lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1ccc(Nc2ccc3[nH]nc(-c4ccncc4)c3c2)c(C#N)c1
InChIKey: OTKCOAYOWHQGDN-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of full length LRRK2 G2019S mutant (unknown origin) by LRRKtide Adapta assay
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 341.37, ALogP 4.25, HBA 5, HBD 2, PSA 86.62, QED 0.58
Compound (SMILES): N#Cc1ccc(Oc2ccc(C(N)=O)cc2)cc1
InChIKey: PQQFJYPJKKMNMX-UHFFFAOYSA-N
Target: Protein mono-ADP-ribosyltransferase PARP15 (SINGLE PROTEIN), Homo sapiens
UniProt: Q460N3
Assay: Inhibition of N-terminal his-tagged human PARP15 expressed in Escherichia coli Rosette2 (DE3)
Measurement: IC50 = 11000 nM (pChEMBL 4.960000038146973)
Descriptors: MW 238.25, ALogP 2.45, HBA 3, HBD 1, PSA 76.11, QED 0.89
Compound (SMILES): [2H]C([2H])([18F])Oc1nc(-c2ccc(OC)cc2)n(-c2ccc(OC)cc2)n1
InChIKey: GRGAGIRZLRLUOU-DZKQDAASSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Inhibition of human COX2
Measurement: IC50 = 840 nM (pChEMBL 6.079999923706055)
Descriptors: MW 329.33, ALogP 3.26, HBA 6, HBD 0, PSA 58.4, QED 0.69
Compound (SMILES): COCCCn1cc(CN(C(=O)[C@H]2CNCCO2)C2CC2)c2cccnc21
InChIKey: AYCFHBROWDHEFM-GOSISDBHSA-N
Target: Renin (SINGLE PROTEIN), Homo sapiens
UniProt: P00797
Assay: Displacement of 125I-labeled angiotensin I from from human plasma renin by gamma counter based competitive radioimmunoassay
Measurement: IC50 = 661 nM (pChEMBL 6.179999828338623)
Descriptors: MW 372.47, ALogP 1.55, HBA 6, HBD 1, PSA 68.62, QED 0.71
Compound (SMILES): CCNC(=O)[C@H]1O[C@@H](n2cnc3c(N[C@@H]4CCC[C@H]4OCc4cccc(Cl)c4)ncnc32)[C@H](O)[C@@H]1O
InChIKey: OWYCVIZROVDXGH-FUWISXPPSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30542
Assay: Inhibition of CA200645 binding to NanoLuc-fused human adenosine A1 receptor expressed in HEK293 cells measured for 10 mins by NanoBRET competition binding assay
Measurement: Ki = 323.59 nM (pChEMBL 6.489999771118164)
Descriptors: MW 516.99, ALogP 1.78, HBA 10, HBD 4, PSA 143.65, QED 0.35
Compound (SMILES): O=C(Nc1ccc2[nH]ncc2c1)[C@]12ON=C(c3cccnc3)[C@H]1[C@@H]1CC[C@H]2C1
InChIKey: RGHYMBULABJHQT-OKNMBPCOSA-N
Target: Aromatase (SINGLE PROTEIN), Homo sapiens
UniProt: P11511
Assay: Inhibition of human placental microsome CYP19 using [1beta-3H]-androstenedione as substrate
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 373.42, ALogP 3.12, HBA 5, HBD 2, PSA 92.26, QED 0.74
Compound (SMILES): O=C(O)COc1ccc(OCc2cccc(-c3ccc4ncoc4c3)c2)cc1F
InChIKey: IOPLKIJUQZDDKU-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor delta (SINGLE PROTEIN), Homo sapiens
UniProt: Q03181
Assay: Agonist activity at pBIND tagged human PPARdelta expressed in human HepG2 cells incubated for 18 hrs by dual luciferase reporter assay
Measurement: EC50 = 3240 nM (pChEMBL 5.489999771118164)
Descriptors: MW 393.37, ALogP 4.68, HBA 5, HBD 1, PSA 81.79, QED 0.49
Compound (SMILES): Cc1cc(-n2ccc(NC(=O)C3(c4ccccc4F)CC3)n2)ccn1
InChIKey: QFTVKKBLQZTIHL-UHFFFAOYSA-N
Target: Very long chain fatty acid elongase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BW60
Assay: Inhibition of ELOVL1 in human HEK2936E cells assessed as reduction of C26:0 LPC synthesis incubated for 48 hrs by cellular assay
Measurement: IC50 = 1600 nM (pChEMBL 5.800000190734863)
Descriptors: MW 336.37, ALogP 3.39, HBA 4, HBD 1, PSA 59.81, QED 0.79
Compound (SMILES): COc1ccc(C2CC(c3ccc(F)cc3)=NN2c2ccc(S(N)(=O)=O)cc2)c(OC)c1OC
InChIKey: WFSMZAYYRDXLQK-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Binding affinity to human recombinant CA1 assessed as inhibition constant incubated for 15 mins prior to testing by phenol red based stopped-flow CO2 hydration assay
Measurement: Ki > 230 nM (pChEMBL 6.638000011444092)
Descriptors: MW 485.54, ALogP 3.85, HBA 7, HBD 1, PSA 103.45, QED 0.55
Compound (SMILES): O=C(CN(Cc1ccc(C(=O)NO)cc1F)C(=O)c1ccccc1F)NC1CCCCC1
InChIKey: JQJAILQGBYOWRZ-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombinant human N-terminal GST-tagged HDAC6 (1 to 1215 residues) expressed in Sf9 insect cells using Z-Lys(Ac)-AMC as fluorogenic substrate incubated for 90 mins by microplate reader analysis
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 445.47, ALogP 3.18, HBA 4, HBD 3, PSA 98.74, QED 0.45
Compound (SMILES): Cc1cc(C)n2c1C=C1C=CC(CCC(=O)NCCCC[C@H](NC(=O)CCNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)CCN3CCC(Oc4ccccc4Cc4ccccc4)CC3)C(C)C)C(N)=O)=[N+]1[B-]2(F)F
InChIKey: CXUZGQJWBLLFNP-QRVRCHAVSA-N
Target: Histamine H1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35367
Assay: Binding affinity to NLuc-tagged human H1R expressed in HEK293T cells using NanoGlo as substrate preincubated for 2 hrs followed by substrate addition measured after 5 min by NanoBRET saturation binding assay
Measurement: Kd = 1288 nM (pChEMBL 5.889999866485596)
Descriptors: MW 1112.1
Compound (SMILES): N/C(=N\C(=O)NCc1ccccc1)NCC1CCc2nc(N)sc2C1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: IJIIQRCZDVTAPE-UHFFFAOYSA-N
Target: Histamine H1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35367
Assay: Displacement of [3H] mepyramine from human histamine H1 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing RGS4 incubated for 60 mins by scintillation counting analysis
Measurement: Kd = 4.5 nM (pChEMBL 8.350000381469727)
Descriptors: MW 358.47, ALogP 1.64, HBA 4, HBD 4, PSA 118.42, QED 0.49
Compound (SMILES): O=C1Nc2ccc(C(=O)O)cc2/C1=C1/Nc2ccccc2/C1=N\O
InChIKey: CBUBUEVQMMYUGL-WAVHTBQISA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin)
Measurement: IC50 = 7.89 nM (pChEMBL 8.100000381469727)
Descriptors: MW 321.29, ALogP 2.35, HBA 5, HBD 4, PSA 111.02, QED 0.37
Compound (SMILES): O=C(Nc1nc2cccc(C3=CCC(NC(=O)C4CC4(F)F)CC3)n2n1)C1CC1
InChIKey: QRQOYUNGZSQNMP-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of recombinant human JAK2 using KTFCGTPEYLAPEVRREPRILSEEEQEMFRDFDYIADWC as substrate incubated for 40 mins in presence of Mg/ATP mixture by [gamma p33]-ATP based scintillation counting method
Measurement: IC50 = 239 nM (pChEMBL 6.619999885559082)
Descriptors: MW 401.42, ALogP 2.79, HBA 5, HBD 2, PSA 88.39, QED 0.81
Compound (SMILES): CC(=O)N[C@H]1CC[C@@H](COc2ccc(-c3ccn[nH]3)nc2)CC1
InChIKey: UCOQDYPCTGWSRE-OKILXGFUSA-N
Target: Cytochrome P450 4F2 (SINGLE PROTEIN), Homo sapiens
UniProt: P78329
Assay: Inhibition of human recombinant CYP4F2 using Luciferin-4F2/3 as substrate incubated for 60 mins in presence of NADPH regenerating system by luminescence based assay
Measurement: IC50 = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 314.39, ALogP 2.55, HBA 4, HBD 2, PSA 79.9, QED 0.89
Compound (SMILES): CCc1nc2c(C(=O)N3CCN(c4cccc(C(F)(F)F)c4)CC3)cnn2c(CC)c1Cc1ccccc1
InChIKey: LHSAVBFGYJXAJG-UHFFFAOYSA-N
Target: RuvB-like 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y230
Assay: Inhibition of full length recombinant His6 tagged human RUVBL2 expressed in Escherichia coli Rosetta cells incubated for 70 mins in presence of ATP by ATPase assay
Measurement: IC50 > 66000 nM (pChEMBL 4.179999828338623)
Descriptors: MW 521.59, ALogP 5.43, HBA 5, HBD 0, PSA 53.74, QED 0.34
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](C)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](C)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(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: FTIDHQMNNMLWHN-XHFWXOQVSA-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 reduction in cAMP accumulation incubated for 2 hrs under dark condition by LANCE cAMP assay
Measurement: EC50 = 0.1259 nM (pChEMBL 9.899999618530273)
Descriptors: MW 3235.66
Compound (SMILES): CC1(C)C(=O)N(c2ccc(C#N)c(C(F)(F)F)c2)C(=S)N1CCCC(=O)NCCOCCOC(=O)CC12CC3CC(CC(C3)C1)C2
InChIKey: NUYCVTGYOUGRSO-UHFFFAOYSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Inhibition of AR LBD in human LNCaP cells
Measurement: IC50 = 156 nM (pChEMBL 6.809999942779541)
Descriptors: MW 662.78, ALogP 5.35, HBA 7, HBD 1, PSA 111.97, QED 0.17
Compound (SMILES): Cc1nc2cnc3ccc(-c4cc(Cl)c(O)c(Cl)c4)cc3c2n1C1CCN(C)CC1
InChIKey: JEESDVDVWGRNFE-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of JAK2 (unknown origin) using Kinase/Tyr 6 peptide as substrate incubated for 1 hrs in presence of ATP by fluorescence microplate reader analysis
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 441.36, ALogP 5.84, HBA 5, HBD 1, PSA 54.18, QED 0.42
Compound (SMILES): CC(=O)N1CCN(c2cccc(NC(=O)c3cc4c(F)ccc(C)c4[nH]3)c2)CC1
InChIKey: KEAFLBCTBFKBID-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase SETD2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BYW2
Assay: Inhibition of SETD2 in human A549 cells assessed as reduction in H3K36me3 incubated for 3 days by in-cell western assay
Measurement: IC50 = 134 nM (pChEMBL 6.869999885559082)
Descriptors: MW 394.45, ALogP 3.54, HBA 3, HBD 2, PSA 68.44, QED 0.71
Compound (SMILES): CCS(=O)(=O)Nc1ccc(Oc2ccc(Cl)cc2)c(-c2cn(C)c(=O)c3ccccc23)c1
InChIKey: LMYMWXJBPLXESU-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of recombinant human BRD4-2 (333 to 460 residues) expressed in bacterial expression system by bromoscan assay
Measurement: Kd = 3.7 nM (pChEMBL 8.430000305175781)
Descriptors: MW 468.96, ALogP 5.41, HBA 5, HBD 1, PSA 77.4, QED 0.41
Compound (SMILES): O=C1NC(Nc2ccccc2)=N/C1=C\c1ccc2c(c1)OCCCO2
InChIKey: QUWLSDMWWFVXHR-PTNGSMBKSA-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 > 10000 nM (pChEMBL 5)
Descriptors: MW 335.36, ALogP 2.79, HBA 5, HBD 2, PSA 71.95, QED 0.83
Compound (SMILES): CCCCCCc1ccc(-c2cn(-c3ccc(CN4CC(C(=O)OC)C4)cc3)nn2)cc1
InChIKey: BYOYTJONKZBHGM-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21453
Assay: Agonist activity at S1P1 receptor (unknown origin) expressed in PathHunter HEK 293 EDG1 Total GPCR Internalization cells assessed as receptor internalization incubated for 90 mins by measuring chemiluminescence signal by microplate reader method
Measurement: EC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 432.57, ALogP 4.66, HBA 6, HBD 0, PSA 60.25, QED 0.34
Compound (SMILES): NCCCCCn1c(CCc2c[nH]c3ccccc23)nnc1Cc1ccc(Cl)c(Cl)c1
InChIKey: AOVCJEBUNBCBTI-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 = 3224 nM (pChEMBL 5.489999771118164)
Descriptors: MW 456.42, ALogP 5.57, HBA 4, HBD 2, PSA 72.52, QED 0.31
Compound (SMILES): Cl.Fc1ccc2[nH]c3c(c2c1)CCNC3c1ccccc1Br
InChIKey: XSQODDGDGBLMEQ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Agonist activity at human 5HT2A receptor stably expressed in Flp-In-T-REx-293 cells assessed as increase in Gq-mediated calcium flux by Fluo-4 direct dye based FLIPR Tetra assay
Measurement: EC50 = 97.72 nM (pChEMBL 7.010000228881836)
Descriptors: MW 345.21, ALogP 4.3, HBA 1, HBD 2, PSA 27.82, QED 0.68
Compound (SMILES): CC(O)CNC(=O)c1cn2c(nc3ccccc32)c(N)n1
InChIKey: RWJRZYAMVMHVLR-UHFFFAOYSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30542
Assay: Displacement of [3H]DPCPX from human A1AR expressed in HEK293 cells membrane assessed as inhibition constant preincubated for 5 mins followed by [3H]DPCPX addition and measured after 1.5 hrs by TopCount scintillation counting method
Measurement: Ki = 56.5 nM (pChEMBL 7.25)
Descriptors: MW 285.31, ALogP 0.58, HBA 6, HBD 3, PSA 105.54, QED 0.65
Compound (SMILES): C[C@@H]1CCCN1Cc1ccc(-c2cnc(N)c3c2CN(C2CCCCC2)C3=O)cc1F
InChIKey: QKGNJQNQCKFAFD-MRXNPFEDSA-N
Target: Activin receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q04771
Assay: Inhibition of ALK2 (unknown origin)
Measurement: IC50 = 60 nM (pChEMBL 7.21999979019165)
Descriptors: MW 422.55, ALogP 4.74, HBA 4, HBD 1, PSA 62.46, QED 0.77
Compound (SMILES): O=C1N(C2CCCCC2)CC[C@@]12C[C@H](O)CN2Cc1ccc(Cl)cc1
InChIKey: LJRACTJNWALOQM-AZUAARDMSA-N
Target: 11-beta-hydroxysteroid dehydrogenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28845
Assay: Inhibition of 11beta-HSD1 in human PBMC cells using 3H-cortisone as substrate assessed as conversion of cortisone to cortisol by ELISA
Measurement: IC50 > 37 nM (pChEMBL 7.432000160217285)
Descriptors: MW 362.9, ALogP 3.21, HBA 3, HBD 1, PSA 43.78, QED 0.9
Compound (SMILES): Cc1cc(-c2ccc3ncc4nc(C)n(C5CCN(C)CC5)c4c3c2)cc(C)c1O
InChIKey: DLJYWTGKRBKCHI-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of JAK3 (unknown origin) using Kinase/Tyr 6 peptide as substrate incubated for 1 hrs in presence of ATP by fluorescence microplate reader analysis
Measurement: IC50 > 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 400.53, ALogP 5.15, HBA 5, HBD 1, PSA 54.18, QED 0.51
Compound (SMILES): NS(=O)(=O)c1ccc(N/C=C/C(=O)c2cccs2)cc1
InChIKey: AHBBHQVRKSPPLX-BQYQJAHWSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Binding affinity to human CA2 assessed as inhibition constant by stopped-flow CO2 hydration assay
Measurement: Ki = 0.48 nM (pChEMBL 9.319999694824219)
Descriptors: MW 308.38, ALogP 2.2, HBA 5, HBD 2, PSA 89.26, QED 0.65
Compound (SMILES): CCCCCCCCCCn1cc[n+](CN2C(=O)c3ccccc3C2=O)c1C.[Br-]
InChIKey: WOCXRUDOFUTNQC-UHFFFAOYSA-M
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Binding affinity to human CA2 assessed as inhibition constant using 4-nitrophenylacetate as substrate by spectrophotometrical analysis
Measurement: Ki = 27.87 nM (pChEMBL 7.550000190734863)
Descriptors: MW 382.53, ALogP 4.48, HBA 3, HBD 0, PSA 46.19, QED 0.33
Compound (SMILES): CN1CCC(N(Cc2ccc(F)cn2)C(=O)NCc2ccc(OCCC(F)(F)F)cc2)CC1
InChIKey: YNRRVXRUYJKRDC-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Inverse agonist activity at 5-HT2A receptor (unknown origin) expressed in mouse NIH3T3 cells using o-nitrophenyl-D-galacto pyranoside incubated for 120 hrs
Measurement: IC50 = 2.23 nM (pChEMBL 8.649999618530273)
Descriptors: MW 468.5, ALogP 4.36, HBA 4, HBD 1, PSA 57.7, QED 0.59
Compound (SMILES): COc1cc2c(cc1Nc1ncc(Cl)c(Nc3ccccc3P(C)(C)=O)n1)CN(C)CCC2
InChIKey: DMJPEYLVIWZSKT-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92918
Assay: Enzymatic Activity Assay: The enzymatic activity of Wild Type HPK1 (MAP4K1) Kinase was measured in the presence or absence of an inhibitor compound of the present disclosure by preparation of a reaction mixture containing a fluorescein tagged peptide (2 micromolar final concentration), ATP (Adenosine Triphosphate, 500 micromolar final concentration) and Wild Type kinase (6 nM final concentration) in a buffer system comprising 50 mM HEPES (Buffer), 3 mM MgCl2, 5% w/v Trehalose, 0.01% Brij 35 (Detergent), 0.1% Pluronic F127 (Surfactant), 0.1 mM EDTA (Ethylenediaminetetraacetic acid), 0.1 mM EGTA (ethylene glycol-bis(β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid) and 1 mM DTT (Dithiothreitol) and at a pH of 7.4. The reactions were quenched by the addition of EDTA to a final concentration of 25 mM. A Caliper EZ reader was used to measure the extent of substrate to product conversion.The peptide substrate used in the HPK1 assay was designed based on the amino acid sequence surrounding serine residue 376 of SLP76-Lymphocyte cytosolic protein 2 (a known intracellular substrate of HPK1). This sequence SSFPQSAsLPPYFSQ was modified as follows for use in Caliper assays of HPK1: the serine residues on either side of serine 376 were replaced with alanine, three lysine residues were added at the N-terminus and a fluorescein tag (FAM) was attached to the C-terminus to produce the sequence, FAM-FPQAAsLPPYFAKKK.
Measurement: IC50 = 5050 nM (pChEMBL 5.300000190734863)
Descriptors: MW 485.96, ALogP 5.25, HBA 7, HBD 2, PSA 79.38, QED 0.46
Compound (SMILES): CC(NC(=O)/N=C(\N)NCCCc1nnc(N)s1)c1cccc(F)c1.Cl.Cl
InChIKey: ZPOWERYUAHMBNR-UHFFFAOYSA-N
Target: Histamine H1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35367
Assay: Displacement of [3H] mepyramine from human histamine H1 receptor stably expressed in baculovirus infected Sf9 cell membrane co-expressing RGS4 incubated for 60 mins by scintillation counting analysis
Measurement: Kd = 4.5 nM (pChEMBL 8.350000381469727)
Descriptors: MW 365.44, ALogP 1.57, HBA 5, HBD 4, PSA 131.31, QED 0.35
Compound (SMILES): N#Cc1ccc(C[C@@H](NC(=O)Nc2ccc(F)cc2)C(=O)N2CCc3ccc(F)cc3C2)cc1
InChIKey: WVCSWBQXDVRHDI-XMMPIXPASA-N
Target: N-formyl peptide receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25090
Assay: Agonist activity at human FPR2 transfected in human HL-60 cells assessed as increase in calcium mobilization measured every 5 seconds for 240 secs by Fluo-4-AM dye based fluorescence assay
Measurement: EC50 = 620 nM (pChEMBL 6.210000038146973)
Descriptors: MW 460.48, ALogP 4.15, HBA 3, HBD 2, PSA 85.23, QED 0.6
Compound (SMILES): Cc1nc(Cn2cc(CN(Cc3ccccc3)C(=O)c3ccc(S(=O)(=O)Nc4ccccc4)cc3)nn2)cs1
InChIKey: JMKNMMBASCLFQI-UHFFFAOYSA-N
Target: LIM domain kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P53671
Assay: Inhibition of recombinant full length LIMK2 (330 to 632 residues) (unknown origin) expressed in HEK293T cells incubated for 2 hrs in presence of tracer K10 by NanoBRET assay
Measurement: IC50 = 323 nM (pChEMBL 6.489999771118164)
Descriptors: MW 558.69, ALogP 4.73, HBA 8, HBD 1, PSA 110.08, QED 0.27
Compound (SMILES): Nc1ccc(COCCCCCCCCCCCCNC(=O)[C@@H]2CN(C(=O)c3ccc(C(=O)N4C[C@@H](C(=O)N[C@H]5C[C@@H]5c5ccccc5)[C@H](C(=O)N[C@H]5C[C@@H]5c5ccccc5)C4)cc3)C[C@H]2C(=O)N[C@H]2C[C@@H]2c2ccccc2)cc1
InChIKey: GVCZRSQQKGKIKB-LMQVKLHQSA-N
Target: Toll-like receptor 1/2 (PROTEIN COMPLEX), Mus musculus
UniProt: Q9EPQ1
Assay: Agonist activity at TLR1/TLR2 in wild type C57BL/6J mouse macrophages assessed as stimulation of TNF alpha release measured for 4 hrs by ELISA based assay
Measurement: EC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 1082.4
Compound (SMILES): Cc1nc2cnc3ccc(-c4ccc(O)c(C#N)c4)cc3c2n1C1CCN(C)CC1
InChIKey: FVOJSZQLURNUJS-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of JAK3 (unknown origin) using Kinase/Tyr 6 peptide as substrate incubated for 1 hrs in presence of ATP by fluorescence microplate reader analysis
Measurement: IC50 > 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 397.48, ALogP 4.4, HBA 6, HBD 1, PSA 77.97, QED 0.54
Compound (SMILES): C[C@@H]1CCCN1Cc1ccc(-c2cnc(N)c3c2CCN(C2CCC(C)(O)CC2)C3=O)cc1F
InChIKey: FLLLMFWYGCMDDN-YMEAHLQLSA-N
Target: Activin receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q04771
Assay: Inhibition of ALK2 (unknown origin)
Measurement: IC50 = 227 nM (pChEMBL 6.639999866485596)
Descriptors: MW 466.6, ALogP 4.15, HBA 5, HBD 2, PSA 82.69, QED 0.71
Compound (SMILES): CNCC[C@@](O)(c1cccc2ccccc12)[C@H](c1ccccc1)c1cc2cc(Br)ccc2nc1OC
InChIKey: GOBOQBZOZDRXCQ-BVRKHOPBSA-N
Target: Voltage-dependent L-type calcium channel subunit alpha-1C (SINGLE PROTEIN), Homo sapiens
UniProt: Q13936
Assay: Inhibition of human Cav1.2
Measurement: IC50 = 750 nM (pChEMBL 6.119999885559082)
Descriptors: MW 541.49, ALogP 6.79, HBA 4, HBD 2, PSA 54.38, QED 0.23
Compound (SMILES): COC(=O)C1CCN(C(=O)c2ccc(N(Cc3ccccc3)Cc3cnc4nc(N)nc(N)c4n3)cc2)CC1
InChIKey: FGQMPGXSJKTERW-UHFFFAOYSA-N
Target: Pteridine reductase 1 (SINGLE PROTEIN), Leishmania major
UniProt: Q01782
Assay: Inhibition of recombinant Leishmania major PTR1 expressed in Escherichia coli BL21 (DE3) cells using H2B as substrate in presence of cytochrome c and NADPH by envision multilabel reader
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 526.6, ALogP 2.82, HBA 10, HBD 2, PSA 153.45, QED 0.34
Compound (SMILES): Nc1nsc(-c2ccc(Cl)cc2)n1
InChIKey: XVSZVIZTUWVCFL-UHFFFAOYSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30542
Assay: Binding affinity to human wild type adenosine A1 receptor expressed in Expi293F cells assessed as dissociation constant by surface plasmon resonance assay
Measurement: Kd = 20700 nM (pChEMBL 4.679999828338623)
Descriptors: MW 211.68, ALogP 2.44, HBA 4, HBD 1, PSA 51.8, QED 0.79
Compound (SMILES): O=C(O)c1ccc2noc(-c3cccc(-c4ccccc4)c3)c2c1
InChIKey: OKXLSSAJRWYJHQ-UHFFFAOYSA-N
Target: Inositol hexakisphosphate kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHH9
Assay: Inhibition of N-terminal 6His-tagged/TEV cleavage site fused recombinant human IP6K2 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 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 315.33, ALogP 4.86, HBA 3, HBD 1, PSA 63.33, QED 0.59
Compound (SMILES): CC(C)c1nnc(N2CC[C@H]2C)c2cnc(Nc3ccnc(N4CC[C@@H](O)[C@@](C)(F)C4)n3)cc12
InChIKey: IPDHOLSNSRKAHB-RGNVDHMSSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of N-terminal GST tagged recombinant wild type human EGFR expressed in baculovirus infected Sf9 insect cells expression system using 5-FAM-EEPLYINSFPAKKK-CONH peptide as substrate preincubated for 10 mins followed by peptide substrate addition in presence of ATP
Measurement: IC50 = 8171 nM (pChEMBL 5.090000152587891)
Descriptors: MW 466.57, ALogP 3.58, HBA 9, HBD 2, PSA 103.19, QED 0.58
Compound (SMILES): CCN(CC)Cc1ccccc1CNC(=O)c1cccc(NC(=O)c2ccc(F)cc2)c1C
InChIKey: FRTOVWOCMZRMLU-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human BChE using acetylthiocholine iodide or butyrylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition by Ellman's method
Measurement: IC50 = 0.26 nM (pChEMBL 9.59000015258789)
Descriptors: MW 447.55, ALogP 5.16, HBA 3, HBD 2, PSA 61.44, QED 0.48
Compound (SMILES): COc1ccc(-c2cccc(C(=O)N(C)C)c2)cc1S(=O)(=O)Nc1ccc2c(c1)C(N(C)C(=O)C1CCCCC1)CCC2
InChIKey: KLABFLKPWCVSRA-UHFFFAOYSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Agonist activity at OX2R (unknown origin)
Measurement: EC50 = 837 nM (pChEMBL 6.079999923706055)
Descriptors: MW 603.78, ALogP 6.28, HBA 5, HBD 1, PSA 96.02, QED 0.33
Compound (SMILES): O=C[C@@H](C[C@@H]1CCNC1=O)NC(=O)[C@@H](CC1CCCCC1)NC(=O)c1cc2ccccc2[nH]1
InChIKey: HPKJGHVHQWJOOT-QKNQBKEWSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of SARS-CoV-2 MPro
Measurement: IC50 = 52.97 nM (pChEMBL 7.28000020980835)
Descriptors: MW 452.56, ALogP 2.45, HBA 4, HBD 4, PSA 120.16, QED 0.44
Compound (SMILES): Cc1ccc([SeH])cc1
InChIKey: GUPVJXUFKMXARC-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Binding affinity to human CA2 assessed as inhibition constant by stopped-flow CO2 hydration assay
Measurement: Ki = 490 nM (pChEMBL 6.309999942779541)
Descriptors: MW 171.1
Compound (SMILES): CNC(=O)c1cc(-c2cnc3cc(-c4cnn(C)c4)c(O[C@H]4CCOC4)nn23)c(F)c(C(F)F)c1
InChIKey: VSDZEHDPNRWKLG-AWEZNQCLSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of recombinant human FGFR3 V555L mutant 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 = 2.6 nM (pChEMBL 8.59000015258789)
Descriptors: MW 486.45, ALogP 3.4, HBA 8, HBD 1, PSA 95.57, QED 0.45
Compound (SMILES): N#Cc1ccc2[nH]cc(CCCCN3CCC(c4cn(-c5ccc(Oc6ccc(Cl)cc6)cc5)c(C5CC5)n4)CC3)c2c1
InChIKey: XKAOVNDHKGECNM-UHFFFAOYSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P31645
Assay: Inhibition of SERT (unknown origin) expressed in human HEK293 cells
Measurement: IC50 = 6.42 nM (pChEMBL 8.1899995803833)
Descriptors: MW 590.17, ALogP 8.75, HBA 5, HBD 1, PSA 69.87, QED 0.17
Compound (SMILES): O=C(O)/C=C/c1ccc2noc(-c3ccc(Oc4ccccc4)cc3)c2c1
InChIKey: YVDZTXLMWMCOOA-NTUHNPAUSA-N
Target: Inositol hexakisphosphate kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHH9
Assay: Inhibition of N-terminal 6His-tagged/TEV cleavage site fused recombinant human IP6K2 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 = 94 nM (pChEMBL 7.03000020980835)
Descriptors: MW 357.37, ALogP 5.38, HBA 4, HBD 1, PSA 72.56, QED 0.49
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](CCSSCCN)C(=O)O
InChIKey: VNHDPTUIKMSTOI-AODXPARNSA-N
Target: Neurotensin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O95665
Assay: Displacement of [3H]NT(8-13) from human NTSR2 expressed in HEK293 cell membranes by radioligand displacement assay
Measurement: Ki = 5.2 nM (pChEMBL 8.279999732971191)
Descriptors: MW 1009.31
Compound (SMILES): COC(=O)[C@@H]1CCCN1C(=O)[C@@H](Cc1ccc(OC(C)(C)C)cc1)N(C)C(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)C[C@H](O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCC(N)=O)N(C)C(=O)[C@@H](NC(=O)OCc1ccccc1)C(C)C
InChIKey: CZXLJTCMHQXVJW-UTMJBIBJSA-N
Target: Cathepsin E (SINGLE PROTEIN), Homo sapiens
UniProt: P14091
Assay: Inhibition of Cathepsin E (unknown origin) using Mca-Gly-Lys-Pro-Ile-Leu-Phe-Phe-Arg-Leu-Lys-(Dnp)-D-Arg-NH2 as substrate incubated for 120 mins by fluorescence assay
Measurement: IC50 = 105 nM (pChEMBL 6.980000019073486)
Descriptors: MW 1113.36
Compound (SMILES): CCCCC(=O)N1CCc2cc(C3CC3NCC3CCNCC3)ccc21
InChIKey: VJJYZGMQBJHIFM-UHFFFAOYSA-N
Target: Lysine-specific histone demethylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NB78
Assay: Inhibition of recombinant human full length LSD2 using biotinylated H3K4Me2 peptide as substrate by TR-FRET assay
Measurement: IC50 = 2550 nM (pChEMBL 5.590000152587891)
Descriptors: MW 355.53, ALogP 3.21, HBA 3, HBD 2, PSA 44.37, QED 0.79
Compound (SMILES): O=C1/C(=C/c2ccccn2)CCc2cc(O)ccc21
InChIKey: GHZCZSPTTZWOSS-FMIVXFBMSA-N
Target: Macrophage migration inhibitory factor (SINGLE PROTEIN), Homo sapiens
UniProt: P14174
Assay: Inhibition of human recombinant MIF enolase activity using phenylpyruvate as substrate
Measurement: IC50 = 65900 nM (pChEMBL 4.179999828338623)
Descriptors: MW 251.28, ALogP 3, HBA 3, HBD 1, PSA 50.19, QED 0.79
Compound (SMILES): COc1cc(OC)c(Cl)c(Nc2ncccc2-c2ncnc(N)n2)c1Cl
InChIKey: QCGVVQQTVSMBOE-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of FGFR2 N549H mutant (unknown origin) by radiometric kinase activity assay
Measurement: IC50 = 31.4 nM (pChEMBL 7.5)
Descriptors: MW 393.23, ALogP 3.58, HBA 8, HBD 2, PSA 108.07, QED 0.68
Compound (SMILES): COC(=O)Nc1cc(-c2cnc(OC[C@@](C)(N)CC(C)C)c(C#N)c2)ccn1
InChIKey: HDBIRBUHIXXLDF-FQEVSTJZSA-N
Target: AP2-associated protein kinase 1 (SINGLE PROTEIN), Mus musculus
UniProt: Q3UHJ0
Assay: Displacement of 3H-LP-927443 from AAK1 in C57BL6 mouse brain homogenate assessed as inhibition constant incubated for 1 hr by liquid scintillation counter analysis
Measurement: Ki = 0.15 nM (pChEMBL 9.819999694824219)
Descriptors: MW 383.45, ALogP 3.34, HBA 7, HBD 2, PSA 123.15, QED 0.75
Compound (SMILES): Cc1cc(Nc2nc(NCc3ccc(F)cc3F)nc3c2cnn3C2CCOCC2)n[nH]1
InChIKey: JWPYZYBMSBDDCD-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase PAK 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O96013
Assay: Inhibition of PAK4 (unknown origin) incubated for 60 mins by time-resolved HTRF assay
Measurement: IC50 = 1750.1 nM (pChEMBL 5.760000228881836)
Descriptors: MW 440.46, ALogP 3.84, HBA 8, HBD 3, PSA 105.57, QED 0.42
Compound (SMILES): COc1cc(Nc2nc(CNCc3ccccc3)cc3c(-c4ccccc4)n[nH]c23)cc(OC)c1OC
InChIKey: JKSSZSSHEYBEPE-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Binding affinity to wild type A3R (unknown origin) expressed in Flp-In-CHO cells assessed as dissociation constant by by Schild analysis
Measurement: Kd = 158.49 nM (pChEMBL 6.800000190734863)
Descriptors: MW 495.58, ALogP 5.68, HBA 7, HBD 3, PSA 93.32, QED 0.23
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(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)NC(=O)[C@H](C)NC1=O
InChIKey: GFOVXAUJTBRTIG-UTUCMRGLSA-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 2 hrs by AlphaScreen-based LDH membrane integrity assay
Measurement: IC50 = 3800 nM (pChEMBL 5.420000076293945)
Descriptors: MW 2143.58
Compound (SMILES): C=CC(=O)Nc1cc(Nc2ncc(Cl)c(O[C@@H]3CO[C@H]4[C@@H]3OC[C@H]4O)n2)ccc1N1CCC(N(C)C)CC1
InChIKey: SPCVIFVPSGHXET-LUGTWXOSSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of GST tagged recombinant human JAK2 expressed in baculovirus infection system by FRET assay
Measurement: IC50 = 437 nM (pChEMBL 6.360000133514404)
Descriptors: MW 545.04, ALogP 2.43, HBA 10, HBD 3, PSA 121.31, QED 0.43
Compound (SMILES): c1ccc(-c2ccc(NC[C@@H]3CC34CCN(CC3CCOCC3)CC4)nn2)cc1
InChIKey: LCTKPIIYTLCURX-NRFANRHFSA-N
Target: Muscarinic acetylcholine receptor M4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08173
Assay: Inhibition of human muscarinic acetylcholine M4 receptor expressed in CHO cells co-expressing Gqi5 in the presence of acetylcholine at EC80 concentration by calcium mobilization assay
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 392.55, ALogP 4.08, HBA 5, HBD 1, PSA 50.28, QED 0.8
Compound (SMILES): Cc1ncsc1-c1ccc(CNC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCCNC(=O)c2ccc(-c3ccc(N4CCN(C)CC4)c(NC(=O)c4c[nH]c(=O)cc4C(F)(F)F)c3)cc2)C(C)(C)C)cc1
InChIKey: KFCLTULBYCCZBG-LTJJNQLXSA-N
Target: WD repeat-containing protein 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P61964
Assay: Displacement of N-(4'-((17-(5,5-difluoro-7-(1H-pyrrol-2-yl)-5H-5l4,6l4-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazaborinin-3-yl)-15-oxo-4,7,10-trioxa-14-azaheptadecyl)carbamoyl)-4-(4-methylpiperazin-1-yl)-[1,1'-biphenyl]-3-yl)-6-hydroxy-4-(trifluoromethyl)nicotinamide tracer from N-/C-terminal NanoLuc-fused full-length WDR5 (unknown origin) transfected in HEK293T cells incubated for 2 hrs by NanoBRET assay
Measurement: IC50 >= 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 998.14, ALogP 5.82, HBA 11, HBD 6, PSA 209.17, QED 0.07
Compound (SMILES): CCN(CC)Cc1ccccc1CNC(=O)c1cccc(NC(=O)c2cccs2)c1
InChIKey: KGYMZHTZFBOJSY-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human BChE using acetylthiocholine iodide or butyrylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition by Ellman's method
Measurement: IC50 = 0.35 nM (pChEMBL 9.460000038146973)
Descriptors: MW 421.57, ALogP 4.77, HBA 4, HBD 2, PSA 61.44, QED 0.52
Compound (SMILES): Cc1c(C#N)cccc1[C@@H](C)Nc1nnc(C)c2cc(C(F)(F)F)c(N3CCOCC3)cc12
InChIKey: KUBGCTZZRWSNPA-OAHLLOKOSA-N
Target: Son of sevenless homolog 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07889
Assay: Inhibiting SOS1-Mediated GTP Nucleotide Exchange by Blocking Mant-GDP Exchange: Table 24: This Example illustrates that exemplary compounds of the present invention prevent KRas-mediated GTP nucleotide exchange mediated by SOS1 to inhibit KRas activity thereby inhibiting the generation of the downstream effector pERK. MKN1 cells (15,000/w) or H358 (30,000/w) were seeded in a black clear flat bottom 96-well cell culture plate (Corning, #3904) and incubated at 37° C. overnight. Assay day 1, cells were dosed with compounds of Formula (I) with a 10 μm starting concentration and serially diluted 3× for a total of 9 concentrations. The cells were incubated for approximately 0.5-1 hour with the compounds solubilized in DMSO at 37° C. Cells were immediately fixed by adding 50 μL of 4% formaldehyde to all wells in a fume hood and the plates were incubated for 20 minutes at room temperature. The formaldehyde was discarded from the plates and 150 μL of ice-cold methanol was added to permeabilize the cells for 10 minutes at −20° C. The methanol was discarded from each of the plates and any liquid remaining in the plate by tapping the plate against paper towels. Cells were then blocked with 150 μL of Odyssey blocking buffer (LI-COR Biosciences #927-50010) using 0.05% Tween for 1 hour at room temperature on a shaker. The blocking buffer was discarded and 50 μL of primary antibodies pERK (cell signaling Technology #9101L; Rabbit, 1:500) and GapDH (Millipore #MAB34; Mouse, 1:5000) diluted in Odyssey blocking buffer was added. The plates were incubated overnight at 4° C. on a shaker. On Assay Day 2, the primary antibody solution was removed. Each plate was washed 3× times with 150 μL of 1×PBST (PBS+0.1% Tween 20) and incubated with 50 μL of secondary antibodies: Anti-Rabbit (LI-COR Biosciences #926-32211) and Anti-Mouse (LI-COR Biosciences #68070) at 1:800 dilution in Odyssey blocking buffer with Tween at room temperature on a shaker for 2 hours (protected from light). The secondary antibody solution as removed and each plate was washed with PBST 3× times. Any liquid remaining was discarded and the plate was imaged using the Licor Odyssey machine according to the manufacturer's instruction, using a set focus length at 3 mm and both 800 nm and 700 nm filters. The GAPDH normalized scan values for each well were divided by the average of vehicle wells to get the % of pERK inhibition. The IC50 values were then calculated with the Graph pad Prism software.
Measurement: IC50 = 779 nM (pChEMBL 6.110000133514404)
Descriptors: MW 455.48, ALogP 5.15, HBA 6, HBD 1, PSA 74.07, QED 0.59
Compound (SMILES): N#Cc1ccc(Oc2ccc3[nH]nc(-c4ccncc4)c3c2)c(C#N)c1
InChIKey: NPUPJCWNSCWJMH-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of full length LRRK2 G2019S mutant (unknown origin) by LRRKtide Adapta assay
Measurement: IC50 = 48 nM (pChEMBL 7.320000171661377)
Descriptors: MW 337.34, ALogP 4.16, HBA 5, HBD 1, PSA 98.38, QED 0.6
Compound (SMILES): N[C@@H]1C[C@@H]1c1cc(F)ccc1F
InChIKey: GKCSCAZEVIMQGV-VXNVDRBHSA-N
Target: Lysine-specific histone demethylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NB78
Assay: Inhibition of LSD2 (unknown origin) (26 to 822 residues) expressed in baculovirus-infected Sf9 insect cells using K4-dimethylated H3 as substrate by peroxidase-coupled method
Measurement: Ki = 53000 nM (pChEMBL 4.28000020980835)
Descriptors: MW 169.17, ALogP 1.78, HBA 1, HBD 1, PSA 26.02, QED 0.68
Compound (SMILES): COc1cc(C2CC(c3ccc(F)cc3)=NN2c2ccc(S(N)(=O)=O)cc2)cc(OC)c1OC
InChIKey: KEILXRPGGJRYAC-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Binding affinity to human recombinant CA9 assessed as inhibition constant incubated for 15 mins prior to testing by phenol red based stopped-flow CO2 hydration assay
Measurement: Ki > 44 nM (pChEMBL 7.35699987411499)
Descriptors: MW 485.54, ALogP 3.85, HBA 7, HBD 1, PSA 103.45, QED 0.55
Compound (SMILES): Fc1ccc(Nc2nc(Nc3ccc(-c4ccsc4)cn3)ncc2Cl)cc1
InChIKey: OEDKOGQVVSSEPE-UHFFFAOYSA-N
Target: Dipeptidyl peptidase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53634
Assay: Inhibition of Cathepsin C in human THP-1 cells using H-Gly-Phe-AFC as substrate pretreated for 1 hr followed by substrate addition and incubated for 60 mins by microplate reader assay
Measurement: IC50 = 104.8 nM (pChEMBL 6.980000019073486)
Descriptors: MW 397.87, ALogP 5.88, HBA 6, HBD 2, PSA 62.73, QED 0.44
Compound (SMILES): COc1cc(C2CC(c3ccccc3)=NN2c2ccc(S(N)(=O)=O)cc2)cc(OC)c1OC
InChIKey: YOMLXNSGACNELZ-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Binding affinity to human recombinant CA1 assessed as inhibition constant incubated for 15 mins prior to testing by phenol red based stopped-flow CO2 hydration assay
Measurement: Ki > 230 nM (pChEMBL 6.638000011444092)
Descriptors: MW 467.55, ALogP 3.72, HBA 7, HBD 1, PSA 103.45, QED 0.57
Compound (SMILES): CCc1cc2ncc(CN3CC4(CCN(c5ccc(C(=O)NC)nc5)CC4)C3)cc2[nH]c1=O
InChIKey: RFJVUEIXGZRLJU-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Inhibition of PARP-1 (unknown origin) binding to DNA assessed as DNA trapping activity
Measurement: IC50 = 158.1 nM (pChEMBL 6.800000190734863)
Descriptors: MW 446.56, ALogP 2.34, HBA 6, HBD 2, PSA 94.22, QED 0.62
Compound (SMILES): COc1cccc(C(=O)Cc2ncc(C(=O)N(C)CCCOc3ccc([N+](=O)[O-])cc3)cn2)c1
InChIKey: RHNUQUBOFJPVQT-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of BuChE (unknown origin) using butyrylthiocholine iodide as substrate by DTNB reagent based Ellman's method
Measurement: IC50 = 2590 nM (pChEMBL 5.590000152587891)
Descriptors: MW 464.48, ALogP 3.36, HBA 8, HBD 0, PSA 124.76, QED 0.18
Compound (SMILES): NC(=O)c1ccc(OCc2cncs2)cc1
InChIKey: QVXUTHMJYRUHJT-UHFFFAOYSA-N
Target: Protein mono-ADP-ribosyltransferase PARP15 (SINGLE PROTEIN), Homo sapiens
UniProt: Q460N3
Assay: Inhibition of human N-terminal 6His-tagged PARP15 (460 to 656 residues) expressed in Escherichia coli Rosetta2 (DE3) cells using NAD+ as substrate incubated for 10 mins by fluorescence based analysis
Measurement: IC50 = 2400 nM (pChEMBL 5.619999885559082)
Descriptors: MW 234.28, ALogP 1.82, HBA 4, HBD 1, PSA 65.21, QED 0.88
Compound (SMILES): Cc1c(Br)cn(CCCc2cn(CCCn3c(C)c(Br)cc(C(=O)NC4CCCCCC4)c3=O)nn2)c(=O)c1NC(=O)C1CCCCCC1
InChIKey: IVYCEOKSLCHODE-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Agonist activity at human CB2 receptor expressed in CHO-K1 cells assessed as enhancement of beta arrestin-2 recruitment incubated for 90 mins by HitHunter chemiluminescence based assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 803.64, ALogP 6.83, HBA 9, HBD 2, PSA 132.91, QED 0.19
Compound (SMILES): CC(C)(C)CNC(=S)Nc1ccc2c(c1)CCN2Cc1ccc(-c2ccccc2)cc1
InChIKey: VCDMFLZHZJGGNT-UHFFFAOYSA-N
Target: Polyunsaturated fatty acid 5-lipoxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P09917
Assay: Inhibition of 5-LOX in human PMNL assessed as reduction in all-trans isomers of LTB4 and 5-HETE formation preincubated for 15 mins followed by A23187 addition and measured after 10 mins by RP-HPLC analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 429.63, ALogP 6.25, HBA 2, HBD 2, PSA 27.3, QED 0.47
Compound (SMILES): COc1cc2c(cc1OC)-c1c(OC)c(OCC3CC3)cc3c1[C@H](C2)N(C)CC3
InChIKey: UBTWSKFVLXHLNQ-SFHVURJKSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Displacement of [3H]LSD from 5-HT2B receptor (unknown origin) assessed as inhibition constant incubated for 90 mins by MicroBeta scintillation counting method
Measurement: Ki = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 395.5, ALogP 4.25, HBA 5, HBD 0, PSA 40.16, QED 0.73
Compound (SMILES): CCCCOC(=O)NS(=O)(=O)c1sc(CC(C)C)nc1-c1ccc(Cn2c(CC)nc3c(C)cc(C)nc32)cc1
InChIKey: ZQCJVWMIJVNZDT-UHFFFAOYSA-N
Target: Type-1 angiotensin II receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30556
Assay: Displacement of 125I-[Sar1,Ile8]ANGII form recombinant human full length AT1 receptor expressed in HEK293 cells incubated for 120 mins by scintillation counting method
Measurement: Ki = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 583.78, ALogP 6.2, HBA 9, HBD 1, PSA 116.07, QED 0.21
Compound (SMILES): Nc1nc(-c2ccco2)c2cnn(Cc3ccc(/C=C/C(=O)NO)cc3)c2n1
InChIKey: HADMBUXJGCALMH-BQYQJAHWSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of HDAC1 (unknown origin) using trypsin and LGK(Ac)-AMC as substrates incubated for 1 hr and measured by fluorescence assay
Measurement: IC50 = 7.1 nM (pChEMBL 8.149999618530273)
Descriptors: MW 376.38, ALogP 2.24, HBA 8, HBD 3, PSA 132.09, QED 0.28
Compound (SMILES): COc1cc2ncnc(N3CCC(CN4CCN(c5ccccn5)CC4)C3)c2cc1OC
InChIKey: FUABZNQUXURVFF-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Displacement of [3H]-5-CT from human 5-HT7 receptor expressed in CHO-K1 cells membrane by scintillation counter analysis
Measurement: Ki = 281.84 nM (pChEMBL 6.550000190734863)
Descriptors: MW 434.54, ALogP 2.69, HBA 8, HBD 0, PSA 66.85, QED 0.59
Compound (SMILES): CCCn1c(=O)[nH]c2nc(-c3cccc(OS(=O)(=O)F)c3)[nH]c2c1=O
InChIKey: FIBQKUPHJMQEDF-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Displacement of [3H]PSB-603 from human adenosine A2B receptor expressed in CHO cell membrane preincubated for 4 hrs followed by [3H]PSB-603 addition and measured after 0.5 hrs by radioligand displacement assay
Measurement: Ki = 70.79 nM (pChEMBL 7.150000095367432)
Descriptors: MW 368.35, ALogP 1.08, HBA 7, HBD 2, PSA 126.91, QED 0.65
Compound (SMILES): Nc1n[nH]c2cc(-c3cn([C@@H]4CN[C@H](C(=O)Nc5ccc(Cl)c(C(F)(F)F)c5)C4)nn3)ccc12
InChIKey: VPZGFKSLFAEGRG-SJCJKPOMSA-N
Target: Bcr/Abl fusion protein (CHIMERIC PROTEIN), Homo sapiens
UniProt: P11274
Assay: Inhibition of Bcr-Abl T315I mutant (unknown origin) incubated for 1 hr in presence of ATP by ADP-Glo kinase assay
Measurement: IC50 = 137.08 nM (pChEMBL 6.860000133514404)
Descriptors: MW 490.88, ALogP 3.62, HBA 7, HBD 4, PSA 126.54, QED 0.35
Compound (SMILES): CSCC[C@@H]1NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H]2CSSC[C@H](NC(=O)CN)C(=O)N[C@@H](CSSC[C@@H](C(=O)O)NC(=O)[C@H](Cc3ccc(O)cc3)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H]3CCCN3C(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC1=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N2
InChIKey: DDMGJRKYXSZHDJ-HVKKXNSXSA-N
Target: Acetylcholine-binding protein (SINGLE PROTEIN), Lymnaea stagnalis
UniProt: P58154
Assay: Displacement of [3H]-epibatidine from Lymnaea stagnalis Acetylcholine-binding protein measured after 1 hr by liquid scintillation counter
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 1787.98
Compound (SMILES): COc1cc(OC)c(Cl)c(Nc2ncccc2-c2ncnc(Nc3ccc(N4CCN(C(C)=O)CC4)cc3)n2)c1Cl
InChIKey: UYQMDAULJCUIOV-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of FGFR2 V564F mutant (unknown origin) by radiometric kinase activity assay
Measurement: IC50 = 3011 nM (pChEMBL 5.519999980926514)
Descriptors: MW 595.49, ALogP 5.41, HBA 10, HBD 2, PSA 117.63, QED 0.27
Compound (SMILES): CCCCOc1nc(N)c2nc(O)n(Cc3ccc(C(=O)NCCOCCNC(=O)CC[C@@H](NC(=O)[C@@H](NC(=O)CNC(=O)/C=C/c4ccc(O)c(OC)c4)C(C)C)C(=O)OCC)cc3)c2n1
InChIKey: YREZZSNAITUJPZ-UQIXBXJYSA-N
Target: Toll-like receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYK1
Assay: Agonist activity at TLR7 in HEK-Blue hTLR7 cells assessed as increase in NFkappaB activation incubated for 18 hrs by SEAP-based spectrophotometry analysis
Measurement: EC50 = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 933.03, ALogP 1.72, HBA 17, HBD 8, PSA 309.57, QED 0.02
Compound (SMILES): COc1cccc2ccc(C(=O)Nc3ccc(S(N)(=O)=O)cc3)nc12
InChIKey: NDNZEVXFMRNEPY-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human recombinant carbonic anhydrase 2 assessed as inhibition constant incubated for 10 mins by phenol red dye based stopped-flow CO2 hydration assay
Measurement: Ki = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 357.39, ALogP 2.14, HBA 5, HBD 2, PSA 111.38, QED 0.74
Compound (SMILES): N.N.Nc1nc2c(ncn2[C@@H]2O[C@@H]3CO[P@@](=O)(S)O[C@H]4[C@@H](F)[C@H](n5cnc6c(N)ncnc65)O[C@@H]4CO[P@@](=O)(S)O[C@@H]2[C@@H]3O)c(=O)[nH]1
InChIKey: PNKHHZCOQKVFMT-RLOXAXCNSA-N
Target: Stimulator of interferon genes protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q86WV6
Assay: Displacement of radiolabeled [3H]-2',3'-cGAMP from wild type human STING incubated for 2 hrs by scintillation counting method
Measurement: IC50 = 3.1 nM (pChEMBL 8.510000228881836)
Descriptors: MW 708.54, ALogP 0.51, HBA 19, HBD 6, PSA 268.96, QED 0.12
Compound (SMILES): CC(C)C[C@@H]1NC(=O)[C@H](CCC(N)=O)NC(=O)[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)CSSC[C@@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](Cc2ccccc2)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N2CCC[C@H]2C(=O)N2CCC[C@H]2C(=O)O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc2ccccc2)NC(=O)CNC(=O)[C@@H]2CCCN2C(=O)[C@@H]2CCCN2C(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC1=O
InChIKey: OFPOZEFXTIZAHE-YZXGFTLRSA-N
Target: Melanocortin receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P41968
Assay: Displacement of [125I]-NDP-alpha-MSH from human MC3R expressed in HEK293 cells by Topcount beta counter analysis
Measurement: Ki = 275.42 nM (pChEMBL 6.559999942779541)
Descriptors: MW 2991.64
Compound (SMILES): CCN(CC)Cc1ccc(C=C2Cc3cc(OC)ccc3C2=O)cc1
InChIKey: RCWXHDBGQZGVNI-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human recombinant MAO-B assessed as reduction in 4-hydroxyquinoline level using kynuramine as a substrate preincubated for 5 mins followed by substrate addition by spectrofluorimetric analysis
Measurement: IC50 = 1590 nM (pChEMBL 5.800000190734863)
Descriptors: MW 335.45, ALogP 4.36, HBA 3, HBD 0, PSA 29.54, QED 0.73
Compound (SMILES): Cc1ccc(S(N)(=O)=O)cc1-c1ccc(-c2c(-c3ccncc3)n[nH]c2C)cc1
InChIKey: PYFQJXSTRIPAOA-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of full-length LRRK2 G2019S mutant (unknown origin) using LRRKtide as substrate incubated for 1 hr in presence of ATP by TR-FRET based ADAPTA assay
Measurement: IC50 = 15.1 nM (pChEMBL 7.820000171661377)
Descriptors: MW 404.5, ALogP 4.07, HBA 4, HBD 2, PSA 101.73, QED 0.54
Compound (SMILES): Cc1nc2cnc3ccc(-c4cnc5[nH]ccc5c4)cc3c2n1-c1ccc(CC#N)cc1
InChIKey: OWRHUAQAKYKWGX-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of PI3Kalpha (unknown origin) using PIP2 as substrate incubated for 1 hr in presence of ATP by Kinase Glo luminescence assay
Measurement: IC50 = 139.1 nM (pChEMBL 6.860000133514404)
Descriptors: MW 414.47, ALogP 5.49, HBA 5, HBD 1, PSA 83.18, QED 0.41
Compound (SMILES): O=C(CNc1cccc(F)c1)Nc1ccc(-c2nc(-c3ccnc(Nc4ccc(OC(F)(F)F)cc4)c3)no2)cc1
InChIKey: FJDOLTIGLRJBOP-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BuChE using butyrylthiocholine iodide as substrate preincubated for 20 mins followed by substrate addition and measured after 5 mins by DTNB-reagent based Ellman's method
Measurement: IC50 = 5510 nM (pChEMBL 5.260000228881836)
Descriptors: MW 564.5, ALogP 6.63, HBA 8, HBD 3, PSA 114.2, QED 0.17