lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=C(CCN1CCCC1)Nc1ccc(-n2cc(-c3cccc(-c4cn(-c5ccc(NC(=O)CCN6CCCC6)cc5)nn4)c3)nn2)cc1
InChIKey: GVZWJDRXVVYKRH-UHFFFAOYSA-N
Target: Telomerase reverse transcriptase (SINGLE PROTEIN), Homo sapiens
UniProt: O14746
Assay: Inhibition of telomerase activity in human A2780 cells incubated for 10 mins by SYBR Green 1 staining based TRAP assay
Measurement: EC50 = 13300 nM (pChEMBL 4.880000114440918)
Descriptors: MW 644.78, ALogP 5.03, HBA 10, HBD 2, PSA 126.1, QED 0.19
Compound (SMILES): CCCCCn1cc(C(=O)N[C@H](C(N)=O)C(C)(C)C)c2cccnc21
InChIKey: QDZHLYBDQFZWCJ-OAHLLOKOSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Agonist activity at human CB1 receptor expressed in AtT-20 cells measured every 2 secs for 2 mins by FLIPR assay
Measurement: EC50 = 3.981 nM (pChEMBL 8.399999618530273)
Descriptors: MW 344.46, ALogP 2.86, HBA 4, HBD 2, PSA 90.01, QED 0.76
Compound (SMILES): N=C(N)NCCC[C@H](N)CNC(=O)NCCCC[C@H](N)C(=O)N[C@H](CCN)C(=O)N1C=CC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)O
InChIKey: YZXHKJDMXHOWRK-WHZJULEDSA-N
Target: Neuropilin-1 (SINGLE PROTEIN), Homo sapiens
UniProt: O14786
Assay: Inhibition of biotinylated human VEGF-A165 binding to recombinant human NRP1 receptor after 2 hrs by chemiluminescence analysis relative to control
Measurement: IC50 = 2900 nM (pChEMBL 5.539999961853027)
Descriptors: MW 682.83, ALogP -3.85, HBA 10, HBD 14, PSA 358.8, QED 0.03
Compound (SMILES): COc1cc(NC(=O)c2ccc(F)c(C#Cc3cc(-c4cnn(C)c4)cnc3N)c2)cc(OC)c1
InChIKey: OPEBMTODKYGJES-UHFFFAOYSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07333
Assay: Inhibition of recombinant CSF1R (unknown origin) using poly (Glu, Tyr)4:1 as substrate measured after 1 hr by ELISA
Measurement: IC50 = 160.3 nM (pChEMBL 6.789999961853027)
Descriptors: MW 471.49, ALogP 3.87, HBA 7, HBD 2, PSA 104.29, QED 0.43
Compound (SMILES): COc1cc2c(Oc3ccc(NS(=O)(=O)c4ccccc4Cl)cc3F)ccnc2cc1OCCCN1CCN(C)CC1
InChIKey: PERKMRIUWVEJGY-UHFFFAOYSA-N
Target: Tyrosine-protein kinase receptor UFO (SINGLE PROTEIN), Homo sapiens
UniProt: P30530
Assay: Inhibition of AXL (unknown origin) phosphorylation after 1 hr by ELISA
Measurement: IC50 = 184 nM (pChEMBL 6.739999771118164)
Descriptors: MW 615.13, ALogP 5.65, HBA 8, HBD 1, PSA 93.23, QED 0.22
Compound (SMILES): O=C(NCc1cccc(C(F)(F)F)c1)c1cccc2c1cnn2Cc1ccccc1
InChIKey: CRLOJHYDLJBMNY-UHFFFAOYSA-N
Target: C-C chemokine receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P32246
Assay: Antagonist activity at recombinant CCR1 (unknown origin) expressed in non-adherent cells co-expressing Galpha16 assessed as inhibition of MIP-1 alpha-induced calcium flux by Fluo-4 NW or Calcium 4 dye based FLIPR TETRA assay
Measurement: IC50 > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 409.41, ALogP 5.03, HBA 3, HBD 1, PSA 46.92, QED 0.5
Compound (SMILES): N#C/C(=C\c1cc(O)c(O)c([N+](=O)[O-])c1)C(=O)N1CCC[C@H]1C(=O)O
InChIKey: YRSBQHMAAXWAQC-LLGDCAAFSA-N
Target: Alpha-ketoglutarate-dependent dioxygenase FTO (SINGLE PROTEIN), Homo sapiens
UniProt: Q9C0B1
Assay: Inhibition of FTO (unknown origin) assessed as reduction in demethylation by measuring N6-mA and A level incubated for 2 hrs by HPLC-MS/MS analysis
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 347.28, ALogP 0.99, HBA 7, HBD 3, PSA 165, QED 0.24
Compound (SMILES): Cn1c(C(=O)NC2(c3ccc(C(CC(=O)O)c4cccnc4)cc3)COC2)cc2c(Cl)c(Cl)ccc21
InChIKey: GAVIPRBFFNZNSO-UHFFFAOYSA-N
Target: D-3-phosphoglycerate dehydrogenase (SINGLE PROTEIN), Homo sapiens
UniProt: O43175
Assay: Inhibition of PHGDH (unknown origin) using 11 nM of PHGDH and 3-PG as substrate incubated for 20 mins in presence of NAD+, PSAT1, PSPH by diaphorase and resazurin dye based fluorescence assay
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 524.4, ALogP 5.14, HBA 5, HBD 2, PSA 93.45, QED 0.35
Compound (SMILES): COC(=O)C1CCN(C(=O)c2ccc(CS(=O)(=O)c3ccc4nc(N)sc4c3)cc2)CC1
InChIKey: SIBBAJXMEUBMDM-UHFFFAOYSA-N
Target: Pteridine reductase 1 (SINGLE PROTEIN), Leishmania major
UniProt: Q01782
Assay: Inhibition of Leishmania major pteridine reductase 1 using di-hydrobiopterine as substrate in presence of NADPH
Measurement: IC50 = 50000 nM (pChEMBL 4.300000190734863)
Descriptors: MW 473.58, ALogP 2.88, HBA 8, HBD 1, PSA 119.66, QED 0.57
Compound (SMILES): O=C(Oc1c(CN2CCOCC2)cc(Cl)c2cccnc12)c1ccco1
InChIKey: XWGBXBKRTBKXTQ-UHFFFAOYSA-N
Target: Hepcidin (SINGLE PROTEIN), Homo sapiens
UniProt: P81172
Assay: Inhibition of human hepcidin-stimulated recombinant C-terminal Halo-tagged human FPN internalization in MDCK cells incubated for 15 to 20 mins by Halo-tagged TMR based fluorescence assay
Measurement: IC50 < 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 372.81, ALogP 3.53, HBA 6, HBD 0, PSA 64.8, QED 0.52
Compound (SMILES): N#CN1CCCC(C(=O)Nc2cc(-c3ccccc3)n[nH]2)C1
InChIKey: SBVBPTHKHJXDIC-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 30 (SINGLE PROTEIN), Homo sapiens
UniProt: Q70CQ3
Assay: Inhibition of untagged human USP30 catalytic domain (57 to 517 residues) expressed in Escherichia coli using TAMRA labeled ubiquitin peptide as substrate preincubated for 30 min followed by substrate addition and measured after 2 hrs by fluorescence polarization assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 295.35, ALogP 2.21, HBA 4, HBD 2, PSA 84.81, QED 0.85
Compound (SMILES): Cc1cc(CN2CCc3c(cc(Cn4ccn(C)c4=N)cc3-c3ccc(F)cc3C)C2=O)ccc1Cl
InChIKey: HNKHSIKLIGVXPW-UHFFFAOYSA-N
Target: WD repeat-containing protein 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P61964
Assay: Competitive inhibition of human N-terminal His6-SUMO tagged WDR5 (22 to 334 residues) expressed in Escherichia coli BL21-Gold(DE3) cells using 10-mer-Thr-FAM peptide as substrate after 1 hr by TR-FRET assay
Measurement: Kd = 0.027 nM (pChEMBL 10.569999694824219)
Descriptors: MW 503.02, ALogP 5.63, HBA 4, HBD 1, PSA 54.02, QED 0.38
Compound (SMILES): CC[C@@H]1CN2CC[C@@]3(C(=O)c4c(OC)cccc4N3Cc3ccccc3)[C@@H]2C[C@@H]1/C(=C\OC)C(=O)OC
InChIKey: OATYCYBMQGFTJB-PAKGBSETSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Mus musculus
UniProt: P32300
Assay: Displacement of [125I]-IBNtxA from mouse delta opioid receptor-1 expressed in CHO cell membranes incubated for 90 mins
Measurement: Ki = 258 nM (pChEMBL 6.590000152587891)
Descriptors: MW 504.63, ALogP 4.46, HBA 7, HBD 0, PSA 68.31, QED 0.31
Compound (SMILES): Cl.O=C(O)CNc1cccc(CN(Cc2cc3ccccc3s2)S(=O)(=O)c2cccnc2)n1
InChIKey: KHLSMGHQVRHYON-UHFFFAOYSA-N
Target: Prostaglandin E2 receptor EP2 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P43116
Assay: Agonist activity at recombinant human EP2 receptor expressed in HEK293 cells assessed as induction of cAMP accumulation after 30 mins
Measurement: EC50 = 3.4 nM (pChEMBL 8.470000267028809)
Descriptors: MW 468.56, ALogP 3.58, HBA 7, HBD 2, PSA 112.49, QED 0.39
Compound (SMILES): CC1CN(c2cnc3cnn(C(C)c4ccc(Cl)cc4Cl)c3n2)CCC1N1CCCCC1
InChIKey: UBRBYLAGHGZRBU-UHFFFAOYSA-N
Target: C-C chemokine receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P51679
Assay: Ca Flux assay: To measure binding of 125I-TARC or 125I-MDC to cells expressing CCR4 (e.g., CEM cells (e.g., ATCC HB-12624)), the 125I-TARC or 125I-MDC is diluted to a concentration of approximately 200 pM in a buffered saline solution (e.g., RPMI supplemented with 0.5% BSA), and added to an equal volume of a suspension of cells (e.g., CEM cells at 5×106 cells/mL). The resulting mixture is incubated for a period of time (e.g., 2 hrs), and the unbound 125I-TARC or 125I-MDC is separated from the cells by filtration, e.g., by passage through GF/B filter plate (Packard Biosciences) pre-treated with 0.3% polyethyleneimine (Sigma), using a Packard Filtermate 96 (Packard Biosciences). The amount of 125I-TARC or 125I-MDC retained with the cells on the filterplate is measured by adding a small amount of scintillation fluid (e.g., 50 μL of Microscint-20 Packard Biosciences)), and reading scintillation on appropriate detection equipment, e.g., a Packard TopCount 383 (Packard Biosciences).
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 473.45, ALogP 5.44, HBA 6, HBD 0, PSA 50.08, QED 0.51
Compound (SMILES): Cn1c(=O)c2c(nc3n2CCN(c2ccc(Cl)cc2)C3)n(C)c1=O
InChIKey: JOJMEKIQIVONGO-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of recombinant human MAO-B expressed in baculovirus infected BTI insect cells preincubated for 30 mins followed by addition of p-tyramine as substrate measured over 45 mins by Amplex Red MAO assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 345.79, ALogP 1.11, HBA 7, HBD 0, PSA 65.06, QED 0.66
Compound (SMILES): Cc1cccc([C@@H](C)Nc2nc(C)nc3ccc(-c4ccc(=O)n(CC(=O)N(C)C)c4)cc23)c1
InChIKey: XKVWHQOYANVVLE-GOSISDBHSA-N
Target: Son of sevenless homolog 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07889
Assay: Inhibition of GST-tagged SOS1 (564 to 1049 amino acids) (unknown origin) assessed as reduction SOS1/6xHis-Tev-tagged K-Ras G12D mutant (1 to 169 residues) interaction incubated for 30 mins by AlphaLISA method
Measurement: IC50 = 26 nM (pChEMBL 7.579999923706055)
Descriptors: MW 455.56, ALogP 4.34, HBA 6, HBD 1, PSA 80.12, QED 0.47
Compound (SMILES): Nc1ncnc2c1c(-c1ccc3nc(OC4CC4)ccc3c1)nn2CC1CCOCC1
InChIKey: NORRNSHOSUHRSH-UHFFFAOYSA-N
Target: Calmodulin-domain protein kinase 1 (SINGLE PROTEIN), Toxoplasma gondii
UniProt: Q9BJF5
Assay: Inhibition of recombinant Toxoplasma gondii CDPK1 using Biotin-C6-PLARTLSVAGLPGKK as substrate after 90 mins in presence of ATP by luciferase reporter gene assay
Measurement: IC50 = 1.8 nM (pChEMBL 8.739999771118164)
Descriptors: MW 416.49, ALogP 3.59, HBA 8, HBD 1, PSA 100.97, QED 0.53
Compound (SMILES): COc1ccccc1Oc1cc(NC(=O)N2CCCc3cc(CN4CCOCC4=O)c(C=O)nc32)ncc1C#N
InChIKey: WSKYMIHJDBNJMP-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22455
Assay: Inhibition of FGFR4 (unknown origin) incubated for 60 mins by caliper microfluidic mobility shift technology based assay
Measurement: IC50 = 71 nM (pChEMBL 7.150000095367432)
Descriptors: MW 542.55, ALogP 3.31, HBA 9, HBD 1, PSA 146.98, QED 0.44
Compound (SMILES): COc1cccc(-n2cc(-c3ccccc3Sc3ccc(C(F)(F)F)cc3)nn2)c1OC
InChIKey: IAJLZDDKCWGKNK-UHFFFAOYSA-N
Target: Virion infectivity factor (SINGLE PROTEIN), Human immunodeficiency virus type 1 group M subtype B (isolate NY5)(HIV-1)
UniProt: P12504
Assay: Antagonist activity against HIV-1 Vif in human H9 cells expressing A3G assessed as inhibition of viral infection measured after 16 hrs by cell-based assay
Measurement: IC50 = 1900 nM (pChEMBL 5.71999979019165)
Descriptors: MW 457.48, ALogP 6.12, HBA 6, HBD 0, PSA 49.17, QED 0.35
Compound (SMILES): CS(=O)(=O)c1cnc(NS(=O)(=O)Cc2cc(Cl)cc(Cl)c2)c(O)n1
InChIKey: OFPXRDIIWHLCII-UHFFFAOYSA-N
Target: Protein S100-A9 (SINGLE PROTEIN), Homo sapiens
UniProt: P06702
Assay: Binding affinity to biotinylated recombinant human S100A9 expressed in Escherichia coli BL21 (DE3)/pET1120 (PLR757 ) assessed as inhibition of S100A9 binding to human IgGiFc tagged recombinant human RAGE incubated for 1 hr by AlphaScreen assay
Measurement: IC50 = 420 nM (pChEMBL 6.380000114440918)
Descriptors: MW 412.28, ALogP 1.83, HBA 7, HBD 2, PSA 126.32, QED 0.77
Compound (SMILES): C#CCSc1nc(Nc2nnnn2C)c(C#N)c(-c2cc(OC)c(OC)c(OC)c2)n1
InChIKey: XYFITTLYBMACFI-UHFFFAOYSA-N
Target: DCN1-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96GG9
Assay: Binding affinity to N-terminal His6-tagged recombinant human DCN1 expressed in Escherichia coli BL21-AI assessed as reduction in DCN1-FAM-labelled N-terminal acetylated UBE2M (1 to 12 residues) protein-protein interaction after 30 mins by fluorescence polarization competitive binding assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 438.47, ALogP 2.03, HBA 12, HBD 1, PSA 132.89, QED 0.31
Compound (SMILES): CCc1sc(NC(=O)C23CC4CC(CC(C4)C2)C3)c(C(=O)OC)c1C
InChIKey: LMFJEFWVETVREV-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]CP55940 from recombinant human CB2R expressed in HEK293 cell membranes measured after 90 mins
Measurement: Ki = 5.92 nM (pChEMBL 8.229999542236328)
Descriptors: MW 361.51, ALogP 4.56, HBA 4, HBD 1, PSA 55.4, QED 0.8
Compound (SMILES): Clc1ccc(Cn2c(CCc3c[nH]c4ccccc34)nnc2C2CCNCC2)cc1Cl
InChIKey: XMKNKILGZIDIQP-UHFFFAOYSA-N
Target: Somatostatin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P30874
Assay: Displacement of [125I]-Tyr-SRIF from recombinant human SST2A receptor expressed in CHOK1 cell membranes after 90 mins by gamma counting method
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 454.41, ALogP 5.37, HBA 4, HBD 2, PSA 58.53, QED 0.41
Compound (SMILES): CN1C[C@H](C(=O)NC(Cc2ccccc2)C(=O)C(N)=O)N(Cc2ccccc2)C1=O
InChIKey: DHTGQFYOAWHVSC-QRWMCTBCSA-N
Target: Calpain-1 catalytic subunit (SINGLE PROTEIN), Homo sapiens
UniProt: P07384
Assay: Inhibition of Cal1 (unknown origin)
Measurement: Ki = 101 nM (pChEMBL 7)
Descriptors: MW 408.46, ALogP 0.7, HBA 4, HBD 2, PSA 112.81, QED 0.63
Compound (SMILES): COC[C@]1(C(=O)N2CC[C@](c3ccc(C(F)(C(F)(F)F)C(F)(F)F)cc3)(S(=O)(=O)c3ccc(F)cc3)C2)CC[C@H](C(=O)O)CC1
InChIKey: VTXAHBUSZIDRJU-ATANMQQVSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at human Gal4-fused RORgammat LBD (267 to 516 residues) expressed in human Jurkat cells measured after 18 hrs by steady-glo luciferase reporter gene assay
Measurement: EC50 = 109 nM (pChEMBL 6.960000038146973)
Descriptors: MW 671.6, ALogP 5.92, HBA 5, HBD 1, PSA 100.98, QED 0.28
Compound (SMILES): Cc1cc(OC2CCCC2)cc(C(=O)Nc2ccccn2)n1
InChIKey: WIHKZGIVEAXIPX-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P41594
Assay: Negative allosteric modulation of human mGlu5 receptor assessed as inhibition of glutamate induced-calcium mobilization
Measurement: IC50 = 182 nM (pChEMBL 6.739999771118164)
Descriptors: MW 297.36, ALogP 3.36, HBA 4, HBD 1, PSA 64.11, QED 0.94
Compound (SMILES): CC/C=C\C(=O)Nc1cc(Nc2nc3c(c(-c4cn(C)c5ccc(F)cc45)n2)CSCC3)c(OC)cc1N(C)CCN(C)C
InChIKey: KQCYTAKJCMXYJE-HJWRWDBZSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of wildtype EGFR (unknown origin) using biotin as substrate in presence of ATP by mobility shift assay based ELISA
Measurement: IC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 617.8, ALogP 6.22, HBA 9, HBD 2, PSA 87.55, QED 0.19
Compound (SMILES): CN(C(=O)CNC(=O)c1ccc2ncsc2c1)C1CCS(=O)(=O)CC1
InChIKey: IBBLUSAOEFRCOU-UHFFFAOYSA-N
Target: Krueppel-like factor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13887
Assay: Inhibition of KLF5 promoter activity in human DLD1 cells by luciferase reporter gene assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 381.48, ALogP 1.06, HBA 6, HBD 1, PSA 96.44, QED 0.85
Compound (SMILES): Oc1ccc2c(c1)CCCC(c1ccc3[nH]ncc3c1)=C2c1ccc(O[C@H]2CCN(CCCF)C2)cc1
InChIKey: JNSMJDOPJIDEFF-MHZLTWQESA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Induction of ERalpha degradation in human MCF7 cells incubated for 4 hrs by Alexafluor-488 conjugate anti-rabbit antibody/Syto-64 staining based immunofluorescence analysis
Measurement: EC50 = 1.5 nM (pChEMBL 8.819999694824219)
Descriptors: MW 497.61, ALogP 6.38, HBA 4, HBD 2, PSA 61.38, QED 0.31
Compound (SMILES): [2H]C1([2H])C([2H])([2H])C([2H])([2H])C([2H])(Sc2ncc(COc3cc(F)c(C#CCOC(=O)NC4CCN(C)CC4)cc3F)n2-c2cccnc2)C1([2H])[2H]
InChIKey: VTJPUMGWNNKTDP-DMBZOWHKSA-N
Target: Transitional endoplasmic reticulum ATPase (SINGLE PROTEIN), Homo sapiens
UniProt: P55072
Assay: Inhibition of p97 (unknown origin) assessed as reduction in ATPase activity by biomol green reagent based assay
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 581.69, ALogP 5.33, HBA 8, HBD 1, PSA 81.51, QED 0.36
Compound (SMILES): C=CC(=O)N1CCC(O)(CNc2ncnc(N)c2-c2ccc(Oc3ccccc3)cc2)CC1
InChIKey: MCPXHVDMIHIMOC-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Enzyme Assay: The following describes a microfluidic, off-chip mobility shift kinase assay used to measure inherent potency of compounds against BTK enzyme. Compounds described by embodiments of the present invention were assayed using this protocol and the data from the same is recorded in Table 2 within the column labeled: Time Dependent BTK Enzyme Assay IC50. These IC50 values are reported in ranges wherein: A<100 nM, B<1 uM, and C>1 uM.2.5× stocks of full-length human BTK (08-080) from CarnaBio USA, Inc., Natick, Mass., 1.6×ATP and appropriate kinKDR peptide substrate (FITC-AHA-EEPLYWSFPAKKK-NH2) were prepared in kinase reaction buffer consisting of 25 mM MgCl2, 0.015% Brij-35 (30%), 100 mM Hepes, pH 7.5, and 10 mM DTT.5 uL of enzyme buffer and 7.5 uL of ATP/kinKDR peptide substrate mix were added to Matrix (#115304) 384-well, sterile, polypropylene plates (Thermo Fisher Scientific, Hudson, N.H.) with 125 nL of serially diluted compounds prepared in 100% DMSO, and incubated for 90 min. at 27 C. Following the incubation period, reactions were stopped by adding 60 uL stop buffer consisting of 100 mM Hepes, pH 7.5, 0.015% Brij-35 (30%), 0.277% Coating Reagent #3 (Caliper Life Sciences, Mountain View, Calif.), 5% DMSO. Stopped reactions were monitored at −2 PSI, −3000 V/−700 V in a LabChip 3000 plate reader from Caliper Life Sciences, a PerkinElmer Company (Hopkinton, Mass.), and the activity was measured by off-chip mobility shift assay measuring the charge/mass difference between substrate and product resulting from peptide phosphorylation. IC50 and efficacy were determined by plotting log [Inhibitor] vs. % Activity in GeneData Screener (Basel, Switzerland). Compounds described by embodiments of the present invention were assayed using this protocol and the data from the same is recorded in Table 2 within the column labeled: Time Dependent PBMC BTK Enzyme Assay IC50.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 445.52, ALogP 3.47, HBA 7, HBD 3, PSA 113.6, QED 0.48
Compound (SMILES): O=C(NC(=S)Nc1ccc([N+](=O)[O-])cc1O)c1ccc([N+](=O)[O-])cc1
InChIKey: IEZFSMIWEFOJSW-UHFFFAOYSA-N
Target: Fructose-bisphosphate aldolase class 2 (SINGLE PROTEIN), Synechocystis sp. (strain PCC 6803 / Kazusa)
UniProt: Q55664
Assay: Inhibition of recombinant Synechocystis sp. PCC 6803 FBA2 R302A mutant expressed in Escherichia coli BL21 (DE3) using FBP as substrate measured over 5 mins
Measurement: Ki = 24400 nM (pChEMBL 4.610000133514404)
Descriptors: MW 362.32, ALogP 2.34, HBA 7, HBD 3, PSA 147.64, QED 0.32
Compound (SMILES): CCNC(=O)Nc1ccc(-c2nccc(N3CCOC[C@@H]3C)n2)cc1
InChIKey: DEJDYNKIJWOSHA-ZDUSSCGKSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of PI3Kalpha (unknown origin) using PIP2 as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by HTRF assay
Measurement: IC50 = 6309.57 nM (pChEMBL 5.199999809265137)
Descriptors: MW 341.42, ALogP 2.51, HBA 5, HBD 2, PSA 79.38, QED 0.89
Compound (SMILES): CCc1cccc(N2CCN(CCCCNC(=O)c3cc4ccccc4o3)CC2)c1Cl
InChIKey: DRRONPWFEYCYOF-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]N-methylspiperone from human dopamine D2L receptor expressed in HEK293 cell membranes incubated for 1 hr by liquid scintillation counting analysis
Measurement: Ki = 6.34 nM (pChEMBL 8.199999809265137)
Descriptors: MW 439.99, ALogP 4.98, HBA 4, HBD 1, PSA 48.72, QED 0.5
Compound (SMILES): CNC(=O)c1cc(Oc2ccc(NC(=O)c3ccc(F)cc3)cc2)ccc1N
InChIKey: UYOKVLAGEOOSOO-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of recombinant human N-terminal GST-tagged BRAF V600E mutant catalytic domain (416 to 766 residues) expressed in baculovirus expression system using human His6-tagged MEK1 (K97R) as substrate preincubated for 20 mins followed by [33P-gamma]ATP addition and measured after 2 hrs by filter-binding assay
Measurement: IC50 = 303 nM (pChEMBL 6.519999980926514)
Descriptors: MW 379.39, ALogP 3.81, HBA 4, HBD 3, PSA 93.45, QED 0.59
Compound (SMILES): Cn1c(Oc2cccc(-c3ccc(C#N)cc3)c2)cc(=O)n(O)c1=O
InChIKey: RFHPPBLTFNJLSQ-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of RNase H activity of full length recombinant HIV1 reverse transcriptase assessed as reduction in nonspecific internal cleavage using HTS1 substrate
Measurement: IC50 = 1200 nM (pChEMBL 5.920000076293945)
Descriptors: MW 335.32, ALogP 2.12, HBA 7, HBD 1, PSA 97.25, QED 0.74
Compound (SMILES): O=C(C1CCCO1)N1CCN(CC(NCc2ccccc2)c2ccccc2)CC1
InChIKey: MUXRVMAFBSHERF-UHFFFAOYSA-N
Target: Hepcidin (SINGLE PROTEIN), Homo sapiens
UniProt: P81172
Assay: Inhibition of human hepcidin-stimulated recombinant C-terminal Halo-tagged human FPN internalization in MDCK cells incubated for 15 to 20 mins by Halo-tagged TMR based fluorescence assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 393.53, ALogP 2.84, HBA 4, HBD 1, PSA 44.81, QED 0.79
Compound (SMILES): FC(F)(F)c1cccc(-c2n[nH]cc2-c2ccncc2)c1
InChIKey: UZOPNNYVHHABCA-UHFFFAOYSA-N
Target: Bifunctional epoxide hydrolase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34913
Assay: Inhibition of soluble epoxide hydrolase (unknown origin)
Measurement: IC50 = 260 nM (pChEMBL 6.579999923706055)
Descriptors: MW 289.26, ALogP 4.16, HBA 2, HBD 1, PSA 41.57, QED 0.77
Compound (SMILES): Cc1cc(N)nc2cc(-c3ccc4c(c3)C(N)CC4)ccc12.Cl.Cl
InChIKey: KAWHQACYSASIOW-UHFFFAOYSA-N
Target: Nitric oxide synthase 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P29476
Assay: Inhibition of rat nNOS expressed in Escherichia coli expression system assessed as reduction in NO production in presence of L-arginine measured for 30 sec by hemoglobin capture assay
Measurement: Ki = 180 nM (pChEMBL 6.75)
Descriptors: MW 289.38, ALogP 3.74, HBA 3, HBD 2, PSA 64.93, QED 0.72
Compound (SMILES): N#CN1CCC(CC(=O)Nc2cc3ccccn3n2)C1
InChIKey: UKZYBBCPTLQFIY-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 30 (SINGLE PROTEIN), Homo sapiens
UniProt: Q70CQ3
Assay: Inhibition of untagged human USP30 catalytic domain (57 to 517 residues) expressed in Escherichia coli using TAMRA labeled ubiquitin peptide as substrate preincubated for 30 min followed by substrate addition and measured after 2 hrs by fluorescence polarization assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 269.31, ALogP 1.47, HBA 5, HBD 1, PSA 73.43, QED 0.86
Compound (SMILES): OB1Oc2ccc3cc(O)ccc3c2C=C1c1ccc(O)c(O)c1
InChIKey: SBZNPOPGBHXOEC-UHFFFAOYSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Inhibition of self-induced aggregation of amyloid beta (1 to 42) (unknown origin) after 48 hrs by thioflavin T-based fluorescence method
Measurement: IC50 = 4600 nM (pChEMBL 5.340000152587891)
Descriptors: MW 320.11
Compound (SMILES): Cn1cccc(C(=O)Nc2cc(C#N)ccc2N2CCC(Oc3cccc(F)c3F)CC2)c1=O
InChIKey: RMGDCLKMBKVFSQ-UHFFFAOYSA-N
Target: G-protein coupled receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P46095
Assay: Modulator activity at GPR6 receptor (unknown origin) expressed in CHO-K1 cells assessed as inhibition of constitutive cAMP activity incubated for 45 mins by Eu-cAMP tracer based HTRF Ultra cAMP assay
Measurement: EC50 = 794.33 nM (pChEMBL 6.099999904632568)
Descriptors: MW 464.47, ALogP 3.84, HBA 6, HBD 1, PSA 87.36, QED 0.62
Compound (SMILES): O=C(Nc1cc(-c2[nH]c(Cc3ccccc3)nc2-c2ccc(F)cc2)ccn1)C1CC1
InChIKey: AFZIRKJTSPMVSW-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: Inhibition of p38alpha MAPK (unknown origin) using ATF-2 as substrate after 1 hr by ELISA
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 412.47, ALogP 5.22, HBA 3, HBD 2, PSA 70.67, QED 0.46
Compound (SMILES): O=C(CCn1cnc2ccccc21)NC1CCN(c2c(F)cc3c(=O)c(C(=O)O)cn(C4CC4)c3c2Cl)C1
InChIKey: KHNOYJMFZRCMEO-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 537.98, ALogP 3.96, HBA 7, HBD 2, PSA 109.46, QED 0.37
Compound (SMILES): Cc1ccc(COc2ccc3cc(/C=C4\SC(=S)N(C(Cc5c[nH]c6ccccc56)C(=O)O)C4=O)ccc3c2)cc1
InChIKey: MCMHPYLLTIIZMQ-MNDYBZJGSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: Inhibition of human recombinant GST-tagged SHP2 (catalytic domain 1116 to 2162 residues) expressed in Escherichia coli BL21 (DE3) using pNPP as substrate measured for 2 mins by colorimetric analysis
Measurement: IC50 = 5810 nM (pChEMBL 5.239999771118164)
Descriptors: MW 578.72, ALogP 7.11, HBA 5, HBD 2, PSA 82.63, QED 0.15
Compound (SMILES): S=C1Sc2ccc(Cl)cc2C2=NCCN12
InChIKey: QTUPZKLWJSUPTJ-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of recombinant human full length C-terminal FLAG-tagged HDAC1 expressed in baculovirus infected Sf9 cells using Boc-Lys(Ac)-AMC as substrate incubated for 1 hr by fluorescence based assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 254.77, ALogP 2.79, HBA 3, HBD 0, PSA 15.6, QED 0.66
Compound (SMILES): COc1ccc(C[C@H](NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](Cc2ccccc2)NC(C)=O)C(C)(C)S)[C@@H](C)O)C(C)(C)S)C(=O)N[C@@H](Cc2ccc3ccccc3c2)C(=O)NC2(C(=O)N[C@@H](CCCNC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(N)=O)CCOCC2)cc1
InChIKey: KBRDLOVXRMCQMR-QSARAGFRSA-N
Target: Interleukin-23 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q5VWK5
Assay: Inhibition of interleukin-23 receptor in human natural killer cells assessed as reduction in IL23/IL18-induced IFNgamma production incubated for 20 to 24 hrs by ELISA
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 1885.16
Compound (SMILES): O=C(/C=C/c1ccc(OCCN2CCC(Cc3ccccc3)CC2)cc1)c1ccc(OCCN2CCC(Cc3ccccc3)CC2)cc1O
InChIKey: JLNYAZSHTLRAFG-QGOAFFKASA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Electrophorus electricus
UniProt: O42275
Assay: Inhibition of Electric eel AChE using acetylthiocholine iodide as substrate after 15 mins by Ellman's method
Measurement: IC50 = 23900 nM (pChEMBL 4.619999885559082)
Descriptors: MW 658.88, ALogP 7.96, HBA 6, HBD 1, PSA 62.24, QED 0.1
Compound (SMILES): CS(=O)(=O)c1cc(C2(C#N)CCC2)cc(NS(=O)(=O)c2cc(Br)cc3cccnc23)c1O
InChIKey: ZMYXSAKLPAHVLY-UHFFFAOYSA-N
Target: WD repeat-containing protein 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P61964
Assay: Displacement of FITC-labelled DEEEIDVVSVE from N-terminal SUMO-fused 6His-tagged WDR5 (unknown origin) (22 to 334 residues) expressed in Escherichia coli BL21(DE3) shaken for 2 mins and incubated for 60 mins by fluorescence polarization assay
Measurement: Kd = 272 nM (pChEMBL 6.570000171661377)
Descriptors: MW 536.43, ALogP 3.85, HBA 7, HBD 2, PSA 137.22, QED 0.47
Compound (SMILES): COc1cc(NC(=O)c2ccc(C(C)C)c(C#Cc3cc(-c4cnn(C)c4)cnc3N)c2)cc(OC)c1
InChIKey: UZJFOSIQWNOWQR-UHFFFAOYSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07333
Assay: Inhibition of recombinant CSF1R (unknown origin) using poly (Glu, Tyr)4:1 as substrate measured after 1 hr by ELISA
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 495.58, ALogP 4.86, HBA 7, HBD 2, PSA 104.29, QED 0.37
Compound (SMILES): NS(=O)(=O)Oc1ccc(-c2ccc3sccc3c2)cc1
InChIKey: LVWGYEZQMYKONG-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human recombinant N-HA-tagged carbonic anhydrase 2 expressed in HEK293T cells using p-nitrophenyl acetate as substrate measured after 30 mins by colorimetric analysis
Measurement: IC50 = 1320 nM (pChEMBL 5.880000114440918)
Descriptors: MW 305.38, ALogP 3.15, HBA 4, HBD 1, PSA 69.39, QED 0.81
Compound (SMILES): CNC(=O)[C@H]1CC[C@@H](n2/c(=N/C(=O)c3ccccc3)[nH]c3ccc(CN4CCCCC4)cc32)CC1
InChIKey: BHCNZTRPBJZHOJ-ZRZAMGCNSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Inhibition of ALK (unknown origin)
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 473.62, ALogP 4.17, HBA 4, HBD 2, PSA 82.49, QED 0.58
Compound (SMILES): c1ccc(Cc2nnc3n2CCNCC3)cc1
InChIKey: KFTASHNEWORFNQ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Displacement of [3H]-mesulergine from recombinant human 5-HT2C receptor transfected in Swiss mouse 3T3 cells after 150 mins by scintillation proximity assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 228.3, ALogP 1.01, HBA 4, HBD 1, PSA 42.74, QED 0.83
Compound (SMILES): Cc1sc2ncc(C(=O)Nc3cc(C#N)ccc3N3CCC(Oc4ccc(F)cc4F)CC3)c(=O)n2c1C
InChIKey: JCQPOZNJSOYDEV-UHFFFAOYSA-N
Target: G-protein coupled receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P46095
Assay: Modulator activity at GPR6 receptor (unknown origin) expressed in CHO-K1 cells assessed as inhibition of constitutive cAMP activity incubated for 45 mins by Eu-cAMP tracer based HTRF Ultra cAMP assay
Measurement: EC50 = 398.11 nM (pChEMBL 6.400000095367432)
Descriptors: MW 535.58, ALogP 4.82, HBA 8, HBD 1, PSA 99.73, QED 0.39
Compound (SMILES): CC(C)N1CCC(Oc2ccc(NC(=O)CN3CCCCC3)cc2)CC1.Cl.Cl
InChIKey: WCEOTRJTRSLKLY-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of [3]-RAMH from recombinant human histamine H3 receptor expressed in CHO-K1 cell membranes after 60 mins by scintillation counting
Measurement: Ki = 3.8 nM (pChEMBL 8.420000076293945)
Descriptors: MW 359.51, ALogP 3.36, HBA 4, HBD 1, PSA 44.81, QED 0.85
Compound (SMILES): COc1ccc(C(=O)Nc2ccc(C(=O)N/N=C3\C(=O)Nc4ccc(Cl)cc43)cc2)cc1
InChIKey: PHLBXDCQCYYHOC-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR-2 (unknown origin) using biotinylated poly-GluTyr (4:1) as substrate after 5 mins by ELISA
Measurement: IC50 = 1830 nM (pChEMBL 5.739999771118164)
Descriptors: MW 448.87, ALogP 3.69, HBA 5, HBD 3, PSA 108.89, QED 0.52
Compound (SMILES): Cn1cc(C2=CCNCC2)c2ccc(C(=O)NS(=O)(=O)C3CC3)cc21
InChIKey: BJCFFDGQFPMUTR-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: Inhibition of human Nav1.7 at -60 mV holding potential by cell-based IonWorks barracuda automated electrophysiology method
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 359.45, ALogP 1.78, HBA 5, HBD 2, PSA 80.2, QED 0.87
Compound (SMILES): O=C1C=CC2(C=C1)OCC(Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1)C(=O)N2c1ccccc1
InChIKey: AUSBKQWPVKTBHB-UHFFFAOYSA-N
Target: N-lysine methyltransferase SMYD2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NRG4
Assay: Inhibition of SMYD2 (unknown origin) using 3H-SAM as substrate incubated for 1 hr by filter binding method
Measurement: IC50 = 18500 nM (pChEMBL 4.730000019073486)
Descriptors: MW 481.39, ALogP 5.34, HBA 3, HBD 0, PSA 46.61, QED 0.56
Compound (SMILES): NS(=O)(=O)c1ccc(-n2nc(C(=O)OCCN3CCOCC3)cc2-c2ccc(C(F)(F)F)cc2)cc1
InChIKey: CWFXEOVJHOPAAC-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Inhibition of COX2 (unknown origin) using arachidonic acid as substrate incubated for 10 mins by Ellman's reagent based COX-1/COX-2 ELISA assay
Measurement: IC50 = 190 nM (pChEMBL 6.71999979019165)
Descriptors: MW 524.52, ALogP 2.69, HBA 8, HBD 1, PSA 116.75, QED 0.47
Compound (SMILES): CCC(CC)C(=O)Nc1cc(F)c2nc(N3CCOCC3)ccc2c1
InChIKey: IWSIXWFLDFXQNZ-UHFFFAOYSA-N
Target: Serine hydroxymethyltransferase, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P34897
Assay: Inhibition of His-tagged human recombinant SHMT2 expressed in Escherichia coli BLR(DE3) assessed as reduction in NADPH level using L-serine, THF and NADP+ incubated for 5 mins by SHMT2-MTHFD coupled reaction based fluorescence assay
Measurement: IC50 = 5130 nM (pChEMBL 5.289999961853027)
Descriptors: MW 345.42, ALogP 3.59, HBA 4, HBD 1, PSA 54.46, QED 0.9
Compound (SMILES): CC/C(=C(/c1ccc(/C=C/C(=O)O)cc1)c1ccc2ncsc2c1)c1ccccc1
InChIKey: MVAQPNJXDLBMSQ-YJFMDEFYSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Induction of ERalpha degradation in human MCF7 cells in phenol red free RPMI medium containing 5% charcoal-stripped FBS incubated for 4 hrs by IRDye 800CW/DRAQ5 dye based in-cell Western assay
Measurement: EC50 = 240 nM (pChEMBL 6.619999885559082)
Descriptors: MW 411.53, ALogP 6.76, HBA 3, HBD 1, PSA 50.19, QED 0.28
Compound (SMILES): CCCOc1cccc(CNC(=O)c2ccc(-c3ccncc3)cc2)c1
InChIKey: LFGRESLGCGHUEH-UHFFFAOYSA-N
Target: Rho-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13464
Assay: Inhibition of human GST-tagged catalytic ROCK1 expressed in baculovirus system using STK S2 peptide substrate and and 33P-ATP after 60 mins by HTRF assay
Measurement: IC50 = 520 nM (pChEMBL 6.28000020980835)
Descriptors: MW 346.43, ALogP 4.47, HBA 3, HBD 1, PSA 51.22, QED 0.69
Compound (SMILES): NC[C@H](CCCCNC(=O)c1ccccc1O)NC(=O)c1cccc(O)c1O
InChIKey: HJKTUTBIUUIOGM-ZDUSSCGKSA-N
Target: Polyunsaturated fatty acid 5-lipoxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P09917
Assay: Inhibition of recombinant human 5-lipoxygenase using arachidonic acid as substrate preincubated for 10 mins followed by susbtrate addition and measured after 10 mins by reverse phase HPLC method
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 387.44, ALogP 1.46, HBA 6, HBD 6, PSA 144.91, QED 0.28
Compound (SMILES): NC(=O)c1nc(-c2c(F)cccc2Cl)oc1Nc1ccc(C(=O)N2CCOCC2)cc1
InChIKey: HEDPDFHTQKEORT-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of JAK3 in human Jurkat cells assessed as reduction in IFN-alpha stimulated JAK3 phosphorylation by caspase3/7 reagent-based Western blot analysis
Measurement: IC50 = 41 nM (pChEMBL 7.389999866485596)
Descriptors: MW 444.85, ALogP 3.45, HBA 6, HBD 2, PSA 110.69, QED 0.62
Compound (SMILES): C=C[C@](C)(O)CC[C@H]1C(=C)C[C@H](O)[C@H]2C(C)(C)CCC[C@]12C
InChIKey: CLGDBTZPPRVUII-VDWQKOAOSA-N
Target: Short transient receptor potential channel 6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y210
Assay: Inhibition of human TRPC6 expressed in thapsigargin pretreated HEK293 cells assessed as reduction in GPCR-induced calcium entry by fluo-4/AM dye based assay
Measurement: IC50 = 1570 nM (pChEMBL 5.800000190734863)
Descriptors: MW 306.49, ALogP 4.47, HBA 2, HBD 2, PSA 40.46, QED 0.75
Compound (SMILES): CCN(CC)C/C=C/C(=O)N1CCOc2cc3ncnc(Nc4ccc(F)c(Cl)c4)c3cc21
InChIKey: LJEDSQBKJCOYJS-AATRIKPKSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR phosphorylation in EGF-stimulated human KB cells preincubated for 1 hr followed by EGF stimulation measured after 6 mins by ELISA
Measurement: IC50 = 27 nM (pChEMBL 7.570000171661377)
Descriptors: MW 469.95, ALogP 4.79, HBA 6, HBD 1, PSA 70.59, QED 0.5
Compound (SMILES): Cc1cc(C#N)cc(C)c1Oc1ccnc(Nc2ccc(CN3CCOCC3)cc2)n1
InChIKey: NYOYRWHDZQWRFQ-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of HIV1 reverse transcriptase p66/p51 using poly(rA)/oligo(dT)16 as template/primer measured after 40 mins by pico-green based spectrofluorometric analysis
Measurement: IC50 = 42 nM (pChEMBL 7.380000114440918)
Descriptors: MW 415.5, ALogP 4.33, HBA 7, HBD 1, PSA 83.3, QED 0.64
Compound (SMILES): O=C(NCc1ncccc1Cl)c1cnn(CCNCCc2nc3ccccc3[nH]2)c1
InChIKey: UNTFICNNARKOSE-UHFFFAOYSA-N
Target: Ferroportin (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NP59
Assay: Inhibition of GFP-tagged human ferroportin expressed in HEK293 #354 cells assessed as induction of ferroportin internalization and degradation incubated overnight by FACS assay
Measurement: EC50 = 43 nM (pChEMBL 7.369999885559082)
Descriptors: MW 423.91, ALogP 2.57, HBA 6, HBD 3, PSA 100.52, QED 0.36
Compound (SMILES): CCCCNc1nc(N)nc(C)c1CCCN.Cl.Cl
InChIKey: VECLJKRSZPMGOJ-UHFFFAOYSA-N
Target: Toll-like receptor 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR97
Assay: Agonist activity at human TLR8 expressed in HEK293 cells assessed as induction of NF-kappaB activity by secreted alkaline phosphatase reporter gene assay
Measurement: EC50 = 2310 nM (pChEMBL 5.639999866485596)
Descriptors: MW 237.35, ALogP 1.47, HBA 5, HBD 3, PSA 89.85, QED 0.62
Compound (SMILES): Cc1nn(-c2ccc(CN)cc2)c(C)c1-c1ccc(CN)cc1
InChIKey: BITNQIMWDMBCOO-UHFFFAOYSA-N
Target: Acid-sensing ion channel 1 (SINGLE PROTEIN), Mus musculus
UniProt: Q6NXK8
Assay: Inhibition of pH 6.6-stimulated mouse ASIC1a homomer expressed in CHOK1 cells assessed as reduction in channel activation by VSD fluorescence assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 306.41, ALogP 3.07, HBA 4, HBD 2, PSA 69.86, QED 0.78
Compound (SMILES): O=C(O)c1cc(Br)cc(NCc2ccc(OCc3ccc(F)cc3)cc2)c1
InChIKey: YXHFIUGXWNQROS-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q07869
Assay: Agonist activity at human PPARalpha expressed in nonhuman mammalian cells assessed as increase in receptor transcriptional activity incubated for 22 to 24 hrs by luciferase reporter gene assay
Measurement: EC50 = 1120 nM (pChEMBL 5.949999809265137)
Descriptors: MW 430.27, ALogP 5.48, HBA 3, HBD 2, PSA 58.56, QED 0.52
Compound (SMILES): CC(C)(C)c1cc(N2C[C@@]3(CCC[C@](C)(Cn4cnc5ccc(C#N)cc54)C3)OC2=O)no1
InChIKey: SPAGPOAKCTZASZ-DQEYMECFSA-N
Target: Transient receptor potential cation channel subfamily V member 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HBA0
Assay: Antagonist activity at TRPV4 (unknown origin)
Measurement: IC50 = 7.5 nM (pChEMBL 8.119999885559082)
Descriptors: MW 447.54, ALogP 5.17, HBA 7, HBD 0, PSA 97.18, QED 0.55
Compound (SMILES): COc1ccc(OCCN2CCN(C(=O)c3cc4ccccc4[nH]3)CC2)cc1
InChIKey: HAZPAMUWUHDPDA-UHFFFAOYSA-N
Target: D(3) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35462
Assay: D3 Radioligand Binding Assay: Compounds were tested for their ability to compete with the orthosteric radioligand [3H]methylspiperone for binding to the D3 DAR using stable HEK cell lines expressing the D3 DAR (Codex Biosciences, Gaithersburg, Md., Catalogue no. CB-80300-206) as described in the detailed protocol below presented in Table 5. Cells were cultured in Dulbecco's modified Eagle's Medium (Corning, catalogue no. 10-013) containing 10% FBS, 1,000 units/mL Penicillin, 1,000 mg/mL Streptomycin, 100 mM sodium pyruvate, 1 μg/mL Gentamicin, and 250 mg/mL G418. All cells were maintained at 37° C. in 500 CO2 and 90% humidity. For radioligand binding assays cells were removed mechanically using calcium-free Earle's balanced salt solution (EBSS). Intact cells were collected by centrifugation and then lysed with 5 mM Tris-HCl and 5 mM MgCl2 at pH 7.4. Homogenates were centrifuged at 30,000×g for 30 minutes. The membranes were re-suspended in EBSS (US Biological, catalogue no. E0249-05) pH 7.4 to a concentration of 16 μg/mL. For competition binding studies, membrane preparations were incubated for 90 minutes at room temperature with various concentrations of compound and a single concentration of [3H]methylspiperone (Perkin Elmer, NET856) in a reaction volume of 250 μL. Non-specific binding was determined in the presence of 4 μM (+)-butaclamol (Sigma-Aldrich, catalogue no. D033). Bound ligand was separated from unbound by filtration through GF/C filters using a PerkinElmer cell harvester and quantified on a Top-count (PerkinElmer). Ki values were determined using Cheng-Prusoff equation from observed IC50 values and ligand Kd values from separate saturation experiments.
Measurement: EC50 = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 379.46, ALogP 3.01, HBA 4, HBD 1, PSA 57.8, QED 0.72
Compound (SMILES): O=C1/C(=C/c2cc(C(F)(F)F)c(O)cc2Br)Sc2ncccc21
InChIKey: ZDOIRYYBDSJZCW-XGICHPGQSA-N
Target: Cyclic GMP-AMP synthase (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N884
Assay: Inhibition of recombinant His6-SUMO tagged human CGAS expressed in Escherichia coli BL21/pLys cells incubated for 20 mins by Kinase Glo chemiluminescence assay
Measurement: IC50 <= 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 402.19, ALogP 4.9, HBA 4, HBD 1, PSA 50.19, QED 0.69
Compound (SMILES): CCc1sc2ncnc(O[C@H](C)C(=O)O)c2c1-c1ccccc1C
InChIKey: MKMVRGIGRXKUGV-LLVKDONJSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Displacement of N-terminal fluorescein labelled Puma-BH3 peptide from TEV-fused His-tagged human Mcl-1 expressed in Escherichia coliBL21(DE3) pLysS cells after 2 hrs by fluorescence polarization assay
Measurement: Ki = 18000 nM (pChEMBL 4.75)
Descriptors: MW 342.42, ALogP 4.08, HBA 5, HBD 1, PSA 72.31, QED 0.76
Compound (SMILES): CCCCN(c1nc2cc(NC(C)=O)ccc2o1)[C@H](C)c1ccc(-c2ccccc2-c2nnn[nH]2)cc1
InChIKey: JEZROQYOPGEECH-GOSISDBHSA-N
Target: Chemerin-like receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99788
Assay: Inhibition of chemR23 in human CAL1 cells assessed as reduction in chemerin-induced intracellular calcium ion concentration preincubated for 45 mins followed by chemerin addition
Measurement: IC50 = 440 nM (pChEMBL 6.360000133514404)
Descriptors: MW 495.59, ALogP 6, HBA 7, HBD 2, PSA 112.83, QED 0.26
Compound (SMILES): C=CC(=O)N1CCN(c2nnc(-c3ccccc3C)c3cc(-c4c(O)cccc4F)c(Cl)cc23)CC1
InChIKey: FUNOSYPGHLIPJK-UHFFFAOYSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Inhibition of GDP bound recombinant human His-tagged KRAS G12C/C118A mutant (1 to 169 residues) assessed as reduction in SOS1-mediated GDP/GTP nucleotide exchange by measuring the disruption between GDP-bound recombinant His-tagged KRAS G12C/C118A (1 to 169 residues) and Ras binding domain of GST-tagged c-RAF (1 to 149 residues) preincubated for 5 mins followed by SOS1 and GTP addition and further incubated for 30 mins by AlphaLISA assay
Measurement: IC50 = 5710 nM (pChEMBL 5.239999771118164)
Descriptors: MW 502.98, ALogP 5.6, HBA 5, HBD 1, PSA 69.56, QED 0.37
Compound (SMILES): C=C1CC[C@H]2[C@@](C)(CCC(=O)N[C@@]2(C)CO)[C@@H]1/C=C/C1=CCOC1=O
InChIKey: KMWVVYHGNIPQHR-WHCBKWPTSA-N
Target: Hexokinase-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P52789
Assay: Inhibition of recombinant human HK2 expressed in Escherichia coli BL21(DE3) using glucose as substrate preincubated for 10 mins followed by substrate addition in presence of ATP by G6PDH/NADP coupled assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 345.44, ALogP 2.28, HBA 4, HBD 2, PSA 75.63, QED 0.61
Compound (SMILES): C=CC(=O)Nc1cc(Nc2nccc(NC(=O)c3ccccc3)n2)c(OC)cc1N(C)C
InChIKey: LCNMSBACQVVJRJ-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of human N-terminal GST-tagged EGFR T790M/L858R double mutant (695 to end residues) expressed in baculovirus infected Sf9 insect cells using Poly (4:1 Glu, Tyr) as substrate after 60 mins in presence of ATP by ADP-Glo assay
Measurement: IC50 = 2.213 nM (pChEMBL 8.649999618530273)
Descriptors: MW 432.48, ALogP 3.67, HBA 7, HBD 3, PSA 108.48, QED 0.47
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](Cc1cscn1)NC(=O)CO)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CC(C)C)C(=O)[C@@]1(C)CO1
InChIKey: HPNLGSDXUWVFAD-ALGPPTDUSA-N
Target: Proteasome Macropain subunit MB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P28074
Assay: Inhibition of human chymotrypsin-like activity of 20S proteasome using Suc-LLVY-AMC as substrate pre-incubated for 10 mins followed by substrate addition and measured after 1 hr by spectrofluorimetry
Measurement: IC50 = 52.1 nM (pChEMBL 7.28000020980835)
Descriptors: MW 643.81, ALogP 1.31, HBA 9, HBD 5, PSA 179.12, QED 0.15
Compound (SMILES): NC(=S)N/N=C/c1cc(CO)cs1
InChIKey: ZDTCNIDSOIIVOZ-XNWCZRBMSA-N
Target: Tyrosinase (SINGLE PROTEIN), Agaricus bisporus
UniProt: O42713
Assay: Inhibition of mushroom tyrosinase using L-dopa as substrate measured for 150 secs by spectrophotometric analysis
Measurement: IC50 = 670 nM (pChEMBL 6.170000076293945)
Descriptors: MW 215.3, ALogP 0.41, HBA 4, HBD 3, PSA 70.64, QED 0.39
Compound (SMILES): Cc1cnc(NC(=O)C2CC2)nc1-c1c[nH]c2c(NC(=O)CN3CCOCC3)cccc12
InChIKey: ALXCGHGMHUVLDR-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of recombinant human N-terminal GST-tagged JAK1 (866 to 1154 residues) expressed in insect cells using FITC-labeled C6-KKHTDDGYMPMSPGVA-NH peptide as substrate after 10 mins in presence of 5 mM ATP by caliper mobility shift assay
Measurement: IC50 = 2400 nM (pChEMBL 5.619999885559082)
Descriptors: MW 434.5, ALogP 2.55, HBA 6, HBD 3, PSA 112.24, QED 0.55
Compound (SMILES): Cn1c(=O)n(C2CCOCC2)c2nc(-c3cnc4ccc(C#N)cn34)ncc21
InChIKey: NGIAQVIDFYSWAE-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Inhibition of recombinant human N-terminal His-tagged JAK3 (795 to 1124 residues) expressed in Sf1 cells using PolyGT-Biotin as substrate measured after 3 to 20 hrs by HTRF assay
Measurement: IC50 = 53 nM (pChEMBL 7.28000020980835)
Descriptors: MW 375.39, ALogP 1.67, HBA 9, HBD 0, PSA 103.03, QED 0.53
Compound (SMILES): N#Cc1c(NCC(N)=O)sc(C(=O)c2ccc(Br)s2)c1N
InChIKey: GFFSEABOLWSAEB-UHFFFAOYSA-N
Target: Maternal embryonic leucine zipper kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q14680
Assay: Inhibition of recombinant human MELK expressed in Escherichia coli using ZIPtide as substrate measured after 0.5 hrs by ADP-Glo assay
Measurement: IC50 = 540 nM (pChEMBL 6.269999980926514)
Descriptors: MW 385.27, ALogP 2.15, HBA 7, HBD 3, PSA 122, QED 0.68
Compound (SMILES): Nc1c(C(=O)N[C@@H]2CC[C@H](c3ccccc3)C2)[nH]c(=O)[nH]c1=O
InChIKey: TXSXSGLGFDRHMM-WDEREUQCSA-N
Target: Endothelial lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5X9
Assay: Inhibition of recombinant human endothelial lipase expressed in African green monkey COS7 cells using HDL as substrate pretreated for 10 mins followed by substrate addition and measured after 30 mins by LC/MS/MS analysis
Measurement: IC50 = 175 nM (pChEMBL 6.760000228881836)
Descriptors: MW 314.35, ALogP 0.71, HBA 4, HBD 4, PSA 120.84, QED 0.67
Compound (SMILES): COc1ccc(-c2cnc3[nH]cc(NS(=O)(=O)c4ccccc4)c3c2)cc1OC
InChIKey: MKPVAQDLIYMDQI-UHFFFAOYSA-N
Target: AP2-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q2M2I8
Assay: Displacement of tracer 222 from GST-tagged recombinant human AAK1 catalytic domain (1 to 510 amino acids) expressed in insect cells shaken for 30 secs and incubated for 1 hr by LanthaScreen Eu kinase binding assay
Measurement: IC50 = 4440 nM (pChEMBL 5.349999904632568)
Descriptors: MW 409.47, ALogP 4.05, HBA 5, HBD 2, PSA 93.31, QED 0.5
Compound (SMILES): Cl.NCc1cc(N2C(=O)CCc3c(OCc4ccccc4)cccc32)ncn1
InChIKey: UKGYDZHWOSDJFW-UHFFFAOYSA-N
Target: Lysyl oxidase homolog 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y4K0
Assay: Inhibition of human LOXL2 expressed in CHO cells assessed as reduction in amine oxidase activity incubated for 2 hrs by Amplex red based fluorescence assay
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 360.42, ALogP 3.13, HBA 5, HBD 1, PSA 81.34, QED 0.76
Compound (SMILES): CN(C)CCC(=O)N1CC(Cn2cc(-c3ccc(Cl)c(NC(=O)c4coc(N)n4)c3)cn2)C1
InChIKey: YDMULDNJYZFNGC-UHFFFAOYSA-N
Target: Bifunctional phosphoribosylaminoimidazole carboxylase/phosphoribosylaminoimidazole succinocarboxamide synthetase (SINGLE PROTEIN), Homo sapiens
UniProt: P22234
Assay: Inhibition of wild type full length human PAICS using CAIR as substrate preincubated for 30 mins followed by substrate addition and measured after 1 hr by ADP2 tracer-based fluorescence assay
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 471.95, ALogP 2.44, HBA 8, HBD 2, PSA 122.52, QED 0.52
Compound (SMILES): COc1cc(CCNc2nc(C#Cc3ccc(Cl)s3)nc3c2ncn3[C@H]2[C@H](O)[C@H](O)[C@@H]3C[C@@H]32)ccc1O
InChIKey: YLLYWESWXSAFKQ-ZIEHKDSXSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30542
Assay: Displacement of [3H]R-PIA from recombinant human A1AR expressed in HEK293 cell membranes measured after 60 mins by liquid scintillation counting method
Measurement: Ki = 649 nM (pChEMBL 6.190000057220459)
Descriptors: MW 538.03, ALogP 3.22, HBA 10, HBD 4, PSA 125.55, QED 0.28