lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CN1CCc2ccc(OCCCCN3CCN(c4cccc(Cl)c4Cl)CC3)cc2C1=O
InChIKey: NVFPJOVGMQRLJI-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P14842
Assay: Displacement of [3H]ketanserin from rat cerebral cortex 5HT2A receptor measured after 15 mins by liquid scintillation counting method
Measurement: Ki = 215.9 nM (pChEMBL 6.670000076293945)
Descriptors: MW 462.42, ALogP 4.6, HBA 4, HBD 0, PSA 36.02, QED 0.56
Compound (SMILES): NS(=O)(=O)c1ccc(CNC(=O)CN2CCN(c3ccc(C(F)(F)F)cc3)CC2)cc1
InChIKey: FQSSPYGJTWIFME-UHFFFAOYSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Inhibition of recombinant human carbonic anhydrase 7 by stopped-flow CO2 hydration assay
Measurement: Ki = 426.8 nM (pChEMBL 6.369999885559082)
Descriptors: MW 456.49, ALogP 1.79, HBA 5, HBD 2, PSA 95.74, QED 0.69
Compound (SMILES): COc1ccc2[nH]cc(CCNC(=O)CN(CCCCCCCCNc3c4c(nc5ccccc35)CCCC4)C(=O)/C=C/c3ccc(O)c(OC)c3)c2c1
InChIKey: OCOGBPYFWRDLHI-RELWKKBWSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of AChE in human erythrocyte hemo-lyzates pre-incubated for 5 mins before addition of acetylthiocholine iodide substrate by Ellman's method
Measurement: IC50 = 43.7 nM (pChEMBL 7.360000133514404)
Descriptors: MW 731.94, ALogP 7.97, HBA 7, HBD 4, PSA 128.81, QED 0.05
Compound (SMILES): C[C@H](NC(=O)[C@H](CC(=O)NC(C)(C)C)NC(=O)C(=O)c1c[nH]c2ccccc12)C(=O)NCc1cccc2ccccc12
InChIKey: WHUGWHDKPJKEDN-SIBVEZHUSA-N
Target: Proteasome subunit beta type-8 (SINGLE PROTEIN), Homo sapiens
UniProt: P28062
Assay: Inhibition of human 20S immunoproteasome beta 5 chymotrypsin-like activity in human KARPAS-1106P cells incubated for 2 hrs by proteasome-Glo assay
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 569.66, ALogP 3.11, HBA 5, HBD 5, PSA 149.26, QED 0.15
Compound (SMILES): COc1nc(-c2csc(Nc3c4c(nn3CCF)CCC4)n2)ccc1-n1cnc(C)c1
InChIKey: FTHWMXAAFNYFAB-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of recombinant CYP1A2 (unknown origin) by fluorescence-based assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 439.52, ALogP 4.11, HBA 9, HBD 1, PSA 82.68, QED 0.47
Compound (SMILES): NC(=O)CNC(=O)[C@H]1O[C@@H](n2cnc3c(N)ncnc32)[C@H](O)[C@@H]1O
InChIKey: YVTKFFQBWQWZGT-FLNNQWSLSA-N
Target: Heat shock protein HSP 90-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P07900
Assay: Displacement of FITC-geldanamycin from HSP90alpha (unknown origin) after 24 hrs by fluorescence polarization assay
Measurement: Kd = 32000 nM (pChEMBL 4.5)
Descriptors: MW 337.3, ALogP -3.37, HBA 10, HBD 5, PSA 191.5, QED 0.38
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)[C@H]1CC12CCN(C)CC2)c1ncc(-c2cnc3cccnc3c2)[nH]1
InChIKey: DHWPAUZGRCCDDS-VWNXMTODSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of HDAC3 (unknown origin) using compound purified by traditional preparative HPLC work-flow
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 502.66, ALogP 4.84, HBA 6, HBD 2, PSA 103.87, QED 0.36
Compound (SMILES): c1ccc(CCCCNC2CCc3ccccc3C2)cc1
InChIKey: TUPBHPRONPKLPN-UHFFFAOYSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q5U3Y7
Assay: Displacement of [3H]DTG from sigma 2 receptor in rat liver membranes incubated for 120 mins by scintillation counting method
Measurement: Ki = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 279.43, ALogP 4.16, HBA 1, HBD 1, PSA 12.03, QED 0.78
Compound (SMILES): Cc1ccc(C(=O)/C=C/C(=O)N2CCc3cc(Nc4ncc(C)c(-c5cnn(C(C)C)c5)n4)ccc3C2)cc1
InChIKey: GHWJXBANKVFCJG-VAWYXSNFSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 ITD mutant in human MOLM13 cells assessed as reduction in cell viability incubated for 72 hrs by MTT assay
Measurement: IC50 = 758 nM (pChEMBL 6.119999885559082)
Descriptors: MW 520.64, ALogP 5.61, HBA 7, HBD 1, PSA 93.01, QED 0.25
Compound (SMILES): COc1cc(/C=C/C(=O)N2CCc3ccccc3C2)ccc1OC(=O)N(C)C
InChIKey: SCZIJKUJAHPGAK-PKNBQFBNSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human serum BuChE using acetylcholine iodide as substrate incubated for 15 mins by Ellman's method
Measurement: IC50 = 9500 nM (pChEMBL 5.019999980926514)
Descriptors: MW 380.44, ALogP 3.35, HBA 4, HBD 0, PSA 59.08, QED 0.76
Compound (SMILES): Nc1nc(-c2ccccn2)nn1C(=O)c1ccc(C(F)(F)F)cc1
InChIKey: OTFGFYGXBRSCPI-UHFFFAOYSA-N
Target: Coagulation factor XII (SINGLE PROTEIN), Homo sapiens
UniProt: P00748
Assay: Inhibition of human coagulation factor XIIA using Boc-Gln-Gly-Arg-AMC as fluorogenic substrate measured at 1 min interval for 1 hr by fluorometric assay
Measurement: IC50 = 3207 nM (pChEMBL 5.489999771118164)
Descriptors: MW 333.27, ALogP 2.63, HBA 6, HBD 1, PSA 86.69, QED 0.78
Compound (SMILES): Cc1cnc2nn(CC(=O)N[C@@H](C)c3ccc(OC(F)(F)F)c(F)c3)c(=O)n2c1
InChIKey: GNOPYFUDIQJLHN-JTQLQIEISA-N
Target: Probable G-protein coupled receptor 139 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6DWJ6
Assay: Agonist activity at human GPR139 expressed in CHO-K1 cells assessed as induction of beta-arrestin 2 recruitment incubated for 90 mins by PathHunter assay
Measurement: EC50 = 1 nM (pChEMBL 9)
Descriptors: MW 413.33, ALogP 2.11, HBA 7, HBD 1, PSA 90.52, QED 0.65
Compound (SMILES): Cc1cc(SC[C@@H]2[C@@H](Sc3nc[nH]n3)[C@H]3[C@H](C(=O)O)[C@H]3[C@]2(N)C(=O)O)ccc1F.Cl
InChIKey: FTKNPFVVQTVKOG-WKHIZERTSA-N
Target: Metabotropic glutamate receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q14416
Assay: Displacement of [3H]-LY459477 from recombinant human mGlu2 receptor expressed in hamster AV12 cell membranes co-expressing rat EAAT1 incubated for 90 mins by top count scintillation method
Measurement: Ki = 5.2 nM (pChEMBL 8.279999732971191)
Descriptors: MW 438.51, ALogP 1.86, HBA 7, HBD 4, PSA 142.19, QED 0.48
Compound (SMILES): C[C@H](COC(=O)CCc1ccccc1OCc1cccc(Oc2ccccc2)c1)OP(=O)(O)OC[C@H](N)C(=O)O
InChIKey: IHGAJIYKOBUMEJ-NLFFAJNJSA-N
Target: Putative P2Y purinoceptor 10 (SINGLE PROTEIN), Mus musculus
UniProt: Q8BFU7
Assay: Agonist activity at mouse P2Y10 expressed in HEK293 cells co-transfected with AP-TGFalpha/Galphaq/i1 assessed as induction of ectodomain shedding of membrane bound AP-TGFalpha after 1 hr by p-NPP substrate based microplate reader analysis
Measurement: EC50 = 290 nM (pChEMBL 6.539999961853027)
Descriptors: MW 573.54, ALogP 4.47, HBA 9, HBD 3, PSA 163.84, QED 0.16
Compound (SMILES): Cc1cc(C)cc(-c2cnc3ncn(-c4cccc(O)c4)c(=O)c3c2CN(C)CCN)c1
InChIKey: UHWCCSHGUZLTTA-UHFFFAOYSA-N
Target: Somatostatin receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P31391
Assay: Agonist activity at human SST4 receptor expressed in CHO-K1 cells assessed as inhibition of NKH477-induced intracellular cAMP accumulation incubated for 20 mins by HTRF assay
Measurement: EC50 = 19.95 nM (pChEMBL 7.699999809265137)
Descriptors: MW 429.52, ALogP 3.16, HBA 7, HBD 2, PSA 97.27, QED 0.49
Compound (SMILES): Cc1ccccc1NC(=O)CSc1nc2ccc(I)cc2c(=O)n1-c1ccc(S(N)(=O)=O)cc1
InChIKey: WFGYUMVMFKMLJB-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human carbonic anhydrase 2 incubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 220.8 nM (pChEMBL 6.659999847412109)
Descriptors: MW 606.47, ALogP 3.68, HBA 7, HBD 2, PSA 124.15, QED 0.2
Compound (SMILES): Cc1c(F)cc(C(=O)NC2CCCCCC2)c(=O)n1Cc1ccc(F)cc1
InChIKey: JVXRSOAAKCNGDD-UHFFFAOYSA-N
Target: Fatty-acid amide hydrolase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O00519
Assay: Inhibition of FAAH in human U937 cells using [ethanolamine-1-3H]AEA as substrate preincubated for 15 mins followed by substrate addition and measured after 15 mins by liquid scintillation spectroscopy
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 374.43, ALogP 3.94, HBA 3, HBD 1, PSA 51.1, QED 0.82
Compound (SMILES): O=C(CCN1CCCc2ccccc21)N1CCCC1CO
InChIKey: SHOIGSCXAHSRKT-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]-NMS from muscarinic M2 receptor (unknown origin) expressed in CHO-K1 cell membranes assessed as inhibition constant by radioligand competition analysis
Measurement: Ki = 5128.61 nM (pChEMBL 5.289999961853027)
Descriptors: MW 288.39, ALogP 1.81, HBA 3, HBD 1, PSA 43.78, QED 0.92
Compound (SMILES): CC(C)(C)c1ccc(NS(=O)(=O)c2ccc(C(=O)NO)cc2)cc1
InChIKey: VTVPRSVAUKGLSS-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant full length human HDAC8 expressed in SF9 baculovirus using FAM- labelled acetylated peptide as substrate measured by Electrophoretic mobility shift assay
Measurement: IC50 = 9.4 nM (pChEMBL 8.029999732971191)
Descriptors: MW 348.42, ALogP 2.9, HBA 4, HBD 3, PSA 95.5, QED 0.58
Compound (SMILES): Cc1cnc(Nc2ccc3c(c2)CCN(C(=O)Nc2cccc(Cl)c2)C3)nc1-c1cnn(C(C)C)c1
InChIKey: MAOHJGCUOWGMSL-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 ITD mutant in human MOLM13 cells assessed as reduction in cell viability incubated for 72 hrs by MTT assay
Measurement: IC50 = 2070 nM (pChEMBL 5.679999828338623)
Descriptors: MW 502.02, ALogP 6.22, HBA 6, HBD 2, PSA 87.97, QED 0.34
Compound (SMILES): FC1(F)CCN(Cc2cncc(-c3cnc4[nH]nc(-c5cc6c(-c7ccoc7)cccc6[nH]5)c4c3)c2)C1
InChIKey: QTGFFLVTSLMQJV-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 104 nM (pChEMBL 6.980000019073486)
Descriptors: MW 496.52, ALogP 6.27, HBA 5, HBD 2, PSA 86.63, QED 0.29
Compound (SMILES): CC1(C)Oc2cc(C34CC5CC(CC(CN=C=S)(C5)O3)C4)cc(O)c2[C@@H]2C[C@H](CO)CC[C@H]21
InChIKey: YXFPKBCMVJQAOF-KHCUROFVSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]CP55940 from human CB2 receptor expressed in HEK293 cell membrane by scintillation counting method
Measurement: Ki = 4.7 nM (pChEMBL 8.329999923706055)
Descriptors: MW 469.65, ALogP 5.33, HBA 6, HBD 2, PSA 71.28, QED 0.46
Compound (SMILES): O=C(Nc1cc2cc(-c3cncs3)ccc2cn1)c1ccc2c(c1)CNCC2
InChIKey: UHRGOZSADKOBED-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 43 nM (pChEMBL 7.369999885559082)
Descriptors: MW 386.48, ALogP 4.26, HBA 5, HBD 2, PSA 66.91, QED 0.55
Compound (SMILES): CN[C@@H]1CC[C@H](N2CC[C@H](Nc3ncnc4ccc(C(F)(F)F)cc34)C2=O)[C@H](NC(C)=O)C1
InChIKey: XAEGFERQJKCQQO-FDPIWHGQSA-N
Target: C-C chemokine receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P41597
Assay: Antagonist activity at CCR2 in human THP1 cells assessed as reduction in MCP1-induced chemotaxis measured after 30 mins by calcein-AM dye based fluorescence assay
Measurement: IC50 = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 464.49, ALogP 2.31, HBA 6, HBD 3, PSA 99.25, QED 0.63
Compound (SMILES): CCc1nc2c(N3CCNCC3)nccc2n1S(=O)(=O)c1cccc(F)c1
InChIKey: UXDZDQRAGSHUBW-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]-8-OH-DPAT from human 5HT1A expressed in HEK293 cell membranes incubated for 1 hr by micro-beta plate reader based analysis
Measurement: Ki = 829 nM (pChEMBL 6.079999923706055)
Descriptors: MW 389.46, ALogP 1.78, HBA 7, HBD 1, PSA 80.12, QED 0.73
Compound (SMILES): O=C(O)c1ccc(Oc2ccc(Cl)cc2NS(=O)(=O)c2ccc(Cl)c(Cl)c2)cc1
InChIKey: SEXCSTOTDUMWPC-UHFFFAOYSA-N
Target: C-C chemokine receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P41597
Assay: Displacement of [3H]-CCR2-RA-(R) from human CCR2b expressed in human U2OS cell membranes pre-incubated for 0 hrs before radio ligand addition and measured after 20 mins by scintillation counting method
Measurement: Ki = 3.981 nM (pChEMBL 8.399999618530273)
Descriptors: MW 472.73, ALogP 5.94, HBA 4, HBD 2, PSA 92.7, QED 0.46
Compound (SMILES): CC(C)CC(=O)Nc1cncc(-c2ccc3[nH]nc(-c4cc5c(-c6ccncc6)cncc5[nH]4)c3c2)c1
InChIKey: FKXJUMVFCPBBEX-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 29 nM (pChEMBL 7.539999961853027)
Descriptors: MW 487.57, ALogP 6.21, HBA 5, HBD 3, PSA 112.24, QED 0.26
Compound (SMILES): COC[C@]12C[C@H]1[C@@](CF)(c1cc(NC(=O)c3ccc(Cl)cn3)ccc1F)N=C(N)S2
InChIKey: BNGBJDRMXVMOAE-NSISKUIASA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of BACE1 in human HEK293 cells transfected with human wild type APP assessed as reduction in Abeta40 production incubated for overnight by ELISA
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 452.91, ALogP 3.76, HBA 6, HBD 2, PSA 89.6, QED 0.7
Compound (SMILES): Nc1nc(-c2ccccn2)nn1C(=O)[C@H]1CCCc2ccccc21
InChIKey: CAVJGRPSJPRJNJ-AWEZNQCLSA-N
Target: Coagulation factor XII (SINGLE PROTEIN), Homo sapiens
UniProt: P00748
Assay: Inhibition of human coagulation factor XIIA using Boc-Gln-Gly-Arg-AMC as fluorogenic substrate measured at 1 min interval for 1 hr by fluorometric assay
Measurement: IC50 = 134 nM (pChEMBL 6.869999885559082)
Descriptors: MW 319.37, ALogP 2.68, HBA 6, HBD 1, PSA 86.69, QED 0.78
Compound (SMILES): O=c1c2c(Cl)cccc2nc([C@@H]2CC3(CC3)CN2c2ncnc3[nH]cnc23)n1-c1ccccc1
InChIKey: JMCOBLCEJSXBNG-SFHVURJKSA-N
Target: Phosphatidylinositol 3-kinase regulatory subunit beta/Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (PROTEIN COMPLEX), Homo sapiens
UniProt: O00459
Assay: Inhibition of human full-length recombinant His-tagged PI3K p110beta/p85beta expressed in baculovirus expression system using PIP2 as substrate measured after 2 hrs by ADP-Glo luminescence assay
Measurement: IC50 = 2641 nM (pChEMBL 5.579999923706055)
Descriptors: MW 469.94, ALogP 4.44, HBA 7, HBD 1, PSA 92.59, QED 0.42
Compound (SMILES): CC1CCCC(C)N1C(=O)CCN1CCCc2ccccc21
InChIKey: ZJKKWZMKWAJTKP-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]-NMS from muscarinic M2 receptor (unknown origin) expressed in CHO-K1 cell membranes assessed as inhibition constant by radioligand competition analysis
Measurement: Ki = 4786.3 nM (pChEMBL 5.320000171661377)
Descriptors: MW 300.45, ALogP 3.62, HBA 2, HBD 0, PSA 23.55, QED 0.85
Compound (SMILES): O=c1cc(CN2CCN(Cc3ccccc3)CC2)c2ccc(OCc3cccc(Br)c3)cc2o1
InChIKey: NCBPILFLMOPZQB-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 preincubated for 10 mins by stopped flow CO2 hydrase assay
Measurement: Ki = 850 nM (pChEMBL 6.070000171661377)
Descriptors: MW 519.44, ALogP 5.45, HBA 5, HBD 0, PSA 45.92, QED 0.3
Compound (SMILES): CO[C@@]12CC[C@@H](N[C@@H](CC(N)=O)C(=O)O)[C@@H]3Oc4c(O)ccc5c4[C@@]31CCN(C)[C@@H]2C5
InChIKey: VJFNAJWMIIUIKO-YQSLKQGWSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Cavia porcellus
UniProt: P41144
Assay: Displacement of [3H]U69,593 from kappa opioid receptor in guinea-pig brain membranes incubated for 30 mins by liquid scintillation counting method
Measurement: Ki = 103 nM (pChEMBL 6.989999771118164)
Descriptors: MW 431.49, ALogP 0.12, HBA 7, HBD 4, PSA 134.35, QED 0.5
Compound (SMILES): COc1cncc(C(=O)Nc2c[nH]nc2C(=O)Nc2ccc(CN(C)C)cc2)c1
InChIKey: IUBMYOISONSWIP-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 6607 nM (pChEMBL 5.179999828338623)
Descriptors: MW 394.44, ALogP 2.38, HBA 6, HBD 3, PSA 112.24, QED 0.57
Compound (SMILES): CN1CCN(Cc2ccc(NC(=O)c3n[nH]c4ccc(-c5cccnc5)cc34)cn2)CC1
InChIKey: ONKHKERFMSOGOO-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 34 nM (pChEMBL 7.46999979019165)
Descriptors: MW 427.51, ALogP 3.02, HBA 6, HBD 2, PSA 90.04, QED 0.51
Compound (SMILES): CCCC(=O)Nc1cncc(-c2ccc3[nH]nc(-c4nc5c(-c6ccncc6)cncc5[nH]4)c3n2)c1
InChIKey: SVVIVDKAJUKQCG-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of recombinant CLK3 (unknown origin) using Ser/Thr 18 peptide as substrate incubated for 1 hr in presence of ATP by FRET assay
Measurement: EC50 = 995 nM (pChEMBL 6)
Descriptors: MW 475.52, ALogP 4.76, HBA 7, HBD 3, PSA 138.02, QED 0.32
Compound (SMILES): CCC(=O)CCCCC[C@H](NC(=O)c1cncs1)c1[nH]c(-c2ccc(F)cc2)nc1C#N
InChIKey: CVDCDYPZZIBFOG-SFHVURJKSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of HDAC2 (unknown origin)
Measurement: IC50 = 51.3 nM (pChEMBL 7.289999961853027)
Descriptors: MW 453.54, ALogP 4.94, HBA 6, HBD 2, PSA 111.53, QED 0.4
Compound (SMILES): CCCc1cc(O)c2c(c1)OC(C)(C)[C@@H]1C[C@H](O)C(C)=C[C@@H]21
InChIKey: JXXVDKGGZIPBOC-KFWWJZLASA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]-CP-55,940 from recombinant human CB2R expressed in HEK293 cell membranes after 90 mins
Measurement: IC50 = 807.7 nM (pChEMBL 6.090000152587891)
Descriptors: MW 302.41, ALogP 3.93, HBA 3, HBD 2, PSA 49.69, QED 0.81
Compound (SMILES): C[C@@H]1CN(c2ccc(C#N)c3ncccc23)C[C@@H]2CN(c3cccc4c3CCNC4)CCN21
InChIKey: TWCOLPRDAQZXDZ-KNQAVFIVSA-N
Target: Toll-like receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYK1
Assay: Inhibition of human TLR7 expressed in HEK-Blue cells assessed as inhibition of R848-induced NF-kappaB and AP-1 activation measured after 20 hrs by quanti-blue based SEAP reporter gene assay
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 438.58, ALogP 3.15, HBA 6, HBD 1, PSA 58.43, QED 0.66
Compound (SMILES): Cc1cc2ccnc(N[C@@H]3CCNC[C@H]3C(=O)NC3CCCC3)c2[nH]c1=O
InChIKey: KAJVIXPYLAGRLE-HZPDHXFCSA-N
Target: ATPase family AAA domain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6PL18
Assay: Inhibition of ATAD2 (unknown origin) by TR-FRET assay
Measurement: IC50 > 39810.72 nM (pChEMBL 4.400000095367432)
Descriptors: MW 369.47, ALogP 1.68, HBA 5, HBD 4, PSA 98.91, QED 0.66
Compound (SMILES): Cc1ccccc1CN1C2CCC1CC(NC(=O)c1ccc3ccccc3c1)C2
InChIKey: WAPWCWXQGLXTRS-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Rattus norvegicus
UniProt: P14842
Assay: Displacement of [3H]-ketanserin from rat cerebral cortex 5HT2A receptor measured after 20 mins by liquid scintillation counter method
Measurement: Ki = 1291 nM (pChEMBL 5.889999866485596)
Descriptors: MW 384.52, ALogP 5.07, HBA 2, HBD 1, PSA 32.34, QED 0.68
Compound (SMILES): C[C@@H](OCc1ccccc1)[C@@H](C#N)NC(=O)[C@H](Cc1cccc(Cl)c1)NC(=O)c1ccc(-c2cncnc2)cc1
InChIKey: VUELCPPLRJAJCW-SPTGULJVSA-N
Target: Procathepsin L (SINGLE PROTEIN), Homo sapiens
UniProt: P07711
Assay: Inhibition of human cathepsin L
Measurement: Ki = 15.85 nM (pChEMBL 7.800000190734863)
Descriptors: MW 554.05, ALogP 4.75, HBA 6, HBD 2, PSA 117, QED 0.28
Compound (SMILES): O=C(/C=C/c1ccc(Cl)cc1)Nc1ccc2oc(=O)ccc2c1
InChIKey: SQCPGWSIAPLGCL-YCRREMRBSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 assessed as inhibition constant preincubated with enzyme for 10 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 88.9 nM (pChEMBL 7.050000190734863)
Descriptors: MW 325.75, ALogP 4.1, HBA 3, HBD 1, PSA 59.31, QED 0.58
Compound (SMILES): O=C(c1ccc(F)c(Cl)c1)N1CCC(F)(CNCCOc2ccccc2F)CC1
InChIKey: FRPYDYUBDGOHLI-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Biased agonist activity at human 5-HT1A receptor stably expressed in CHO-K1 cells assessed as increase in ERK1/2 phosphorylation after 15 mins by Alphalisa assay
Measurement: EC50 = 5.754 nM (pChEMBL 8.239999771118164)
Descriptors: MW 426.87, ALogP 4.23, HBA 3, HBD 1, PSA 41.57, QED 0.67
Compound (SMILES): Cc1cnc(Nc2ccc3c(c2)CCN(C/C=C/C(=O)O)C3)nc1-c1cnn(C(C)C)c1
InChIKey: SNRUIWMOAHSUGQ-SNAWJCMRSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 ITD mutant in human MOLM13 cells assessed as reduction in cell viability incubated for 72 hrs by MTT assay
Measurement: IC50 = 845 nM (pChEMBL 6.070000171661377)
Descriptors: MW 432.53, ALogP 3.97, HBA 7, HBD 2, PSA 96.17, QED 0.55
Compound (SMILES): CNC(=O)c1sc(-c2ccnc(NC(=O)C3CC3)c2)nc1OCCCc1cn(CCNc2c3c(nc4ccccc24)CCCC3)nn1
InChIKey: ALRPJVIDEJKLDX-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of recombinant human N-terminal His6-tagged GSK-3beta H350L mutant expressed in baculovirus infected Sf21 cells using GSM as substrate incubated for 30 mins in presence of ATP by kinase-glo luminescence assay
Measurement: IC50 = 64.3 nM (pChEMBL 7.190000057220459)
Descriptors: MW 651.8, ALogP 5.06, HBA 11, HBD 3, PSA 148.84, QED 0.15
Compound (SMILES): COc1ccc(OC)c2c1c(OC)cc1c(=O)cc(-c3ccc(N4CCN(C)CC4)cc3)oc12
InChIKey: XXGYKUVWHMEKFY-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of recombinant human CYP1A2 using 7-ethoxyresorufin as substrate after 50 mins in presence of NADP+ by EROD assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 460.53, ALogP 4.39, HBA 7, HBD 0, PSA 64.38, QED 0.41
Compound (SMILES): Cc1ncnc(C2CC2)c1-c1ncc2nc(NCc3ccc(S(C)(=O)=O)cn3)c(=O)n([C@@H](C)C3CC3)c2n1
InChIKey: HVVHIBHBDCYLDI-HNNXBMFYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Antagonist activity at RORgamma in human whole blood assessed as inhibition of IL-17 production
Measurement: IC50 = 140 nM (pChEMBL 6.849999904632568)
Descriptors: MW 532.63, ALogP 3.21, HBA 11, HBD 1, PSA 145.51, QED 0.36
Compound (SMILES): O=C(NO)c1ccc(NC(=O)c2ccc(F)cc2)cc1
InChIKey: ACOLSUZRXNFSQW-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant full length human HDAC8 expressed in SF9 baculovirus using FAM- labelled acetylated peptide as substrate measured by Electrophoretic mobility shift assay
Measurement: IC50 = 567 nM (pChEMBL 6.25)
Descriptors: MW 274.25, ALogP 2.2, HBA 3, HBD 3, PSA 78.43, QED 0.59
Compound (SMILES): O=C(/C(=N/O)Nc1ccc(F)c(Br)c1)c1cncs1
InChIKey: CPKUGJMEEMFIAF-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of human TDO expressed in Escherichia coli Rosetta using tryptophan as substrate incubated for 1 hr by methylene blue based assay
Measurement: IC50 = 11808 nM (pChEMBL 4.929999828338623)
Descriptors: MW 344.17, ALogP 3.13, HBA 5, HBD 2, PSA 74.58, QED 0.29
Compound (SMILES): Cc1ccc(C#Cc2cccc(-c3nn(-c4nc(C(=O)O)cs4)c(CCC4CC4)c3Cc3ccc(S(N)(=O)=O)c(F)c3)c2)s1
InChIKey: LBOHZVFKDXCHAX-UHFFFAOYSA-N
Target: L-lactate dehydrogenase A chain (SINGLE PROTEIN), Homo sapiens
UniProt: P00338
Assay: Inhibition of GS[HiBiT]GS-tagged LDHA (unknown origin) expressed in HEK-293T cells measured after 1 hr by CESTA
Measurement: IC50 = 152 nM (pChEMBL 6.820000171661377)
Descriptors: MW 646.79, ALogP 6.18, HBA 8, HBD 2, PSA 128.17, QED 0.18
Compound (SMILES): N=C(N)NCCCCCNC(=O)NC[C@H](NC(=O)[C@@H]1CCCN1S(=O)(=O)c1ccccc1)C(=O)O
InChIKey: ZEDVVTNZWFMRKR-IRXDYDNUSA-N
Target: Integrin alpha-V/beta-1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P06756
Assay: Cell adhesion assay to SW480: The blockade of integrin alpha 5 beta 1 provides a novel target for the treatment of asthma. As shown in FIGS. 1A and 1B, delivery of ATN-161, a low affinity yet specific inhibitor of alpha5beta1, reduces the magnitude of airway narrowing in vivo in mice sensitized and challenged with ovalbumin, a widely used model of allergic asthma. In the same model, it was found that mice with a specific deletion of this integrin in smooth muscle also have reduced airway narrowing. The intracellular actin-myosin cross-bridging pathway serves as a useful target. Modulating the interactions of the cell and the extracellular matrix impairs the ability of the smooth muscle to transmit tension effectively. The blockade of integrin alpha 5 beta 1 was tested in vitro with human cell lines as well as in vivo with a mouse model of airway hyperresponsiveness. Novel compounds as described herein, and identified in Table 1, have been synthesized and tested in vitro for their ability to inhibit cell adhesion mediated by alpha5beta1 (adhesion of the colon carcinoma cell line SW480 to fibronectin, a response that is entirely dependent on binding of alpha5beta1 to fibronectin).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 511.61, ALogP -0.64, HBA 6, HBD 7, PSA 206.81, QED 0.1
Compound (SMILES): O=C(Nc1c[nH]nc1-c1nc(-c2ccc(CN3CCOCC3)cc2)c[nH]1)c1cccc(Cl)c1
InChIKey: OMUPVSAQBBZOJH-UHFFFAOYSA-N
Target: Aurora kinase B (SINGLE PROTEIN), Homo sapiens
UniProt: Q96GD4
Assay: Inhibition of Aurora B (unknown origin) incubated for 40 mins in presence of ATP by Kinase-glo luminescence assay
Measurement: IC50 = 583 nM (pChEMBL 6.230000019073486)
Descriptors: MW 462.94, ALogP 4.2, HBA 5, HBD 3, PSA 98.93, QED 0.4
Compound (SMILES): C[C@@H]1COCCN1c1nc(-c2cnc(N)nc2C(F)F)nc(N2CCOCC2)n1
InChIKey: BSJSHEXWIGDLOO-SNVBAGLBSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Displacement of alexa fluor 647-labeled kinase tracer 314 from recombinant human N-terminal GST-fused mTOR (1360 to 2549 residues) expressed in baculovirus expression system by TR-FRET assay
Measurement: Ki = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 408.41, ALogP 0.91, HBA 10, HBD 1, PSA 115.41, QED 0.78
Compound (SMILES): NS(=O)(=O)c1ccc(Cc2c(-c3ccc(F)c(C#CC(F)F)c3)nn(-c3nc(C(=O)O)cs3)c2CC2CC2)cc1F
InChIKey: IDFGVAKRSVUJAR-UHFFFAOYSA-N
Target: L-lactate dehydrogenase A chain (SINGLE PROTEIN), Homo sapiens
UniProt: P00338
Assay: Inhibition of GS[HiBiT]GS-tagged LDHA (unknown origin) expressed in HEK-293T cells measured after 1 hr by CESTA
Measurement: IC50 = 163 nM (pChEMBL 6.789999961853027)
Descriptors: MW 604.61, ALogP 4.78, HBA 7, HBD 2, PSA 128.17, QED 0.22
Compound (SMILES): O/N=C/c1cc(Cl)cc(CN2CCN(c3ccncc3)CC2)c1O
InChIKey: HSRDSKPYSLWCCY-RGVLZGJSSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Binding affinity to paraoxon-inhibited human erythrocyte AChE assessed as dissociation constant preincubated with paraoxon for 15 mins followed by compound and acetylthiocholine addition and measured every 5 to 10 mins for 120 mins by DTNB based Ellman's method
Measurement: Kd = 990 nM (pChEMBL 6)
Descriptors: MW 346.82, ALogP 2.57, HBA 6, HBD 2, PSA 72.19, QED 0.51
Compound (SMILES): O=C(Nc1cncc(-c2cnc3[nH]nc(-c4cc5cccnc5[nH]4)c3c2)c1)c1ccccc1
InChIKey: AFBARBOQEJYQMP-UHFFFAOYSA-N
Target: Proto-oncogene Wnt-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P04628
Assay: The screening assay for Wnt activity: SW480 colon carcinoma cells were transduced with a lentiviral vector expressing luciferase with a human Sp5 promoter consisting of a sequence of eight TCF/LEF binding sites. SW480 cells stably expressing the Sp5-Luc reporter gene and a hygromycin resistance gene were selected by treatment with 150 μg/mL of hygromycin for 7 days. These stably transduced SW480 cells were expanded in cell culture and used for all further screening activities. Each compound was dissolved in DMSO as a 10 mM stock and used to prepare compound source plates. Serial dilution (1:3, 10-point dose-response curves starting from 10 μM) and compound transfer was performed using the ECHO 550 (Labcyte, Sunnyvale, Calif.) into 384-well white solid bottom assay plates (Greiner Bio-One) with appropriate DMSO backfill for a final DMSO concentration of 0.1%. For Sp5-Luc reporter gene assays, the cells were plated at 4,000 cells/well in 384-well plates with medium containing 1% fetal bovine serum and incubated overnight at 37° C. and 5% CO2. Following incubation, 20 μl of BrightGlo luminescence reagent (Promega) was added to each well of the 384-well assay plates. The plates were placed on an orbital shaker for 2 min and then luminescence was quantified using the Envision (Perkin Elmer) plate reader. Readings were normalized to DMSO only treated cells, and normalized activities were utilized for EC50 calculations using the dose-response log (inhibitor) vs. responsevariable slope (four parameters) nonlinear regression feature available in GraphPad Prism 5.0 (or Dotmatics).
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 431.46, ALogP 4.82, HBA 5, HBD 3, PSA 112.24, QED 0.37
Compound (SMILES): NS(=O)(=O)c1ccc(Cc2c(-c3cccc(C#CC4CC45CC5)c3)nn(-c3nc(C(=O)O)cs3)c2CCC2CC2)cc1F
InChIKey: IWLRASIOXMYZEJ-UHFFFAOYSA-N
Target: L-lactate dehydrogenase A chain (SINGLE PROTEIN), Homo sapiens
UniProt: P00338
Assay: Inhibition of GS[HiBiT]GS-tagged LDHA (unknown origin) expressed in HEK-293T cells measured after 1 hr by CESTA
Measurement: IC50 = 175 nM (pChEMBL 6.760000228881836)
Descriptors: MW 616.74, ALogP 5.57, HBA 7, HBD 2, PSA 128.17, QED 0.24
Compound (SMILES): O=C(CCN1CCCc2ccccc21)N1CCCC(CO)C1
InChIKey: ZRVVOMWYBLFQTG-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: Displacement of [3H]-NMS from muscarinic M1 receptor (unknown origin) expressed in CHO-K1 cell membranes assessed as inhibition constant by radioligand competition analysis
Measurement: Ki = 1445.44 nM (pChEMBL 5.840000152587891)
Descriptors: MW 302.42, ALogP 2.06, HBA 3, HBD 1, PSA 43.78, QED 0.93
Compound (SMILES): CCCCC(Nc1nc2nn(C)cc2c2nc(-c3ccco3)nn12)C(=O)OCC
InChIKey: DEXIRCWPIAOKEJ-UHFFFAOYSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30542
Assay: Displacement of [3H]CCPA from human A1 receptor expressed in CHO cell membrane by radioligand binding assay
Measurement: Ki = 388 nM (pChEMBL 6.409999847412109)
Descriptors: MW 397.44, ALogP 2.8, HBA 10, HBD 1, PSA 112.37, QED 0.45
Compound (SMILES): NS(=O)(=O)c1ccc(NS(=O)(=O)CCNC(=O)Nc2ccc([N+](=O)[O-])cc2)cc1
InChIKey: UMYGCMORXGSBRC-UHFFFAOYSA-N
Target: Carbonic anhydrase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P43166
Assay: Inhibition of recombinant human carbonic anhydrase 7 incubated for 15 mins prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 222.6 nM (pChEMBL 6.650000095367432)
Descriptors: MW 443.46, ALogP 0.81, HBA 7, HBD 4, PSA 190.6, QED 0.34
Compound (SMILES): O=C(O)c1cccc(Nc2ccc([N+](=O)[O-])c3c([N+](=O)[O-])cccc23)c1
InChIKey: DEBLYSMOATYNAJ-UHFFFAOYSA-N
Target: Aldo-keto reductase family 1 member C1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q04828
Assay: Inhibition of human AKR1C1 using S-tetralol as substrate in presence of NADP by fluorescence method
Measurement: IC50 = 15400 nM (pChEMBL 4.809999942779541)
Descriptors: MW 353.29, ALogP 4.1, HBA 6, HBD 2, PSA 135.61, QED 0.52
Compound (SMILES): O=S(=O)(N[C@@H]1CCN(CCCc2noc3ccccc23)C1)c1ccc(F)cc1
InChIKey: XIRROHSGQGQXTD-MRXNPFEDSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-methylspiperone from recombinant human D2 receptor expressed in CHOK1 cell membranes measured after 60 mins by microbeta counting method
Measurement: Ki = 95.5 nM (pChEMBL 7.019999980926514)
Descriptors: MW 403.48, ALogP 2.95, HBA 5, HBD 1, PSA 75.44, QED 0.66
Compound (SMILES): O[C@@H]1[C@H](O)CO[C@H]1Cn1cnc2c(NCc3cccc(I)c3)nc(Cl)nc21
InChIKey: YNJLPUNKRNXONY-MBNYWOFBSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Agonist activity at PPARgamma LBD (unknown origin) assessed as increase in recruitment of coactivator peptide fluorescein-TRAP220/DRIP by TR-FRET assay
Measurement: EC50 = 9950 nM (pChEMBL 5)
Descriptors: MW 501.71, ALogP 1.82, HBA 8, HBD 3, PSA 105.32, QED 0.36
Compound (SMILES): COc1cc(NC2CN(CCCF)C2)ccc1[C@@H]1c2ccc3[nH]ncc3c2C[C@@H](C)N1CC(F)F
InChIKey: IVBCTFVBWGUGKC-DXPJPUQTSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Binding Assay : hERG (human ether go go-related gene) potassium channels are essential for normal electrical activity in the heart. Arrhythmia can be induced by a blockage of hERG channels by a diverse group of drugs. This side effect is a common reason for drug failure in preclinical safety trials and therefore minimisation of hERG channel blocking activity may be a desirable property for drug candidates.The purpose of the hERG binding assay is to evaluate the effects of test compounds on the voltage-dependent potassium channel encoded by the human ether go go-related gene (hERG) using a constitutively expressing CHO cell line on the Nanion Syncropatch 384PE automated patch clamp system.The assay was conducted as follows with all reagents used at room temperature unless otherwise stated.Reagent Preparations Include:1. Internal IC700 solution used to perfuse the underside of chip (in mM), KF 130, KCl 20, MgCl2 1, EGTA 10 and HEPES 10, (all Sigma-Aldrich; pH 7.2-7.3 using 10 M KOH, 320 mOsm) and supplemented with 25 □M escin.2. External and cell buffer (in mM), NaCl 137, KCl 4, HEPES 10, D-glucose 10, CaCl2 2, MgCl2 1 (pH7.4, NaOH)3. NMDG reference buffer used to establish a stable baseline prior to the addition of test compounds, NaCl 80, KCl 4, CaCl2 2, MgCl2 1, NMDG Cl 60, D-Glucose monohydrate 5, HEPES 10 (pH7.4 NaOH 298 mOsm)4. Seal enhancer used to improve seal quality of cells, NaCl 80, KCl 3, CaCl2 10, HEPES 10, MgCl2 1 (pH7.4 NaOH)
Measurement: IC50 = 2.1 nM (pChEMBL 8.680000305175781)
Descriptors: MW 487.57, ALogP 4.63, HBA 5, HBD 2, PSA 56.42, QED 0.46
Compound (SMILES): O=C(CCN1CCCc2ccccc21)N1CCC1
InChIKey: VDGCBKQFUSCJOT-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: Displacement of [3H]-NMS from muscarinic M1 receptor (unknown origin) expressed in CHO-K1 cell membranes assessed as inhibition constant by radioligand competition analysis
Measurement: Ki = 4466.84 nM (pChEMBL 5.349999904632568)
Descriptors: MW 244.34, ALogP 2.06, HBA 2, HBD 0, PSA 23.55, QED 0.81
Compound (SMILES): CC(C)(C)c1n[nH]c2c1C(c1ccccc1OCCS(C)(=O)=O)N(c1ccc(-c3ccon3)cc1)C2=O
InChIKey: ZLCFGJCVZRSHRY-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 520.61, ALogP 4.54, HBA 7, HBD 1, PSA 118.39, QED 0.38
Compound (SMILES): Cc1ccc(-n2c(-c3sc(NC(=O)c4ccco4)nc3-c3ccccc3)nc3ccccc3c2=O)cc1
InChIKey: QKNTUQSKNADJQQ-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Rattus norvegicus
UniProt: P30543
Assay: Displacement of [3H]MSX2 from adenosine receptor A2A in rat brain striatum membranes incubated for 30 mins by radioligand competition assay
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 504.57, ALogP 6.33, HBA 7, HBD 1, PSA 90.02, QED 0.3
Compound (SMILES): CCOC(=O)[C@@]12C[C@@H]1[C@@H](n1cnc3c(NC)nc(C#Cc4ccc(F)s4)nc31)[C@H](O)[C@@H]2O
InChIKey: JOXIPFXPBCNFCC-RUZZFIIFSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Mus musculus
UniProt: Q61618
Assay: Displacement of [125I]AB-MECA from mouse adrenergic A3 receptor expressed in HEK293 cell membranes assessed as inhibitor constant by radio ligand binding assay
Measurement: Ki = 625 nM (pChEMBL 6.199999809265137)
Descriptors: MW 457.49, ALogP 1.31, HBA 10, HBD 3, PSA 122.39, QED 0.4
Compound (SMILES): CS(=O)(=O)CCNC(=O)C(O)c1ccc2c(c1)CCc1c(-c3noc(-c4ccccc4)c3C(F)(F)F)noc1-2
InChIKey: HFVGEVPZXZGOMH-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99500
Assay: Agonist activity at human S1P3 expressed in CHO cell membranes assessed as stimulation of [35S]-GTPgamma-S binding measured after 45 mins by liquid scintillation counting method
Measurement: EC50 = 6200 nM (pChEMBL 5.210000038146973)
Descriptors: MW 561.54, ALogP 3.98, HBA 8, HBD 2, PSA 135.53, QED 0.35
Compound (SMILES): CCNCc1cncc(-c2cnc3[nH]nc(-c4cc5c(-c6cccnc6)ccnc5[nH]4)c3c2)c1
InChIKey: ZUNJXHXOXILKJJ-UHFFFAOYSA-N
Target: Proto-oncogene Wnt-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P04628
Assay: The screening assay for Wnt activity: SW480 colon carcinoma cells were transduced with a lentiviral vector expressing luciferase with a human Sp5 promoter consisting of a sequence of eight TCF/LEF binding sites. SW480 cells stably expressing the Sp5-Luc reporter gene and a hygromycin resistance gene were selected by treatment with 150 μg/mL of hygromycin for 7 days. These stably transduced SW480 cells were expanded in cell culture and used for all further screening activities. Each compound was dissolved in DMSO as a 10 mM stock and used to prepare compound source plates. Serial dilution (1:3, 10-point dose-response curves starting from 10 μM) and compound transfer was performed using the ECHO 550 (Labcyte, Sunnyvale, Calif.) into 384-well white solid bottom assay plates (Greiner Bio-One) with appropriate DMSO backfill for a final DMSO concentration of 0.1%. For Sp5-Luc reporter gene assays, the cells were plated at 4,000 cells/well in 384-well plates with medium containing 1% fetal bovine serum and incubated overnight at 37° C. and 5% CO2. Following incubation, 20 μl of BrightGlo luminescence reagent (Promega) was added to each well of the 384-well assay plates. The plates were placed on an orbital shaker for 2 min and then luminescence was quantified using the Envision (Perkin Elmer) plate reader. Readings were normalized to DMSO only treated cells, and normalized activities were utilized for EC50 calculations using the dose-response log (inhibitor) vs. responsevariable slope (four parameters) nonlinear regression feature available in GraphPad Prism 5.0 (or Dotmatics).
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 446.52, ALogP 4.73, HBA 6, HBD 3, PSA 108.06, QED 0.34
Compound (SMILES): C[C@H](NC(=O)[C@H](CCC(=O)NC(C)(C)C)NC(=O)CCc1ccccc1)C(=O)NCc1ccc(F)c2ccccc12
InChIKey: LEKFHXQPKLJWJC-IDISGSTGSA-N
Target: Proteasome Macropain subunit MB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28074
Assay: Inhibition of human 20S constitutive proteasome beta 5 chymotrypsin-like activity in human HeLa cells incubated for 2 hrs by proteasome-Glo assay
Measurement: IC50 = 2031 nM (pChEMBL 5.690000057220459)
Descriptors: MW 562.69, ALogP 3.91, HBA 4, HBD 4, PSA 116.4, QED 0.27
Compound (SMILES): COC[C@@H](C)Nc1cc(NC(=O)N2CCCc3cc(CN4CCN(C)CC4=O)c(C=O)nc32)ncc1C#N
InChIKey: ODGIYJISIWJCTG-QGZVFWFLSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of recombinant non-phosphorylated FGFR4 kinase domain (442 to 753) (unknown origin) expressed in Sf9 insect cells using 5-Fluo-Ahx-KKKKEEIYFFFG-NH2 peptide as substrate in presence of ATP measured after 60 mins by caliper microfluidic mobility shift assay
Measurement: IC50 = 1.5 nM (pChEMBL 8.819999694824219)
Descriptors: MW 520.59, ALogP 1.87, HBA 9, HBD 2, PSA 143.79, QED 0.5
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CCC[C@@H](Nc3ncc(Cl)c(-c4c[nH]c5ccccc45)n3)C2)nc1
InChIKey: RVJLYMOGPFRCQZ-QGZVFWFLSA-N
Target: Cyclin-dependent kinase 7/ cyclin H (PROTEIN COMPLEX), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7/Cyclin H (unknown origin)
Measurement: IC50 = 919 nM (pChEMBL 6.039999961853027)
Descriptors: MW 501.98, ALogP 4.51, HBA 6, HBD 3, PSA 115.9, QED 0.33
Compound (SMILES): Cc1c(Nc2ccc(S(=O)(=O)N3CCN(C)CC3)cc2F)nc2ccc(Nc3cnn(C4CC4)c3)cn2c1=O
InChIKey: BFSKPRUNBBMNCF-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Selectivity interaction (NIBR principial panel (12 GPCRs, 3 nuclear receptors, 3 transporters, and 7 other enzymes)) EUB0000254b PTGS2
Measurement: IC50 = 800 nM (pChEMBL 6.099999904632568)
Descriptors: MW 552.64, ALogP 3.1, HBA 10, HBD 2, PSA 116.87, QED 0.36
Compound (SMILES): COC(=O)N[C@H](C(=O)N1CCC[C@H]1c1ncc(-c2ccc(C#CC#Cc3cnc([C@@H]4CCCN4C(=O)[C@H](NC(=O)OC)c4ccccc4)[nH]3)cc2)[nH]1)C(C)C.Cl.Cl
InChIKey: FFQVKTCXABDWBR-GVYXSLNHSA-N
Target: Nonstructural protein 5A (SINGLE PROTEIN), Hepatitis C virus
UniProt: Q5L478
Assay: Inhibition of HCV genotype 1a NS5A infected in Huh7 cells assessed as reduction in viral replication incubated 3 days and measured by bright Glo-luciferase reporter gene assay
Measurement: IC50 = 0.276 nM (pChEMBL 9.5600004196167)
Descriptors: MW 744.85, ALogP 5.01, HBA 8, HBD 4, PSA 174.64, QED 0.17
Compound (SMILES): CN(C)c1nc(-c2ccc(S(N)(=O)=O)cc2)cn2c(=O)n(-c3ccccc3)nc12
InChIKey: SMRAUEYCFQUGMY-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of human CA1 incubated for 15 mins by stopped- flow CO2 hydrase assay method
Measurement: Ki = 2093 nM (pChEMBL 5.679999828338623)
Descriptors: MW 410.46, ALogP 1.26, HBA 8, HBD 1, PSA 115.59, QED 0.54
Compound (SMILES): O=C(O)CC1(C(=O)NCc2nc(-c3ccccc3)cs2)Cc2ccccc2C1
InChIKey: MQSGWKNPGWVMGT-UHFFFAOYSA-N
Target: Angiotensin-converting enzyme (SINGLE PROTEIN), Oryctolagus cuniculus
UniProt: P12822
Assay: Inhibition of rabbit ACE using Abz-FRK(DNP)-P as substrate measured for every 30 sec for 5 mins by UV-fluorescence based assay
Measurement: Ki > 57000 nM (pChEMBL 4.24399995803833)
Descriptors: MW 392.48, ALogP 3.69, HBA 4, HBD 2, PSA 79.29, QED 0.67
Compound (SMILES): O=C(CCN1CCCc2ccccc21)N1CCC[C@H]1CO
InChIKey: SHOIGSCXAHSRKT-HNNXBMFYSA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: Displacement of [3H]-NMS from muscarinic M1 receptor (unknown origin) expressed in CHO-K1 cell membranes assessed as inhibition constant by radioligand competition analysis
Measurement: Ki = 14125.38 nM (pChEMBL 4.849999904632568)
Descriptors: MW 288.39, ALogP 1.81, HBA 3, HBD 1, PSA 43.78, QED 0.92
Compound (SMILES): C[C@@H]1CCC[C@H](C)N1C(=O)CCN1CCCc2ccccc21
InChIKey: ZJKKWZMKWAJTKP-IYBDPMFKSA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: Displacement of [3H]-NMS from muscarinic M1 receptor (unknown origin) expressed in CHO-K1 cell membranes assessed as inhibition constant by radioligand competition analysis
Measurement: Ki = 1148.15 nM (pChEMBL 5.940000057220459)
Descriptors: MW 300.45, ALogP 3.62, HBA 2, HBD 0, PSA 23.55, QED 0.85
Compound (SMILES): Cl.NC[C@H]1C[C@@H]1c1c(OCC2CC2)ccc2c1CCO2
InChIKey: AJMUJJINXBRVEL-YLAFAASESA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Agonist activity at human 5-HT2B receptor expressed in human Flp-In-293 cells assessed as induction of calcium flux incubated for 1 hr by Fluo-4 direct dye based FLIPR assay
Measurement: EC50 = 269 nM (pChEMBL 6.570000171661377)
Descriptors: MW 259.35, ALogP 2.47, HBA 3, HBD 1, PSA 44.48, QED 0.88
Compound (SMILES): COC(=O)N[C@H](C(=O)N1CCC[C@H]1c1ncc(-c2ccc(C#CC#Cc3cnc([C@@H]4CCCN4C(=O)[C@H](NC(=O)OC)c4ccccc4)[nH]3)c(-c3cccc(C(C)(C)C)c3)c2)[nH]1)C(C)C.Cl.Cl
InChIKey: HMKVCBFOXCELJA-MFVNDEGASA-N
Target: Nonstructural protein 5A (SINGLE PROTEIN), Hepatitis C virus
UniProt: Q5L478
Assay: Inhibition of HCV genotype 2a NS5A infected in Huh7 cells assessed as reduction in viral replication incubated 3 days and measured by bright Glo-luciferase reporter gene assay
Measurement: IC50 = 0.104 nM (pChEMBL 9.979999542236328)
Descriptors: MW 877.06, ALogP 7.97, HBA 8, HBD 4, PSA 174.64, QED 0.1
Compound (SMILES): C[C@H]1C=C(C2=Nc3cc(Cl)ccc3Nc3ccc(F)cc32)CCN1C
InChIKey: JJZQCWGLYTVPFB-LBPRGKRZSA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: Agonist activity at muscarinic M1 receptor (unknown origin) expressed in CHO cells
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 355.84, ALogP 5.31, HBA 3, HBD 1, PSA 27.63, QED 0.75
Compound (SMILES): CCn1c2ccccc2c2ccc(NCC(=O)N3CCCCC3)cc21
InChIKey: WCEUZVJNVIQHES-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: Displacement of [3H]-NMS from muscarinic M1 receptor (unknown origin) expressed in CHO-K1 cell membranes assessed as inhibition constant by radioligand competition analysis
Measurement: Ki = 43651.58 nM (pChEMBL 4.360000133514404)
Descriptors: MW 335.45, ALogP 4.24, HBA 3, HBD 1, PSA 37.27, QED 0.77
Compound (SMILES): Cc1ccc(N2CCN(CCC(=O)NCc3ccc(S(N)(=O)=O)cc3)CC2)cc1
InChIKey: CZJGYUVULOPGEQ-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 by stopped-flow CO2 hydration assay
Measurement: Ki = 78.9 nM (pChEMBL 7.099999904632568)
Descriptors: MW 416.55, ALogP 1.47, HBA 5, HBD 2, PSA 95.74, QED 0.71
Compound (SMILES): CO[C@H]1C[C@](CC#N)(n2cc(-c3nc(-c4cnn(C)c4)cn4nccc34)cn2)C1
InChIKey: VYWKECFAYKXBQW-UKIBZPOASA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: JAK Caliper Enzyme Assay at 1 mM ATP: Compounds were added to a 384-well plate. Reaction mixtures contained 10 mM HEPES, pH 7.4, 10 mM MgCl2, 0.01% BSA, 0.0005% Tween 20, 1 mM ATP and 1 μM peptide substrate. The JAK1 and TYK2 assays contained 1 μM of the IRStide peptide (5FAM-KKSRGDYMTMQID) and the JAK2 and JAK3 assays contained 1 μM of the JAKtide peptide (FITC-KGGEEEEYFELVKK). The assays were initiated by the addition of 20 nM JAK1, 1 nM JAK2, 1 nM JAK or 1 nM TYK2 enzyme and were incubated at room temperature for three hours for JAK1, 60 minutes for JAK2, 75 minutes for JAK3 or 135 minutes for TYK2. Enzyme concentrations and incubation times were optimized for each new enzyme preps and were modified slightly over time to ensure 20% to 30% phosphorylation. The assays were stopped with 15 μL of 180 mM HEPES, pH 7.4, 20 mM EDTA, and 0.2% Coating Reagent 3. The assay plates were placed on a Caliper Life Science LC3000 instrument, and each well was sampled using appropriate separation conditions to measure the unphosphorylated and phosphorylated peptide.
Measurement: IC50 = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 388.44, ALogP 2.41, HBA 9, HBD 0, PSA 98.85, QED 0.52
Compound (SMILES): Cc1cc(O)cc(C)c1C[C@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)CCN1Cc2ccccc2C[C@H](NC(=O)[C@@H](CCCNC(=N)N)NC(=O)[C@@H](N)Cc2c(C)cc(O)cc2C)C1=O)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)O)C(C)(C)C
InChIKey: RUHXXMOCSLYNBV-YRHYFRTJSA-N
Target: Neurotensin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30989
Assay: Displacement of [125I]-neurotensin from human recombinant NTS1 stably expressed in CHO-K1 cell membranes incubated for 60 mins by gamma counter method
Measurement: Ki = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 1366.72
Compound (SMILES): CS(=O)(=O)N1C[C@@H](NS(=O)(=O)c2ccc(-c3ccccc3)cc2)C[C@@H]1C(=O)NO
InChIKey: BZIYLYICROTDCU-DOTOQJQBSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human CA2 incubated for 15 mins by stopped-flow CO2 hydration kinetic assay based Cheng-Prusoff equation analysis
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 439.52, ALogP 0.54, HBA 6, HBD 3, PSA 132.88, QED 0.44
Compound (SMILES): C=CC(=O)Nc1cc2c(Nc3ccc(OCc4cccc(F)c4)c(Cl)c3)ncnc2cc1OCc1cn(CCCCC(=O)NO)nn1
InChIKey: SSAKQDBVDKDWIF-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR L858R/T790M (unknown origin) by mobility shift assay
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 661.09, ALogP 5.72, HBA 11, HBD 4, PSA 165.41, QED 0.05