lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](Cc1ccc(I)cc1)C(=O)N1Cc2ccccc2C[C@H]1C(N)=O
InChIKey: GYPFKQQJLPOFKF-NFGXINMFSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Mus musculus
UniProt: P56450
Assay: Antagonist activity at mouse MC4R expressed in HEK293 cells assessed as inhibition of NDP-MSH induced-cAMP accumulation after 2 hrs by alpha screen assay
Measurement: Ki = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 803.71, ALogP -0.73, HBA 7, HBD 10, PSA 274.5, QED 0.04
Compound (SMILES): Oc1ccc(N2CCN(CCCCOc3ccn4nccc4c3)CC2)c2c1OCCO2
InChIKey: ASSMUHYHXZFLKM-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]spiperone from human D3R expressed in CHO cell membranes by radioligand binding assay
Measurement: Ki = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 424.5, ALogP 2.79, HBA 8, HBD 1, PSA 71.7, QED 0.58
Compound (SMILES): Cc1cc2cc(C)c1CCOC(=O)Nc1ccc(S(=O)(=O)C3CC3)c(c1)CN(C)C(=O)[C@@H]2Nc1ccc2cc[nH]c(=O)c2c1
InChIKey: YJTFTQFUZXRAGN-SSEXGKCCSA-N
Target: Coagulation factor X (SINGLE PROTEIN), Homo sapiens
UniProt: P00742
Assay: Inhibition of tissue factor/factor 7a activated human coagulation factor-10a using S2765 as substrate pretreated with substrate for 15 mins followed by enzyme and tissue factor/factor 7a addition measured for 60 mins
Measurement: Ki = 2800 nM (pChEMBL 5.550000190734863)
Descriptors: MW 614.72, ALogP 5, HBA 7, HBD 3, PSA 137.67, QED 0.29
Compound (SMILES): Cc1csc2cc([C@H](C)Nc3ncnc(N)c3C#N)c(-c3cccc(CN4CCC(CN(C)Cc5ccccn5)CC4)c3)c(=O)n12
InChIKey: YPPYEVMVSNICSZ-DEOSSOPVSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of recombinant human His6-tagged PI3Kgamma (144 to 1102 residues) using DiC8-PIP2 as substrate preincubated for 15 mins followed by substrate addition measured after 60 mins by ADP-Glo assay
Measurement: IC50 >= 199.53 nM (pChEMBL 6.699999809265137)
Descriptors: MW 633.83, ALogP 5.49, HBA 11, HBD 2, PSA 128.47, QED 0.21
Compound (SMILES): CSCC[C@H](NC(=O)[C@@H]1Cc2cn(nn2)C[C@H](NC(=O)[C@@H](N)CCCCN)C(=O)N[C@@H](Cc2cnc[nH]2)C(=O)N[C@H](Cc2ccccc2)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc2ccc3ccccc3c2)C(=O)N1)C(=O)O
InChIKey: BBLWQFDNXHGJOD-NFVVVWSGSA-N
Target: Melanocortin receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P32245
Assay: Agonist activity at EYFP-fused human MC4R expressed in HEK293 cells assessed as increase in cAMP accumulation after 30 mins by luminescent enzymatic complementation based assay
Measurement: EC50 = 89.3 nM (pChEMBL 7.050000190734863)
Descriptors: MW 1122.33
Compound (SMILES): CC(C)(C)OC(=O)n1c(C[C@@H]2N=C(c3ccccc3)c3ccccc3N(CCCCC(=O)NO)C2=O)cc2ccccc21
InChIKey: PZLYPFKNXALWJZ-MHZLTWQESA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of human KDAC6 using FITC-labeled histone H4 acetylated peptide as substrate after 60 mins by fluorescence assay
Measurement: IC50 = 6920 nM (pChEMBL 5.159999847412109)
Descriptors: MW 580.69, ALogP 5.9, HBA 7, HBD 2, PSA 113.23, QED 0.15
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]2CCCN2C(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)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(=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](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](CO)NC1=O
InChIKey: QDZGFDPPYKKFMB-DWYUSWDISA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Inhibition of biotinylated K-Ras G12D mutant (unknown origin) assessed as reduction in SOS1 (564 to 1049 residues)-mediated BODIPY-GDP-GTP exchange after 1 hr in presence of DTT by TR-FRET assay
Measurement: IC50 = 7.4 nM (pChEMBL 8.130000114440918)
Descriptors: MW 2535.02
Compound (SMILES): COc1ccc(F)cc1[C@@H]1C[C@H]1CNCc1ccccc1Cl.Cl
InChIKey: GQHLQQKMSQROLY-NQQJLSKUSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Agonist activity at human 5-HT2A receptor expressed in Flp-IN HEK293 cells assessed as induction of calcium flux measured every second for 5 mins by Fluo-4 dye based FLIPR assay
Measurement: EC50 = 2990 nM (pChEMBL 5.519999980926514)
Descriptors: MW 319.81, ALogP 4.38, HBA 2, HBD 1, PSA 21.26, QED 0.85
Compound (SMILES): CC1(C)[C@H](Nc2c(C(N)=O)cnn3cc(-c4ccccc4C#N)cc23)CC[C@]1(C)N
InChIKey: YQHCRXKZHSEECN-XXBNENTESA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of GST-tagged JAK2 (unknown origin) after 3 hrs by Caliper assay
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 402.5, ALogP 3.29, HBA 6, HBD 3, PSA 122.23, QED 0.62
Compound (SMILES): NS(=O)(=O)c1ccc(NC(=O)CCCc2ccc(N(CCCl)CCCl)cc2)cc1
InChIKey: UGEYCAWQKPWDOT-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Binding affinity to recombinant human carbonic anhydrase 12 after 15 mins by stopped-flow CO2 hydration assay
Measurement: Ki = 689 nM (pChEMBL 6.159999847412109)
Descriptors: MW 458.41, ALogP 3.58, HBA 4, HBD 2, PSA 92.5, QED 0.5
Compound (SMILES): Cc1cc(/C=C/C#N)cc(C)c1Oc1nc(NC2CCN(Cc3ccccc3F)CC2)nc2ccsc12
InChIKey: YXGAZZMPWMOHSV-AATRIKPKSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of HIV1 3B reverse transcriptase Y188L mutant infected in human MT4 cells assessed as protection against virus induced cytotoxicity after 5 days by MTT assay
Measurement: EC50 = 139 nM (pChEMBL 6.860000133514404)
Descriptors: MW 513.64, ALogP 6.85, HBA 7, HBD 1, PSA 74.07, QED 0.27
Compound (SMILES): CCN(CCCCCCOc1ccc2c(c1)NC(=O)CC2)Cc1ccccc1
InChIKey: ITQBNPTWCHUZFK-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of recombinant human MAO-A expressed in baculovirus infected BTI insect cells using kynuramine as substrate after 30 mins by fluorescence assay
Measurement: IC50 = 1200 nM (pChEMBL 5.920000076293945)
Descriptors: MW 380.53, ALogP 5.03, HBA 3, HBD 1, PSA 41.57, QED 0.56
Compound (SMILES): Cc1ccc(CN2C(=O)CCc3cc4cc(c32)OC/C=C/CO[C@H]2C[C@@H](CO)N(C2)c2cc(n3ncc(Cl)c3n2)N4)cc1
InChIKey: ZIMJUFXTVRWAEU-PTVJGBQLSA-N
Target: B-cell lymphoma 6 protein (SINGLE PROTEIN), Homo sapiens
UniProt: P41182
Assay: Inhibition of GAL4 DNA binding domain fused BCL6 BTB domain (unknown origin) expressed in HEK 293T/17 cells after 24 hrs by Bright-Glo luciferase cell reporter assay
Measurement: IC50 = 794.33 nM (pChEMBL 6.099999904632568)
Descriptors: MW 601.11, ALogP 4.82, HBA 9, HBD 2, PSA 104.46, QED 0.32
Compound (SMILES): Cc1n[nH]c(C)c1-c1nc(-c2nc(C3(c4ccccc4)CC3)n(C)n2)cnc1N
InChIKey: RYEDWDSERPNXBB-UHFFFAOYSA-N
Target: PI3K p110 beta/p85 alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of recombinant human His6-tagged PI3K p110beta/p85alpha using DiC8-PIP2 as substrate preincubated for 15 mins followed by substrate addition measured after 60 mins by ADP-Glo assay
Measurement: IC50 > 31622.78 nM (pChEMBL 4.5)
Descriptors: MW 386.46, ALogP 2.94, HBA 7, HBD 2, PSA 111.19, QED 0.56
Compound (SMILES): Cc1cc(OCCCc2c3n(c4c(-c5c(C)nn(C)c5C)c(Cl)ccc24)CCCN(c2cccc4c(C(=O)O)cn(C)c24)C3=O)cc(C)c1Cl
InChIKey: SIUYYHMJPRXSEZ-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Inhibition of FITC-Bak-BH3 binding to MBP-fused MCL1 (172 to 327 residues) (unknown origin) expressed in Escherichia coli BL21 CodonPlus (DE3) RIL after 3 hrs in presence of 1% FBS by TR-FRET assay
Measurement: Ki = 1.6 nM (pChEMBL 8.800000190734863)
Descriptors: MW 712.68, ALogP 8.83, HBA 7, HBD 1, PSA 94.52, QED 0.16
Compound (SMILES): O=C1Nc2ccccc2C(c2ccccc2)=N[C@H]1Cc1cn(C(c2ccccc2)(c2ccccc2)c2ccccc2)cn1
InChIKey: CZWWFRADEDMKMN-DHUJRADRSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of human KDAC8 after 60 mins by fluorescence assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 558.69, ALogP 7.12, HBA 4, HBD 1, PSA 59.28, QED 0.21
Compound (SMILES): CN1CC[C@]23c4c5ccc(O)c4O[C@H]2C(=O)/C(=C/c2ccccc2)C[C@@]3(O)[C@H]1C5
InChIKey: BAYMCCNRWJPNES-QHQLREDOSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Displacement of [3H]DAMGO from human MOR expressed in CHO cells
Measurement: Ki = 17.5 nM (pChEMBL 7.760000228881836)
Descriptors: MW 389.45, ALogP 2.44, HBA 5, HBD 2, PSA 70, QED 0.73
Compound (SMILES): O=C(NCc1cccnc1)c1cnc2c(SSc3cccc4cc(C(=O)NCc5cccnc5)cnc34)cccc2c1
InChIKey: IECYCFVBSXMNAZ-UHFFFAOYSA-N
Target: STAM-binding protein (SINGLE PROTEIN), Homo sapiens
UniProt: O95630
Assay: Inhibition of AMSH (unknown origin) using DiUbK63TAMRA as substrate by fluorescence assay
Measurement: IC50 = 3500 nM (pChEMBL 5.460000038146973)
Descriptors: MW 588.72, ALogP 6.23, HBA 8, HBD 2, PSA 109.76, QED 0.19
Compound (SMILES): Cc1n[nH]cc1-c1cc2nc(CN3CCCC3)[nH]c(=O)c2s1
InChIKey: MUYIKPWUBQUQAV-UHFFFAOYSA-N
Target: Cell division cycle 7-related protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: O00311
Assay: Inhibition of Cdc7 in human HeLa cells assessed as reduction in MCM2 phosphorylation at ser40 residues after 7 hrs by Western blot analysis
Measurement: IC50 = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 315.4, ALogP 2.28, HBA 5, HBD 2, PSA 77.67, QED 0.78
Compound (SMILES): O=C(c1ccccc1)N1C[C@H]2CC34CCC1C2C31CCN(CC2CC2)C4Cc2ccc(O)cc21
InChIKey: SXFYWVBYZTXUFW-BXGNEPPVSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Displacement of [3H]U-69,593 from human recombinant KOR expressed in CHO cell membranes
Measurement: Ki = 0.362 nM (pChEMBL 9.4399995803833)
Descriptors: MW 454.61, ALogP 4.61, HBA 3, HBD 1, PSA 43.78, QED 0.74
Compound (SMILES): CCOC(=O)Nc1ccc2ncc(-c3cccnc3)n2n1
InChIKey: CEIVAPWZRJLAEW-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK1 (SINGLE PROTEIN), Mus musculus
UniProt: P22518
Assay: Inhibition of GST tagged recombinant mouse CLK1 expressed in Escherichia coli using RS peptide as substrate after 30 mins by [gamma-33P]ATP based scintillation counting analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 283.29, ALogP 2.36, HBA 6, HBD 1, PSA 81.41, QED 0.8
Compound (SMILES): O=C(NCc1cccc(OCCSc2nc[nH]n2)c1)c1nc2ccccc2c(=O)[nH]1
InChIKey: OXTBPBSHWBJLJN-UHFFFAOYSA-N
Target: Stromelysin-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P09238
Assay: Inhibition of APMA-activated recombinant human MMP-10 using Cy3-PLGLK(Cy5Q)AR-NH2 peptide as substrate measured after 40 mins by spectrofluorimetric method
Measurement: IC50 = 140 nM (pChEMBL 6.849999904632568)
Descriptors: MW 422.47, ALogP 2.14, HBA 7, HBD 3, PSA 125.65, QED 0.29
Compound (SMILES): O=C(O)c1ccccc1S[C@H]1CN[C@H](C(=O)O)C1
InChIKey: YPBDKMOKCCZSBI-APPZFPTMSA-N
Target: Glutamate receptor ionotropic, kainate 3 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P42264
Assay: Displacement of [3H]kainic acid from eGFP-fused recombinant rat full length GluK3 receptor expressed in HEK293T/17 cells by liquid scintillation counting method
Measurement: Ki = 22000 nM (pChEMBL 4.659999847412109)
Descriptors: MW 267.31, ALogP 1.29, HBA 4, HBD 3, PSA 86.63, QED 0.76
Compound (SMILES): NS(=O)(=O)c1nnc(/N=C/c2cccc(/C=N/c3nnc(S(N)(=O)=O)s3)c2)s1
InChIKey: YIQRFEPXEHEUFQ-IAGONARPSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human carbonic anhydrase 9 incubated for 10 mins by stopped flow CO2 hydrase assay
Measurement: Ki = 0.5 nM (pChEMBL 9.300000190734863)
Descriptors: MW 458.53, ALogP 0.19, HBA 12, HBD 2, PSA 196.6, QED 0.49
Compound (SMILES): CC(C)N1CCN(CCCOc2ccc3c(c2)NC(=O)CC3)CC1
InChIKey: LNSJHGDEBCQKEU-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of recombinant human MAO-A expressed in baculovirus infected BTI insect cells using kynuramine as substrate after 30 mins by fluorescence assay
Measurement: IC50 = 9400 nM (pChEMBL 5.03000020980835)
Descriptors: MW 331.46, ALogP 2.37, HBA 4, HBD 1, PSA 44.81, QED 0.81
Compound (SMILES): CCCc1cc(OC(=O)c2c(O)cc(O)cc2CCC)cc(O)c1C(=O)O
InChIKey: KDWGMSJHASISHI-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P17706
Assay: Inhibition of TCPTP (unknown origin) using p-nitrophenyl phosphate substrate incubated for 30 mins
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 374.39, ALogP 3.63, HBA 6, HBD 4, PSA 124.29, QED 0.43
Compound (SMILES): CCCCCC[C@@H]1C(=O)O[C@H]1C(=O)NCCC[C@H](NC(=O)[C@H](C)NC(=O)OCc1ccccc1)C(=O)OCc1ccccc1
InChIKey: FOAWQVCSTWCVPS-QWMXJGQVSA-N
Target: Proteasome component C5 (SINGLE PROTEIN), Homo sapiens
UniProt: P20618
Assay: Inhibition of caspase-like activity of 20S proteasome in human red blood cells pretreated for 20 mins followed by Z-Leu-Leu-Glu-AMC substrate addition by fluorescence assay
Measurement: IC50 = 2160 nM (pChEMBL 5.670000076293945)
Descriptors: MW 609.72, ALogP 3.94, HBA 8, HBD 3, PSA 149.13, QED 0.13
Compound (SMILES): CCc1ccn2ccnc2c1N1CCCN([C@@H](CC(N)=O)C2CCN(C(=O)[C@H]3C[C@@H]4CC[C@H]3O4)CC2)CC1
InChIKey: CERHKHQEGFSIHF-OJJQZRKESA-N
Target: Atypical chemokine receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P25106
Assay: Displacement of [125I]CXCL12 from human CXCR7 expressed in CHO-K1 cell membranes after 2 hrs by scintillation counting method
Measurement: Ki = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 522.69, ALogP 2.46, HBA 7, HBD 1, PSA 96.41, QED 0.6
Compound (SMILES): Cc1cccc(CS(=O)(=O)n2c(=O)[nH]c3ccc(Cl)cc32)c1
InChIKey: LWOSHVCTGZMBAC-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of HIV-1 reverse transcriptase E138K mutant assessed as reduction in dTTP incorporation using poly(rA)/oligo(dT)16 as template/primer after 40 mins by PicoGreen dye based spectrofluorometric analysis
Measurement: IC50 = 7600 nM (pChEMBL 5.119999885559082)
Descriptors: MW 336.8, ALogP 2.67, HBA 4, HBD 1, PSA 71.93, QED 0.8
Compound (SMILES): CC1CN(c2cncnc2)Cc2cc(C(=O)Nc3cccc(CN4CCN(C)CC4)c3)ccc21
InChIKey: DHZNVMSRZBNIKF-UHFFFAOYSA-N
Target: Mast/stem cell growth factor receptor Kit (SINGLE PROTEIN), Homo sapiens
UniProt: P10721
Assay: Inhibition of recombinant human His-tagged c-kit cytoplasmic domain (544 to 976 residues) expressed in baculovirus expression system using Ser/Thr 6 as substrate measured after 1 hr by FRET-based Z'-Lyte assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 456.59, ALogP 3.6, HBA 6, HBD 1, PSA 64.6, QED 0.63
Compound (SMILES): Cc1ccccc1Oc1cccc(COc2ccccc2CCC(=O)OCCCOP(=O)(O)OC[C@H](N)C(=O)O)c1
InChIKey: BLHLLFXSUUNFAX-VWLOTQADSA-N
Target: Probable G-protein coupled receptor 34 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UPC5
Assay: Agonist activity at human GPR34 expressed in HEK293 cells co-transfected with AP-TGFalpha/chimeric Galphaq/i1 assessed as induction of AP-TGFalpha release after 1 hr
Measurement: EC50 = 181.97 nM (pChEMBL 6.739999771118164)
Descriptors: MW 587.56, ALogP 4.78, HBA 9, HBD 3, PSA 163.84, QED 0.11
Compound (SMILES): CC1(C)NC(=O)c2c(Cl)cc(Nc3ccncn3)c(=O)n21
InChIKey: VMPOUPXTRIFPLU-UHFFFAOYSA-N
Target: MAP kinase-interacting serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HBH9
Assay: Mnk Biochemical Enzymatic Assay: Compounds are screened for Mnk inhibition using the ADP-Glo kinase assay kit (Promega, catalogue No. V9101). All kinase reactions are performed in Reaction Buffer E (15 mM HEPES pH7.4, 20 mM NaCl, 1 mM EGTA, 10 mM MgCl2, 0.1 mg/ml BGG, and 0.02% Tween-20). Final Mnk1 reactions contained 10 nM recombinant Mnk1 (Life Technologies, PR9138A), 100 μM Mnk substrate peptide Ac-TATKSGSTTKNR-NH2 (American Peptide Company), 300 μM ATP, and varying concentrations of the inhibitory compound of interest. Final Mnk2 reactions contained 3 nM recombinant Mnk2 (Life Technologies, PV5607), 50 μM Mnk substrate peptide Ac-TATKSGSTTKNR-NH2 (American Peptide Company), 10 μM ATP, and varying concentrations of the inhibitory compound of interest. Final DMSO concentration in each reaction is 1%. Kinase reactions are carried out in 96-well half-area white flat-bottom polystyrene plates in a final volume of 25 μl. Mnk1/2 enzymes are pre-incubated with compound and peptide substrate for 5 minutes prior to the addition of ATP. After the addition of ATP, kinase reactions are incubated at room temperature for 40 minutes. Reactions are subsequently stopped by the addition of 25 μl of ADP-Glo Reagent and incubating for an additional 40 minutes. The final luminescent signal used for kinase activity readout is produced by the addition of 45 μl of Kinase Detection Reagent (ADP-Glo kit, Promega) and incubating for 40 minutes. The luminescent signal is detected using a Victor 2 multilabel counter (Perkin Elmer) and the concentration of compound necessary to achieve inhibition of enzyme activity by 50% (IC50) is calculated using signals from an 8-point compound dilution series.
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 305.73, ALogP 1.47, HBA 6, HBD 2, PSA 88.91, QED 0.88
Compound (SMILES): COC(=O)Nc1cc(-c2ccc(OC[C@@](C)(N)CC(C)C)c(C3CC3)c2)ccn1
InChIKey: WFKGXEHYQJXRJE-QHCPKHFHSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin) incubated for 10 mins in presence of NADPH by LC-MS/MS analysis
Measurement: IC50 = 16300 nM (pChEMBL 4.789999961853027)
Descriptors: MW 397.52, ALogP 4.95, HBA 5, HBD 2, PSA 86.47, QED 0.66
Compound (SMILES): CC(C)(N)c1nc(-c2ccc(OC(F)(F)F)cc2)c[nH]1
InChIKey: AGORGFNWYAUYSU-UHFFFAOYSA-N
Target: Sodium channel protein type 2 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q99250
Assay: Inhibition of 50% inactivated recombinant human Nav1.2 expressed in HEK293 cells at holding potential of -120 mV by manual patch electrophysiology method
Measurement: IC50 = 16000 nM (pChEMBL 4.800000190734863)
Descriptors: MW 285.27, ALogP 3.17, HBA 3, HBD 2, PSA 63.93, QED 0.91
Compound (SMILES): CC(C)n1cnc2c(Nc3cc(N)cc(Cl)c3)nc(N[C@@H]3CCNC3)nc21
InChIKey: GPXCDUCDIFDAGL-CYBMUJFWSA-N
Target: Dual specificity protein kinase CLK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P49759
Assay: Inhibition of human CLK1 using substrate ERMRPRKRQGSVRRRV in presence of [gamma-33P]ATP after 40 mins by scintillation counter method
Measurement: IC50 = 118 nM (pChEMBL 6.929999828338623)
Descriptors: MW 386.89, ALogP 3.16, HBA 8, HBD 4, PSA 105.71, QED 0.5
Compound (SMILES): CCCCCCCCCCCCCCCC(=O)N[C@@H](CCC(=O)NCCCC[C@H](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](CO)NC(=O)[C@H](CO)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](NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@@H](N)Cc1cnc[nH]1)[C@@H](C)O)[C@@H](C)O)C(C)C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@H](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](CCCNC(=N)N)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)O)C(C)C)[C@@H](C)CC)C(=O)O
InChIKey: YSDQQAXHVYUZIW-QCIJIYAXSA-N
Target: Glucagon-like peptide 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P43220
Assay: Agonist activity at GLP-1R (unknown origin) expressed in candidate selection CHO cells assessed as cAMP accumulation incubated for 30 mins by plate reader method
Measurement: EC50 = 0.95 nM (pChEMBL 9.020000457763672)
Descriptors: MW 3751.26
Compound (SMILES): CC(=O)N[C@H](Cc1ccc2ccccc2c1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](Cc1ccc(I)cc1)C(=O)N[C@@H](Cc1ccc(-c2ccccc2)cc1)C(N)=O
InChIKey: BUMLYNRSGDYSCP-JPYDVTDNSA-N
Target: Melanocortin receptor 5 (SINGLE PROTEIN), Mus musculus
UniProt: P41149
Assay: Agonist activity at mouse MC5R expressed in HEK293 cells assessed as induction of cAMP accumulation after 2 hrs by alpha screen assay
Measurement: EC50 = 67000 nM (pChEMBL 4.170000076293945)
Descriptors: MW 908.84, ALogP 3.85, HBA 6, HBD 8, PSA 221.39, QED 0.03
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](C)NC(=O)[C@@H]2CCCN2C(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)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(=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: PQEWSIAVSMDXLM-KJIAAENESA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Inhibition of biotinylated K-Ras G12D mutant (unknown origin) assessed as reduction in SOS1 (564 to 1049 residues)-mediated BODIPY-GDP-GTP exchange after 1 hr in presence of DTT by TR-FRET assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 2518.98
Compound (SMILES): C[C@@H](N)[C@@H]1CC[C@]2(C(=O)OCc3ccccc3)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC[C@H](O)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
InChIKey: BRMYJHHZBRQLRJ-HYKGQQBESA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Uncompetitive inhibition of electric eel AChE using acetylthiocholine iodide as substrate preincubated for 20 mins followed by substrate addition measured every 1 min for 30 mins by Cornish-Bowden plot method
Measurement: Ki = 47810 nM (pChEMBL 4.320000171661377)
Descriptors: MW 549.84, ALogP 7.52, HBA 4, HBD 2, PSA 72.55, QED 0.38
Compound (SMILES): CN(CCc1ccc(Cl)cc1Cl)C1CCN(c2nc(N)n[nH]2)CC1
InChIKey: CYCAZTRKOUNUPH-UHFFFAOYSA-N
Target: Chitotriosidase-1 (SINGLE PROTEIN), Mus musculus
UniProt: Q9D7Q1
Assay: Inhibition of mouse recombinant full length C-terminal His-tagged chitotriosidase expressed in CHO-K1 cells using 4-methylumbelliferyl-beta-D-N,N',N\"\"-triacetylchitotrioside as substrate after 60 mins by fluorescence assay
Measurement: IC50 = 47600 nM (pChEMBL 4.320000171661377)
Descriptors: MW 369.3, ALogP 2.84, HBA 5, HBD 2, PSA 74.07, QED 0.85
Compound (SMILES): C[C@@]1(c2cc(CNCCC(F)(F)F)c(F)cc2F)CCSC(N)=N1
InChIKey: DCYWNJDSKJXMKI-AWEZNQCLSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Inhibition of BACE2 (unknown origin) by cell free assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 367.39, ALogP 3.67, HBA 4, HBD 2, PSA 50.41, QED 0.62
Compound (SMILES): NC(=O)c1cnn2cccc2c1NCc1cccc(NC(=O)COc2c(F)c(F)c(F)c(F)c2F)c1
InChIKey: QATGCJSYNNGRKH-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of His-tagged TYK2 (unknown origin) using fluoresceinated peptide as substrate after 3 hrs by caliper assay
Measurement: IC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 505.4, ALogP 3.76, HBA 6, HBD 3, PSA 110.75, QED 0.19
Compound (SMILES): C=CC(=O)Nc1cccc(OC(C)C)c1Nc1ncc(OCc2c(Cl)c(OC)cc(OC)c2Cl)cn1
InChIKey: RECRQTJWRQFZCQ-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of His-tagged cytoplasmic recombinant human FGFR4 (781 to 1338 residues) expressed in baculovirus expression system using Tyr 4 peptide as substrate incubated for 1 hr by FRET-based Z'-Lyte assay
Measurement: IC50 = 202.3 nM (pChEMBL 6.690000057220459)
Descriptors: MW 533.41, ALogP 6.03, HBA 8, HBD 2, PSA 103.83, QED 0.29
Compound (SMILES): N=C(NCCCOc1ccc(F)cc1)Nc1ccc(Cl)cc1
InChIKey: YIXQZLPGNXXTFM-UHFFFAOYSA-N
Target: Androgen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P10275
Assay: Antagonist activity at full length human androgen receptor expressed in mammalian expression system measured after 22 to 24 hrs by luciferase reporter gene assay
Measurement: EC50 = 12680 nM (pChEMBL 4.900000095367432)
Descriptors: MW 321.78, ALogP 3.88, HBA 2, HBD 3, PSA 57.14, QED 0.43
Compound (SMILES): CC(C)(C)c1ccc(CN2[C@@H]3CC[C@@H]2CC(c2cccc(O)c2)C3)cc1
InChIKey: KRAVJMABYSXIPY-FGZHOGPDSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Displacement of [3H]DPN from recombinant human delta opioid receptor expressed in CHOK1 cell membranes
Measurement: Ki = 31.62 nM (pChEMBL 7.5)
Descriptors: MW 349.52, ALogP 5.6, HBA 2, HBD 1, PSA 23.47, QED 0.78
Compound (SMILES): COc1ccccc1N1CCC2(CCN(CCCSc3nnc(-c4ccccc4)n3C)CC2)CC1
InChIKey: KVHHUZUNLIGTBY-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Antagonist activity at recombinant human D3 receptor expressed in CHOK1 cells assessed as inhibition of dopamine-induced beta arrestin2 recruitment preincubated for 30 mins followed by dopamine addition and measured after 90 mins by coelenterazine-based beta-galactosidase reporter gene assay
Measurement: IC50 = 41.4 nM (pChEMBL 7.380000114440918)
Descriptors: MW 491.71, ALogP 5.36, HBA 7, HBD 0, PSA 46.42, QED 0.31
Compound (SMILES): CC(C)(C)[C@@H]1OCCC[C@@H]1CNc1cc(F)c(S(=O)(=O)Nc2nccs2)cc1Cl
InChIKey: MAOFMAFTHDKOCO-SJKOYZFVSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of human recombinant CYP3A4 expressed in baculovirus-infected insect cells using 7-Benzoyloxy-4-trifluoromethyl coumarin substrate in presence of NADP+ by fluorescence based assay
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 462.01, ALogP 4.99, HBA 6, HBD 2, PSA 80.32, QED 0.63
Compound (SMILES): Fc1cccc(-c2nn3c(Cn4nnc5ccccc54)nnc3s2)c1
InChIKey: HNYXILOYZDAKIG-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase, H3 lysine-79 specific (SINGLE PROTEIN), Homo sapiens
UniProt: Q8TEK3
Assay: Binding affinity to human N-terminal 6His-tagged DOT1L (1 to 416 residues) expressed in Escherichia coli BL21(DE3) after 150 secs by SPR-based binding assay
Measurement: Kd = 17270 nM (pChEMBL 4.760000228881836)
Descriptors: MW 351.37, ALogP 2.78, HBA 8, HBD 0, PSA 73.79, QED 0.5
Compound (SMILES): CCc1nc2ccc(N3CCN(CC(=O)N4CC(O)C4)CC3)cn2c1N(C)c1nc(-c2ccc(F)cc2)c(C#N)s1
InChIKey: KPMRDQYWRDQDBQ-UHFFFAOYSA-N
Target: Autotaxin (SINGLE PROTEIN), Homo sapiens
UniProt: Q13822
Assay: Human ENPP2 (hENPP2) Assay: Compound IC50 values are determined in a hENPP2 (UniProtKB/SwissProt Sequence ref Q13822) biochemical assay using LPC as substrate. 5 μL of a dilution series of compound, starting from 20 μM highest concentration, 1/5 dilution, is added to the wells. hENPP2 is used at a final concentration of 1 μg/mL or 3 μg/mL (it will be appreciated by the skilled person that the potency read out is independent of the enzyme concentration). The enzyme is diluted in 50 mM Tris-HCl pH 8.5, 500 mM NaCl, 5 mM KCl, 10 mM CaCl2, 0.1% fatty acid free BSA in a total volume of 10 μL. the reaction is started by the addition of 10 μL of 150 μM LPC (palmitoyl 16:0) diluted in the same buffer as described above and the mixture is incubated at 37° C. for 30 min. The reaction is terminated and choline quantified by the addition of a 25 μL of a mixture containing 0.6 U/mL of choline oxidase, 0.6 U/mL of peroxydase, 1.8 mM TOOS, 1.2 mM amino-antipyrine, 20 mM EGTA (stop-developer solution) diluted in the buffer described above. Luminescence is read on the Envision after an incubation of 30 min at room temperature (Excitation 555 nm, excitation light=70%).
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 574.69, ALogP 3.12, HBA 10, HBD 1, PSA 104.24, QED 0.36
Compound (SMILES): Cl.Oc1ccc(CCN(CCc2cccc(O)c2)CC2CCCCC2)cc1
InChIKey: YLZVVCFAABRLNX-UHFFFAOYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Agonist activity at human kappa opioid receptor expressed in CHO cell membranes after 60 mins by [35S]GTPgammaS binding assay
Measurement: EC50 = 22.2 nM (pChEMBL 7.650000095367432)
Descriptors: MW 353.51, ALogP 4.77, HBA 3, HBD 2, PSA 43.7, QED 0.72
Compound (SMILES): C#CCN1C[C@H](C(=O)NO)[C@H](NS(=O)(=O)c2ccc(OCc3cc(C)nc4ccccc34)cc2)C1
InChIKey: BGZRRZZFIZMAOA-LADGPHEKSA-N
Target: Disintegrin and metalloproteinase domain-containing protein 17 (SINGLE PROTEIN), Mus musculus
UniProt: Q9Z0F8
Assay: Inhibition of TACE in mouse RAW264.7 cells assessed as inhibition of LPS-stimulated TNFalpha production pretreated for 1 hr followed by LPS stimulation for 4 hrs by ELISA
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 494.57, ALogP 1.84, HBA 7, HBD 3, PSA 120.86, QED 0.25
Compound (SMILES): Cc1ccc(N2CCN(CCNC(=O)Nc3ccc(S(N)(=O)=O)cc3)CC2)cc1
InChIKey: CGHQYGFXZZCOJG-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 incubated for 15 mins prior to testing by stopped flow CO2 hydration assay
Measurement: Ki > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 417.54, ALogP 1.59, HBA 5, HBD 3, PSA 107.77, QED 0.66
Compound (SMILES): CNCc1ccc(-c2cncc(CCc3cc(C)cc(N)n3)c2)cc1
InChIKey: DWEUCJPXVJGNQN-UHFFFAOYSA-N
Target: Nitric oxide synthase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P29474
Assay: Inhibition of human endothelial NOS expressed in Escherichia coli using L-arginine as substrate assessed as reduction in NO production by measuring oxidation of oxyHb to metHb measured for 6 mins by hemoglobin- NO capture assay
Measurement: Ki = 68539 nM (pChEMBL 4.159999847412109)
Descriptors: MW 332.45, ALogP 3.54, HBA 4, HBD 2, PSA 63.83, QED 0.72
Compound (SMILES): Cc1ccc(Br)c(COc2ccc(CCC(=O)O)cc2C)c1
InChIKey: FSTAUQNZQYZTBV-UHFFFAOYSA-N
Target: Free fatty acid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O14842
Assay: Agonist activity at human FFA1 receptor expressed in human U2OS cells co-expressing Galpha16 assessed as calcium mobilization by Fluo-4 dye based FLIPR assay
Measurement: EC50 > 31622.78 nM (pChEMBL 4.5)
Descriptors: MW 363.25, ALogP 4.66, HBA 2, HBD 1, PSA 46.53, QED 0.81
Compound (SMILES): C#CCN(CCCCCOc1ccc2c(c1)NC(=O)CC2)Cc1ccccc1
InChIKey: MUNZMFHAPSTYQA-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of recombinant human MAO-A expressed in baculovirus infected BTI insect cells using kynuramine as substrate after 30 mins by fluorescence assay
Measurement: IC50 = 8900 nM (pChEMBL 5.050000190734863)
Descriptors: MW 376.5, ALogP 4.26, HBA 3, HBD 1, PSA 41.57, QED 0.5
Compound (SMILES): NS(=O)(=O)c1ccc(N2C(=O)c3ccc4c5c(ccc(c35)C2=O)C(=O)N(c2ccc(S(N)(=O)=O)cc2)C4=O)cc1
InChIKey: UZGDAMQMGBFGTG-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human CA12 pre-incubated for 10 mins by stopped-flow CO2 hydrase assay
Measurement: Ki = 28.3 nM (pChEMBL 7.550000190734863)
Descriptors: MW 576.57, ALogP 1.74, HBA 8, HBD 2, PSA 195.08, QED 0.34
Compound (SMILES): Cc1cnccc1-c1cc2c(N[C@@H]3CC[C@](C)(N)C3(C)C)c(C(N)=O)cnn2c1
InChIKey: KIQUQFVYSGGMCG-GCJKJVERSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of GST-tagged JAK2 (unknown origin) after 3 hrs by Caliper assay
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 392.51, ALogP 3.12, HBA 6, HBD 3, PSA 111.33, QED 0.63
Compound (SMILES): Cc1cc(C#N)cc(C)c1Oc1nc(NC2CCN(Cc3ccc(S(N)(=O)=O)cc3)CC2F)nc2ccsc12
InChIKey: JAAQLKKKVDWIAR-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of HIV1 3B reverse transcriptase Y188L mutant infected in human MT4 cells assessed as protection against virus induced cytotoxicity after 5 days by MTT assay
Measurement: EC50 = 13.9 nM (pChEMBL 7.860000133514404)
Descriptors: MW 566.68, ALogP 4.64, HBA 9, HBD 2, PSA 134.23, QED 0.33
Compound (SMILES): O=c1n(Cc2ccc(Cl)cc2)c2sc3c(c2c2ncnn12)CCN(C1COC1)C3
InChIKey: YNHRARXBLWKRFA-UHFFFAOYSA-N
Target: Dual specificity calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B (SINGLE PROTEIN), Homo sapiens
UniProt: Q01064
Assay: IMAP TR-FRET assay: The IMAP TR-FRET PDE assay was optimized for concentration of enzyme, Calmodulin, cAMP or cGMP substrate, DMSO tolerance, and incubation time. Into each well of a solid white 1536 well plate (Corning) was dispensed 250 pg full-length recombinant NH-terminal GST tagged human PDE1b enzyme (BPS Bioscience Cat #60011, San Diego, Calif.) in 2.5 μL IMAP BSA reaction buffer (Molecular Devices, Sunnyvale, Calif.) containing 10 U/mL Calmodulin and 2.5 mM CaCl2 (Sigma Aldrich.) After a brief centrifugation, 30 nL compound was added by transfer from 1 mM stock in DMSO using a Kalypsys 1536 Pintool. Plates were incubated for 5 minutes at room temperature before dispensing 1.5 μL of 533 nM 5-carboxy fluorescein (FAM)-labeled cAMP (Molecular Devices, Sunnyvale, Calif.) for a final concentration of 200 nM. After a brief centrifugation, the plates were incubated for 30 minutes at room temperature. The assay was terminated by adding 5 μL IMAP binding reagent/Tb complex (Molecular Devices, Sunnyvale, Calif.) to each well. Plates were incubated 1 hour at room temperature and read on a Viewlux multimode plate reader (Perkin Elmer). The instrument was set to excite using the DUG11 filter and measure using 490/10 nm and 520/10 nm filters.
Measurement: EC50 < 100 nM (pChEMBL 7)
Descriptors: MW 427.92, ALogP 2.56, HBA 8, HBD 0, PSA 64.66, QED 0.5
Compound (SMILES): CC[C@@H](CO)Nc1ccc2ncc(-c3ccnc(N)n3)n2n1
InChIKey: FJAIARRQBXWUMX-VIFPVBQESA-N
Target: Dual specificity protein kinase CLK1 (SINGLE PROTEIN), Mus musculus
UniProt: P22518
Assay: Inhibition of GST tagged recombinant mouse CLK1 expressed in Escherichia coli using RS peptide as substrate after 30 mins by [gamma-33P]ATP based scintillation counting analysis
Measurement: IC50 = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 299.34, ALogP 0.95, HBA 8, HBD 3, PSA 114.25, QED 0.64
Compound (SMILES): CC1=CC[C@@H]2[C@@H](C1)c1c(O)cc(C(C)(C)C(=O)OCCBr)cc1OC2(C)C
InChIKey: KTCLPOUSDJTKJF-HZPDHXFCSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P20272
Assay: Binding Assay: All the cannabinoids discussed in this invention are tested for their ability to bind to CB1 and CB2 receptors using membranes from rat brain or HEK293 cells expressing either mCB2 or hCB2, respectively via competition-equilibrium binding using [3H]CP-55,940. Results are analyzed using nonlinear regression to determine ligand IC50 (Prism by GraphPad Software, Inc.).
Measurement: Ki = 2.9 nM (pChEMBL 8.539999961853027)
Descriptors: MW 437.37, ALogP 5.22, HBA 4, HBD 1, PSA 55.76, QED 0.4
Compound (SMILES): Cn1nc(-c2cnc(N)c(-n3nnc4ccccc43)n2)nc1C1(S(C)(=O)=O)CC1
InChIKey: QOEPYORBBSKFRD-UHFFFAOYSA-N
Target: PI3K p110 beta/p85 alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P27986
Assay: Inhibition of recombinant human His6-tagged PI3K p110beta/p85alpha using DiC8-PIP2 as substrate preincubated for 15 mins followed by substrate addition measured after 60 mins by ADP-Glo assay
Measurement: IC50 = 19952.62 nM (pChEMBL 4.699999809265137)
Descriptors: MW 411.45, ALogP 0.62, HBA 11, HBD 1, PSA 147.36, QED 0.51
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@@H]2CCCN2C(=O)[C@H](Cc2c[nH]c3ccccc23)N(C)C(=O)[C@H](CCCNC(=N)N)N(C)C(=O)[C@@H](Cc2ccccc2)NC(=O)[C@H](Cc2cnc[nH]2)N(C)C(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H]2CSSC[C@H](NC1=O)C(=O)N[C@@H](Cc1ccccc1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(=O)O)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N2
InChIKey: ASVPOLVJNKXRRI-NNTZBWPESA-N
Target: Melanocyte-stimulating hormone receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q01726
Assay: Agonist activity at human MC1R expressed in low doxycyclin-treated HEK293 cell membranes assessed as increase in cAMP production after 45 mins by HTRF method
Measurement: EC50 = 3467.37 nM (pChEMBL 5.460000038146973)
Descriptors: MW 1757.08
Compound (SMILES): CN[C@H](C)Cc1cc(C#N)cc(OCc2ccc3c(C)cc(N)nc3c2)c1
InChIKey: PUGNZMCPLRURSU-OAHLLOKOSA-N
Target: Nitric oxide synthase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P29474
Assay: Inhibition of recombinant human full-length eNOS expressed in Escherichia coli BL21(DE3) assessed as reduction in nitric oxide production using L-arginine as substrate measured for 5 mins in presence of calmodulin/10 uM H4B by hemoglobin capture assay
Measurement: Ki = 16100 nM (pChEMBL 4.789999961853027)
Descriptors: MW 360.46, ALogP 3.73, HBA 5, HBD 2, PSA 83.96, QED 0.7
Compound (SMILES): Cc1ccc(NC(=O)c2cccc(C(F)(F)F)c2)cc1NC(=O)c1cncc(-c2cnn(C)c2)c1
InChIKey: BMEXIUCHJUGPRB-UHFFFAOYSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07333
Assay: Inhibition of recombinant human His-tagged CSF1R cytoplasmic domain (538 to 910 residues) expressed in baculovirus expression system using fluorescent-polyGT as substrate preincubated for 10 mins followed by substrate measured after 1 hr in presence of 500 uM ATP by LanthaScreen TR-FRET assay
Measurement: IC50 = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 479.46, ALogP 5.31, HBA 5, HBD 2, PSA 88.91, QED 0.41
Compound (SMILES): O=c1[nH]c(-c2ccc(OCc3ccc(F)cc3F)cc2)nc2ccccc12
InChIKey: JHDBNFXRMWLNDK-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of human CYP2D6 expressed in yeast microsomal membranes using 7-ethoxy-methyloxy-3-cyanocoumarin as substrate by fluorescence assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 364.35, ALogP 4.45, HBA 3, HBD 1, PSA 54.98, QED 0.58
Compound (SMILES): CCNC(=O)c1cc2c(N3CCOC[C@@H]3C)ccnc2n1C
InChIKey: SYYSMZCCSNLTHZ-NSHDSACASA-N
Target: Oxidized purine nucleoside triphosphate hydrolase (SINGLE PROTEIN), Homo sapiens
UniProt: P36639
Assay: Affinity Biochemical interaction (PPiLight Biochemical Assay (full-length human NUDT1)) EUB0000587a NUDT1
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 302.38, ALogP 1.55, HBA 5, HBD 1, PSA 59.39, QED 0.93
Compound (SMILES): COc1cc2c(cc1Nc1ncc(Cl)c(Nc3ccccc3S(=O)(=O)C(C)C)n1)C1CNCCN1CC2
InChIKey: COMVVKFCZPWGAV-UHFFFAOYSA-N
Target: Insulin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06213
Assay: Inhibition of insulin receptor kinase (unknown origin) using TK as substrate after 30 mins by HTRF assay
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 543.09, ALogP 4.31, HBA 9, HBD 3, PSA 108.48, QED 0.4
Compound (SMILES): NS(=O)(=O)c1ccc(/N=C/c2ccccc2/C=N/c2ccc(S(N)(=O)=O)cc2)cc1
InChIKey: WNKWCHDPGJJDPC-RNIAWFEPSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human carbonic anhydrase 9 incubated for 10 mins by stopped flow CO2 hydrase assay
Measurement: Ki = 21.8 nM (pChEMBL 7.659999847412109)
Descriptors: MW 442.52, ALogP 2.48, HBA 6, HBD 2, PSA 145.04, QED 0.56
Compound (SMILES): Nc1cc(Nc2nccc3nc(-c4c(Cl)cccc4Cl)[nH]c23)ncn1
InChIKey: GYBXQCLWSUJTMN-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of JAK2 (unknown origin) assessed as reduction in EPO-mediated STAT5 phosphorylation by cell based readout assay
Measurement: EC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 372.22, ALogP 4.05, HBA 6, HBD 3, PSA 105.4, QED 0.5
Compound (SMILES): O=S(=O)(NCCN1CC=C(c2c[nH]c3ccc(Cl)cc23)CC1)c1ccc2ccccc2c1
InChIKey: BXCDGOZRLHWEFT-UHFFFAOYSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Homo sapiens
UniProt: P31645
Assay: Displacement of [3H]-imipramine from human serotonin transporter expressed in HEK-293 cell membranes after 30 mins by scintillation counting
Measurement: Ki = 2.7 nM (pChEMBL 8.569999694824219)
Descriptors: MW 466.01, ALogP 5.04, HBA 3, HBD 2, PSA 65.2, QED 0.42
Compound (SMILES): Cl.O=C(O)c1cc([C@H]2CCN[C@@H]2C(=O)O)ccc1Cl
InChIKey: MWFIVBKDCYATMH-QJVKKXMWSA-N
Target: Glutamate NMDA receptor; Grin1/Grin2b (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P35439
Assay: Antagonist activity at recombinant rat GluN1a/GluN2B expressed in Xenopus laevis oocytes assessed as inhibition of glycine/glutamate-mediated current responses by two-electrode voltage clamp method
Measurement: Ki = 10000 nM (pChEMBL 5)
Descriptors: MW 269.68, ALogP 1.57, HBA 3, HBD 3, PSA 86.63, QED 0.78
Compound (SMILES): C[C@H](NC(=O)c1c(CN2CCC(N3CCCCC3)CC2)c(-c2cccc(C(F)(F)F)c2)nc2ccccc12)c1ccccc1
InChIKey: CPDKCWNAYYOWLG-VWLOTQADSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG by patchXpress electrophysiology assay
Measurement: IC50 = 1200 nM (pChEMBL 5.920000076293945)
Descriptors: MW 600.73, ALogP 7.86, HBA 4, HBD 1, PSA 48.47, QED 0.23
Compound (SMILES): Nc1n[nH]c(N2CCC(N(CCc3ccc(Cl)cc3)Cc3cccc4ccccc34)CC2)n1
InChIKey: NYPZTUJJTVSIOH-UHFFFAOYSA-N
Target: Chitotriosidase-1 (SINGLE PROTEIN), Mus musculus
UniProt: Q9D7Q1
Assay: Inhibition of mouse recombinant full length C-terminal His-tagged chitotriosidase expressed in CHO-K1 cells using 4-methylumbelliferyl-beta-D-N,N',N\"\"-triacetylchitotrioside as substrate after 60 mins by fluorescence assay
Measurement: IC50 = 573 nM (pChEMBL 6.239999771118164)
Descriptors: MW 461.01, ALogP 4.91, HBA 5, HBD 2, PSA 74.07, QED 0.41
Compound (SMILES): C[C@H]1CNC(=N)N1CCc1cccnc1
InChIKey: GIQJQATVWVFAFP-VIFPVBQESA-N
Target: NIcotinic acetylcholine receptor alpha-3/beta-4/alpha-5 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P20420
Assay: Displacement of [3H]epibatidine from rat alpha3beta4alpha5 nAChR expressed in HEK cells after 2 hrs
Measurement: Ki = 1619 nM (pChEMBL 5.789999961853027)
Descriptors: MW 204.28, ALogP 0.85, HBA 2, HBD 2, PSA 52.01, QED 0.77
Compound (SMILES): COc1ccc(CCc2nc3cc(-c4c(C)noc4C)ccc3n2CCN2CCOCC2)cc1
InChIKey: RQFUKBAHMUVXDA-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of BRD4 (unknown origin) by fluorescence polarization assay
Measurement: IC50 = 1500 nM (pChEMBL 5.820000171661377)
Descriptors: MW 460.58, ALogP 4.43, HBA 7, HBD 0, PSA 65.55, QED 0.39
Compound (SMILES): C=CS(=O)(=O)Nc1cccc(CNc2c(C(N)=O)cnn3cccc23)c1
InChIKey: LFAMGDQKRVEQOC-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of His-tagged TYK2 (unknown origin) using fluoresceinated peptide as substrate after 3 hrs by caliper assay
Measurement: IC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 371.42, ALogP 1.93, HBA 6, HBD 3, PSA 118.59, QED 0.59
Compound (SMILES): CNC(=O)NCCc1cccc2ccc(OC)nc12
InChIKey: CFXGKPVZFUDUFH-UHFFFAOYSA-N
Target: Melatonin receptor type 1B (SINGLE PROTEIN), Homo sapiens
UniProt: P49286
Assay: Intrinsic activity at human MT2 receptor expressed in CHO cell membranes after 1 hr by [35S]GTPgammaS binding assay
Measurement: EC50 = 0.09 nM (pChEMBL 10.050000190734863)
Descriptors: MW 259.31, ALogP 1.71, HBA 3, HBD 2, PSA 63.25, QED 0.88
Compound (SMILES): COc1cc(OC)c(Cl)c(N2Cc3cnc(N(C)C)nc3N(C3CCN(C(=O)/C=C/CN(C)C)CC3)C2=O)c1Cl
InChIKey: ZVJJERYMYFMJGK-BQYQJAHWSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Inhibition of human recombinant His-tagged FGFR1 cytoplasmic domain (308 to 731 residues) expressed in baculovirus using Tyr-4 peptide after 1 hr by FRET-based Z'-Lyte assay
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 592.53, ALogP 3.92, HBA 8, HBD 0, PSA 94.58, QED 0.43
Compound (SMILES): c1cn(-c2cc(NC3=NC[C@@]4(CN5CCC4CC5)O3)ncn2)cn1
InChIKey: RLXBHTUZCPORKT-INIZCTEOSA-N
Target: Neuronal acetylcholine receptor subunit alpha-7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q05941
Assay: Displacement of [125I]alpha-bungarotoxin from rat alpha7 nAChR expressed in HEK293 cell membranes incubated for 2 hrs and measured by gamma counting method
Measurement: Ki = 3.3 nM (pChEMBL 8.479999542236328)
Descriptors: MW 325.38, ALogP 0.92, HBA 8, HBD 1, PSA 80.46, QED 0.88
Compound (SMILES): N#Cc1c(N)nc(N)nc1N[C@H](c1nc2cccc(Cl)c2c(=O)n1-c1cc[nH]n1)C1CC1
InChIKey: YMHCSLZTNCXUIU-HNNXBMFYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of human full length PI3Kgamma using PIP2/ATP as substrate after 30 mins by TR-FRET assay
Measurement: IC50 = 199 nM (pChEMBL 6.699999809265137)
Descriptors: MW 448.88, ALogP 2.15, HBA 10, HBD 4, PSA 177.21, QED 0.36
Compound (SMILES): c1ccc2c(c1)CN[C@@H](CN(CCCCNCC1CCCCC1)[C@H]1CCCc3cccnc31)C2
InChIKey: LGZXNSNDFUQXOX-WDYNHAJCSA-N
Target: C-X-C chemokine receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P61073
Assay: Agonist activity at CXCR4 in human CCRF-CEM cells assessed as induction of Ca2+ flux measured for 90 secs by calcium dye-based fluorescence assay
Measurement: EC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 460.71, ALogP 5.43, HBA 4, HBD 2, PSA 40.19, QED 0.46
Compound (SMILES): COC[C@@H](C)NCc1cc([C@]2(C)CCSC(N)=N2)c(F)cc1F
InChIKey: HKFFPSFZJNYNQZ-HWPZZCPQSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of BACE1 (unknown origin) using biotin-GLTNIKTEEISEISYEVEFR-C[oregon green]KK-OH as substrate after 3 hrs by fluorescence polarization assay
Measurement: IC50 = 4180 nM (pChEMBL 5.380000114440918)
Descriptors: MW 343.44, ALogP 2.76, HBA 5, HBD 2, PSA 59.64, QED 0.83
Compound (SMILES): COc1ccc(N(C)c2cnc(SCc3c(F)cccc3F)n2-c2ccc(F)cc2)cc1OC
InChIKey: DEBXSGITWCYLOY-UHFFFAOYSA-N
Target: G-protein coupled bile acid receptor 1 (SINGLE PROTEIN), Mus musculus
UniProt: Q80SS6
Assay: TGR5/CRE Luciferase Assay: In the following tables TGR5 activation by compounds and subsequent increase in intracellular cAMP were evaluated using a luciferase reporter gene assay. Human embryonic kidney (HEK) 293 cells were transiently co-transfected with pCMV tag4b-TGR5 h (to follow hTGR5 activation) or pCMV AC6-TGR5m (to follow mTGR5 activation) expression plasmids and the pCRE TA-Luciferase reporter plasmid using the JET PEI reagent (Polyplus transfection). Transfected cells were seeded in 96-well plates and incubated overnight with the test compounds at increasing concentrations tested in duplicate. Lithocolic acid (LCA) at 10 μM was used as a positive reference compound. The cAMP-dependent luciferase expression was followed using the BrightGlo reagent according to the manufacturer (Promega) instructions. Luminescence was read with a Mithras plate reader (Berthold). Data were expressed as percentage of the 10 μM LCA value and EC50 values were calculated using XL fit 5 software or GraphPad Prism 5. Concentration-response curves were fitted by a nonlinear regression analysis to a 4 parameter logistic equation.
Measurement: EC50 = 1 nM (pChEMBL 9)
Descriptors: MW 485.53, ALogP 6.37, HBA 6, HBD 0, PSA 39.52, QED 0.27
Compound (SMILES): CC(=O)N[C@H](Cc1ccc2ccccc2c1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](Cc1ccc(I)cc1)C(=O)N[C@@H](Cc1csc2ccccc12)C(N)=O
InChIKey: QOKVJCWRNJMDNT-NUXXNWGHSA-N
Target: Melanocortin receptor 5 (SINGLE PROTEIN), Mus musculus
UniProt: P41149
Assay: Agonist activity at mouse MC5R expressed in HEK293 cells assessed as induction of cAMP accumulation after 2 hrs by alpha screen assay
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 888.83, ALogP 3.39, HBA 7, HBD 8, PSA 221.39, QED 0.03
Compound (SMILES): O=S(=O)(Nc1nccs1)c1cc(Cl)c(NC[C@H]2CCC[C@H](O)C2)cc1F
InChIKey: IGVXQZZYKDNDIF-QWRGUYRKSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of human recombinant CYP3A4 expressed in baculovirus-infected insect cells using 7-Benzoyloxy-4-trifluoromethyl coumarin substrate in presence of NADP+ by fluorescence based assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 419.93, ALogP 3.7, HBA 6, HBD 3, PSA 91.32, QED 0.66
Compound (SMILES): O=C1CCc2ccc(OCCCCN3CCCN(c4ccc(O)c5oc(=O)ccc45)CC3)cc2N1
InChIKey: DMEAUWNQEDPHFL-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: Displacement of [3H]spiperone from human D3R expressed in CHO cell membranes by radioligand binding assay
Measurement: Ki = 240 nM (pChEMBL 6.619999885559082)
Descriptors: MW 477.56, ALogP 3.75, HBA 7, HBD 2, PSA 95.25, QED 0.4
Compound (SMILES): O=C(C(=S)N1CCOCC1)c1ccc([N+](=O)[O-])cc1
InChIKey: MWOIENLQRWUAHG-UHFFFAOYSA-N
Target: D-3-phosphoglycerate dehydrogenase (SINGLE PROTEIN), Homo sapiens
UniProt: O43175
Assay: Inhibition of PHGDH in human HL60 cells assessed as reduction in cell viability in serine repleted medium after 5 days by presto blue assay
Measurement: IC50 = 17600 nM (pChEMBL 4.75)
Descriptors: MW 280.3, ALogP 1.44, HBA 5, HBD 0, PSA 72.68, QED 0.36