descriptors: MW 257.34, ALogP 3.08, HBA 4, HBD 1, PSA 61.03, QED 0.89
Compound (SMILES): O=C(OC1C[N+]2(CCCc3ccc(Cl)cc3)CCC1CC2)C(O)(c1ccccc1)c1ccccc1.[Br-]
InChIKey: FJFQEWXDAAGRNY-UHFFFAOYSA-M
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]NMS from human M2R expressed in CHOK1 cell membranes incubated for 2 hrs by microbeta scintillation counting method
Measurement: Ki = 0.11 nM (pChEMBL 9.960000038146973)
Descriptors: MW 491.05, ALogP 5.36, HBA 3, HBD 1, PSA 46.53, QED 0.34
Compound (SMILES): NCCCC[C@@H](/C=C/c1ccccn1)NC(=O)[C@H](Cc1ccccc1)NC(=O)OCc1ccccc1
InChIKey: KRGZEMMZXSVNPT-OMEUSSCHSA-N
Target: Cruzipain (SINGLE PROTEIN), Trypanosoma cruzi
UniProt: P25779
Assay: Inhibition of Trypanosoma cruzi cruzain assessed as rate constant for enzyme-inhibitor-substrate complex using Cbz-Phe-Arg-AMC as substrate measured up to 40 mins by fluorescence assay
Measurement: Ki = 870 nM (pChEMBL 6.059999942779541)
Descriptors: MW 486.62, ALogP 4.25, HBA 5, HBD 3, PSA 106.34, QED 0.31
Compound (SMILES): CCc1cccc(N2CCN(C[C@H](O)CCNC(=O)c3cc4ccccc4[nH]3)CC2)c1Cl
InChIKey: OIRZLTZLOKARTG-HXUWFJFHSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Radioligand Binding Assay: Binding at dopamine D2-like receptors was determined using previously described methods. Membranes were prepared from HEK293 cells expressing human D2R, D3R or D4R, grown in a 50:50 mix of DMEM and Ham's F12 culture media, supplemented with 20 mM HEPES, 2 mM L-glutamine, 0.1 mM non-essential amino acids, 1× antibiotic/antimycotic, 10% heat-inactivated fetal bovine serum, and 200 μg/mL hygromycin (Life Technologies, Grand Island, N.Y.) and kept in an incubator at 37° C. and 5% CO2. Upon reaching 80-90% confluence, cells were harvested using pre-mixed Earle's Balanced Salt Solution (EBSS) with 5 μM EDTA (Life Technologies) and centrifuged at 3000 rpm for 10 min at 21° C. The supernatant was removed and the pellet was resuspended in 10 mL hypotonic lysis buffer (5 mM MgCl2.6H2O, 5 mM Tris, pH 7.4 at 4° C.) and centrifuged at 20,000 rpm for 30 min at 4° C. The pellet was then resuspended in fresh EBSS buffer made from 8.7 g/L Earle's Balanced Salts without phenol red (US Biological, Salem, Mass.), 2.2 g/L sodium bicarbonate, pH to 7.4. A Bradford protein assay (Bio-Rad, Hercules, Calif.) was used to determine the protein concentration and membranes were diluted to 500 μg/mL and stored in a −80° C. freezer for later use.
Measurement: Ki = 0.245 nM (pChEMBL 9.609999656677246)
Descriptors: MW 455, ALogP 3.69, HBA 4, HBD 3, PSA 71.6, QED 0.49
Compound (SMILES): COc1ccccc1CCN1CCN(CCc2ccccc2)CC1.Cl.Cl
InChIKey: NIXVAHBANQDTBY-UHFFFAOYSA-N
Target: Synaptic vesicular amine transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q01827
Assay: Inhibition of [3H]DTBZ binding to VMAT2 in rat whole brain homogenate (excluding cerebellum) after 30 mins by liquid scintillation spectrometric analysis
Measurement: Ki = 1070 nM (pChEMBL 5.96999979019165)
Descriptors: MW 324.47, ALogP 3.1, HBA 3, HBD 0, PSA 15.71, QED 0.78
Compound (SMILES): Cc1ccc(-c2cn(Cc3ccc(-c4cccnc4)cc3)nn2)cc1
InChIKey: GXCMCDVHMWZWJF-UHFFFAOYSA-N
Target: Angiopoietin-1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q02763
Assay: Inhibition of TIE2 (unknown origin) after 4 hrs by ADP-Glo reagent based luminescent assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 326.4, ALogP 4.36, HBA 4, HBD 0, PSA 43.6, QED 0.56
Compound (SMILES): Cc1cc(=O)[nH]c(-n2ncc(C(=O)NCc3cnccn3)c2C)n1
InChIKey: IJKCWMRSQBOVJR-UHFFFAOYSA-N
Target: Sepiapterin reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P35270
Assay: Inhibition of SPR in human SK-N-BE(2) cells assessed as reduction in BH4 levels incubated for 6 to 48 hrs by LCMS analysis
Measurement: IC50 = 23000 nM (pChEMBL 4.639999866485596)
Descriptors: MW 325.33, ALogP 0.29, HBA 7, HBD 2, PSA 118.45, QED 0.71
Compound (SMILES): O=C(Nc1ccccc1C(=O)NCCCN1CCOCC1)c1ccccc1F
InChIKey: MOHLHDFBECGAEQ-UHFFFAOYSA-N
Target: B-cell lymphoma 3 protein (SINGLE PROTEIN), Homo sapiens
UniProt: P20749
Assay: Inhibition of Bcl-3 in human MDA-MB-231 cells assessed as reduction in NF-kappaB signalling incubated for 24 hrs by NF-kappaB promoter dependent luciferase reporter gene assay
Measurement: IC50 = 2500 nM (pChEMBL 5.599999904632568)
Descriptors: MW 385.44, ALogP 2.53, HBA 4, HBD 2, PSA 70.67, QED 0.72
Compound (SMILES): COc1cc([C@](O)(CCN(C)C)[C@@H](c2cc3cc(Br)ccc3nc2OC)c2cccc(OC)c2OC)cc(OC)n1
InChIKey: GQTLJYIGFBZGEF-GRKNLSHJSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 = 2200 nM (pChEMBL 5.659999847412109)
Descriptors: MW 626.55, ALogP 5.41, HBA 9, HBD 1, PSA 95.4, QED 0.22
Compound (SMILES): CCC(CC)CN(CCCCCN1[C@@H]2CC[C@H]1C[C@@H](c1cccc(C(N)=O)c1)C2)C(=O)CO
InChIKey: BAJJIHKMLNYVEG-QEIWAGNOSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Displacement of [3H]-DPN from recombinant human mu opioid receptor expressed in CHO-K1 cell membranes by radioligand binding assay
Measurement: Ki = 0.631 nM (pChEMBL 9.199999809265137)
Descriptors: MW 457.66, ALogP 3.92, HBA 4, HBD 2, PSA 86.87, QED 0.44
Compound (SMILES): CCCCn1c(=O)sc2cc(C(=O)C34CC5CC(CC(C5)C3)C4)ccc21
InChIKey: HTOZGCRKKAPERF-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Displacement of [3H]-CP-55940 from human CB1 receptor expressed in CHO cell membranes after 1 hr by beta-counting analysis
Measurement: Ki = 780 nM (pChEMBL 6.110000133514404)
Descriptors: MW 369.53, ALogP 5.26, HBA 4, HBD 0, PSA 39.07, QED 0.67
Compound (SMILES): CCN(CC)C(=O)c1cnn(-c2nc(C)cc(=O)[nH]2)c1C
InChIKey: OKQHEISUJBGZGK-UHFFFAOYSA-N
Target: Sepiapterin reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P35270
Assay: Inhibition of SPR in human SK-N-BE(2) cells assessed as reduction in BH4 levels incubated for 6 to 48 hrs by LCMS analysis
Measurement: IC50 = 6400 nM (pChEMBL 5.190000057220459)
Descriptors: MW 289.34, ALogP 1.05, HBA 5, HBD 1, PSA 83.88, QED 0.91
Compound (SMILES): CC(=O)c1ccc(OCCCCCCCCCCN2CCC(Cc3ccccc3)CC2)cc1O
InChIKey: OVZMDTJXAYWBKF-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of electric eel AChE using acetylthiocholine iodide incubated for 15 mins as substrate by Ellman's method
Measurement: IC50 = 9200 nM (pChEMBL 5.039999961853027)
Descriptors: MW 465.68, ALogP 7.05, HBA 4, HBD 1, PSA 49.77, QED 0.23
Compound (SMILES): CC(=O)N[C@H]1CCSC[C@@H](C(=O)N[C@@H](Cc2ccc(NC(=N)N)cc2)C(=O)N[C@@H](Cc2c[nH]c3ccccc23)C(=O)N[C@@](C)(CCCCN)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC1=O
InChIKey: KORXSNOOCQGZEU-SWJUGPKHSA-N
Target: Interleukin-23 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q5VWK5
Assay: Inhibition of interleukin-23 receptor in human DB cells assessed as reduction in IL-23-stimulated STAT3 phosphorylation incubated for 30 mins by HTRF assay
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 1621.81
Compound (SMILES): N#CN1CC[C@H](N2CCN(c3cccc(-c4ccccn4)c3)S2(=O)=O)C1
InChIKey: AJDNGBAAKMPCJE-KRWDZBQOSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 30 (SINGLE PROTEIN), Homo sapiens
UniProt: Q70CQ3
Assay: Biochemical Assay: Dilution plates were prepared at 21 times the final concentration (2100 μM for a final concentration of 100 μM) in 50% DMSO in a 96-well polypropylene V-bottom plate (Greiner #651201). A typical 8-point dilution series to be 100, 30, 10, 3, 1, 0.3, 0.1, 0.03 μM final. Reactions were performed in duplicate in black 384 well plates (small volume, Greiner 784076) in a final reaction volume of 21 μl. Either 1 μl of 50% DMSO or diluted compound was added to the plate. USP30 was diluted in reaction buffer (40 mM Tris, pH 7.5, 0.005% Tween 20, 0.5 mg/ml BSA, 5 mMbeta-mercaptoethanol) to the equivalent of 0.05 μl/well and 10 μl of diluted USP30 was added to the compound. Enzyme and compound were incubated for 30 min at room temp. Reactions were initiated by the addition of 50 nM of TAMRA labelled peptide linked to ubiquitin via an iso-peptide bond as fluorescence polarisation substrate. Reactions were read immediately after addition of substrate and following a 2 hr incubation at room temperature. Readings were performed on a Pherastar Plus (BMG Labtech). λ Excitation 540 nm; λ Emission 590 nm.
Measurement: IC50 = 0.55 nM (pChEMBL 9.260000228881836)
Descriptors: MW 369.45, ALogP 1.67, HBA 5, HBD 0, PSA 80.54, QED 0.77
Compound (SMILES): Cc1ccc(S(=O)(=O)n2cc3c(=O)oc4ccccc4c3n2)cc1
InChIKey: XMNYKQMRFJRIEC-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42338
Assay: Inhibition of PI3Kbeta (unknown origin) using diC8-PI(4,5)P2 as substrate incubated for 3 hrs by fluorescence polarization assay
Measurement: IC50 = 4640 nM (pChEMBL 5.329999923706055)
Descriptors: MW 340.36, ALogP 2.69, HBA 6, HBD 0, PSA 82.17, QED 0.52
Compound (SMILES): COc1ccc2c(c1)c(-c1[nH]c(NCc3ccccc3)nc1C)cn2S(=O)(=O)c1ccccc1
InChIKey: WKDOWEAWARBZNI-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H]LSD from human 5HT6 receptor expressed in HEK293 cells measured after 1 hr by liquid scintillation counter method
Measurement: Ki = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 472.57, ALogP 5.2, HBA 6, HBD 2, PSA 89.01, QED 0.34
Compound (SMILES): COc1ccc(C2=NN(C(C)C)C(=O)[C@@H]3CC=CC[C@H]23)cc1C#CC(=O)Nc1ccn(CCCC#N)n1
InChIKey: XXYACLQBWLJHFO-XZOQPEGZSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4B (SINGLE PROTEIN), Homo sapiens
UniProt: Q07343
Assay: Inhibition of human PDE4B catalytic domain using cAMP as substrate incubated for 20 mins by PDELight HTS cAMP phosphodiesterase Kit based luminometry
Measurement: Ki = 1258.93 nM (pChEMBL 5.900000095367432)
Descriptors: MW 498.59, ALogP 3.72, HBA 7, HBD 1, PSA 112.61, QED 0.36
Compound (SMILES): Nc1ncc(-c2ccc(S(=O)(=O)NC3CC3)cc2)nc1-c1ccc2c(c1)CCNC2=O
InChIKey: HARLYEHXSUZPND-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13043
Assay: Inhibition of MST1 (unknown origin) pre-incubated for 10 mins before addition of 50 uM ATP and Z'-Lyte S/T Pep7 and further incubated for 1 hr
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 435.51, ALogP 2.12, HBA 6, HBD 3, PSA 127.07, QED 0.56
Compound (SMILES): C[C@]12CCC(=O)C=C1[C@@H](O)C[C@@H]1[C@@H]2CC[C@]2(C)C(=O)CC[C@@H]12
InChIKey: WVAMBAWFDOYFOD-BMSLSITRSA-N
Target: Aromatase (SINGLE PROTEIN), Homo sapiens
UniProt: P11511
Assay: Inhibition of aromatase in human placental microsomes using [1beta-3H]AD as substrate incubated for 20 mins in presence of NADPH
Measurement: IC50 = 14996.85 nM (pChEMBL 4.820000171661377)
Descriptors: MW 302.41, ALogP 3.06, HBA 3, HBD 1, PSA 54.37, QED 0.75
Compound (SMILES): O=C(c1ccc2c(c1)CS(=O)(=O)N2)N1CCc2nc(-c3ccccc3)[nH]c(=O)c2C1
InChIKey: XRENRYGQQDHQAY-UHFFFAOYSA-N
Target: Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P13995
Assay: Inhibition of recombinant MTHFD2 (unknown origin) assessed as reduction in methenyl-THF formation using tetrahydrofolate, NAD and formaldehyde incubated for 30 mins by NAD-dependent dehydrogenase assay
Measurement: IC50 = 8300 nM (pChEMBL 5.079999923706055)
Descriptors: MW 422.47, ALogP 1.89, HBA 5, HBD 2, PSA 112.23, QED 0.66
Compound (SMILES): CN1CC(C#CC#Cc2cc3n(c2)C(=O)N(CC[C@](C)(C(=O)NO)S(C)(=O)=O)C3)C1
InChIKey: ZGSSRMCYVIDZBN-HXUWFJFHSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 432.5, ALogP -0.11, HBA 7, HBD 2, PSA 111.95, QED 0.38
Compound (SMILES): O=C(Nc1ccc2c(c1)S(=O)(=O)NC2=O)c1cccc(Cl)c1
InChIKey: CYENLQPYUWQGCP-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human carbonic anhydrase 2 preincubated for 15 mins by stopped flow CO2 hydration assay
Measurement: Ki = 6020 nM (pChEMBL 5.21999979019165)
Descriptors: MW 336.76, ALogP 2.02, HBA 4, HBD 2, PSA 92.34, QED 0.88
Compound (SMILES): Cl.Cl.O=c1[nH]c2ccccc2n1CCCCN1CCN(c2ccc(F)cc2)CC1
InChIKey: FWSJSKKCYDQTDG-UHFFFAOYSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9R0C9
Assay: Displacement of [3H](+)-pentazocine from sigma1 receptor in rat brain membranes after 120 mins by radioligand binding assay
Measurement: Ki = 144 nM (pChEMBL 6.840000152587891)
Descriptors: MW 368.46, ALogP 3.07, HBA 4, HBD 1, PSA 44.27, QED 0.68
Compound (SMILES): FC(F)(F)c1ccc(COc2ccc(Nc3ncnc4cc5c(cc34)OCCOCCOCCOCCO5)cc2)cc1
InChIKey: WFNYSPFKUIPLIQ-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR2 (unknown origin) using TK substrate incubated for 60 mins by FRET assay
Measurement: IC50 = 46.4 nM (pChEMBL 7.329999923706055)
Descriptors: MW 585.58, ALogP 5.79, HBA 9, HBD 1, PSA 93.19, QED 0.31
Compound (SMILES): CCN1CCN(Cc2ccc(Nc3ncc(F)c(-c4cnn5c4[C@H](C)CCCC5)n3)nc2)CC1
InChIKey: XPMRMPBWKVMUTB-GOSISDBHSA-N
Target: CDK6/cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Inhibition of human full length GST-tagged CDK6 (1 to 326(end) amino acids)/Cyclin D3 (1 to 292(end) amino acids) expressed in baculovirus expression system assessed as inhibition constant using Ulight-4E-BP1 as substrate preincubated for 30 mins followed by substrate addition and incubated for 90 mins by TR-FRET assay
Measurement: Ki = 37 nM (pChEMBL 7.429999828338623)
Descriptors: MW 464.59, ALogP 4.04, HBA 8, HBD 1, PSA 75, QED 0.59
Compound (SMILES): C#CCOc1ccccc1-c1cc(-c2ccccc2OCC#C)nc(N)n1
InChIKey: XGNJPCLWXNJTRH-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of electric eel AChE assessed as reduction in production of H202 using acetylcholine as substrate incubated for 15 mins followed by substrate addition by horse radish peroxidase/Amplex red reagent based fluorescence assay
Measurement: IC50 = 5190 nM (pChEMBL 5.289999961853027)
Descriptors: MW 355.4, ALogP 3.42, HBA 5, HBD 1, PSA 70.26, QED 0.69
Compound (SMILES): CC(=O)COc1cccc2cc(-c3ccc(C)cc3)c(=O)oc12
InChIKey: FTEWBMZFUKFKEC-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Displacement of [3H]NECA from human adenosine receptor A2A expressed in CHO cell membranes by radioligand competition assay
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 308.33, ALogP 3.74, HBA 4, HBD 0, PSA 56.51, QED 0.69
Compound (SMILES): NC(=O)c1cc(-c2ccc(F)cc2)c2sc(CN3CCOCC3)cc2n1
InChIKey: UZDVXPXNFPZFKV-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P31421
Assay: Negative allosteric modulation of rat mGlu2R expressed in HEK293 cells co-expressing Galpha15 assessed as decrease in glutamate-induced calcium mobilization preincubated for 2.3 mins followed by glutamate addition and measured after 1.7 mins by Fluo-4-AM dye based fluorescence assay
Measurement: IC50 = 3890.45 nM (pChEMBL 5.409999847412109)
Descriptors: MW 371.44, ALogP 3.03, HBA 5, HBD 1, PSA 68.45, QED 0.77
Compound (SMILES): Cc1cc(Cl)c2cc(C(=O)N[C@H](C)c3ccc(S(=O)(=O)CC(=O)NO)cc3)n(C)c2c1
InChIKey: DZJLQVCDJJVKSO-CYBMUJFWSA-N
Target: D-3-phosphoglycerate dehydrogenase (SINGLE PROTEIN), Homo sapiens
UniProt: O43175
Assay: Inhibition of PHGDH in human MDA-MB-468 cells assessed as reduction in [13C3]-serine production incubated for 180 mins by LC/MS/MS analysis
Measurement: IC50 = 135.7 nM (pChEMBL 6.869999885559082)
Descriptors: MW 463.94, ALogP 2.91, HBA 6, HBD 3, PSA 117.5, QED 0.38
Compound (SMILES): C[C@@H](Nc1ncnc2[nH]cnc12)C1=Nc2cccc(Cl)c2S(=O)(=O)N1c1ccccc1
InChIKey: XIKOUZAURDUGPE-GFCCVEGCSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P42336
Assay: Inhibition of His-tagged recombinant human full length PI3K p110alpha/p85alpha expressed in baculovirus expression system using lipid substrate incubated for 60 mins by kinase-Glo reagent based luminescence assay
Measurement: IC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 453.92, ALogP 3.75, HBA 7, HBD 2, PSA 116.23, QED 0.49
Compound (SMILES): C=CC(=O)N1CC(NC(=O)Cn2c(C)c(C(=O)N3CCc4c(cccc4OC)C3)c3cc(Br)ccc32)C1
InChIKey: RYHAEQRORAWGQZ-UHFFFAOYSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Inhibition of KRAS G12C mutant in human MIAPaCa2 cells assessed as reduction in EGF-induced ERK1/2 phosphorylation incubated for 4 hrs followed by EGF addition by luminescence based assay
Measurement: IC50 = 1680 nM (pChEMBL 5.78000020980835)
Descriptors: MW 565.47, ALogP 3.43, HBA 5, HBD 1, PSA 83.88, QED 0.46
Compound (SMILES): O=C(O)c1ccc(-n2cc(C(=O)c3c(Cl)cccc3C(F)(F)F)c3ccccc32)cc1
InChIKey: VSKGLHFFVHEIJX-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: FRET Assay: The assay was run in black 384 well plates (Greiner cat no: 784900). Various concentrations of test ligands in 0.1 microlitres DMSO were dispensed to assay plates using an Labcyte Echo acoustic dispenser. Two pre-mixes were prepared and incubated for 1 hr at room temp in the dark. Pre-mix 1 comprised 100 nM Protein (Biotinylated HN-Avi-MBP-TCS-hRORg (258-518)) and 60 nM Streptavidin APC in assay buffer, 50 mM MOPS pH7.4, 50 mM KF, 0.003% (w/v) CHAPS, 10 mM DTT and 0.01% (w/v) BSA and pre-mix 2 comprised 160 nM biotinylated SRC-1 peptide (NCOA1-677-700) and 20 nM Europium-W8044 labelled Streptavidin in assay buffer. Five microlitres of pre-mix 2 was dispensed to assay plates containing test compound and incubated for 15 minutes prior to adding five microlitres of pre-mix 1. Plates were incubated at room temperature for 1 hour in the dark, prior to reading in a Pherastar multi-mode plate reader using HTRF filter set (ex 320, em 612 and 665). The FRET signal at 665 nM was divided by the signal at 612 nM and multiplied by 10,000 to generate a signal ratio value for each well. The raw data was transformed to % effect using the equation:Compound % effect=100*[(X−min)/(max−min)],where X represents the normalized value for the compound based on the Min (vehicle) and Max (reference compound) inhibition control.
Measurement: IC50 = 97.4 nM (pChEMBL 7.010000228881836)
Descriptors: MW 443.81, ALogP 6.23, HBA 3, HBD 1, PSA 59.3, QED 0.38
Compound (SMILES): COc1cccc(-n2cc(NC(=O)c3cccc(NS(=O)(=O)c4ccccc4)c3)cn2)c1
InChIKey: ZJFHPZCFLNJSIZ-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR2 (unknown origin) incubated for 30 mins by enzyme immunoassay
Measurement: IC50 = 9220 nM (pChEMBL 5.039999961853027)
Descriptors: MW 448.5, ALogP 3.93, HBA 6, HBD 2, PSA 102.32, QED 0.45
Compound (SMILES): COc1cc(NCc2cc3cc(C(C)(C)C)ccc3[nH]c2=O)ccc1C#N
InChIKey: OEDVWCKFJJKSQV-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: IDH1-R132H and IDH1-R132C Enzymatic Assay: Assays were performed in a 384-well black plate. An aliquot of 250 nL of compound was incubated with 10 μL of 30 nM IDH1-R132H or 10 nM IDH1-R132C recombinant protein in assay buffer (50 mM Tris pH=7.5, 150 mM NaCl, 5 mM MgCl2, 0.1% (w/v) Bovine Serum Albumin, and 0.01% Triton X-100) in each well at 25° C. for 15 minutes. After the plate was centrifuged briefly, an aliquot of 10 μL of 2 mM α-ketoglutarate and 20 μM NADPH solution prepared in assay buffer was then added to each well and the reaction was maintained at 25° C. for 45 minutes. An aliquot of 10 μL of diaphorase solution (0.15 U/mL diaphorase and 30 μM Resazurin in assay buffer) was added to each well. The plate was maintained at 25° C. for 15 minutes and then read on a plate reader with excitation and emission wavelengths at 535 nm and 590 nm, respectively. The IC50 of a given compound was calculated by fitting the dose response curve of inhibition of NADPH consumption at a given concentration with the four parameter logistic equation.
Measurement: IC50 = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 361.45, ALogP 4.32, HBA 4, HBD 2, PSA 77.91, QED 0.73
Compound (SMILES): CC1=NC(c2cn(S(=O)(=O)c3ccccc3)c3ccc(C)cc23)CN1
InChIKey: NROCYIRJNRNAGU-UHFFFAOYSA-N
Target: Kallikrein-7 (SINGLE PROTEIN), Homo sapiens
UniProt: P49862
Assay: Inhibition of thermolysin activated recombinant human C-terminal 10-His tagged KLK7 (E23 to H252 residues) using MOCAc-Arg-Pro-Lys-Pro-Val-Glu-Nva-Trp-Arg-Lys(Dnp)-NH2 as substrate preincubated for 10 mins followed by substrate addition and measured after 30 mins by fluorescence analysis
Measurement: IC50 = 17000 nM (pChEMBL 4.769999980926514)
Descriptors: MW 353.45, ALogP 3.25, HBA 5, HBD 1, PSA 63.46, QED 0.79
Compound (SMILES): Cc1ccc2c(N)c(C(=O)NCCc3ccc([C@H]4CCNC4)cc3)sc2n1
InChIKey: LOXAOCPVUHKVJO-INIZCTEOSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 25 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHP3
Assay: Inhibition of recombinant C-terminal 6-His tagged human USP25 using ubiquitin-rhodamine 110 as substrate preincubated for 30 mins followed by substrate addition and measured after 45 mins by fluorescence based assay
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 380.52, ALogP 3.24, HBA 5, HBD 3, PSA 80.04, QED 0.63
Compound (SMILES): Nc1ccc(CCc2nc(CCC(=O)NO)cs2)cc1
InChIKey: HHDSOEQPXTYNID-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of human recombinant HDAC1 using fluorogenic HDAC substrate 3 pre-incubated for 30 mins followed by HDAC developer addition and measured after 15 mins by fluorogenic assay
Measurement: IC50 = 1060 nM (pChEMBL 5.96999979019165)
Descriptors: MW 291.38, ALogP 1.95, HBA 5, HBD 3, PSA 88.24, QED 0.43
Compound (SMILES): COc1cc(CCC(=O)Nc2cc(-c3[nH]c(SC)nc3-c3ccc(F)cc3)ccn2)cc(OC)c1OC
InChIKey: NAXXGCGMDSLZMI-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Competitive inhibition of human recombinant full length GSK3beta using YRRAAVPPSPSLSRHSSPHQ(pS)EDEEE as substrate preincubated with enzyme for 10 mins followed by substrate and 25 uM ATP addition measured after 60 mins by ADP-Glo luminescence assay
Measurement: IC50 = 363 nM (pChEMBL 6.440000057220459)
Descriptors: MW 522.6, ALogP 5.6, HBA 7, HBD 2, PSA 98.36, QED 0.26
Compound (SMILES): CC1(C)Cc2cc(NC(=O)c3cnn4cc(C(N)=O)cnc34)c(N3CCOCC3)cc2O1
InChIKey: HBIARFMLDXJMQN-UHFFFAOYSA-N
Target: Interleukin-1 receptor-associated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWZ3
Assay: Inhibition of IRAK4 in human THP1-Xblue-MD2-CD14 cells assessed as reduction in LPS-induced NFkappaB transcription by measuring alkaline phosphatase level preincubated for 1 hr followed by LPS stimulation and measured after 20 hrs by quanti-blue reagent based reporter assay
Measurement: IC50 = 56 nM (pChEMBL 7.25)
Descriptors: MW 436.47, ALogP 1.63, HBA 8, HBD 2, PSA 124.08, QED 0.64