lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CN(C)CCCNc1ccn2ncc(-c3ccc4c(c3)OCO4)c2n1
InChIKey: DQYRQFLRDJTHQM-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase receptor Ret (SINGLE PROTEIN), Homo sapiens
UniProt: P07949
Assay: Inhibition of RET V804M mutant (unknown origin)expressed in human BaF3 cells assessed as reduction in cell viability incubated for 48 hrs by celltiter glo luminescence cell viability assay
Measurement: IC50 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 339.4, ALogP 2.49, HBA 7, HBD 1, PSA 63.92, QED 0.7
Compound (SMILES): Cc1cc(=O)[nH]c(-n2ncc(C(=O)NC3CCCC3)c2C(C)C)n1
InChIKey: INJUATZBIMTKKQ-UHFFFAOYSA-N
Target: Sepiapterin reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P35270
Assay: Inhibition of SPR in human SK-N-BE(2) cells assessed as reduction in BH4 levels incubated for 6 to 48 hrs by LCMS analysis
Measurement: IC50 = 6100 nM (pChEMBL 5.210000038146973)
Descriptors: MW 329.4, ALogP 2.06, HBA 5, HBD 2, PSA 92.67, QED 0.9
Compound (SMILES): C(=N/c1ccc(-c2nc3ccccc3o2)cc1)\c1ccccc1
InChIKey: BPFKQENQKSWMSP-KGENOOAVSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human serum BChE using butyrylthiocholine iodide as substrate after 10 mins measured for every mins by Ellman's method
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 298.35, ALogP 5.25, HBA 3, HBD 0, PSA 38.39, QED 0.48
Compound (SMILES): CSc1nc(-c2ccc(F)cc2)c(-c2ccnc(NC(=O)C3CCC3)c2)[nH]1
InChIKey: INQWDEQHGSDBDR-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Competitive inhibition of human recombinant full length GSK3beta using YRRAAVPPSPSLSRHSSPHQ(pS)EDEEE as substrate preincubated with enzyme for 10 mins followed by substrate and 25 uM ATP addition measured after 60 mins by ADP-Glo luminescence assay
Measurement: IC50 = 132 nM (pChEMBL 6.880000114440918)
Descriptors: MW 382.46, ALogP 4.74, HBA 4, HBD 2, PSA 70.67, QED 0.63
Compound (SMILES): Cc1cc(=O)[nH]c(-n2ncc(C(=O)N3CCCC(C(F)(F)F)C3)c2C)n1
InChIKey: AEXGQVGIARFTOD-UHFFFAOYSA-N
Target: Sepiapterin reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P35270
Assay: Inhibition of SPR in human SK-N-BE(2) cells assessed as reduction in BH4 levels incubated for 6 to 48 hrs by LCMS analysis
Measurement: IC50 = 2900 nM (pChEMBL 5.539999961853027)
Descriptors: MW 369.35, ALogP 1.99, HBA 5, HBD 1, PSA 83.88, QED 0.88
Compound (SMILES): COC(=O)c1cccc(COc2c(-c3ccc(OCCOCCOCCn4cc(CCCCOc5ccc6c(=O)cc(-c7ccccc7)oc6c5)nn4)cc3)oc3ccccc3c2=O)c1
InChIKey: WDTNQVLDVIDALR-UHFFFAOYSA-N
Target: Broad substrate specificity ATP-binding cassette transporter ABCG2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UNQ0
Assay: Inhibition of BCRP in human MCF7/MX100 cells assessed as reversal of topotecan resistance after 5 days by MTS/PMS assay
Measurement: EC50 = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 877.95, ALogP 8.7, HBA 14, HBD 0, PSA 163.58, QED 0.05
Compound (SMILES): COc1cc2c(cc1OC)C1Cc3ccc(O)cc3CN1CC2
InChIKey: NGOGJFCDUNGDRX-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Antagonist activity at D2 receptor (unknown origin) expressed in CHOK1 cells assessed as inhibition of dopamine-induced calcium flux preincubated for 60 mins at 37 degC followed by 15 mins incubation under room temperature and subsequent dopamine addition measured after 20 secs for 100 secs by calcium-4 dye based FLIPR assay
Measurement: IC50 = 1530 nM (pChEMBL 5.820000171661377)
Descriptors: MW 311.38, ALogP 3.06, HBA 4, HBD 1, PSA 41.93, QED 0.93
Compound (SMILES): CCOc1cc(C(=O)O)cc(-c2ccc(C(=O)NCNC(=O)CCN(O)C=O)o2)c1
InChIKey: ZVUCDJYSVFEOKT-UHFFFAOYSA-N
Target: Bone morphogenetic protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P13497
Assay: Inhibition of C-terminal FLAG-6x-His epitope tagged and N-terminal human RAGE signal sequence tagged human BMP1 (23 to 721 amino acids) expressed in CHO-E1 cells pre-incubated for 10 mins before promyostatin peptide substrate addition and measured after 30 mins using 50 nM BMP1 by FRET based assay
Measurement: IC50 < 199.53 nM (pChEMBL 6.699999809265137)
Descriptors: MW 419.39, ALogP 1.08, HBA 7, HBD 4, PSA 158.41, QED 0.18
Compound (SMILES): N#Cc1ccc2[nH]c(-c3ccc(-c4ccc(O[C@H]5CC[C@@H](CC(=O)O)CC5)nc4)nc3)nc2c1
InChIKey: ZSOYHMGKJFRGOK-MOBUCQHHSA-N
Target: Diacylglycerol O-acyltransferase 1 (SINGLE PROTEIN), Mus musculus
UniProt: Q9Z2A7
Assay: Inhibition of mouse DGAT1
Measurement: IC50 = 17.8 nM (pChEMBL 7.75)
Descriptors: MW 453.5, ALogP 4.97, HBA 6, HBD 2, PSA 124.78, QED 0.42
Compound (SMILES): CN(C)C(=O)c1ccc(N(Cc2ccc(C#N)cc2)C(=O)c2ccc(O)cc2O)cc1
InChIKey: FLCLKDRMVXBLHR-UHFFFAOYSA-N
Target: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 4, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q16654
Assay: Inhibition of PDHK4 (unknown origin) by radiometric biochemical kinase assay
Measurement: IC50 = 399 nM (pChEMBL 6.400000095367432)
Descriptors: MW 415.45, ALogP 3.52, HBA 5, HBD 2, PSA 104.87, QED 0.66
Compound (SMILES): NS(=O)(=O)c1ccc(C(=O)NNC(=O)c2ccc(Cl)cc2)cc1
InChIKey: ROPYUEWYRBFDOG-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human recombinant MAO-B expressed in insect cells microsomes assessed as inhibition of 4-hydroxyquinoline formation using kynuramine as substrate incubated for 20 mins by fluorescence spectrophotometry analysis
Measurement: IC50 = 11700 nM (pChEMBL 4.929999828338623)
Descriptors: MW 353.79, ALogP 1.06, HBA 4, HBD 3, PSA 118.36, QED 0.71
Compound (SMILES): CCNC(=O)Nc1ccc(-c2nc(C(C)(C)S(C)(=O)=O)cc([C@@]34CCOC[C@@H]3C4)n2)cc1
InChIKey: NWPWUFFZHOWRDZ-QMHKHESXSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3Kdelta (unknown origin) using PIP2 as substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by HTRF assay
Measurement: IC50 = 15848.93 nM (pChEMBL 4.800000190734863)
Descriptors: MW 458.58, ALogP 3.24, HBA 6, HBD 2, PSA 110.28, QED 0.69
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](C(C)C)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@@H]2CCCN2C(=O)[C@H](Cc2cnc[nH]2)NC1=O
InChIKey: YNTHWMGRAUMNFY-KOQODJNWSA-N
Target: Type-1 angiotensin II receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30556
Assay: Agonist activity at human AT1R expressed in HEK293 cells incubated for 30 mins by IP1 accumulation assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 756.9, ALogP 1.27, HBA 8, HBD 7, PSA 214.72, QED 0.17
Compound (SMILES): Cc1ccc(-c2ccc(/C=C3/SC(=N)NC3=O)o2)c([N+](=O)[O-])c1
InChIKey: AMQWJXRKJIUZAW-NTUHNPAUSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of human GSK-3beta H350L mutant (2 to end residues) at 10 uM using phospho GS2 peptide as substrate after 40 mins by [gamma-33ATP] radiometric assay
Measurement: IC50 = 320 nM (pChEMBL 6.5)
Descriptors: MW 329.34, ALogP 3.3, HBA 6, HBD 2, PSA 109.23, QED 0.51
Compound (SMILES): Cc1n[nH]cc1-c1cc2nc([C@@H]3CCC(C)(C)N3)[nH]c(=O)c2s1
InChIKey: JBGVICNHTUXKQA-JTQLQIEISA-N
Target: Cyclin-dependent kinase 2/cyclin E1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24864
Assay: Inhibition of N-terminal GST-tagged full-length human CDK2 (1 to 298 residues)/Cyclin E (1 to 410 residues) expressed in baculovirus expression system using histone H1 as susbtrate after 90 mins by Kinase-Glo luminescence assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 329.43, ALogP 2.89, HBA 5, HBD 3, PSA 86.46, QED 0.67
Compound (SMILES): O=C(O)C1CCCN(CC/C=C\C(c2ccccc2)(c2ccccc2)c2ccccc2)C1
InChIKey: OOVKPEDIGJRFSH-JMIUGGIZSA-N
Target: Sodium- and chloride-dependent GABA transporter 1 (SINGLE PROTEIN), Mus musculus
UniProt: P31648
Assay: Inhibition of mouse GAT1 expressed in HEK293 cells assessed as reduction in [3H]GABA uptake preincubated for 25 mins followed by [3H]GABA addition and measured after 4 mins by microbeta liquid scintillation counting method
Measurement: IC50 = 40738.03 nM (pChEMBL 4.389999866485596)
Descriptors: MW 425.57, ALogP 5.76, HBA 2, HBD 1, PSA 40.54, QED 0.37
Compound (SMILES): CCC(C)(C)c1ccc(OCCCN2CCCC2)cc1
InChIKey: KMJZIGCXRSSFHL-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human MAO-B expressed in baculovirus infected BTI insect cells using p-tyramine as substrate preincubated for 30 mins followed by substrate addition and measured after 1 hr by fluorescence-based Amplex Red MAO assay
Measurement: IC50 = 4.5 nM (pChEMBL 8.350000381469727)
Descriptors: MW 275.44, ALogP 4.24, HBA 2, HBD 0, PSA 12.47, QED 0.69
Compound (SMILES): NS(=O)(=O)c1cccc(Nc2ncc3c(n2)CCCC3)c1
InChIKey: ASNDURJGUUDPHG-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 5/CDK5 activator 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q15078
Assay: Inhibition of recombinant full length N-terminal GST tagged human CDK5/p25 expressed in baculovirus infected sf9 cells using histone H1 as substrate measured after 60 mins in presence of ATP by ADP-Glo kinase assay
Measurement: Ki = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 304.38, ALogP 1.75, HBA 5, HBD 2, PSA 97.97, QED 0.9
Compound (SMILES): CNC(=O)Cc1ccc(Nc2cc(-c3cccc(Cl)c3)nc3c2CCC3)cc1
InChIKey: NKNXGHSIYQVARV-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4B (SINGLE PROTEIN), Homo sapiens
UniProt: Q07343
Assay: Kinetic Assay: Assays are performed in 96-well plates in a total volume of 200 μl/well. Compounds are dissolved in dimethylsulfoxide (DMSO) and added to plates in a volume of 10 μl followed by addition of 165 μl of assay mix. Plates are pre-incubated at 25° C. for 15 min and the reactions are initiated by the addition of 25 μl of cAMP followed by thorough mixing. Reaction rates are measured by monitoring the decrease in fluorescence using excitation at 355 nm and emission at 460 nm for a period of 10 min in a fluorescence plate reader. Initial rates (slopes) are determined from linear portions of the progress curves. Final concentrations of assay components are as follows: 50 mM Tris, pH 8, 10 mM MgCl2, 50 mM KCl, 2% DMSO, 5 mM tris(2-carboxyethyl)phosphine (TCEP), 0.4 mM phosphenolpyruvate (PEP), 0.01 mM NADH, 0.04 mM adenosine triphosphate (ATP), 0.004 mM cAMP, 7.5 units myokinase from yeast, 1.6 units pyruvate kinase, 2 units lactate dehydrogenase, and either 0.5 nM human PDE4D7 or 10 nM human PDE4B1. All data are percent normalized relative to controls and are presented as percent inhibition. An inhibitory concentration 50% (IC50) value is calculated by fitting of a sigmoidal dose response curve. Human PDE4D7 contained a mutation of serine 54 to aspartic acid to mimic activation by cAMP-dependent protein kinase A (PKA). Human PDE4B1 contained a corresponding mutation of serine 133 to aspartic acid to also mimic PKA activation.
Measurement: IC50 < 1000 nM (pChEMBL 6)
Descriptors: MW 391.9, ALogP 4.92, HBA 3, HBD 2, PSA 54.02, QED 0.65
Compound (SMILES): C=CC(=O)N1CCC(n2nc(-c3cc(C=O)n(C)n3)c3c(N)ncnc32)C1
InChIKey: LNASRTLHHDPXCY-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q62689
Assay: Inhibition of JAK2 in Lewis rat T cells assessed as reduction in IL-2-induced cell proliferation measured after 72 hrs by alamar blue staining based fluorescence assay
Measurement: IC50 = 630 nM (pChEMBL 6.199999809265137)
Descriptors: MW 366.39, ALogP 0.58, HBA 9, HBD 1, PSA 124.82, QED 0.53
Compound (SMILES): CCOC(=O)[C@H](C)N[P@@](=O)(CC/C=C(\C)CO)Oc1ccccc1
InChIKey: YGSLLMNEAQXTQJ-RBEULTJKSA-N
Target: Butyrophilin subfamily 3 member A1 (SINGLE PROTEIN), Homo sapiens
UniProt: O00481
Assay: Activation of butyrophilin 3A1 in human K562 cells assessed as interferon-gamma production pretreated for 60 mins followed by HMBPP-treated Vgamma9Vdelta2 T cells addition and measured after 20 hrs by ELISA
Measurement: EC50 = 79 nM (pChEMBL 7.099999904632568)
Descriptors: MW 355.37, ALogP 3.13, HBA 5, HBD 2, PSA 84.86, QED 0.38
Compound (SMILES): O=C(NO)c1ccc(N(Cc2ccc(C(F)(F)F)cc2)C(=O)CN(Cc2ccccc2C(F)(F)F)S(=O)(=O)c2ccc(F)cc2)cc1
InChIKey: NQSRGIZQPUUKDT-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombinant human HDAC6 expressed in SF9 baculoviral system using FAM-labeled acetylated peptide as substrate by EMSA
Measurement: IC50 = 93 nM (pChEMBL 7.03000020980835)
Descriptors: MW 683.6, ALogP 6.41, HBA 5, HBD 2, PSA 107.02, QED 0.11
Compound (SMILES): COc1cccc(-c2cc(NC(=O)C3CN(C#N)CCO3)on2)c1
InChIKey: CMIIRZQQBWCEDQ-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 328.33, ALogP 1.47, HBA 7, HBD 1, PSA 100.62, QED 0.85
Compound (SMILES): N#Cc1ccc(N2CCC(C(=O)N3N=CC[C@H]3c3cc(F)cc(F)c3)CC2)nn1
InChIKey: LRSFJHOMTHDOLZ-SFHVURJKSA-N
Target: Receptor-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13546
Assay: Inhibition of human GST/His-tagged RIP1 (1 to 375 residues) expressed in baculovirus expression system assessed as reduction in autophosphorylation measured after 4 hrs in presence of ATP by ADP-Glo luminescence assay
Measurement: IC50 = 7.9 nM (pChEMBL 8.100000381469727)
Descriptors: MW 396.4, ALogP 2.8, HBA 6, HBD 0, PSA 85.48, QED 0.8
Compound (SMILES): COc1ccc(-c2cc(OCCCCCCC(=O)NO)c3ncnc(C)c3c2)cn1
InChIKey: IYAYMZXZYXPCOM-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of recombinant human PI3Kalpha using PIP2 as substrate incubated for 1 hr by kinase-glo assay
Measurement: IC50 = 102 nM (pChEMBL 6.989999771118164)
Descriptors: MW 410.47, ALogP 3.84, HBA 7, HBD 2, PSA 106.46, QED 0.3
Compound (SMILES): O=C(CCCCc1nnc[nH]1)N1CCc2nc(NC3Cc4ccccc4C3)ncc2C1
InChIKey: RETKKMHFGPNHKX-UHFFFAOYSA-N
Target: Autotaxin (SINGLE PROTEIN), Homo sapiens
UniProt: Q13822
Assay: Inhibition of autotaxin in healthy human plasma assessed as reduction in LPA level after 3 hrs by mass spectrometric analysis
Measurement: IC50 = 92 nM (pChEMBL 7.039999961853027)
Descriptors: MW 417.52, ALogP 2.47, HBA 6, HBD 2, PSA 99.69, QED 0.57
Compound (SMILES): CCN1CCN(C(=O)c2nc(-c3ccc4c(c3)N(C3CCCC3)[C@H](C)C(=O)N4C)n(-c3ccc(C)cc3)n2)CC1
InChIKey: BTLDMCGLVZIYNM-JOCHJYFZSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Fluorescence Polarization Assay: Expression and purification of the BRD4(I) recognition domain: colonies of newly transformed plasmid DNA from E. coli BL21(DE3)-condon plus-RIL cells were cultivated in 50 mL of Terrific Broth medium containing 50 μg/mL kanamycin and 34 μg/mL chloramphenicol at 37° C. overnight (starting culture). The starting culture was then diluted 100-fold in 1 L of fresh TB medium and the cells were grown at 37° C. to an optical density of about 0.8 at  and then the temperature was lowered to 16° C. When the system was equilibrated at 16° C., the optical density at  was approximately 1.2, and protein expression was induced with 0.2 mmol of isopropyl-β-D-thiogalactopyranoside (IPTG) overnight at 16° C. Bacteria were harvested by centrifugation (4000×g, 20 minutes, 4° C.) and stored as a pellet at −80° C. The cells expressing His 6-tagged protein was resuspend in lysis buffer [50 mmol 4-hydroxyethylpiperazineethanesulfonic acid (HEPES), 25° C., pH 7.5, 500 mmol NaCl, 10 mmol imidazole, 5% glycerol and freshly added 0.5 mmol of tris(2-carboxyethyl)phosphine hydrochloride (TCEP) and 1 mmol of phenylmethanesulfonyl fluoride (PMSF)] and lysed at 4° C. using JN 3000PLUS high pressure homogenizer (JNBIO-Guangzhou, China). The lysate was clarified by centrifugation (12,000×g for 1 hour at 4° C.) and applied to a nickel-nitriloacetate agarose column. The column was washed once with 50 mL of wash buffer containing 30 mmol of imidazole. The protein was eluted using imidazole in an elution buffer in a stepwise elution (100-250 mmol imidazole in 50 mmol HEPES, 25° C., pH 7.5, 500 mmol NaCl, 5% glycerol). All fractions were collected and monitored by SDS-polyacrylamide gel electrophoresis (Bio-Rad Criterion TM Precast Gels, 4-12% Bis-Tris, 1.0 mm, from Bio-Rad, CA). After 1 mmol of dithiothreitol (DTT) was added, the eluted proteins were treated with tobacco plaque virus (TEV) protease overnight at 4° C. to remove the His6 tag. The protein was concentrated and further purified by size exclusion chromatography on a Superdex 75 16/60 HiLoad gel filtration column. The samples were monitored by SDS-polyacrylamide gel electrophoresis and concentrated to 8-10 mg/mL with gel filtration buffer, 10 mmol Hepes pH 7.5, 500 mM NaCl, 1 mmol DTT, and used for protein binding assays and crystallization.
Measurement: IC50 = 4.96 nM (pChEMBL 8.300000190734863)
Descriptors: MW 541.7, ALogP 4.13, HBA 7, HBD 0, PSA 77.81, QED 0.48
Compound (SMILES): COC(=O)c1nn([C@@H]2O[C@H](COS(N)(=O)=O)[C@@H](O)[C@H]2O)c2ncnc(N)c12
InChIKey: RMJQRYXNLIWVFQ-TZQXKBMNSA-N
Target: Ubiquitin-like modifier-activating enzyme ATG7 (SINGLE PROTEIN), Homo sapiens
UniProt: O95352
Assay: Inhibition of recombinant His-tagged human ATG7 incubated for 105 mins in presence of GST-tagged ATG3 and Flag-tagged Gabarap and measured after 2 hrs by FRET assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 404.36, ALogP -2.97, HBA 13, HBD 4, PSA 215, QED 0.37
Compound (SMILES): C[C@H]1SC(N)=N[C@](C)(c2cc(NC(=O)c3ccc(OC(F)F)cn3)ccc2F)[C@H]1F
InChIKey: SRRMWNUUTHJEGI-YPUWOAEVSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of human BACE1 using Biotin-XSEVNLDAEFRHDSGC as substrate incubated for 2 hrs by fluorescence method
Measurement: IC50 = 4.77 nM (pChEMBL 8.319999694824219)
Descriptors: MW 442.44, ALogP 4.08, HBA 6, HBD 2, PSA 89.6, QED 0.68
Compound (SMILES): CC1(C)[C@@H](O)CC[C@]2(C)[C@H]3C(=O)C=C4[C@@H]5C[C@@](C)(CO)CC[C@]5(C)CC[C@@]4(C)[C@]3(C)CC[C@@H]12
InChIKey: JCGXIYQLRYPHDG-DQOTWGJISA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Inhibition of human recombinant COX2 expressed in baculovirus infected sf21 cells assessed as decrease in PGE2 formation using arachidonic acid as substrate preincubated for 10 mins followed by substrate addition measured after 45 mins by LC-MS analysis
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 456.71, ALogP 6.32, HBA 3, HBD 2, PSA 57.53, QED 0.49
Compound (SMILES): CN1C(=O)S/C(=C\c2cc(OCc3ccc(N)nc3)c(O)cc2Br)C1=O
InChIKey: PELLLOGHRNZVIV-RZNTYIFUSA-N
Target: Cyclic GMP-AMP synthase (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N884
Assay: Inhibition of CGAS in human THP1 cells transfected with interferon stimulatory DNA and measured after 16 hrs by Gaussia luciferase reporter gene assay
Measurement: IC50 = 2500 nM (pChEMBL 5.599999904632568)
Descriptors: MW 436.29, ALogP 3.38, HBA 7, HBD 2, PSA 105.75, QED 0.71
Compound (SMILES): CN1c2ccccc2N([C@@H]2CCN(C#N)C2)S1(=O)=O
InChIKey: ZYRPSQXKZGZTJB-SNVBAGLBSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 30 (SINGLE PROTEIN), Homo sapiens
UniProt: Q70CQ3
Assay: Biochemical Assay: Dilution plates were prepared at 21 times the final concentration (2100 μM for a final concentration of 100 μM) in 50% DMSO in a 96-well polypropylene V-bottom plate (Greiner #651201). A typical 8-point dilution series to be 100, 30, 10, 3, 1, 0.3, 0.1, 0.03 μM final. Reactions were performed in duplicate in black 384 well plates (small volume, Greiner 784076) in a final reaction volume of 21 μl. Either 1 μl of 50% DMSO or diluted compound was added to the plate. USP30 was diluted in reaction buffer (40 mM Tris, pH 7.5, 0.005% Tween 20, 0.5 mg/ml BSA, 5 mMbeta-mercaptoethanol) to the equivalent of 0.05 μl/well and 10 μl of diluted USP30 was added to the compound. Enzyme and compound were incubated for 30 min at room temp. Reactions were initiated by the addition of 50 nM of TAMRA labelled peptide linked to ubiquitin via an iso-peptide bond as fluorescence polarisation substrate. Reactions were read immediately after addition of substrate and following a 2 hr incubation at room temperature. Readings were performed on a Pherastar Plus (BMG Labtech). λ Excitation 540 nm; λ Emission 590 nm.
Measurement: IC50 = 0.66 nM (pChEMBL 9.180000305175781)
Descriptors: MW 278.34, ALogP 0.74, HBA 4, HBD 0, PSA 67.65, QED 0.71
Compound (SMILES): Cc1ccc2c(N)c(C(=O)NCCc3ccc(N4CCC5(CCCNC5)CC4)cc3)sc2n1
InChIKey: ZJRQDCSKGNNTNV-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 25 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHP3
Assay: Inhibition of recombinant C-terminal 6-His tagged human USP25 using ubiquitin-rhodamine 110 as substrate preincubated for 30 mins followed by substrate addition and measured after 45 mins by fluorescence based assay
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 463.65, ALogP 4.13, HBA 6, HBD 3, PSA 83.28, QED 0.53
Compound (SMILES): Cl.NOC(c1ccccc1)c1ccc(Cl)c(Cl)c1
InChIKey: PBZNCQQGLHOIGW-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6ZQW0
Assay: Inhibition of IDO2 (unknown origin) using L-tryptophan as substrate by spectrophotometric method
Measurement: IC50 = 32000 nM (pChEMBL 4.5)
Descriptors: MW 268.14, ALogP 3.97, HBA 2, HBD 1, PSA 35.25, QED 0.85
Compound (SMILES): N.N.N.N.Nc1ncnc2c1ncn2[C@@H]1O[C@H](COP(=O)(O)OP(=O)(O)OP(=O)(O)O)[C@H]2OCO[C@H]21
InChIKey: JUSWNBNJCUGXNH-WHEJUCFXSA-N
Target: P2X purinoceptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P51575
Assay: Antagonist activity at human P2X1R transfected in human 1321N1 cells assessed as inhibition of ATP-induced calcium influx
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 519.19, ALogP -0.61, HBA 14, HBD 5, PSA 257.13, QED 0.27
Compound (SMILES): C=C1CCC(c2ccc(O)cc2)CC1
InChIKey: YGKNWJASJUQVMN-UHFFFAOYSA-N
Target: Estrogen receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: Q92731
Assay: Agonist activity at estrogen receptor beta (unknown origin) after 22 hrs by cell-based luciferase reporter gene assay
Measurement: EC50 = 101 nM (pChEMBL 7)
Descriptors: MW 188.27, ALogP 3.61, HBA 1, HBD 1, PSA 20.23, QED 0.67
Compound (SMILES): Cc1c(C(=O)N2CCC(O)(C3(C#N)CC3)CC2)cnn1-c1nn2cccc2c(=O)[nH]1
InChIKey: WZHFPKKMCCCJPI-UHFFFAOYSA-N
Target: Sepiapterin reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P35270
Assay: Inhibition of SPR in human PBMC cells assessed as reduction in BH4 production incubated for 12 to 48 hrs by LCMS analysis
Measurement: IC50 = 330 nM (pChEMBL 6.480000019073486)
Descriptors: MW 407.43, ALogP 0.79, HBA 8, HBD 2, PSA 132.31, QED 0.66
Compound (SMILES): COc1ccc(-c2nc3ccccc3c(=O)[nH]2)cc1OCC(=O)NC1CCCCC1
InChIKey: VAWMVQAKEDXTNH-UHFFFAOYSA-N
Target: CDK2/Cyclin A2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P20248
Assay: Inhibition of human full length N-terminal GST-fused CDK2 (M1 to L298 residues)/human full length Cyclin-A2 (M1 to L432 residues) expressed in Sf9 cells using histone H1 as substrate measured after 1 hr by ADP-glo luminescence assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 407.47, ALogP 3.43, HBA 5, HBD 2, PSA 93.31, QED 0.65
Compound (SMILES): COc1cccc(C(C)(C)NC[C@@H](O)[C@H](Cc2ccccc2)NC(=O)c2cc(C(=O)N(C)C)cc(N3CCCCC3)c2)c1
InChIKey: CLPJFWBCLJHKBP-AJQTZOPKSA-N
Target: Cathepsin D (SINGLE PROTEIN), Homo sapiens
UniProt: P07339
Assay: Inhibition of human cathepsin D using DABCYL-Glu-Arg-Nle-Phe-Leu-Ser-Phe-Pro-EDANS as substrate preincubated for 30 mins followed by substrate addition and measured every min for 8 to 15 mins by FRET assay
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 586.78, ALogP 4.61, HBA 6, HBD 3, PSA 94.14, QED 0.29
Compound (SMILES): COc1ncc(-c2ccc(-c3cnc4c(c3)CN(C)C4=O)s2)cc1NS(=O)(=O)c1ccc(F)cc1F
InChIKey: ZYYGNLSPUWSHQW-UHFFFAOYSA-N
Target: Perforin-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14222
Assay: Inhibition of perforin in human KHYG-1 cells pre-treated with compound for 20 mins assessed as reduction in KHYG-1 cells-mediated cell lysis of human K562 cells measured after 4 hrs by 51Cr release based gamma counting method
Measurement: IC50 = 4430 nM (pChEMBL 5.349999904632568)
Descriptors: MW 528.56, ALogP 4.55, HBA 7, HBD 1, PSA 101.49, QED 0.39
Compound (SMILES): COc1ccc(-c2cc3c([nH]c(=O)n3-c3cc(OC)c(OC)c(OC)c3)c(C(N)=O)n2)cc1O
InChIKey: WUZIEGHVPAZRFN-UHFFFAOYSA-N
Target: Katanin p60 ATPase-containing subunit A1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75449
Assay: Binding affinity to N-terminal human Katanin p60 (8 to 229 residues) expressed in Escherichia coli Rosetta (DE3) assessed as dissociation constant by SPR analysis
Measurement: Kd = 9155 nM (pChEMBL 5.039999961853027)
Descriptors: MW 466.45, ALogP 2.22, HBA 9, HBD 3, PSA 150.92, QED 0.38
Compound (SMILES): O=[N+]([O-])c1ccc(/C=N/Nc2nnc(-c3ccncc3)o2)cc1
InChIKey: NFJFOCDCCGFTGX-CXUHLZMHSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Inhibition of human recombinant COX-2 by EIA method
Measurement: IC50 = 41 nM (pChEMBL 7.389999866485596)
Descriptors: MW 310.27, ALogP 2.49, HBA 8, HBD 1, PSA 119.34, QED 0.44
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)C(C)(C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H]1CCCN1C(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc1ccccc1)NC(=O)CCc1ccccc1)C(C)C)C(C)(C)C)C(N)=O
InChIKey: IULYTZQGJOTQNO-HJVHQOEPSA-N
Target: Tissue factor pathway inhibitor (SINGLE PROTEIN), Homo sapiens
UniProt: P10646
Assay: Inhibition of C-terminus 10x-His-taged human TFPI-1 (29 to 282 residues) assessed as inhibition of factor 10a using S-2222 substrate incubated for 115 mins by micro-plate reader based assay
Measurement: EC50 = 9.6 nM (pChEMBL 8.020000457763672)
Descriptors: MW 2492.91
Compound (SMILES): C/C(=N\NC(=O)c1nc(N)n(-c2ccc(S(N)(=O)=O)cc2)n1)c1ccncc1
InChIKey: GMKRIMHCHCHCCT-UFFVCSGVSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human carbonic anhydrase-2 incubated for 15 mins by stopped flow CO2 hydrase assay
Measurement: Ki = 8.5 nM (pChEMBL 8.069999694824219)
Descriptors: MW 400.42, ALogP 0.05, HBA 9, HBD 3, PSA 171.24, QED 0.4
Compound (SMILES): O=C(/C=C/CN1CCCC1)N1CCOc2cc3ncnc(Nc4ccc(F)c(Cl)c4)c3cc21
InChIKey: JMIAHUUVJVWQPL-ONEGZZNKSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR (unknown origin) using FAM-labeled peptide substrate preincubated for 10 mins followed by substrate addition measured after 40 mins by caliper motility shift assay
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 467.93, ALogP 4.54, HBA 6, HBD 1, PSA 70.59, QED 0.56
Compound (SMILES): CCS(=O)(=O)c1ccc(CC(=O)Nc2ccc(C(C)(C)C#N)cc2)cc1
InChIKey: FVCLKKTYTOAOQT-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at human biotinylated HN-Avi-MBPS-TCS-RORC2 (258 to 518 residues) assessed as recruitment of SRC-1-derived coactivator measured after 15 mins by FRET assay
Measurement: IC50 = 316.23 nM (pChEMBL 6.5)
Descriptors: MW 370.47, ALogP 3.46, HBA 4, HBD 1, PSA 87.03, QED 0.84
Compound (SMILES): COc1ccc(N2CCN(CC(O)COc3cccc4[nH]c5ccccc5c34)CC2)cc1
InChIKey: FSPXYUHQVJZGHG-UHFFFAOYSA-N
Target: Alpha-1B adrenergic receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P15823
Assay: Antagonistic activity at alpha1B adrenoceptor in Sprague-Dawley rat spleen assessed as inhibition of noradrenaline-induced contractions after 0.5 hrs in presence of alpha2/beta adrenoceptor blocker yohimbine, propranolol by Schild plot analysis
Measurement: Kd = 6918.31 nM (pChEMBL 5.159999847412109)
Descriptors: MW 431.54, ALogP 3.89, HBA 5, HBD 2, PSA 60.96, QED 0.46
Compound (SMILES): O=C(C1=C(O)C(=O)N(c2ccc(Br)cc2F)C1C1CCCCC1)c1ccccc1
InChIKey: HULVCFFGXHJBLU-UHFFFAOYSA-N
Target: C-C chemokine receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P32246
Assay: Displacement of [3H]-CCR2-RA-[R] from human TEV protease site linked CCR1 expressed in human U20S cell membranes co-expressing Gal4-VP16 transcription factor after 120 mins by scintillation spectrometry
Measurement: Ki = 27.54 nM (pChEMBL 7.559999942779541)
Descriptors: MW 458.33, ALogP 5.58, HBA 3, HBD 1, PSA 57.61, QED 0.61
Compound (SMILES): Cc1ccc(-c2cc(=O)n3nc(C)c(-c4ccc(F)cc4)c3[nH]2)cc1
InChIKey: HWALOOIILHWQMX-UHFFFAOYSA-N
Target: PAS domain-containing serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RG2
Assay: Inhibition of purified human PASK expressed in insect cells incubated for 10 mins using MBP protein by kinase-Glo luminescent kinase assay
Measurement: IC50 <= 10000 nM (pChEMBL 5)
Descriptors: MW 333.37, ALogP 4.11, HBA 3, HBD 1, PSA 50.16, QED 0.6
Compound (SMILES): O=C1N(c2ccc(-c3ccccc3)cc2)C(=O)C2(CCNCC2)N1c1ncccn1
InChIKey: DIFDHZPOYNCBOH-UHFFFAOYSA-N
Target: Egl nine homolog 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9GZT9
Assay: Inhibition of N-terminal His6-tagged truncated PHD2 (181 to 426 residues) (unknown origin) expressed in Escherichia coli BL21 DE3 using H1F1-alpha NODD as substrate preincubated for 15 mins followed by substrate addition and measured after 15 mins by mass spectrometry
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 399.45, ALogP 3.24, HBA 5, HBD 1, PSA 78.43, QED 0.68
Compound (SMILES): Cc1nnc2ccc(C(=O)NC3CN(c4ncc(C#N)cc4Cl)C3)cc2c1C
InChIKey: IFYUHWDEWAPWJY-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 4 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P31423
Assay: Positive allosteric modulation of rat M4 receptor expressed in CHO cells co-expressing Gqi5 assessed as increase in acetylcholine-induced calcium mobilization incubated with EC20 ACh for 140 secs and subsequent EC80 Ach addition further incubated for 120 secs by Fluo-4-AM dye based fluorescence assay
Measurement: EC50 = 138 nM (pChEMBL 6.860000133514404)
Descriptors: MW 392.85, ALogP 2.79, HBA 6, HBD 1, PSA 94.8, QED 0.74
Compound (SMILES): CNC(=O)Nc1cc(Oc2c(F)cccc2F)c(C2CC2)cn1
InChIKey: YUYQXJJCKOEZRT-UHFFFAOYSA-N
Target: Hexokinase-4 (SINGLE PROTEIN), Homo sapiens
UniProt: P35557
Assay: Activation of human recombinant glucokinase using 5 mM glucose monitored over 5 mins in presence of NAD+ by glucose 6-phosphate dehydrogenase coupled assay
Measurement: EC50 = 38 nM (pChEMBL 7.420000076293945)
Descriptors: MW 319.31, ALogP 3.78, HBA 3, HBD 2, PSA 63.25, QED 0.9
Compound (SMILES): O=C(CCCCc1ccc2c(c1)OCO2)N1CCCC1
InChIKey: SUUYFWPFLGFWRW-UHFFFAOYSA-N
Target: N-acylethanolamine-hydrolyzing acid amidase (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q5KTC7
Assay: Inhibition of rat NAAA expressed in HEK293 cells using heptadecenoylethanolamide as substrate after 30 mins HPLC-MS/MS analysis
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 275.35, ALogP 2.75, HBA 3, HBD 0, PSA 38.77, QED 0.78
Compound (SMILES): NC(=O)c1ccccc1Nc1cc(Nc2ccc(F)cn2)ncc1C(N)=O
InChIKey: HZNQENBILSFKNN-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Inhibition of TYK2 JH2 in human KIT225 cells assessed as reduction of IFNalpha induced STAT1 phosphorylation by AlphaLISA assay
Measurement: IC50 = 37 nM (pChEMBL 7.429999828338623)
Descriptors: MW 366.36, ALogP 2.3, HBA 6, HBD 4, PSA 136.02, QED 0.53
Compound (SMILES): CC(C)(C)c1cc(-c2cn3c(=O)n(-c4ccccc4)nc3c(N)n2)ccc1O
InChIKey: FQPMECRNRDRAPV-UHFFFAOYSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30542
Assay: Displacement of [3H]CCPA from human adenosine A1 receptor expressed in CHO cell membranes by radioligand competition assay
Measurement: Ki > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 375.43, ALogP 3.13, HBA 7, HBD 2, PSA 98.44, QED 0.56
Compound (SMILES): CC(C)NCCCOc1ccc(O)c(O)c1
InChIKey: DUTXSNDEOIVBOG-UHFFFAOYSA-N
Target: Beta-1 adrenergic receptor (SINGLE PROTEIN), Mus musculus
UniProt: P34971
Assay: Displacement of [3H]-CGP-12177 from murine beta1-adrenergic receptor expressed in HEK293T cells after 60 mins by radioligand competition binding assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 225.29, ALogP 1.86, HBA 4, HBD 3, PSA 61.72, QED 0.51
Compound (SMILES): CC(C)(C)OC(=O)N(Cc1ccc(C(C)(C)C)cc1)c1ccc(C(=O)NO)cc1
InChIKey: SZBZYDVFLPQCJT-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant full length human HDAC8 expressed in baculovirus infected Sf9 cells using FAM-RHKK-TFAc as substrate incubated for 3 hrs by electrophoretic mobility shift assay
Measurement: IC50 = 635 nM (pChEMBL 6.199999809265137)
Descriptors: MW 398.5, ALogP 5.04, HBA 4, HBD 2, PSA 78.87, QED 0.56
Compound (SMILES): O=c1[nH]cnc2c(-n3cc(CCN4CCC(c5ccc(-c6cccnc6)cc5)CC4)cn3)nccc12
InChIKey: JRDMCDIQZVMPPB-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGL1
Assay: Inhibition of KDM5B (unknown origin) assessed as decrease in demethylation of substrate using peptide (H3(1-21)K4-Me3-GGKBiotin) as substrate and 2OG as cosubstrate pre-incubated for 15 mins before substrate addition followed by centrifugation for 15 secs and measured after 20 mins by Alphascreen assay
Measurement: IC50 = 80 nM (pChEMBL 7.099999904632568)
Descriptors: MW 477.57, ALogP 3.99, HBA 7, HBD 1, PSA 92.59, QED 0.4
Compound (SMILES): COc1nc2ccc(C(O)(c3ccc(C)nc3C)c3cnnn3C)cc2c(Cl)c1C
InChIKey: ACQHAIZGTGISMN-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: ThermoFluor Assay: ThermoFluor is a fluorescence based assay that estimates ligand binding affinities by measuring the effect of a ligand on protein thermal stability (Pantoliano, M. W., Petrella, E. C., Kwasnoski, J. D., Lobanov, V. S., Myslik, J., Graf, E., Carver, T., Asel, E., Springer, B. A., Lane, P., and Salemme, F. R. (2001) High-density miniaturized thermal shift assays as a general strategy for drug discovery. J Biomol Screen 6, 429-40, and Matulis, D., Kranz, J. K., Salemme, F. R., and Todd, M. J. (2005) Thermodynamic stability of carbonic anhydrase: measurements of binding affinity and stoichiometry using ThermoFluor. Biochemistry 44, 5258-66). This approach is applicable to a wide variety of systems, and rigorous in theoretical interpretation through quantitation of equilibrium binding constants (KD).In a ThermoFluor experiment where protein stability is monitored as the temperature is steadily increased, an equilibrium binding ligand causes the midpoint of an unfolding transition (Tm) to occur at a higher temperature. The shift in the melting point described as a ΔTm is proportional to the concentration and affinity of the ligand. The compound potency may be compared as a rank order of either ΔTm values at a single compound concentration or in terms of KD values, estimated from concentration response curves.
Measurement: Kd = 290 nM (pChEMBL 6.539999961853027)
Descriptors: MW 423.9, ALogP 3.63, HBA 7, HBD 1, PSA 85.95, QED 0.54
Compound (SMILES): CNC(=O)c1cnc(Nc2ccc(C(F)(F)F)cn2)cc1Nc1cccc(-c2ncn(C)n2)c1OC
InChIKey: WIXZZUOTUAIJAZ-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Mus musculus
UniProt: Q9R117
Assay: Inhibition of TYK2 in mouse whole blood assessed as decrease in IFNalpha-induced STAT1 phosphorylation preincubated for 1 hr followed by stimulation with IFN-alpha for 15 mins by fluorescence analysis
Measurement: IC50 = 700 nM (pChEMBL 6.159999847412109)
Descriptors: MW 498.47, ALogP 4.15, HBA 9, HBD 3, PSA 118.88, QED 0.35
Compound (SMILES): Cn1cc(NC(=O)c2cccc(-c3cncc(Cl)c3)n2)c(C(N)=O)n1
InChIKey: HVOIKNMEWFMNPX-UHFFFAOYSA-N
Target: Interleukin-1 receptor-associated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NWZ3
Assay: IMAP Technology: The kinase activity of IRAK4 is determined by its ability to catalyze the phosphorylation of a fluorescent polypeptide substrate. The extent of phosphorylation is measured using IMAP technology (Molecular Devices) where the phosphorylated fluorescent substrate binds to the large M(III)-based nanoparticles which reduces the rotational speed of the substrate and thus increases its fluorescent polarization (FP).Specific compounds of the instant invention were tested in the assay described above and were found to have IC50 values of ≦20 μM against substrate.Procedure: A 20 μl reaction mixture contains 10 mM TriHCl, pH 7.2, 0.5 nM GST tagged IRAK4 (SignalChem), 100 nM fluorescent peptide substrate (RP7030, Molecular Devices), 100 μM ATP, 1 mM DTT, 1 mM MgCl2, and 0.01% Tween 20. The reaction is initiated by the addition of ATP. After incubation for 30 minutes at 25° C., 60 μl of Progressive IMAP Reagent (Molecular Devices) is added to stop the reaction. Change in RP7030's FP is determined by a FP reader (Analyst HT, LJL BioSystems).
Measurement: IC50 = 91 nM (pChEMBL 7.039999961853027)
Descriptors: MW 356.77, ALogP 1.88, HBA 6, HBD 2, PSA 115.79, QED 0.74
Compound (SMILES): Cl.Cl.NC(Cc1c[nH]c2ccccc12)C(=O)NCCCCCCNc1c2c(nc3cc(Cl)ccc13)CCCC2
InChIKey: JDPFLTTTZILSHX-UHFFFAOYSA-N
Target: Nitric oxide synthase 3 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q62600
Assay: Inhibition of nNOS in Wistar rat cortical homogenates incubated for 30 mins
Measurement: IC50 = 33000 nM (pChEMBL 4.480000019073486)
Descriptors: MW 518.11, ALogP 5.91, HBA 4, HBD 4, PSA 95.83, QED 0.19
Compound (SMILES): CC1=C(SC(C)C)C(=O)c2ccccc2C1=O
InChIKey: JBMPJFZKNXELGQ-UHFFFAOYSA-N
Target: M-phase inducer phosphatase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P30305
Assay: Inhibition of recombinant Cdc25B (unknown origin) using OMFP as substrate measured every 30 sec for 10 mins by fluorometric assay
Measurement: IC50 = 9100 nM (pChEMBL 5.039999961853027)
Descriptors: MW 246.33, ALogP 3.48, HBA 3, HBD 0, PSA 34.14, QED 0.8
Compound (SMILES): Cc1ccc2c(N)c(C(=O)NC[C@@H](C)c3ccc(N4CC5CCC(C4)N5)c(C#N)c3)sc2n1
InChIKey: NSXWVLYZUZRLNB-FTXHTYHOSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 28 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RU2
Assay: Biochemical Assay: USP28: The assay was performed in a final volume of 20 uL in assay buffer containing 20 mM Tris-HCl (pH 8.0, (1M Tris-HCl, pH 8.0 solution; Corning 46-031-CM)), 2 mM CaCl2 (1M Calcium Chloride solution; Sigma #21114) 2 mM BME (2-Mercaptoethanol; Sigma 63689-25ML -F), 0.01% Prionex (0.22 uM filtered, Sigma #G-0411), and 0.01% Triton X-100. Stock compound solutions were stored at â20° C. as 10 mM in DMSO. Up to 1 month prior to the assay, 2 mM test compounds were pre-dispensed into assay plates (Black, low volume; Corning #3820) and frozen at â20° C. Prestamped assay plates were allowed to come to room temperature on the day of the assay. For the screen, 100 nL of 2 mM was pre-dispensed for a final screening concentration of 10 uM (DMSO(fc)=0.5%). Enzyme (USP28, construct USP28 (USP28-5(1-1077)-TEV-6*His; LifeSensors) concentration and incubation times were optimized for the maximal signal-to -background while maintaining initial velocity conditions at a fixed substrate concentration. The final concentration of the enzyme in the assay was 400 pM. Final substrate (Ub-Rh110; Ubiquitin -Rhodamine 110, R&D Systems #U-555) concentration was 25 nM with [Ub-Rh110] Km. 10 uL of 2x enzyme was added to assay plates (pre-stamped with compound) either simultaneously with 2xUb-Rh110 or preincubated with USP28 40 minutes prior to the addition of 10 uL of 2xUb -Rh110 to compound plates. Plates were incubated stacked for 90 minutes at room temperature before fluorescence was read on the Envision (Excitation at 485 nm and Emission at 535 nm; Perkin Elmer) or on the PheraSTAR (Excitation at 485 nm and Emission at 535 nm; BMG Labtech).
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 460.61, ALogP 3.53, HBA 7, HBD 3, PSA 107.07, QED 0.54
Compound (SMILES): CC(C)(C#N)c1cccc(-c2ccnc3[nH]ncc23)c1
InChIKey: JXGKWKHETDHDCC-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of JAK2 (unknown origin) using polyE4Y peptide as substrate incubated for 60 mins in presence of [33P] gammaATP by microbeta liquid scintillation counter
Measurement: Ki = 270 nM (pChEMBL 6.570000171661377)
Descriptors: MW 262.32, ALogP 3.43, HBA 3, HBD 1, PSA 65.36, QED 0.77
Compound (SMILES): C=CC(=O)Nc1cccc(-n2c(=O)ccc3oc4ccc(-c5cccnc5)cc4c32)c1
InChIKey: FVCDPGCMEGFTQT-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of PI3Kalpha (unknown origin) by ADP-gloassay
Measurement: IC50 = 855 nM (pChEMBL 6.070000171661377)
Descriptors: MW 407.43, ALogP 4.92, HBA 5, HBD 1, PSA 77.13, QED 0.43
Compound (SMILES): Cc1c(C(=O)N2CCC(O)(C3CC3)CC2)cnn1-c1nn2cccc2c(=O)[nH]1
InChIKey: CVKFBTAZHCYSFD-UHFFFAOYSA-N
Target: Sepiapterin reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P35270
Assay: Inhibition of SPR in human PBMC cells assessed as reduction in BH4 production incubated for 12 to 48 hrs by LCMS analysis
Measurement: IC50 = 72 nM (pChEMBL 7.139999866485596)
Descriptors: MW 382.42, ALogP 0.89, HBA 7, HBD 2, PSA 108.52, QED 0.7
Compound (SMILES): N#CCC(=O)Nc1csc(-c2ccc(Cl)c(Cl)c2)n1
InChIKey: CCXHNQKXOCPCFZ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Induction of human c-ABL phosphorylation at Y245/Y412 residues in bacmam-induced HEK-MSR2 cell lysates by in-cell Western blot analysis
Measurement: EC50 = 15848.93 nM (pChEMBL 4.800000190734863)
Descriptors: MW 312.18, ALogP 3.97, HBA 4, HBD 1, PSA 65.78, QED 0.93
Compound (SMILES): C#CCNS(=O)(=O)c1ccc(CCN(Cc2cc(Cl)ccc2OCCC)C(=O)Cc2ccsc2)cc1
InChIKey: SFPYRFRNYALLHS-UHFFFAOYSA-N
Target: NACHT, LRR and PYD domains-containing protein 3 (SINGLE PROTEIN), Mus musculus
UniProt: Q8R4B8
Assay: Inhibition of NLRP3 in mouse peritoneal macrophages assessed as inhibition of LPS and ATP-induced IL-1beta production pre-stimulated with LPS for 4.5 hrs before compound addition with ATP for 30 mins by ELISA
Measurement: IC50 = 1590 nM (pChEMBL 5.800000190734863)
Descriptors: MW 545.13, ALogP 4.92, HBA 5, HBD 1, PSA 75.71, QED 0.31
Compound (SMILES): C=CC(=O)Nc1cccc(-c2c(-c3ccccc3OC)oc3ncnc(N[C@H](CO)c4ccccc4)c23)c1
InChIKey: PDGXQCBYLSUPPW-HSZRJFAPSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of GST-tagged human EGFR D770_N771insNPG mutant using poly(Glu, Tyr) 4:1 substrate incubated for 120 mins by kinase-Glo plus luminescent kinase assay
Measurement: IC50 = 0.636 nM (pChEMBL 9.199999809265137)
Descriptors: MW 506.56, ALogP 5.84, HBA 7, HBD 3, PSA 109.51, QED 0.22
Compound (SMILES): CS(=O)(=O)NC(=O)c1ccc(-c2ccc(Cl)c(Cl)c2)cc1
InChIKey: OANGKKPLBYQNSA-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Displacement of [3H]dofetilide from human ERG expressed in HEK293 cells after 45 mins by scintillation counting analysis
Measurement: Ki > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 344.22, ALogP 3.35, HBA 3, HBD 1, PSA 63.24, QED 0.93
Compound (SMILES): NS(=O)(=O)c1ccc(-c2noc(-c3ccncc3)n2)cc1
InChIKey: BLIIAHGNPLZXHR-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human carbonic anhydrase 9 assessed as reduction in CO2 hydration after 15 mins by phenol red staining-based stopped flow assay
Measurement: Ki = 0.44 nM (pChEMBL 9.359999656677246)
Descriptors: MW 302.31, ALogP 1.45, HBA 6, HBD 1, PSA 111.97, QED 0.78
Compound (SMILES): N#CN1CC[C@@H](NC(=O)c2ccc(-c3ccnnc3)cc2F)C1
InChIKey: ZGOOADAFZDDZME-CYBMUJFWSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 30 (SINGLE PROTEIN), Homo sapiens
UniProt: Q70CQ3
Assay: Inhibition of human USP30 catalytic domain (57 to 517 residues) using ubiquitin-rhodamine 110 as substrate preincubated for 30 min followed by substrate addition and measured after 2 hrs by fluorescence intensity kinetic assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 311.32, ALogP 1.57, HBA 5, HBD 1, PSA 81.91, QED 0.87
Compound (SMILES): C[C@@H](O)c1ccc2c(N)c(C(=O)NCCc3ccc(N4CCNCC4)cc3)sc2n1
InChIKey: BNTQUFKUUAKTHO-CQSZACIVSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 28 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RU2
Assay: Inhibition of TEV-cleavable hexa-histidine tagged USP28 (1 to 1077 residues) (unknown origin) using ubiquitin-rhodamine 110 as substrate and measured after 90 mins by fluorescence based assay
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 425.56, ALogP 2.31, HBA 7, HBD 4, PSA 103.51, QED 0.48
Compound (SMILES): Cc1c(-c2ccncc2)ccc2c1CCNC2=O
InChIKey: YTAWESHUWVTJNG-UHFFFAOYSA-N
Target: Protein mono-ADP-ribosyltransferase PARP11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR21
Assay: Inhibition of full length human His-SUMO-tagged PARP11 expressed in Escherichia coli BL21 assessed as reduction in MARylation of His6-tagged SRPK2 substrate after 60 mins in presence of NAD+ by chemifluorescence assay
Measurement: IC50 = 21200 nM (pChEMBL 4.670000076293945)
Descriptors: MW 238.29, ALogP 2.34, HBA 2, HBD 1, PSA 41.99, QED 0.83
Compound (SMILES): N#CN1CC[C@@H](NC(=O)c2ncc(-c3ccccc3)cn2)C1
InChIKey: QEHDEJVTUAFCHT-CQSZACIVSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 30 (SINGLE PROTEIN), Homo sapiens
UniProt: Q70CQ3
Assay: Inhibition of human USP30 catalytic domain (57 to 517 residues) using ubiquitin-rhodamine 110 as substrate preincubated for 30 min followed by substrate addition and measured after 2 hrs by fluorescence intensity kinetic assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 293.33, ALogP 1.43, HBA 5, HBD 1, PSA 81.91, QED 0.87
Compound (SMILES): Cc1cc(C)cc(Oc2cccc(-c3c(C)nnn3C3CCN(C(=N)N)CC3)n2)c1
InChIKey: LTVHUTQVMLLORB-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to human partial length BRD4 bromodomain 2 long isoform (K333 to E460 residues) expressed in bacterial expression system by BROMOscan assay
Measurement: Kd = 940 nM (pChEMBL 6.03000020980835)
Descriptors: MW 405.51, ALogP 3.59, HBA 6, HBD 2, PSA 105.94, QED 0.51
Compound (SMILES): O=C(Nc1cc(-c2cn(CCNc3c4c(nc5ccccc35)CCCC4)nn2)ccn1)Nc1cccc2c1C1CCCCN1C2=O
InChIKey: BNBWNJAILLASJW-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human recombinant AChE using ATCh as substrate preincubated for 20 mins followed by substrate addition and measured for 3 mins by Ellman method
Measurement: IC50 = 11.4 nM (pChEMBL 7.940000057220459)
Descriptors: MW 613.73, ALogP 6.2, HBA 8, HBD 3, PSA 129.96, QED 0.2
Compound (SMILES): COc1ccc(CCN(C(=O)OC2CCCN(C)C2)c2ccccc2)cc1OC
InChIKey: RXRKWRRWTOGCKS-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M5 (SINGLE PROTEIN), Homo sapiens
UniProt: P08912
Assay: Displacement of [3H]NMS from human M5 AChR expressed in CHO cell membranes after 1 to 2 hrs by liquid scintillation spectrometry method
Measurement: Ki = 4490 nM (pChEMBL 5.349999904632568)
Descriptors: MW 398.5, ALogP 3.98, HBA 5, HBD 0, PSA 51.24, QED 0.71
Compound (SMILES): CCc1ccc(C(=O)Nc2cc(CN3CCN(C)CC3)cc(C(F)(F)F)c2)cc1-c1cccc(-c2cnc3ccnn3c2)c1
InChIKey: WWIJZOWOWLGRSG-UHFFFAOYSA-N
Target: Bcr/Abl fusion protein (CHIMERIC PROTEIN), Homo sapiens
UniProt: P11274
Assay: Inhibition of human recombinant full length His-tagged Bcr-Abl expressed in baculovirus expression system using tyrosine-2 peptide as substrate after 1 hr in presence of 10 mM ATP by FRET based Z'-LYTE assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 598.67, ALogP 6.64, HBA 6, HBD 1, PSA 65.77, QED 0.23
Compound (SMILES): CNCCN1CCC(c2cc(CN(C)C(=O)c3cccc(Oc4ccccc4)c3)ccn2)CC1
InChIKey: VUIITYLFSAXKIQ-UHFFFAOYSA-N
Target: Histone-arginine methyltransferase CARM1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86X55
Assay: Affinity On-target Cellular interaction: (Western Blot (dimethylation of MED12, Med12me2a/Med12, in HEK293T cells) ) EUB0000230b CARM1
Measurement: IC50 = 43 nM (pChEMBL 7.369999885559082)
Descriptors: MW 458.61, ALogP 4.54, HBA 5, HBD 1, PSA 57.7, QED 0.51