lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cn1ccnc1SCC1CCN(S(=O)(=O)c2ccc3c(c2)CCCO3)CC1
InChIKey: HOTZXRMCYPMGDN-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: Antagonist activity at human muscarinic M1 receptor expressed in CHO cells assessed as inhibition of acetylcholine-induced calcium mobilization by by Fluo-4AM staining based fluorescence assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 407.56, ALogP 2.94, HBA 6, HBD 0, PSA 64.43, QED 0.71
Compound (SMILES): Fc1ccc(COC2CCN(Cc3ncc4ccccn34)CC2)cc1F
InChIKey: AVDBUQOCOAGNPB-UHFFFAOYSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99720
Assay: Displacement of [3H] Pentazocine from sigma 1 receptor in HEK293 cell membrane
Measurement: Ki = 144.54 nM (pChEMBL 6.840000152587891)
Descriptors: MW 357.4, ALogP 3.79, HBA 4, HBD 0, PSA 29.77, QED 0.7
Compound (SMILES): COc1cc(CCc2cc(-c3nc4ccc(CN5CCN(C)CC5)cc4[nH]3)n[nH]2)cc(OC)c1
InChIKey: TUFWCZFZSQLLMZ-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of recombinant human N-terminal GST-tagged FGFR3 (436 to 806 residues) expressed in baculovirus expression system using IGF-1Rtide peptide as substrate preincubated for 10 mins followed by substrate addition and measured after 1 hrs in the presence of ATP by ADP-Glo reagent based luminescence assay
Measurement: IC50 = 14.35 nM (pChEMBL 7.840000152587891)
Descriptors: MW 460.58, ALogP 3.5, HBA 6, HBD 2, PSA 82.3, QED 0.42
Compound (SMILES): CC(C)(C)CNC(=S)Nc1ccc2c(c1)CCN2CCCCN
InChIKey: VKEQTJPLMSOYKG-UHFFFAOYSA-N
Target: Bifunctional epoxide hydrolase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34913
Assay: Inhibition of human recombinant sEH assessed as reduction in 6-methoxynaphthaldehyde formation using PHOME as substrate preincubated for 1 min followed by substrate addition and measured after 60 mins by fluorescence based analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 334.53, ALogP 3.12, HBA 3, HBD 3, PSA 53.32, QED 0.55
Compound (SMILES): Cc1ccc(CO[C@H]2CCCN(Cc3ccc(C#N)cc3)C2)cc1
InChIKey: PPZBZJPCFRFDCX-NRFANRHFSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99720
Assay: Displacement of [3H] Pentazocine from sigma 1 receptor in HEK293 cell membrane
Measurement: Ki = 13.8 nM (pChEMBL 7.860000133514404)
Descriptors: MW 320.44, ALogP 4.05, HBA 3, HBD 0, PSA 36.26, QED 0.83
Compound (SMILES): COc1nc(C)ccc1-c1cnc2sc(N3CCC(O)(CN)CC3)nn12
InChIKey: MIYJPKCVTQPVFU-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Kinase Biological Assay: Binding reactions were assembled by combining kinases, liganded affinity beads, and test compounds in 1× binding buffer (20% SeaBlock, 0.17×PBS, 0.05% Tween 20, 6 mM DTT). Test compounds were prepared as 111× stocks in 100% DMSO. Kds were determined using an 11-point 3-fold compound dilution series with three DMSO control points. All compounds for Kd measurements are distributed by acoustic transfer (non-contact dispensing) in 100% DMSO. The compounds were then diluted directly into the assays such that the final concentration of DMSO was 0.9%. All reactions performed in polypropylene 384-well plate. Each was a final volume of 0.02 ml. The assay plates were incubated at room temperature with shaking for 1 hour and the affinity beads were washed with wash buffer (1×PBS, 0.05% Tween 20). The beads were then re-suspended in elution buffer (1×PBS, 0.05% Tween 20, 0.5 μM non-biotinylated affinity ligand) and incubated at room temperature with shaking for 30 minutes. The kinase concentration in the eluates was measured by qPCR. Binding constants (Kds) were calculated with a standard dose-response curve using the Hill equation: Response=Background+(Signal−Background)/[1+(KdHill Slope/DoseHill Slope)]
Measurement: Kd > 100 nM (pChEMBL 7)
Descriptors: MW 374.47, ALogP 1.46, HBA 9, HBD 2, PSA 101.8, QED 0.71
Compound (SMILES): Cc1nc(NC(=O)NC(=O)C2CCCC2)ccc1Oc1ccnc(-c2cnn(C)c2)c1
InChIKey: AMZWYWQCAVGQIH-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P16234
Assay: Inhibition of N-terminal GST-tagged PDGFRalpha (unknown origin) (550 to 1089 residues) measured by spectrophotometric analysis
Measurement: IC50 = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 420.47, ALogP 3.82, HBA 7, HBD 2, PSA 111.03, QED 0.65
Compound (SMILES): Cc1ccc(NC(=O)c2ccc(NC(=O)N3CCN(C(=O)c4cc(Cc5n[nH]c(=O)c6ccccc56)ccc4F)CC3)cc2)cc1
InChIKey: PBOOUBWKFXDCRA-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase tankyrase-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H2K2
Assay: Inhibition of TNKS2 (unknown origin) using biotin-NAD+ as substrate incubated for 1 hr in the presence of deoxy-oligonucleotide by ELISA analysis relative to control
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 618.67, ALogP 5.2, HBA 5, HBD 3, PSA 127.5, QED 0.24
Compound (SMILES): COc1ccc(/C=C/C=C2C(=O)NC(=O)NC2=O)cc1
InChIKey: IXYLVJHFJKDHRM-NSCUHMNNSA-N
Target: Sortase A (SINGLE PROTEIN), Staphylococcus aureus
UniProt: Q9S446
Assay: Inhibition of recombinant Staphylococcus aureus sortase A deltaN24 transpeptidation expressed in Escherichia coli BL21 (DE3) cells using Abz-LPATG-Dnp as substrate preincubated for 20 mins followed by substrate addition and measured every 1 min for 15 mins by FRET assay
Measurement: IC50 = 370 nM (pChEMBL 6.429999828338623)
Descriptors: MW 272.26, ALogP 1, HBA 4, HBD 2, PSA 84.5, QED 0.63
Compound (SMILES): O=C(c1ccc(OCCN2C=Cc3ccccc3C2)cc1)c1c(-c2ccc(O)cc2)oc(=O)c2cc(O)ccc12
InChIKey: QLYZYLKQDKMAOV-UHFFFAOYSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Antagonist activity at ERalpha in human MCF7 cells assessed as downregulation of ERalpha
Measurement: IC50 > 100 nM (pChEMBL 7)
Descriptors: MW 531.56, ALogP 5.97, HBA 7, HBD 2, PSA 100.21, QED 0.25
Compound (SMILES): CCC(C)n1cc(C)c2c(C(=O)NCc3c(O)nn(CC)c3C)cc(-c3ccc(N4CCNCC4)nc3)cc21
InChIKey: MQDSSXUQHUNJLJ-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase EZH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15910
Assay: Enzyme Assay: The assays were performed in a buffer consisting of 20 mM bicine (pH=7.6), 0.5 mM DTT, 0.005% BSG, 100 mM KCl and 0.002% Tween20, prepared on the day of use. Compounds in 100% DMSO (1 μL) were spotted into polypropylene 384-well V-bottom plates (Greiner) using a Platemate 2×3 outfitted with a 384-channel pipet head (Thermo). DMSO (1 μL) was added to columns 11, 12, 23, 24, rows A-H for the maximum signal control, and SAH, a known product and inhibitor of PRC2 (1 μL) was added to columns 11, 12, 23, 24, rows I-P for the minimum signal control. A cocktail (40 μL) containing the wild-type PRC2 enzyme and chicken erythrocyte oligonucleosome was added by Multidrop Combi (Thermo). The compounds were allowed to incubate with PRC2 for 30 min at 25° C., then a cocktail (10 μL) containing a mixture of non-radioactive and 3H-SAM was added to initiate the reaction (final volume=51 μL). The final concentrations were as follows: wild-type PRC2 enzyme is 4 nM, non-radioactive SAM is 430 nM, 3H-SAM was 120 nM, chicken erythrocyte olignonucleosome was 120 nM, SAH in the minimum signal control wells was 1 mM and the DMSO concentration was 1%. The assay was stopped by the addition of non-radioactive SAM (10 μL) to a final concentration of 600 μM, which diluted the 3H-SAM to a level where its incorporation into the chicken erythrocyte olignonucleosome substrate was no longer detectable. 5 μL of the reaction in the 384-well polypropylene plate was then transferred to a 384-well Flashplate and the chicken erythrocyte nucleosomes were immobilized to the surface of the plate, which was then washed three times with 0.1% Tween20 in a Biotek ELx405 plate washer.
Measurement: IC50 = 1467 nM (pChEMBL 5.829999923706055)
Descriptors: MW 529.69, ALogP 4.55, HBA 8, HBD 3, PSA 100.24, QED 0.31
Compound (SMILES): CC(C)Oc1ccc(-c2cccc(S(=O)(=O)N[C@@H](Cc3cccc(C(=N)N)c3)C(=O)N3CCC(NC(=O)NC(C)(C)C)CC3)c2)cc1
InChIKey: OVSAOEYRJCDJPA-HKBQPEDESA-N
Target: Coagulation factor X (SINGLE PROTEIN), Homo sapiens
UniProt: P00742
Assay: Binding affinity to FXa (unknown origin) using Mes-DArg-Pro-Arg-AMC as substrate
Measurement: Ki = 439 nM (pChEMBL 6.360000133514404)
Descriptors: MW 662.86, ALogP 4.4, HBA 6, HBD 5, PSA 166.71, QED 0.15
Compound (SMILES): CN(C)CC#Cc1ccc2[nH]c3c(c2c1)-c1nc(N)ncc1CCC3
InChIKey: DORZPJWJOBMQKC-UHFFFAOYSA-N
Target: 1-phosphatidylinositol 3-phosphate 5-kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2I7
Assay: Inhibition of PIKFYVE in HEK293 cells by NanoBRET assay
Measurement: IC50 = 3.981 nM (pChEMBL 8.399999618530273)
Descriptors: MW 331.42, ALogP 2.61, HBA 4, HBD 2, PSA 70.83, QED 0.67
Compound (SMILES): CC(=O)Nc1ccc(Nc2ncnc(N[C@@H](CC(C)C)C(=O)OC(C)(C)C)n2)cc1
InChIKey: GKKXAQNAEUEDNC-KRWDZBQOSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes using phenacetin as substrate preincubated for 10 mins followed by NADPH addition and measured after 10 mins by LC/MS/MS analysis
Measurement: IC50 = 26800 nM (pChEMBL 4.570000171661377)
Descriptors: MW 414.51, ALogP 3.74, HBA 8, HBD 3, PSA 118.13, QED 0.56
Compound (SMILES): Cc1nnc(C2CCN(c3ccc(Nc4nccc(-c5ccc(C(=O)NCC#N)cc5)n4)cc3)CC2)s1
InChIKey: RJSRGYNITUBKSL-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of human JAK3 kinase domain
Measurement: IC50 = 102 nM (pChEMBL 6.989999771118164)
Descriptors: MW 510.63, ALogP 4.68, HBA 9, HBD 2, PSA 119.72, QED 0.34
Compound (SMILES): O=C(Cc1cnccn1)N[C@@H](Cc1coc2ccccc12)B(O)O
InChIKey: CDFIDSVYHTYZIG-HNNXBMFYSA-N
Target: Proteasome Macropain subunit MB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28074
Assay: Inhibition of 20S proteasome beta5 subunit in human A549 cells using Suc-LLVY-luciferin substrate preincubated for 2 hrs followed by substrate addition and measured after 30 mins by luminometric analysis
Measurement: IC50 = 328 nM (pChEMBL 6.480000019073486)
Descriptors: MW 325.13
Compound (SMILES): CC(C)Oc1ccc(-c2cn(-c3ccc(CN4CC(C(=O)[O-])C4)cc3)nn2)cc1C#N.[Na+]
InChIKey: TVVBCRCOWGXMBD-UHFFFAOYSA-M
Target: Sphingosine 1-phosphate receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99500
Assay: Agonist activity at S1P3 receptor (unknown origin) expressed in PathHunter CHO-K1 EDG1 beta-arrestin cells assessed as induction of beta-arrestin 2 recruitment incubated for 90 mins by measuring chemiluminescence signal by microplate reader method
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 417.47, ALogP 3.11, HBA 7, HBD 1, PSA 104.27, QED 0.63
Compound (SMILES): COc1ccc2c(c1)c(CCNC(C)=O)cn2Cc1cc(OC)c(OC)cc1[N+](=O)[O-]
InChIKey: AJPOWRPZSWEQQN-UHFFFAOYSA-N
Target: Melatonin receptor type 1B (SINGLE PROTEIN), Homo sapiens
UniProt: P49286
Assay: Displacement of 2-[125I]iodomelatonin from human melatonin MT2 receptor stably expressing in human HEK293 cell membranes under dark condition by radioligand based competition binding assay
Measurement: Ki = 275.42 nM (pChEMBL 6.559999942779541)
Descriptors: MW 427.46, ALogP 3.3, HBA 7, HBD 1, PSA 104.86, QED 0.41
Compound (SMILES): COc1ccc2nc(-c3ccccc3OC)cc(C(=O)NCCc3ccc(S(N)(=O)=O)cc3)c2c1
InChIKey: TZINIZADJDODMS-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human recombinant carbonic anhydrase 9 assessed as inhibition constant incubated for 10 mins by phenol red dye based stopped-flow CO2 hydration assay
Measurement: Ki = 67.7 nM (pChEMBL 7.170000076293945)
Descriptors: MW 491.57, ALogP 3.54, HBA 6, HBD 2, PSA 120.61, QED 0.39
Compound (SMILES): C[C@@H]1CCC[C@H](C)N1c1nnc2ccc(O[C@@H]3CC[C@H](NC(=O)Nc4cc(C(C)(C)C)nn4-c4cnn(CCN(C)C)c4)c4ccccc43)cn12
InChIKey: NEOFBONIFALDKM-MAOWDPDTSA-N
Target: Mitogen-activated protein kinase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: P53778
Assay: Inhibition of recombinant human full length His-tagged p38gamma expressed in baculovirus expression system preincubated for 2 hrs followed by ATP addition and measured after 1 hr by Alpha screen assay
Measurement: IC50 = 805 nM (pChEMBL 6.090000152587891)
Descriptors: MW 693.9, ALogP 6.51, HBA 11, HBD 2, PSA 122.67, QED 0.18
Compound (SMILES): CC(C)NC[C@@H](C(=O)N1CCN(c2ncnc3c2[C@H](C)CC(=O)N3)CC12CC2)c1ccc(Cl)cc1
InChIKey: MLQQEZBDGZMPOB-YLJYHZDGSA-N
Target: RAC-beta serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31751
Assay: Inhibition of recombinant AKT2 (120 to 481 end residues) (unknown origin) catalytic domain expressed in Sf21 cells using peptide substrate incubated for 1 hr in presence of ATP by caliper off-chip mobility shift assay
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 497.04, ALogP 3.54, HBA 6, HBD 2, PSA 90.46, QED 0.64
Compound (SMILES): COC(=O)Nc1cc(-c2ccc(OC[C@@](C)(N)CC(C)C)c(C#N)c2)ccn1
InChIKey: LJJCAJZWKRIPDY-NRFANRHFSA-N
Target: AP2-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q2M2I8
Assay: Inhibition of full length human AAK1 expressed in HEK293F cells assessed as suppression of AP2 phosphorylation measured after 3 hrs by Western blot analysis based cellular assay
Measurement: IC50 = 0.8 nM (pChEMBL 9.100000381469727)
Descriptors: MW 382.46, ALogP 3.94, HBA 6, HBD 2, PSA 110.26, QED 0.75
Compound (SMILES): Fc1ccc2c(Cc3nnc(Cc4cccc(Cl)c4)n3CCCc3c[nH]cn3)c[nH]c2c1
InChIKey: RQGQSCHSKCCJEJ-UHFFFAOYSA-N
Target: Somatostatin receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P31391
Assay: Displacement of [125I]-Tyr-SRIF 14 from human SST4 receptor expressed in membrane measured after 90 mins by gamma counting analysis
Measurement: Ki = 0.5 nM (pChEMBL 9.300000190734863)
Descriptors: MW 448.93, ALogP 5.09, HBA 4, HBD 2, PSA 75.18, QED 0.35
Compound (SMILES): COc1cc(OC)c(Cl)c(Nc2ncccc2-c2ncnc(Nc3cnn(C4CCOCC4)c3)n2)c1Cl
InChIKey: HVIMAXORBAESDU-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of FGFR3 V555M mutant (unknown origin) by radiometric kinase activity assay
Measurement: IC50 = 1170 nM (pChEMBL 5.929999828338623)
Descriptors: MW 543.42, ALogP 5.29, HBA 11, HBD 2, PSA 121.13, QED 0.3
Compound (SMILES): CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@H](C)[C@@H](O)c1ccccc1)OC)N(C)C(=O)[C@@H](NC(=O)[C@H](C(C)C)N(C)C(=O)OCc1ccc(NC(=O)[C@H](CCCNC(N)=O)NC(=O)[C@@H](NC(=O)CCCCCN2C(=O)CC(SCCC(=O)NC(Cc3cn(CCOCCOCCNCCCCCCOc4cc(OCCCc5c(C)n[nH]c5C)cc(C(=O)O)c4)nn3)C(=O)NCCCCCC(=O)NCCCC[C@H](NC(=O)N[C@@H](CCC(=O)O)C(=O)O)C(=O)O)C2=O)C(C)C)cc1)C(C)C
InChIKey: IJMMNCBKNCOUSD-VNEVVWSASA-N
Target: Glutamate carboxypeptidase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q04609
Assay: Binding affinity to human recombinant PSMA assessed as inhibition constant by fluorescence polarization assay
Measurement: Ki = 14.7 nM (pChEMBL 7.829999923706055)
Descriptors: MW 2479.02
Compound (SMILES): CCCCCCNNC(=O)c1ccc(-c2ccc(CNC(C)=O)cc2)cc1
InChIKey: TYHZHMRYNRDNRX-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of recombinant human HDAC3 using p53 (Ac-RHKK(Acetyl)-AMC) as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by fluorescence based analysis
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 367.49, ALogP 3.8, HBA 3, HBD 3, PSA 70.23, QED 0.44
Compound (SMILES): O=C(O)C(=O)O.O=C1CCc2ccccc2N1CCCN1CCN(c2ccc([N+](=O)[O-])cc2)CC1
InChIKey: LDXSXPYWVKXZBO-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]N-methylspiperone from human D4.4 receptor expressed in HEK293T cell membrane incubated for 1 hr by MicroBeta scintillation counting method
Measurement: Ki = 6.607 nM (pChEMBL 8.180000305175781)
Descriptors: MW 394.48, ALogP 3.09, HBA 5, HBD 0, PSA 69.93, QED 0.56
Compound (SMILES): Nc1nc(N)c2nc(CNc3ccc(C(=O)c4ccccc4)cc3)cnc2n1
InChIKey: CZUHYAFUFAOCJF-UHFFFAOYSA-N
Target: Bifunctional dihydrofolate reductase-thymidylate synthase (SINGLE PROTEIN), Trypanosoma brucei brucei
UniProt: Q27783
Assay: Inhibition of recombinant Trypanosoma brucei DHFR-TS expressed in Escherichia coli BL21 (DE3) cells using dihydrofolate as substrate in presence of NADPH by spectrophotometric analysis
Measurement: IC50 = 990 nM (pChEMBL 6)
Descriptors: MW 371.4, ALogP 2.43, HBA 8, HBD 3, PSA 132.7, QED 0.46
Compound (SMILES): Cn1c(-c2ccc(Cl)cc2)nc2cc(C(=O)O)ccc21
InChIKey: DLKYQVYABKLKQM-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human recombinant CA9 incubated for 15 mins prior to testing by phenol red based stopped-flow CO2 hydration assay
Measurement: IC50 > 360 nM (pChEMBL 6.443999767303467)
Descriptors: MW 286.72, ALogP 3.59, HBA 3, HBD 1, PSA 55.12, QED 0.78
Compound (SMILES): O=C(N[C@@H]1CCCN(c2ncnc3[nH]ccc23)C1)[C@H](Nc1cc(Cl)cc(Cl)c1)C1CC1
InChIKey: GAWQIOVCXHLEAP-VQIMIIECSA-N
Target: Tyrosine-protein kinase Tec (SINGLE PROTEIN), Homo sapiens
UniProt: P42680
Assay: Binding affinity to human partial length TEC (L341 to D620 residues ) expressed in bacterial expression system assessed dissociation constant by Kinomescan method
Measurement: Kd = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 459.38, ALogP 4.24, HBA 5, HBD 3, PSA 85.94, QED 0.51
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)[C@@H]1CCCN1C(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CSCCCOCc1ccccc1)NC(=O)[C@H](CO)NC(=O)CN)C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)O
InChIKey: YSZJRYHGYXUZDF-NUJRNOJUSA-N
Target: Appetite-regulating hormone (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBU3
Assay: Displacement of C-terminal Cys-tagged human LEAP2-SmBiT tracer from C-terminal Cys-tagged human Ghrelin expressed in HEK293T cells by microplate reader based NanoBiT-binding assay
Measurement: IC50 = 70.79 nM (pChEMBL 7.150000095367432)
Descriptors: MW 3408.99
Compound (SMILES): O=C(O)C(=O)O.O=C1CCc2ccccc2N1CCCN1CCN(c2ccc(Cl)c(Cl)c2)CC1
InChIKey: OPAHJQLPXLOCOP-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]N-methylspiperone from human D4.4 receptor expressed in HEK293T cell membrane incubated for 1 hr by MicroBeta scintillation counting method
Measurement: Ki = 0.871 nM (pChEMBL 9.0600004196167)
Descriptors: MW 418.37, ALogP 4.48, HBA 3, HBD 0, PSA 26.79, QED 0.72
Compound (SMILES): CCC[C@H](C)COc1ccc([C@H](Cn2cc(C(=O)NC)nn2)NC(=O)[C@@H](C)c2ccccc2)cc1
InChIKey: LSFIFBCTMZGYCP-SKPFHBQLSA-N
Target: G protein-coupled receptor 88 (SINGLE PROTEIN), Mus musculus
UniProt: Q9EPB7
Assay: Agonist activity at wild type GPR88 expressed in mouse striatal membrane assessed as [35S] GTPgammaS binding incubated for 1 hr by liquid scintillation counting method
Measurement: EC50 = 8900 nM (pChEMBL 5.050000190734863)
Descriptors: MW 477.61, ALogP 4.11, HBA 6, HBD 2, PSA 98.14, QED 0.41
Compound (SMILES): Cc1cc(N)nc(C#CCCN(C)C)c1
InChIKey: SWAXYJVGMJZMLB-UHFFFAOYSA-N
Target: Nitric oxide synthase, inducible (SINGLE PROTEIN), Homo sapiens
UniProt: P35228
Assay: Inhibition of human iNOS using L-arginine as substrate assessed as reduction in NO production in the presence of NADPH by NO-hemoglobin capture assay
Measurement: Ki = 29835 nM (pChEMBL 4.53000020980835)
Descriptors: MW 203.29, ALogP 1.28, HBA 3, HBD 1, PSA 42.15, QED 0.74
Compound (SMILES): O=C1NC(c2ccccc2)Cc2[nH]c(-c3ccncc3)cc21
InChIKey: GRXTWQXVRAIPAQ-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase N1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16512
Assay: Inhibition of PKN1 (unknown origin) by TR-FRET-based tracer displacement assay dependent Cheng-Prusoff equation analysis
Measurement: Ki = 260 nM (pChEMBL 6.579999923706055)
Descriptors: MW 289.34, ALogP 3.1, HBA 2, HBD 2, PSA 57.78, QED 0.76
Compound (SMILES): CC(=O)NCc1cc(Cl)ccc1Cn1c(=S)[nH]c(=O)c2[nH]ccc21
InChIKey: CZYBHRFKMUJCPS-UHFFFAOYSA-N
Target: Thyroid peroxidase (SINGLE PROTEIN), Homo sapiens
UniProt: P07202
Assay: Inhibition of human recombinant TPO (1 to 839 residues) expressed in baculovirus-infected insect cells measured after 15 mins in presence of H2O2 by chemiluminescence assay
Measurement: IC50 = 1400 nM (pChEMBL 5.849999904632568)
Descriptors: MW 362.84, ALogP 2.72, HBA 4, HBD 3, PSA 82.68, QED 0.62
Compound (SMILES): Cc1cc(-c2ccc(/N=N/c3c(N)c(S(=O)(=O)O)cc4cc(S(=O)(=O)O)ccc34)c(C)c2)ccc1/N=N/c1c(N)ccc2cc(S(=O)(=O)O)ccc12
InChIKey: OFGVQLJUXSRVEG-HVMBLDELSA-N
Target: Sentrin-specific protease 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HC62
Assay: Binding Assay: The binding of SPI-01 to the enzyme-substrate complex was investigated. CSP analysis was carried out on the 40 kDa complex of 15N-labeled full length precursor SUMO-1-GGHSTV (SUMO-1-FL) with unlabeled SENP1-C603S. An equimolar amount of SPI-01 was added to the 1:1 enzyme-substrate complex. The only observed CSP on the 15N-labeled precursor SUMO-1-FL was on the C-terminal residues S99 and V101 (FIGS. 7 and 8) (Song et al., PNAS 101:14373-8 (2004)). This result indicates that SPI-01 binds the enzyme-substrate complex at the interface between SENP and the C-terminal tails of precursor SUMO-FL. X-ray crystal structures showed that the C-terminal tail of precursor SUMO sits in and projects out of the catalytic tunnel of SENPs (Shen et al., Nat. Struct. Mol. Biol. 13:1069-77 (2006)). In the case of SENP1, the region that interacts with the projected C-terminus is predominantly acidic and favors the C-terminus of SUMO-1, which is polar and positively charged, over that of SUMO-2, whose C-terminus is mainly hydrophobic (Shen et al., Nat. Struct. Mol. Biol. 13:1069-77 (2006); and Shen et al., The Biochemical Journal 397:279-88 (2006)).
Measurement: IC50 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 760.83, ALogP 8.01, HBA 12, HBD 5, PSA 264.59, QED 0.06
Compound (SMILES): NS(=O)(=O)c1ccc(Nc2nc(C(=O)OCCCCc3ccccc3)cs2)cc1
InChIKey: YYFKWNUXFSZHLG-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 incubated for 15 mins by phenol red based stopped-flow CO2 hydration assay
Measurement: Ki = 86.8 nM (pChEMBL 7.059999942779541)
Descriptors: MW 431.54, ALogP 3.71, HBA 7, HBD 2, PSA 111.38, QED 0.39
Compound (SMILES): Cc1nc(C)n(CC(=O)N2CCN(c3sc(C(F)(F)F)nc3-c3cnc(OC(C)C)nc3)C[C@H]2C)n1
InChIKey: FSVSKYZTMULUBO-CYBMUJFWSA-N
Target: C-X-C chemokine receptor type 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49682
Assay: Antagonist activity at recombinant human CXCR3 in human U2SO cells assessed as reduction in CXCL10-induced beta-arrestin recruitment by TANGO assay
Measurement: IC50 = 138 nM (pChEMBL 6.860000133514404)
Descriptors: MW 524.57, ALogP 3.35, HBA 10, HBD 0, PSA 102.16, QED 0.48
Compound (SMILES): O=S(=O)(c1ccccc1)N1CCc2cc(C3CC3NCC3CCN(Cc4ccccc4)CC3)ccc21
InChIKey: TZKHPQREDHGACS-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of human recombinant MAO-A expressed in baculovirus infected BTI insect cells using luminogenic MAO substrate incubated for 1 hr by luciferin-based luminescence assay
Measurement: IC50 = 15910 nM (pChEMBL 4.800000190734863)
Descriptors: MW 501.7, ALogP 4.8, HBA 4, HBD 1, PSA 52.65, QED 0.48
Compound (SMILES): CC(=O)N[C@@H](CCCCN=[N+]=[N-])C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H]1CSSC[C@@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(N)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CC(=O)O)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)[C@H](Cc2ccc(-c3ccccc3)cc2)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]2[C@@H](c3ccccc3)CCN2C1=O
InChIKey: PVEWEDGJMHIKGE-GAXNGBBSSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Inhibition of KRAS in human ASPC1 cells harboring KRAS G12D mutant assessed as inhibition of ERK phosphorylation incubated for 18 hrs by AlphaScreen-based LDH membrane integrity assay
Measurement: IC50 = 6800 nM (pChEMBL 5.170000076293945)
Descriptors: MW 2184.59
Compound (SMILES): CCCC[Si](C)(C)c1cc(O)c(C2CCCCC2)c(OC)c1
InChIKey: SNVQUUCKBACSNX-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Agonist activity at recombinant human CB2 receptor expressed in CHO cells assessed as inhibition of forskolin-induced cAMP accumulation preincubated for 15 mins followed by forskolin stimulation and measured after 15 mins by HTRF assay
Measurement: EC50 = 706.65 nM (pChEMBL 6.150000095367432)
Descriptors: MW 320.55
Compound (SMILES): COc1cc2nc(NCCCN3CCCCC3)nc(NC3CCN(Cc4ccccc4)CC3)c2cc1OC
InChIKey: SKAXHFHMJFPVDU-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase EHMT2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96KQ7
Assay: Inhibition of G9a (unknown origin) assessed as reduction in substrate methylation using histone H3 and SAM as substrate measured after 15 to 60 mins by microfluidic capillary electrophoresis analysis
Measurement: Ki = 3260 nM (pChEMBL 5.489999771118164)
Descriptors: MW 518.71, ALogP 5.01, HBA 8, HBD 2, PSA 74.78, QED 0.34
Compound (SMILES): C=C(C(N)=O)[C@@H](NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@@H](C)N(C)C(=O)[C@@H](N)Cc1c(C)cc(O)cc1C)c1ccco1
InChIKey: RATBBTRECYJTEP-XYFUKPFPSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Displacement of [3H]DPDPE from DOP (unknown origin) stably expressed in HEK293 cells by liquid scintillation counter analysis
Measurement: Ki = 33.32 nM (pChEMBL 7.480000019073486)
Descriptors: MW 628.73, ALogP 2.43, HBA 7, HBD 6, PSA 196.78, QED 0.12
Compound (SMILES): Nc1ncc(-c2cnn(C3CCNCC3)c2)c2c1C(=O)N(C1C3CC4CC(C3)CC1C4)CC2
InChIKey: WSNLCMQIUFLQBS-UHFFFAOYSA-N
Target: Bone morphogenetic protein receptor type-1A (SINGLE PROTEIN), Homo sapiens
UniProt: P36894
Assay: Inhibition of ALK3 (unknown origin)
Measurement: IC50 = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 446.6, ALogP 3.27, HBA 6, HBD 2, PSA 89.07, QED 0.76
Compound (SMILES): COCC(=O)N[C@@H](Cc1coc2ccccc12)B(O)O
InChIKey: MSKOQFOAPAPXPT-LBPRGKRZSA-N
Target: Proteasome Macropain subunit MB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28074
Assay: Inhibition of 20S proteasome beta5 subunit in human A549 cells using Suc-LLVY-luciferin substrate preincubated for 2 hrs followed by substrate addition and measured after 30 mins by luminometric analysis
Measurement: IC50 = 520 nM (pChEMBL 6.28000020980835)
Descriptors: MW 277.09
Compound (SMILES): COCc1nn(Cc2ccc(Cn3ccccc3=O)cc2)cc1C(=O)NCc1cc(OC)n(C)n1
InChIKey: AKTSEYYIYFHXQV-UHFFFAOYSA-N
Target: Coagulation factor XI (SINGLE PROTEIN), Homo sapiens
UniProt: P03951
Assay: Determination of the % Inhibition for FXIa: FXIa inhibitory activity in vitro was determined using standard published methods (see e.g. Johansen et al., Int. J. Tiss. Reac. 1986, 8, 185; Shori et al., Biochem. Pharmacol., 1992, 43, 1209; Sturzebecher et al., Biol. Chem. Hoppe-Seyler, 1992, 373, 1025). Human FXIa (Enzyme Research Laboratories) was incubated at 25° C. with the fluorogenic substrate Z-Gly-Pro-Arg-AFC and 40 μM of the test compound (or alternatively at various concentrations of the test compound in order to determine IC50). Residual enzyme activity (initial rate of reaction) was determined by measuring the change in optical absorbance at 410 nm and the IC50 value for the test compound was determined.
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 476.54, ALogP 1.96, HBA 9, HBD 1, PSA 105.2, QED 0.38
Compound (SMILES): O=C(Cc1ccccc1)N[C@@H](Cc1coc2ccccc12)B(O)O
InChIKey: XRRMRPLIEUPSEG-KRWDZBQOSA-N
Target: Proteasome Macropain subunit MB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28074
Assay: Inhibition of 20S proteasome beta5 subunit in human A549 cells using Suc-LLVY-luciferin substrate preincubated for 2 hrs followed by substrate addition and measured after 30 mins by luminometric analysis
Measurement: IC50 = 573 nM (pChEMBL 6.239999771118164)
Descriptors: MW 323.16
Compound (SMILES): CC(=O)N1CCc2c(nc(C)n2[C@@H]2C[C@H]3CC[C@@H](C2)N3CC[C@H](NC(=O)C2CCC(F)(F)CC2)c2ccsc2)C1
InChIKey: CHNHYOHQPDHUOP-QYOOZWMWSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 573.75, ALogP 5.4, HBA 6, HBD 1, PSA 70.47, QED 0.48
Compound (SMILES): CN[C@@H](C)C(=O)N[C@@H](CNC(=O)c1cc(S(=O)(=O)F)ccc1OC)C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1ccccc1)C(N)=O
InChIKey: IQCPDUVZKKMYAI-ZMVGRULKSA-N
Target: Baculoviral IAP repeat-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13490
Assay: Antagonist activity at N-terminal His-tagged cIAP1-BIR3 domain (unknown origin) expressed in Escherichia coli BL21 using AVPIAQKSEK-biotinylated peptide as substrate incubated for 2 hrs by DELFIA assay
Measurement: IC50 = 153 nM (pChEMBL 6.820000171661377)
Descriptors: MW 648.71, ALogP -0.62, HBA 9, HBD 5, PSA 206.1, QED 0.17
Compound (SMILES): C#CCN(C)S(=O)(=O)c1ccc(CCN(Cc2cc(Cl)ccc2OCCC)C(=O)Cc2ccsc2)cc1
InChIKey: UTNFSSRVCLQXAQ-UHFFFAOYSA-N
Target: Interferon-inducible protein AIM2 (SINGLE PROTEIN), Mus musculus
UniProt: Q91VJ1
Assay: Inhibition of AIM2 inflammasome in LPS-primed mouse J774.A1 cells assessed as reduction in IL-1beta secretion preincubated for 1 hr followed by poly(dA:dT) addition and measured after 4 hrs by ELISA
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 559.15, ALogP 5.26, HBA 5, HBD 0, PSA 66.92, QED 0.27
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](N)CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSCCN)C(=O)O
InChIKey: NNUWMQVRIRHDOH-JDQHVGNYSA-N
Target: Neurotensin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30989
Assay: Displacement of [3H]NT(8-13) from human NTSR1 F2.65C mutant expressed in HEK293 cell membranes by radioligand displacement assay
Measurement: Ki = 51 nM (pChEMBL 7.289999961853027)
Descriptors: MW 995.29, ALogP -1.28, HBA 14, HBD 15, PSA 399.18, QED 0.02
Compound (SMILES): [2H]C([2H])([2H])NC(=O)c1cncc(-c2cnn3cc(-c4ccn(C(C)C)n4)c(N[C@H]4CCOC4)nc23)c1
InChIKey: XGJBIMKIGAOMPJ-JBKGLDERSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of N-terminal GST tagged recombinant human FGFR2 (400 to 821 residues) expressed in an Sf9 infected baculovirus expression system using biotin-EQEDEPEGDYFEWLE-amide as substrate preincubated for 5 to 10 mins followed by substrate addition and measured after 1 hr by HTRF assay
Measurement: IC50 = 0.2 nM (pChEMBL 9.699999809265137)
Descriptors: MW 446.52, ALogP 2.8, HBA 9, HBD 2, PSA 111.26, QED 0.47
Compound (SMILES): O=C(O)Cc1ccc(O)cc1Nc1c(Cl)cccc1Cl
InChIKey: CFUMXZGGBYQFQS-UHFFFAOYSA-N
Target: Calcium/calmodulin-dependent protein kinase type II subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UQM7
Assay: Displacement of [3H]HOCPCA from recombinant full length CaMK2alpha (unknown origin) expressed in HEK293 cell homogenates assessed as inhibition constant measured after 60 mins by liquid scintillation counting method
Measurement: Ki = 800 nM (pChEMBL 6.099999904632568)
Descriptors: MW 312.15, ALogP 4.07, HBA 3, HBD 3, PSA 69.56, QED 0.8
Compound (SMILES): COc1cc(/C=C/c2cc(/C=C/c3ccc(O)c(OC)c3)n(-c3ccc(C(C)C)cc3)n2)ccc1O
InChIKey: QBUBFIKFAGMXBZ-YDWXAUTNSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Inhibition of amyloid beta 42 secretion transfected in human H4 cells incubated for 20 to 24 hrs by LPECL assay
Measurement: IC50 = 4400 nM (pChEMBL 5.360000133514404)
Descriptors: MW 482.58, ALogP 6.76, HBA 6, HBD 2, PSA 76.74, QED 0.29
Compound (SMILES): Cc1cnc(Nc2ccc(N3CCC(N4CCOCC4)CC3)cc2)nc1-c1ccc(C(=O)NCC#N)cc1
InChIKey: LKTNBLBEAJCSNG-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of human JAK3 kinase domain
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 511.63, ALogP 3.75, HBA 8, HBD 2, PSA 106.41, QED 0.46
Compound (SMILES): CC(C)NC[C@@H](C(=O)N1CCN(c2ncnc3c2[C@H](C)CC(=O)N3)C[C@@H]1C)c1ccc(Cl)cc1.O=CO
InChIKey: UVILZAYPAZXMBS-VYZBTARASA-N
Target: RAC-gamma serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y243
Assay: Inhibition of recombinant N-terminal GST tagged AKT2 (108 to 479 end residues) (unknown origin) catalytic domain expressed in Sf21 cells using peptide substrate incubated for 1 hr in presence of ATP by caliper off-chip mobility shift assay
Measurement: IC50 = 8.5 nM (pChEMBL 8.069999694824219)
Descriptors: MW 485.03, ALogP 3.39, HBA 6, HBD 2, PSA 90.46, QED 0.65
Compound (SMILES): COc1ccc(C(=O)Nc2cc(Nc3nccc(-c4cn(C)c5ccccc45)n3)c(OC)cc2N(C)CCN(C)C)nc1
InChIKey: VYDMNIKAMFEVQV-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR L858R/T790M/C797S mutant (unknown origin) by mobility shift assay
Measurement: IC50 > 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 580.69, ALogP 5.04, HBA 10, HBD 2, PSA 109.67, QED 0.22
Compound (SMILES): CC(C)C[C@](C)(N)COc1cnc(-c2ccnc(Cl)c2)cc1Cl
InChIKey: QLODJNVFPYXMCX-KRWDZBQOSA-N
Target: AP2-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q2M2I8
Assay: AAK1 Kinase Assay: The assays were performed in U-bottom 384-well plates. The final assay volume was 30 μl prepared from 15 μl additions of enzyme and substrates (fluoresceinated peptide (5-FAM)-Aha-KEEQSQITSQVTGQIGWR-NH2 and ATP) and test compounds in assay buffer (10 mM Tris-HCL pH 7.4, 10 mM MgCl2, 0.01% Tween-20 and 1.0 mM DTT). The reactions were initiated by the combination of bacterially expressed, GST-Xa-hAAK1 with substrates and test compounds. The reactions were incubated at room temperature for 3 hours and terminated by adding 60 μl of 35 mM EDTA buffer to each sample. The reactions were analyzed on the Caliper LabChip 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison to EDTA quenched control reactions for 100% inhibition and vehicle-only reactions for 0% inhibition. The final concentration of reagents in the assays are ATP, 22 μM; (5-FAM)-Aha-KEEQSQITSQVTGQIGWR-NH2, 1.5 μM; GST-Xa-hAAK1, 3.5 nM; and DMSO, 1.6%. Dose response curves were generated to determine the concentration required inhibiting 50% of kinase activity (IC50). Compounds were dissolved at 10 mM in dimethylsulfoxide (DMSO) and evaluated at eleven concentrations. IC50 values were derived by non-linear regression analysis.
Measurement: IC50 = 2.2 nM (pChEMBL 8.65999984741211)
Descriptors: MW 354.28, ALogP 4.59, HBA 4, HBD 1, PSA 61.03, QED 0.77
Compound (SMILES): CC(C)NC[C@@H](C(=O)N1CCN(c2ncnc3c2[C@H](C)OC(=O)N3)CC1)c1ccc(Cl)cc1
InChIKey: DHMFFVNUPLZBKN-MAUKXSAKSA-N
Target: RAC-gamma serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y243
Assay: Inhibition of recombinant N-terminal GST tagged AKT2 (108 to 479 end residues) (unknown origin) catalytic domain expressed in Sf21 cells using peptide substrate incubated for 1 hr in presence of ATP by caliper off-chip mobility shift assay
Measurement: IC50 = 0.2 nM (pChEMBL 9.699999809265137)
Descriptors: MW 472.98, ALogP 3.18, HBA 7, HBD 2, PSA 99.69, QED 0.67
Compound (SMILES): Cn1ccc2ncnc(Nc3ccc(F)cc3OC(CF)CF)c21
InChIKey: HIIXSKLGSBCTAH-UHFFFAOYSA-N
Target: Eukaryotic translation initiation factor 4E (SINGLE PROTEIN), Homo sapiens
UniProt: P06730
Assay: Inhibition of eIF4E (unknown origin)
Measurement: IC50 = 19.95 nM (pChEMBL 7.699999809265137)
Descriptors: MW 336.32, ALogP 3.54, HBA 5, HBD 1, PSA 51.97, QED 0.75
Compound (SMILES): Cn1nc(-c2ccccc2)c2cnnc(N3CCOCC3)c21
InChIKey: ZMGCMNQAPWXRRM-UHFFFAOYSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30542
Assay: Displacement of CA200645 from NLuc human A1 receptor expressed in HEK293 cells assessed as inhibition constant by NanoBRET binding assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 295.35, ALogP 1.87, HBA 6, HBD 0, PSA 56.07, QED 0.72
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@@H](N)Cc1c[nH]cn1)[C@@H](C)O)[C@@H](C)O)C(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(N)=O)C(C)C
InChIKey: CBWAKBRUJUZANA-DMYQYOQPSA-N
Target: Glucagon-like peptide 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P43220
Assay: Agonist activity at human GLP-1R expressed in CHO cells coexpressing beta-arrestin-2 assessed as stimulation intracellular calcium mobilization measured after 180 secs by Fluo-3-AM dye based fluorescence assay
Measurement: EC50 = 2511.89 nM (pChEMBL 5.599999904632568)
Descriptors: MW 3265.68
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H]1CSSC[C@H](NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](Cc2c[nH]cn2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@@H](N)CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N2CCC[C@H]2C(=O)N2CCC[C@H]2C(=O)NCC(=O)N[C@@H](Cc2ccccc2)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](Cc2ccccc2)C(=O)N1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)O
InChIKey: VOCXANHYYBVTET-FJLKTBADSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Displacement of [125I]-NDP-alpha-MSH from human MC4R expressed in CHO cells by Topcount beta counter analysis
Measurement: Ki = 117.49 nM (pChEMBL 6.929999828338623)
Descriptors: MW 2907.47
Compound (SMILES): Nc1nc(N)c2nc(C(=O)NCc3cccc(C(F)(F)F)c3)cnc2n1
InChIKey: XJIGBPBDYCDOJG-UHFFFAOYSA-N
Target: Bifunctional dihydrofolate reductase-thymidylate synthase (SINGLE PROTEIN), Trypanosoma brucei brucei
UniProt: Q27783
Assay: Inhibition of recombinant Trypanosoma brucei DHFR-TS expressed in Escherichia coli BL21 (DE3) cells using dihydrofolate as substrate in presence of NADPH by spectrophotometric analysis
Measurement: IC50 = 100000 nM (pChEMBL 4)
Descriptors: MW 363.3, ALogP 1.53, HBA 7, HBD 3, PSA 132.7, QED 0.64
Compound (SMILES): CN(c1ncnc2[nH]ccc12)N1CC[C@@H](C(=O)NCC(F)(F)F)C1
InChIKey: OJAZQFYFIVPIPW-SECBINFHSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of JAK3 (unknown origin)
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 342.33, ALogP 1.31, HBA 5, HBD 2, PSA 77.15, QED 0.88
Compound (SMILES): OCC1Cc2c(-c3cc(-c4ccccc4)ccn3)cccc2-c2c(O)ccc(-c3ccc(Br)cc3)c21
InChIKey: QREMQPVDTOTTLU-UHFFFAOYSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of SARS-CoV 3CL protease using Dabcyl-KNSTLQSGLRKE-Edan as substrate incubated for 30 mins and measured by FRET assay
Measurement: IC50 = 5350 nM (pChEMBL 5.269999980926514)
Descriptors: MW 534.45, ALogP 7.85, HBA 3, HBD 2, PSA 53.35, QED 0.25
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@H](Cc2ccc(-c3ccccc3)cc2)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]2[C@H](c3ccccc3)CCN2C(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCCN=[N+]=[N-])NC(C)=O)CSSC[C@@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(N)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CC(=O)O)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CO)NC1=O
InChIKey: XXQPIXFEFKTHCE-XUWBOYEDSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Inhibition of KRAS in human ASPC1 cells harboring KRAS G12D mutant assessed as inhibition of ERK phosphorylation incubated for 18 hrs by AlphaScreen-based LDH membrane integrity assay
Measurement: IC50 = 19000 nM (pChEMBL 4.71999979019165)
Descriptors: MW 2226.68
Compound (SMILES): COC(=O)Nc1cc(-c2cc(OC)c(OC[C@@](C)(N)CC(C)C)cn2)ccn1
InChIKey: YPICVZJBBZPDDD-FQEVSTJZSA-N
Target: AP2-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q2M2I8
Assay: AAK1 Kinase Assay: The assays were performed in U-bottom 384-well plates. The final assay volume was 30 μl prepared from 15 μl additions of enzyme and substrates (fluoresceinated peptide (5-FAM)-Aha-KEEQSQITSQVTGQIGWR-NH2 and ATP) and test compounds in assay buffer (10 mM Tris-HCL pH 7.4, 10 mM MgCl2, 0.01% Tween-20 and 1.0 mM DTT). The reactions were initiated by the combination of bacterially expressed, GST-Xa-hAAK1 with substrates and test compounds. The reactions were incubated at room temperature for 3 hours and terminated by adding 60 μl of 35 mM EDTA buffer to each sample. The reactions were analyzed on the Caliper LabChip 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product. Inhibition data were calculated by comparison to EDTA quenched control reactions for 100% inhibition and vehicle-only reactions for 0% inhibition. The final concentration of reagents in the assays are ATP, 22 μM; (5-FAM)-Aha-KEEQSQITSQVTGQIGWR-NH2, 1.5 μM; GST-Xa-hAAK1, 3.5 nM; and DMSO, 1.6%. Dose response curves were generated to determine the concentration required inhibiting 50% of kinase activity (IC50). Compounds were dissolved at 10 mM in dimethylsulfoxide (DMSO) and evaluated at eleven concentrations. IC50 values were derived by non-linear regression analysis.
Measurement: IC50 = 4.3 nM (pChEMBL 8.369999885559082)
Descriptors: MW 388.47, ALogP 3.47, HBA 7, HBD 2, PSA 108.59, QED 0.71
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@@H]2CCCN2C(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCCNC(=N)N)N(C)C(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2cnc[nH]2)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H](NC(C)=O)CSCc2cccc(c2)CSC[C@@H](C(N)=O)NC1=O
InChIKey: QXPVZJDKFVQDGO-ZQZJLAJUSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Displacement of [125I]-NDP-alpha-MSH from human MC4R expressed in HEK2936E cell membrane measured after 16 to 23 hrs by 1450 microbeta trilux scintillation proximity assay
Measurement: Ki = 1288.25 nM (pChEMBL 5.889999866485596)
Descriptors: MW 1319.63
Compound (SMILES): O=C1NC(N2CCCC2)=N/C1=C\c1ccc2c(c1)OCO2
InChIKey: CTXSEYUOXKGIMM-XFFZJAGNSA-N
Target: Dual specificity protein kinase CLK1 (SINGLE PROTEIN), Mus musculus
UniProt: P22518
Assay: Inhibition of GST-fused mouse recombinant CLK1 expressed in Escherichia coli using GRSRSRSRSRSR peptide as substrate incubated for 30 mins in presence of ATP by scintillation counting method
Measurement: IC50 = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 285.3, ALogP 1.34, HBA 5, HBD 1, PSA 63.16, QED 0.79
Compound (SMILES): CCCC[C@@H]1NC(=O)[C@@H]2CSCc3cccc(c3)CSC[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](Cc3c[nH]c4ccccc34)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc3ccccc3)NC(=O)[C@H](Cc3cnc[nH]3)NC(=O)CNC1=O)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1c[nH]c3ccccc13)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N2
InChIKey: NOLFWMRTIVNJFP-WPTGWSDQSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Displacement of [125I]-NDP-alpha-MSH from human MC4R expressed in HEK2936E cell membrane measured after 16 to 23 hrs by 1450 microbeta trilux scintillation proximity assay
Measurement: Ki = 35.48 nM (pChEMBL 7.449999809265137)
Descriptors: MW 2159.55
Compound (SMILES): O=C(N/N=C/c1ccc(Cl)cc1)c1ccc(CN2CCC(CO)CC2)cc1
InChIKey: GBCKWGVZGJBNEH-YDZHTSKRSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of Electrophorus electricus AchE assessed as inhibition constant
Measurement: Ki = 3555 nM (pChEMBL 5.449999809265137)
Descriptors: MW 385.9, ALogP 3.31, HBA 4, HBD 2, PSA 64.93, QED 0.59
Compound (SMILES): Cn1c(-c2ccc(Cl)cc2)nc2cc(C(=O)NO)ccc21
InChIKey: LCPNXPYEBSLZPD-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human recombinant CA9 incubated for 15 mins prior to testing by phenol red based stopped-flow CO2 hydration assay
Measurement: IC50 > 360 nM (pChEMBL 6.443999767303467)
Descriptors: MW 301.73, ALogP 3.01, HBA 4, HBD 2, PSA 67.15, QED 0.56
Compound (SMILES): CCCN1CCN(c2ccc3c(c2)C2CC3CCN2C(=O)OCc2ccccc2)CC1
InChIKey: FFCRKESJGXTNRJ-UHFFFAOYSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99720
Assay: Displacement of [3H](+)-pentazocine from human sigma 1 receptor transfected in human HEK293T cells assessed as inhibition constant by radioligand competition binding assay
Measurement: Ki = 29.51 nM (pChEMBL 7.53000020980835)
Descriptors: MW 419.57, ALogP 4.79, HBA 4, HBD 0, PSA 36.02, QED 0.7
Compound (SMILES): CC(C)C[C@@H]1NC(=O)[C@@H]2CSSC[C@@H]3NC(=O)[C@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@@H](Cc4ccccc4)NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@H](CCCNC(=N)N)NC3=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)N[C@@H](CC(=O)O)C(=O)N[C@H](Cc3ccccc3)C(=O)N[C@@H](C(C)C)C(=O)N2)NC(=O)CNC(=O)CNC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H]2CCCN2C1=O
InChIKey: MKXYXLLDTVYISF-UDVWPFKFSA-N
Target: Integrin alpha-IIb/beta-3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P08514
Assay: Inhibition of alpha2bbeta3 integrin receptor expressed on human surface of platelets
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 2111.49
Compound (SMILES): CN(c1ncnc2[nH]ccc12)N1CCC[C@@H](C(=O)NCC(F)(F)F)C1
InChIKey: YLZUWAQFDDIFRW-SNVBAGLBSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of JAK3 (unknown origin)
Measurement: IC50 = 6.2 nM (pChEMBL 8.210000038146973)
Descriptors: MW 356.35, ALogP 1.7, HBA 5, HBD 2, PSA 77.15, QED 0.87
Compound (SMILES): CC1(C)CN(C(=O)[C@H](Cc2ccc(C#N)cc2)NC(=O)Nc2ccc(F)cc2)c2ccccc21
InChIKey: HYUWZRSPJCQRMB-QHCPKHFHSA-N
Target: N-formyl peptide receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25090
Assay: Antagonist activity at human FPR2 transfected in human HL-60 cells assessed as inhibition of WKYMVM-induced intracellular calcium mobilization preincubated for 10 mins followed by WKYMVM addition measured every 5 seconds for 240 secs by Fluo-4-AM dye based fluorescence assay
Measurement: IC50 = 2700 nM (pChEMBL 5.570000171661377)
Descriptors: MW 456.52, ALogP 4.75, HBA 3, HBD 2, PSA 85.23, QED 0.58
Compound (SMILES): Cn1ncc2cc(CN3CCC(OCc4cccc(C(F)(F)F)c4)CC3)ccc21
InChIKey: JCHUVGUKPFGRNQ-UHFFFAOYSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99720
Assay: Displacement of [3H] Pentazocine from sigma 1 receptor in HEK293 cell membrane
Measurement: Ki = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 403.45, ALogP 4.77, HBA 4, HBD 0, PSA 30.29, QED 0.61
Compound (SMILES): Cc1nnc(CCCN/C(N)=N/C(=O)NCc2ccccc2)s1.O=C(O)C(F)(F)F
InChIKey: BJZJRMFZFBZAIL-UHFFFAOYSA-N
Target: Histamine H2 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P25021
Assay: Displacement of [3H]UR-DE257 from human histamine H2 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing RG-Salpha S incubated for 60 mins by scintillation counting analysis
Measurement: Ki = 5623.41 nM (pChEMBL 5.25)
Descriptors: MW 332.43, ALogP 1.59, HBA 4, HBD 3, PSA 105.29, QED 0.42
Compound (SMILES): CCCCN(CCCC)c1ccc2cc(/C=C/c3cc[n+](C)c4ccccc34)ccc2c1.[I-]
InChIKey: DRLMXPLSCQLHRQ-UHFFFAOYSA-M
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Binding affinity to amyloid beta (1 to 40) (unknown origin) oligomer
Measurement: Kd = 20100 nM (pChEMBL 4.699999809265137)
Descriptors: MW 423.62, ALogP 7.39, HBA 1, HBD 0, PSA 7.12, QED 0.25
Compound (SMILES): O=C(O)c1ccc2noc(-c3ccc(N4CCCCC4)cc3)c2c1
InChIKey: VFEMRZGFUMBNCU-UHFFFAOYSA-N
Target: Inositol hexakisphosphate kinase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96PC2
Assay: Inhibition of N-terminal 6His-sumo-tagged recombinant human IP6K3 expressed in Escherichia coli assessed as inorganic phosphate release using InsP6 as substrate in presence of ATP measured after 60 to 120 mins by malachite green based colorimetric - DIPP1 coupled enzyme assay
Measurement: IC50 = 1790 nM (pChEMBL 5.75)
Descriptors: MW 322.36, ALogP 4.18, HBA 4, HBD 1, PSA 66.57, QED 0.78