lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1ccc(-c2ccc(CO[C@H]3C[C@@H](N=C=S)C3)nc2)nc1
InChIKey: LBBCJWGQDYTJDQ-FZNQNYSPSA-N
Target: N-acylethanolamine-hydrolyzing acid amidase (SINGLE PROTEIN), Homo sapiens
UniProt: Q02083
Assay: Inhibition of Test Compounds NAAA Assay: In order to have an assay method more conducive to high-throughput screening than those published for measuring the NAE hydrolyzing activity of NAAA, the fluorogenic PEA analog N-(4-methyl coumarin)palmitamide (PAMCA), which is hydrolyzed to fluorescent 7-amino-4-methyl coumarin (AMC) and palmitic acid, was developed. For three point concentration inhibition assays with hNAAA the following procedure was used. Purified activated NAAA (final concentration of 0.25 μg/mL) was incubated in assay buffer (100 mM citrate-phosphate buffer, pH 4.5, 3 mM DTT, 0.1% Triton X-100, 0.05% BSA, and 150 mM NaCl) made up to a total volume of 180 μL, followed by addition of the compound dissolved in 10 μL DMSO (along with DMSO neat for the control sample) with the final concentrations for each compound of 100, 10, and 1 μM, in triplicate on a 96 well plate. These samples were allowed to incubate for 15 min at room temperature and then 10 μL of a PAMCA stock solution in DMSO (final PAMCA concentration [5 μM]) was added. After 5 minutes of agitation on a shaking plate, the reaction was allowed to proceed at 37° C. for 120 minutes, with fluorescence readings taken every 10 minutes at a wavelength of 460 nm (using an excitation wavelength of 360 nm) on a Synergy HT Plate Reader using Gen5 software from Bio-Tek. The enzyme activity was calculated by converting the relative fluorescence units to AMC formed, using a standard curve of AMC.
Measurement: IC50 = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 327.41, ALogP 3.3, HBA 6, HBD 0, PSA 56.6, QED 0.6
Compound (SMILES): O=C(NCc1ccncc1)Nc1ccc2nc(-c3cccc(OC(F)(F)F)c3)nn2c1
InChIKey: AZUMPVOTKJTXOL-UHFFFAOYSA-N
Target: Nicotinamide phosphoribosyltransferase (SINGLE PROTEIN), Homo sapiens
UniProt: P43490
Assay: Activation of human NAMPT assessed as increase in NMN production by fluorescence based analysis
Measurement: EC50 = 350 nM (pChEMBL 6.460000038146973)
Descriptors: MW 428.37, ALogP 4.01, HBA 6, HBD 2, PSA 93.44, QED 0.5
Compound (SMILES): CCc1nc2c(C)cc(-c3ccc(CN4CCC[C@H]4CO)cc3)cn2c1NC(=O)NCc1ccc(OC)c(Cl)c1
InChIKey: LONJOWMAPSGSKR-VWLOTQADSA-N
Target: Autotaxin (SINGLE PROTEIN), Homo sapiens
UniProt: Q13822
Assay: Inhibition of human ATX using FS-3 as substrate preincubated for 45 mins followed by substrate addition and measured every 1 min for 30 mins by fluorescence microplate reader assay
Measurement: IC50 = 497 nM (pChEMBL 6.300000190734863)
Descriptors: MW 562.11, ALogP 5.81, HBA 6, HBD 3, PSA 91.13, QED 0.24
Compound (SMILES): NS(=O)(=O)c1ccc(Cc2c(-c3ccc(F)c(OCC4CC4(F)F)c3)nn(-c3nc(C(=O)O)cs3)c2CC2CC2)cc1F
InChIKey: ACECJHMAHJGXGH-UHFFFAOYSA-N
Target: L-lactate dehydrogenase A chain (SINGLE PROTEIN), Homo sapiens
UniProt: P00338
Assay: Inhibition of recombinant human LDHA using sodium pyruvate as substrate preincubated for 5 mins followed by diaphorase/resazurin addition and measured after 20 mins by fluorescence based assay
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 636.65, ALogP 5.2, HBA 8, HBD 2, PSA 137.4, QED 0.22
Compound (SMILES): O=C(Nc1cncc(OCC2CCN(Cc3ccc(F)cc3)CC2)c1)c1ccnc(NC(=O)C2CC2)c1
InChIKey: YNKUUJYZUJYJRR-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human recombinant AChE preincubated for 1 min in presence of DNTB followed by addition of acetylthiocholine iodide substrate and measured after 20 mins by Ellman's method
Measurement: IC50 = 1 nM (pChEMBL 9)
Descriptors: MW 503.58, ALogP 4.51, HBA 6, HBD 2, PSA 96.45, QED 0.45
Compound (SMILES): CCCCCCCCCCCC[C@]1(CO)NC[C@H](O)[C@@H](O)[C@@H]1O.Cl
InChIKey: OMCNHJYXBNRTEN-DVKVAQLYSA-N
Target: Sucrase-isomaltase, intestinal (SINGLE PROTEIN), Rattus norvegicus
UniProt: P23739
Assay: Inhibition of rat intestinal sucrase using p-nitrophenyl glycoside as substrate assessed as release of p-nitrophenol measured by spectrometric assay
Measurement: IC50 = 1200 nM (pChEMBL 5.920000076293945)
Descriptors: MW 331.5, ALogP 1.71, HBA 5, HBD 5, PSA 92.95, QED 0.35
Compound (SMILES): O=C(O)c1cccc(COc2ccc(Cl)cc2Cl)n1
InChIKey: KMRBNGORDVGEJX-UHFFFAOYSA-N
Target: Mas-related G-protein coupled receptor member X4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96LA9
Assay: Antagonist activity at human MRGPRX4 expressed in HEK cells incubated in dark for 1 hr at 37 degree C and then incubated for 30 mins at room temperature in presence of 10 pM of bilirubin by HTRF assay
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 298.12, ALogP 3.67, HBA 3, HBD 1, PSA 59.42, QED 0.94
Compound (SMILES): [2H]C([2H])(C1CCOCC1)N1C[C@H]2C[C@H](Nc3ccc(-c4cc(F)cc(F)c4F)nn3)C[C@H]2C1
InChIKey: ITSKPCHXUYILTR-VRBVDISKSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Antagonist activity at human muscarinic M2 receptor expressed in CHO cells co-expressing Gqi5 assessed as inhibition of acetylcholine-induced calcium mobilization
Measurement: IC50 = 4700 nM (pChEMBL 5.329999923706055)
Descriptors: MW 432.49, ALogP 4.11, HBA 5, HBD 1, PSA 50.28, QED 0.72
Compound (SMILES): CCOc1cccc(C(=O)Nc2cccc(C(=O)O)c2)c1
InChIKey: AAFBQBNJYIIFEH-UHFFFAOYSA-N
Target: Bile acid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RI1
Assay: Agonist activity at FXR-LBD (unknown origin) assessed by ligand binding ability incubated for 3 hrs in absence of light measured by TR-FRET Coactivator assay
Measurement: EC50 = 2348 nM (pChEMBL 5.630000114440918)
Descriptors: MW 285.3, ALogP 3.04, HBA 3, HBD 2, PSA 75.63, QED 0.88
Compound (SMILES): CC(=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C)NC(=O)[C@@H](CCCNC(=N)N)NCCCCC1CCN(CC(=O)N2c3ccccc3NC(=O)c3ccccc32)CC1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: LYWNKHWCBIBPPS-WVADTLRHSA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: Displacement of [3H]-NMS from human muscarinic M1 receptor expressed in CHO cell membranes assessed as inhibition constant by radioligand competition analysis
Measurement: Ki = 52.48 nM (pChEMBL 7.28000020980835)
Descriptors: MW 832.02, ALogP 0.94, HBA 10, HBD 11, PSA 292.85, QED 0.05
Compound (SMILES): C=CC(=O)N1CCC[C@@H](NC(=O)c2sc3nccc4c3c2NC(=O)N4c2ccccc2)C1
InChIKey: JWSQOLWJHPFPNP-CQSZACIVSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Kinase Lanthascreen Binding Assay: A BTK kinase lanthascreen binding assay monitors compound binding to unphosphorylated-BTK kinase domain (UP-BTK), by competing with a fluorescent labeled tracer. UP-BTK, consisting of the kinase domain of non-phosphorylated BTK protein (389-659aa), was produced in a Baculovirus/insect cell expression system. Into a 384-well plate, 2 ng of GST-tagged human BTK (389-659aa) was incubated with compound, 50 nM of Tracer 236 and 2 nM anti-GST antibody for 60 minutes using an optimized Lanthascreen assay. After 60 minutes, plates were read at 340 nM and 615/665 nM in an Infinite F500 (Tecan).
Measurement: IC50 = 398 nM (pChEMBL 6.400000095367432)
Descriptors: MW 447.52, ALogP 3.89, HBA 5, HBD 2, PSA 94.64, QED 0.59
Compound (SMILES): CCC(Oc1cccc(Cl)c1Cl)c1nc(N)nc(N2CCN(C)CC2)n1
InChIKey: WBFUPJYWMYUSBO-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H]LSD from human 5-HT6 receptor expressed in HEK293 cells incubated for 1 hr by microbeta counting method
Measurement: Ki = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 397.31, ALogP 3.04, HBA 7, HBD 1, PSA 80.4, QED 0.83
Compound (SMILES): CCCCC1(c2cc(OC)c3cc(Cc4ccccn4)c(=O)oc3c2)CCCC1
InChIKey: QTDMMVRSQBVSOE-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Displacement of [3H]-CP55940 from human recombinant CB1 receptor expressed in CHO-K1 cell membrane measured after 3 hrs by scintillation spectrometry
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 391.51, ALogP 5.79, HBA 4, HBD 0, PSA 52.33, QED 0.48
Compound (SMILES): COc1cc(NC(=O)[C@H](N)CC2CC2)ccc1-c1cnco1
InChIKey: SHPOANSEVGYKCU-CYBMUJFWSA-N
Target: AP2-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q2M2I8
Assay: Inhibition of recombinant GST-Xa-tagged human AAK1 (30 to 330 residues) using 5-FAM-labelled Alla-KEEQSQITSQVTGQIGWR-NH2 peptide as substrate incubated for 3 hrs in presence of ATP by electrophoretic analysis
Measurement: IC50 = 45 nM (pChEMBL 7.349999904632568)
Descriptors: MW 301.35, ALogP 2.42, HBA 5, HBD 2, PSA 90.38, QED 0.85
Compound (SMILES): COc1ccccc1C1=C(Nc2ccc(Nc3ccccc3)cc2)C(=O)NC1=O
InChIKey: KZRKLOQHZJQWRB-UHFFFAOYSA-N
Target: STE20-like serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H2G2
Assay: Binding affinity human SLK by binding displacement assay
Measurement: Ki = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 385.42, ALogP 3.92, HBA 5, HBD 3, PSA 79.46, QED 0.56
Compound (SMILES): CC(C)n1c(=O)c2cnc(Nc3ccc4c(c3)CCNC4)nc2n1-c1ccc(F)c(C(C)(C)F)n1
InChIKey: JCFAHNQHNCQXGI-UHFFFAOYSA-N
Target: Wee1-like protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P30291
Assay: Inhibition of human recombinant full length GST-tagged Wee1 expressed in baculovirus expression system using fluorescent-PolyGT substrate preincubated with enzyme for 10 mins followed by incubation with substrate and ATP for 1 hr by LanthaScreen Terbium Labeled TR-FRET assay
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 479.54, ALogP 4.29, HBA 8, HBD 2, PSA 89.66, QED 0.44
Compound (SMILES): O=c1cc(-c2ccc(O)cc2)oc2c(CN3CCN(c4cncnc4)CC3)c(O)cc(O)c12
InChIKey: FKVHDFTTYJQKSR-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P09874
Assay: Inhibition of recombinant human full-length PARP-1 using biotinylated substrate
Measurement: IC50 = 29.5 nM (pChEMBL 7.53000020980835)
Descriptors: MW 446.46, ALogP 2.69, HBA 9, HBD 3, PSA 123.16, QED 0.43
Compound (SMILES): CC(C)c1ccc(CNC(=O)[C@@H]2CCCN(c3cccc(OC(C)(C)C(=O)O)c3)C2)cc1
InChIKey: RWRLBVSCKJARNJ-OAQYLSRUSA-N
Target: beta-catenin-B-cell lymphoma 9 protein complex (PROTEIN COMPLEX), Homo sapiens
UniProt: O00512
Assay: Inhibition of C-terminal 6-His-tagged beta-catenin (1 to 781 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3)-N-terminal biotinylated human BCL9 (350 to 375 residues) protein-protein interaction incubated for 1 hr by Alphascreen assay
Measurement: IC50 = 51000 nM (pChEMBL 4.289999961853027)
Descriptors: MW 438.57, ALogP 4.58, HBA 4, HBD 2, PSA 78.87, QED 0.63
Compound (SMILES): COc1cccc(S(=O)(=O)c2c(C)c(C(=O)O)n(CCCOc3cc(C)c(Cl)c(C)c3)c2C)c1
InChIKey: KDYJJSREURFPKB-UHFFFAOYSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Inhibition of FITC-labeled Bak BH3 peptide binding to GST-tagged MCL1 (171 to 327 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) incubated for 30 mins fluorescence polarization-based competitive binding assay
Measurement: Ki = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 506.02, ALogP 5.38, HBA 6, HBD 1, PSA 94.83, QED 0.39
Compound (SMILES): CCn1c(-c2cnc(C)nc2)nc2c(O[C@H]3CCN(C(=O)c4cocn4)C3)ncnc21
InChIKey: GTDNUYQEEDHPIM-AWEZNQCLSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Biochemical Assay: The PI3-Kinase biochemical assay was optimized using the HTRF kit provided by Upstate (Millipore). The assay kit contains six reagents: 1) 4× Reaction Buffer; 2) native PIP2 (substrate); 3) Stop (EDTA); 4) Detection Mix A (Streptavidin-APC); 5) Detection Mix B (Eu-labeled Anti-GST plus GST-tagged PH-domain); 6) Detection Mix C. In addition, the following items were obtained or purchased; PI3Kinase (alpha 14-602, beta 14-603, gamma 14-558 and delta 14-604 from Upstate; Millipore), dithiothreitol (Sigma, D-5545), Adenosine-5′ triphosphate (InVitrogen, Cat#AS001A), native PIP3 (PI(3,4,5)P3, diC8, H+, CELLSIGNALS, INC. Cat #907) DMSO (Sigma, 472301).PI3Kinase Reaction Buffer is prepared by dilution the stock 1:4 with de-ionized water. DTT, PIP2 and Biotin-PIP3 were added to 1536 assay plate at a final concentration of 5 mM, 5 mM and 25 nM on the day of use. Enzyme addition and compound pre-incubation are initiated by the addition of 1.25 ul of PI3K (at twice its final concentration) in the 1× reaction buffer to all wells using a BioRaptor. Plates are incubated at room temperature for 15 minutes. Reactions are initiated by addition of 1.25 ul of 2× substrate solution (PIP2 and ATP in 1× reaction buffer) using BioRaptor. Plates are incubated in humidified chamber at room temperature for one hour. Reactions are quenched by addition of 0.625 uL of stop solution to all wells using the BioRaptor. The quenched reactions are then processed to detect product formation by adding 0.625 uL of Detection Solution to all wells using the BioRaptor (Detection mix C, Detection Mix A, and Detection Mix B combined together in an 18:1:1 ratio prepared 2 hours prior to use). Following a one hour incubation in the dark, the HTRF signal is measured on the Envision plate reader set for 330 nm excitation and dual emission detection at 620 nM (Eu) and 665 nM (APC).
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 420.43, ALogP 1.89, HBA 10, HBD 0, PSA 124.95, QED 0.48
Compound (SMILES): Cn1cc2c(-c3cc(F)c(CN4Cc5ocnc5C4=O)c(F)c3)cccc2n1
InChIKey: ZNBYMBVVUXAANF-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: Positive allosteric modulation of human muscarinic acetylcholine M1 receptor expressed in CHO cells in presence of acetylcholine at EC20 concentration by calcium mobilization assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 380.35, ALogP 3.66, HBA 5, HBD 0, PSA 64.16, QED 0.54
Compound (SMILES): CC(=O)n1cc(/C=C2/N=C(c3ncccn3)N(c3ccc(S(N)(=O)=O)cc3)C2=O)c2ccccc21
InChIKey: GUQIGNOAQKOBTM-DEDYPNTBSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of human CA1 by stopped-flow assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 486.51, ALogP 2.57, HBA 8, HBD 1, PSA 140.61, QED 0.44
Compound (SMILES): CC(F)(F)COc1ncncc1CNc1ncc(C#N)c(N[C@@H]2CC[C@H](O)C(C)(C)C2)n1
InChIKey: FMKGJQHNYMWDFJ-CVEARBPZSA-N
Target: Protein kinase C theta type (SINGLE PROTEIN), Homo sapiens
UniProt: Q04759
Assay: Inhibition of PKA-theta (unknown origin) using Fam-labelled S6-derived peptide incubated for 2 hrs by TR-FRET assay
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 447.49, ALogP 3.14, HBA 9, HBD 3, PSA 128.87, QED 0.56
Compound (SMILES): COCC(C)n1c(=O)[nH]c2cnc3cc(-c4c(C)noc4C)c(OC)cc3c21
InChIKey: XTPZHDYKHVXXQH-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of BRD4 in human PBMC assessed as reduction in LPS-induced IL-6 secretion incubated for 18 to 24 hrs by MSD assay
Measurement: IC50 = 1584.89 nM (pChEMBL 5.800000190734863)
Descriptors: MW 382.42, ALogP 3.37, HBA 7, HBD 1, PSA 95.17, QED 0.57
Compound (SMILES): C[C@@H](C(=O)O)[C@H]1Cc2c(c(O)c3ccccc3c2O[C@@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)C(=O)O1
InChIKey: PWLCUNDXYKDDOQ-KBARCFKISA-N
Target: Bifunctional epoxide hydrolase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34913
Assay: Inhibition of sEH (unknown origin) expressed in baculovirus expression system incubated for 1 hr
Measurement: IC50 = 600 nM (pChEMBL 6.21999979019165)
Descriptors: MW 464.42, ALogP -0.47, HBA 10, HBD 6, PSA 183.21, QED 0.31
Compound (SMILES): CNC(=O)[C@H]1Cc2c([nH]c3ccccc23)CN1C(=O)C[C@@H](Cc1cccc(F)c1)NC(=O)C1CO1
InChIKey: UMWWEZMNPBLTBD-SHVQYXQLSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of recombinant human N-terminal His-tagged BTK expressed in baculovirus infected in Sf9 cells incubated for 1 hr by TR-FRET assay
Measurement: IC50 = 232 nM (pChEMBL 6.630000114440918)
Descriptors: MW 478.52, ALogP 1.82, HBA 4, HBD 3, PSA 106.83, QED 0.45
Compound (SMILES): COc1cccc(OC)c1-c1cc(C(=O)N[C@@H](CCN2CCCC2)CC(=O)NC2CCC2)nn1C1CCCC1.Cl
InChIKey: OFCFZNZPXDWOEE-FTBISJDPSA-N
Target: Apelin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35414
Assay: Agonist activity at human APJ receptor expressed in CHO cells assessed as inhibition of forskolin-induced cAMP accumulation measured after 40 mins by TR-FRET assay
Measurement: EC50 = 167 nM (pChEMBL 6.78000020980835)
Descriptors: MW 537.71, ALogP 4.33, HBA 7, HBD 2, PSA 97.72, QED 0.42
Compound (SMILES): CNc1nc(C)c(-c2nc(Nc3cccc(N4CCNCC4)c3)ncc2C(F)(F)F)s1
InChIKey: NNVQFONYTZIEBC-UHFFFAOYSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of recombinant human full length CDK9/Cyclin T1 using KTFCGTPEYLAPEVRREPRILSEEEQEMFRDFDYIADWC as substrate incubated for 40 mins in presence of [gamma-33P]-ATP by scintillation counting method
Measurement: Ki = 49 nM (pChEMBL 7.309999942779541)
Descriptors: MW 449.51, ALogP 4.12, HBA 8, HBD 3, PSA 78, QED 0.54
Compound (SMILES): COC(=O)[C@H](CO)NC(=O)CNC(=O)C(=O)[C@@H]1CCCN1C(=O)CNC(=O)c1ccnc2ccccc12
InChIKey: CDSHGZWMVFUTHH-ROUUACIJSA-N
Target: Prolyl endopeptidase FAP (SINGLE PROTEIN), Homo sapiens
UniProt: Q12884
Assay: Inhibition of SF-tagged FAP (unknown origin) expressed in Drosophila S2 cells using fluorogenic substrate by spectrometric analysis
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 513.51, ALogP -1.71, HBA 9, HBD 4, PSA 184.1, QED 0.21
Compound (SMILES): O=C(NCCO)c1cccc2c1CCN2c1cc(Cc2cc(F)c(F)c(F)c2)ccn1
InChIKey: HJQCELFTHPDMIP-UHFFFAOYSA-N
Target: G-protein coupled receptor 52 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2T5
Assay: Agonist activity at GPR52 (unknown origin) expressed in CHO-K1 or HEK293 cells assessed as intracellular cAMP accumulation incubated for 1 hr by HTRF assay
Measurement: EC50 = 8.87 nM (pChEMBL 8.050000190734863)
Descriptors: MW 427.43, ALogP 3.51, HBA 4, HBD 2, PSA 65.46, QED 0.59
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@@H](N)CCC(=O)O)C(=O)N[C@@H](Cc1cccs1)C(=O)N[C@@H](CC(C)C)[C@H](O)CNc1ccc(C)c(C(=O)O)c1
InChIKey: QYCZMLHIMXMNNY-BITPWIMXSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of recombinant BACE-1 (unknown origin) using H-Ile-Lys-Thr-Glu-Glu-Ile-Ser-Glu-Val-Asn-Leu-Asp-Ala-Glu-Phe-Arg-His-Asp-Ser-Gly-NH2 peptide as substrate incubated for 90 mins by analytical HPLC analysis
Measurement: IC50 = 4900 nM (pChEMBL 5.309999942779541)
Descriptors: MW 675.85, ALogP 2.51, HBA 9, HBD 8, PSA 220.18, QED 0.1
Compound (SMILES): CS(=O)(=O)c1ccc(-c2cc3cnc4[nH]ccc4c3n2-c2cnn(CCC#N)c2)cc1
InChIKey: IJZVMNCBGFXTEM-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of recombinant human N-terminal His-tagged JAK2 (826 to 1132 residues) expressed in baculovirus expression system
Measurement: IC50 = 61 nM (pChEMBL 7.210000038146973)
Descriptors: MW 430.49, ALogP 3.69, HBA 7, HBD 1, PSA 109.36, QED 0.46
Compound (SMILES): Cc1cc(C#N)cc(C)c1Oc1nc(Nc2ccc(C#N)cc2)ncc1-c1ccncc1
InChIKey: HACWYLSZXQMKMD-UHFFFAOYSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of wild type HIV-1 reverse transcriptase assessed as reduction in biotin-dUTP incorporation in presence of template-primer incubated for 60 mins followed by transferring to streptavidin-coated plate and further incubation for 60 mins by ELISA
Measurement: IC50 = 570 nM (pChEMBL 6.239999771118164)
Descriptors: MW 418.46, ALogP 5.43, HBA 7, HBD 1, PSA 107.51, QED 0.46
Compound (SMILES): CCOC(=O)c1cccnc1-c1ccn(C)n1
InChIKey: LOSZDMWXPPROFU-UHFFFAOYSA-N
Target: Bifunctional arginine demethylase and lysyl-hydroxylase JMJD6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6NYC1
Assay: Inhibition of JMJD6 (unknown origin) by Succinate-Glo assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 231.25, ALogP 1.66, HBA 5, HBD 0, PSA 57.01, QED 0.75
Compound (SMILES): C=CC(=O)N1CCC(c2cnn3c(C(N)=O)c(-c4ccc(Oc5ccc(F)cc5)cc4)[nH]c23)CC1
InChIKey: OHNHHVQLIDCGPV-UHFFFAOYSA-N
Target: Tyrosine-protein kinase BTK (SINGLE PROTEIN), Homo sapiens
UniProt: Q06187
Assay: Inhibition of full-length N-terminal GST tagged BTK (1 to 659 residues) (unknown origin) expressed in Sf21 insect cells using NH2-ETVYSEVRK-biotin as substrate preincubated for 1 hr followed by ATP addition and measured after 2 hrs by ELISA
Measurement: IC50 = 494 nM (pChEMBL 6.309999942779541)
Descriptors: MW 473.51, ALogP 4.25, HBA 5, HBD 2, PSA 105.72, QED 0.41
Compound (SMILES): CC(C)CCc1cccc(C(=O)Nc2c(O)c3ccc(-c4ccc(C(=O)O)cc4)cc3oc2=O)c1
InChIKey: BCXGRDIUOQODOY-UHFFFAOYSA-N
Target: Microtubule-associated protein 1 light chain 3 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H492
Assay: Displacement of sGFP-p62-LIR peptide from human N-terminal SNAP-fused LC3A by time-resolved FRET assay
Measurement: Ki = 18900 nM (pChEMBL 4.71999979019165)
Descriptors: MW 471.51, ALogP 5.7, HBA 5, HBD 3, PSA 116.84, QED 0.3
Compound (SMILES): O=Cc1ccc2c(c1)[nH]c1c(NC(=O)C3CC3)nccc12
InChIKey: PQSDMIBFNQMFIW-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of human full length GSK3beta expressed in baculovirus in Sf9 insect cells using YRRAAVPPSPSLSRHSSPHQ(pS)EDEEE as substrate by ADP-Glo kinase assay
Measurement: IC50 = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 279.3, ALogP 2.88, HBA 3, HBD 2, PSA 74.85, QED 0.72
Compound (SMILES): Cc1ccnc(C(C)C)c1-n1c(=O)nc(N(C)C2CN(C(=O)C3CO3)C2)c2cc(Cl)c(-c3ccccc3F)nc21
InChIKey: NGAWGYKFZKABRO-UHFFFAOYSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Inhibition of GDP-bound KRAS G12C mutant (1 to 169 residues) (unknown origin) assessed as inhibition of SOS-mediated nucleotide exchange pretreated with KRAS for 5 mins followed by incubation with SOS (564 to 1049 residues) and GTP for 30 mins and later incubated with GST-tagged cRAF (1 to 149 residues) for 10 mins by AlphaLISA assay
Measurement: IC50 = 13800 nM (pChEMBL 4.860000133514404)
Descriptors: MW 563.03, ALogP 4.11, HBA 8, HBD 0, PSA 96.75, QED 0.33
Compound (SMILES): CC(C)(C)C(=O)N(CC(=O)Nc1ccc2c(c1)CC1(C2)C(=O)Nc2ncccc21)Cc1ccccc1CNC(=N)N
InChIKey: JLHNNVWWPUUIQC-UHFFFAOYSA-N
Target: Protein ADM2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z4H4
Assay: Antagonist activity at human AM2 expressed in 1321N1 cells assessed as inhibition of forskolin-induced cAMP accumulation preincubated for 30 mins followed by forskolin addition in presence of IBMX and measured after 15 mins by TR-FRET assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 553.67, ALogP 3.07, HBA 5, HBD 5, PSA 153.3, QED 0.22
Compound (SMILES): COc1cc(OC)c(F)c(N2Cc3cnc4[nH]c(C(=O)N(C)C)cc4c3N(C)C2=O)c1F
InChIKey: NPSZJJIMEFKICH-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Enzymatic Assay: The inhibitor potency of the exemplified compounds was measured in an enzyme assay that measures peptide phosphorylation using FRET measurements to detect product formation. Inhibitors were serially diluted in DMSO and a volume of 0.5 μL was transferred to the wells of a 384-well plate. For FGFR3, a 10 μL volume of FGFR3 enzyme (Millipore) diluted in assay buffer (50 mM HEPES, 10 mM MgCl2, 1 mM EGTA, 0.01% Tween-20, 5 mM DTT, pH 7.5) was added to the plate and pre-incubated for 5-10 minutes. Appropriate controls (enzyme blank and enzyme with no inhibitor) were included on the plate. The assay was initiated by the addition of a 10 μL solution containing biotinylated EQEDEPEGDYFEWLE peptide substrate (SEQ ID NO: 1) and ATP (final concentrations of 500 nM and 140 μM respectively) in assay buffer to the wells. The plate was incubated at 25° C. for 1 hr. The reactions were ended with the addition of 10 μL/well of quench solution (50 mM Tris, 150 mM NaCl, 0.5 mg/mL BSA, pH 7.8; 30 mM EDTA with Perkin Elmer Lance Reagents at 3.75 nM Eu-antibody PY20 and 180 nM APC-Streptavidin). The plate was allowed to equilibrate for 1 hr before scanning the wells on a PheraStar plate reader (BMG Labtech).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 445.43, ALogP 3.14, HBA 5, HBD 1, PSA 91, QED 0.67
Compound (SMILES): Cn1ccc2c(-c3ccc(C(=O)O)c(C4CCCC4)c3)ccnc21
InChIKey: QVKRXPQUPKYNFR-UHFFFAOYSA-N
Target: Calcium/calmodulin-dependent protein kinase kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RR4
Assay: Inhibition of human CAMKK2 using CAMKKtide as substrate assessed as residual activity by [gamma-33P]-ATP assay relative to control
Measurement: IC50 = 56 nM (pChEMBL 7.25)
Descriptors: MW 320.39, ALogP 4.6, HBA 3, HBD 1, PSA 55.12, QED 0.77
Compound (SMILES): CCCCc1oc2ccccc2c1C(=O)c1cc(I)c(OCCCN2CCOCC2)c(I)c1
InChIKey: VDAGTFJFMMEIIQ-UHFFFAOYSA-N
Target: NAD-dependent protein deacetylase sirtuin-3, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NTG7
Assay: Activation of recombinant human SIRT3 assessed as lysyl deacetylase activity using (Gln-Pro-Lys-Lys(Ac)) peptide substrate by fluorescent assay
Measurement: EC50 = 780 nM (pChEMBL 6.110000133514404)
Descriptors: MW 673.33, ALogP 6.32, HBA 5, HBD 0, PSA 51.91, QED 0.14
Compound (SMILES): O=S(=O)(c1ccccc1)n1ccc2c(OCCNCC3CC3)cccc21
InChIKey: XVBRENVJHDFZHI-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H]LSD from human 5HT6 receptor expressed in CHO-K1 membrane incubated for 60 mins by solid scintillation counting analysis
Measurement: Ki = 2.7 nM (pChEMBL 8.569999694824219)
Descriptors: MW 370.47, ALogP 3.26, HBA 5, HBD 1, PSA 60.33, QED 0.62
Compound (SMILES): Cc1cc(-c2ccc(F)cc2O)c2ncn(C)c(=O)c2c1
InChIKey: MGFXHHOKVFWFMP-UHFFFAOYSA-N
Target: Proteinase-activated receptor 4 (SINGLE PROTEIN), Mus musculus
UniProt: O88634
Assay: Antagonist activity at PAR4 in ICR mouse platelet-rich plasma assessed as inhibition of PAR4 AP AYPGKF-NH2-induced platelet aggregation by photo-turbidimetry assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 284.29, ALogP 2.75, HBA 4, HBD 1, PSA 55.12, QED 0.75
Compound (SMILES): C[C@@H](Nc1ccc([N+](=O)[O-])c(NCCCNC(=S)NCCC(=O)O)c1)c1ccccc1
InChIKey: BKROZOOEYLKPEZ-OAHLLOKOSA-N
Target: NAD-dependent protein deacylase sirtuin-5, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NXA8
Assay: Inhibition of human recombinant SIRT5 (34 to 269 residues) using Ac-Leu-Gly-Ser-Lys(Su)-AMC as substrate in presence of NAD+ by fluorescence based analysis
Measurement: IC50 = 42200 nM (pChEMBL 4.380000114440918)
Descriptors: MW 445.55, ALogP 3.51, HBA 6, HBD 5, PSA 128.56, QED 0.14
Compound (SMILES): Fc1ccc(-c2ccnc3c2c(-c2ccccc2)nn3-c2ccccc2)cc1
InChIKey: YUJQCKBKJPDNIA-UHFFFAOYSA-N
Target: CDK2/Cyclin A2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P20248
Assay: Inhibition of CDK2/Cyclin A2 (unknown origin) after 10 mins by ADP-Glo reagent based assay
Measurement: IC50 = 41.5 nM (pChEMBL 7.380000114440918)
Descriptors: MW 365.41, ALogP 5.89, HBA 3, HBD 0, PSA 30.71, QED 0.4
Compound (SMILES): COc1cc2c(NCC3CCN(c4ccc(C(=O)NO)cc4)CC3)cc(-c3ccc(C)o3)nc2cc1OCCCN1CCCC1
InChIKey: ZBCTVJOKADNKNK-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: Inhibition of full length human C-terminal His-tagged/C-terminal Flag-tagged HDAC1 using fluorogenic acetylated peptide as substrate incubated for 30 mins by fluorescence plate reader assay
Measurement: IC50 = 78 nM (pChEMBL 7.110000133514404)
Descriptors: MW 613.76, ALogP 6.12, HBA 9, HBD 3, PSA 112.33, QED 0.1
Compound (SMILES): CCOC(=O)c1cc(-c2ccn(C)n2)ncc1C(F)(F)F
InChIKey: NVNYGLORZHOVFH-UHFFFAOYSA-N
Target: Bifunctional arginine demethylase and lysyl-hydroxylase JMJD6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6NYC1
Assay: Inhibition of JMJD6 (unknown origin) by Succinate-Glo assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 299.25, ALogP 2.68, HBA 5, HBD 0, PSA 57.01, QED 0.82
Compound (SMILES): Cc1cc(-c2c(C)nn(C)c2C)cnc1-c1nnc(N(C)Cc2ccc3ncc(-c4cccc(CN(C)C)c4)n3c2)o1
InChIKey: JOQXSAZJQQAWOQ-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLAG-tagged MER (unknown origin) transfected in Cos-7cells assessed as phosphorylation level incubated for 1 hr by ELISA
Measurement: IC50 = 31.62 nM (pChEMBL 7.5)
Descriptors: MW 561.69, ALogP 5.47, HBA 10, HBD 0, PSA 93.41, QED 0.24
Compound (SMILES): Cn1cc(-c2ccc(NC(=O)c3cn(CC4CCOCC4)cc(-c4ccc(C(F)(F)F)cc4)c3=O)cc2)c2c(N)ncnc21
InChIKey: STZMYLKPKCSIEC-UHFFFAOYSA-N
Target: Tyrosine-protein kinase receptor UFO (SINGLE PROTEIN), Homo sapiens
UniProt: P30530
Assay: Inhibition of AXL (unknown origin) by ELISA
Measurement: IC50 = 0.4 nM (pChEMBL 9.399999618530273)
Descriptors: MW 602.62, ALogP 5.74, HBA 8, HBD 2, PSA 117.06, QED 0.26
Compound (SMILES): CC1(C)[C@H]2CC[C@]1(C)N(Cc1cn(-c3cccc(Br)c3)nn1)C(=O)C2
InChIKey: MGTYMYCKTQIWQM-DJJJIMSYSA-N
Target: Heat shock protein HSP 90-alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P07900
Assay: Inhibition of recombinant human N terminal his-tagged HSP90 alpha (1 to 732 residues) expressed in Escherichia coli measured after 60 mins by Flourescence polarization assay
Measurement: IC50 = 0.71 nM (pChEMBL 9.149999618530273)
Descriptors: MW 403.32, ALogP 3.96, HBA 4, HBD 0, PSA 51.02, QED 0.78
Compound (SMILES): CSCC[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@@H](N)Cc1ccccc1)[C@@H](C)O)C(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(N)=O)[C@@H](C)O
InChIKey: BZPYDUFQFNJPLZ-OQXMJBBDSA-N
Target: Glucagon receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P47871
Assay: Displacement of 125I-glucagon from human GCGR expressed in HEK293 cells membranes incubated for 6 hrs by liquid scintillation counting method
Measurement: IC50 = 5779 nM (pChEMBL 5.239999771118164)
Descriptors: MW 2984.4
Compound (SMILES): N#Cc1cc(-c2nccc(N)n2)ccc1OCc1ccccc1
InChIKey: VJGJCLFWCLLYMJ-UHFFFAOYSA-N
Target: Xanthine dehydrogenase/oxidase (SINGLE PROTEIN), Bos taurus
UniProt: P80457
Assay: Inhibition of bovine milk xanthine oxidase assessed as reduction in uric acid formation using xanthine as substrate preincubated for 15 mins followed by substrate addition measured for every 30 sec by spectrophotometric analysis
Measurement: IC50 = 347 nM (pChEMBL 6.460000038146973)
Descriptors: MW 302.34, ALogP 3.18, HBA 5, HBD 1, PSA 84.82, QED 0.8
Compound (SMILES): Cc1cnc(Nc2ccc3c(c2)CCN3C(=O)[C@H]2CCCN2C(=O)C2(C#N)CC2)nc1-c1cnn(C(C)C)c1
InChIKey: VSGYCSBFPMVRDP-XMMPIXPASA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of recombinant human JAK2 (808 to end residues) KTFCGTPEYLAPE as substrate measured after 40 mins in presence of [gamm33P]ATP by scintillation counting based radiometry assay
Measurement: IC50 = 3.8 nM (pChEMBL 8.420000076293945)
Descriptors: MW 524.63, ALogP 4.16, HBA 8, HBD 1, PSA 120.04, QED 0.51
Compound (SMILES): CN1CCN(C2CCN(C(=O)Nc3cc(Oc4ccc(NC(=O)c5cn(C6CC6)c(=O)n(-c6ccc(F)cc6)c5=O)cc4)ncn3)CC2)CC1
InChIKey: BQOPPXMDAUTYSM-UHFFFAOYSA-N
Target: Tyrosine-protein kinase receptor UFO (SINGLE PROTEIN), Homo sapiens
UniProt: P30530
Assay: Inhibition of recombinant human GST-tagged Axl incubated for 1 hr by ADP-glo based luminometry analysis
Measurement: IC50 = 7.1 nM (pChEMBL 8.149999618530273)
Descriptors: MW 683.74, ALogP 3.55, HBA 11, HBD 2, PSA 146.93, QED 0.28
Compound (SMILES): Fc1cc2ncn([C@H]3C[C@@H]4[C@@H](CNC(c5ccc(Cl)cc5)C(F)(F)F)[C@@H]4C3)c2cc1F
InChIKey: YRBZTSFREOOWCL-RPDPBQHOSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in human HeLa cells using tryptophan as substrate incubated for 24 hrs by RFMS assay
Measurement: IC50 = 0.52 nM (pChEMBL 9.279999732971191)
Descriptors: MW 455.86, ALogP 6.06, HBA 3, HBD 1, PSA 29.85, QED 0.47
Compound (SMILES): Cc1ccc2c(c1)c1c[n+](C)ccc1n2CCC(=O)N1c2ccccc2Sc2ccccc21.[I-]
InChIKey: BIUNFSSTZHGILH-UHFFFAOYSA-M
Target: Glutamate NMDA receptor; GRIN1/GRIN2A (PROTEIN COMPLEX), Homo sapiens
UniProt: Q12879
Assay: Inhibition of human GluN1-1a/NR2A receptor expressed in transgenic mouse fibroblast cells assessed as inhibition of L-glutamate-induced excitotoxicity by measuring LDH activity by cell based assay
Measurement: IC50 = 900 nM (pChEMBL 6.050000190734863)
Descriptors: MW 450.59, ALogP 6.15, HBA 3, HBD 0, PSA 29.12, QED 0.31
Compound (SMILES): CC(C)[C@H](NCc1ccc2c(Nc3cccc(-c4ccc5c(c4)OCCO5)c3Cl)nsc2c1)C(=O)O
InChIKey: YEZSTOPHUQVJED-VWLOTQADSA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NZQ7
Assay: Inhibition of Tag2-PD-1/Tag1-PDL-1 (unknown origin) interaction incubated for 15 mins by TR-FRET assay
Measurement: IC50 = 73.7 nM (pChEMBL 7.130000114440918)
Descriptors: MW 524.04, ALogP 6.33, HBA 7, HBD 3, PSA 92.71, QED 0.25
Compound (SMILES): CO[C@H]1CC[C@@H](Nc2cc(NCc3cnccc3C(F)(F)F)ncc2C#N)CC1
InChIKey: KLBAFFQVHQFLEL-IYBDPMFKSA-N
Target: Protein kinase C theta type (SINGLE PROTEIN), Homo sapiens
UniProt: Q04759
Assay: Inhibition of PKA-theta (unknown origin) using Fam-labelled S6-derived peptide incubated for 2 hrs by TR-FRET assay
Measurement: IC50 = 58 nM (pChEMBL 7.239999771118164)
Descriptors: MW 405.42, ALogP 4.35, HBA 6, HBD 2, PSA 82.86, QED 0.74
Compound (SMILES): O=C(Nc1ccc(S(=O)(=O)Nc2ccccc2)cc1)c1ccc2ccccc2c1
InChIKey: JKGBGHHHADBGHV-UHFFFAOYSA-N
Target: Probable G-protein coupled receptor 27 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NS67
Assay: Agonist activity at human GPR27 expressed in HEK293 cells co-expressing FnLArrb2.GPR27V2LFc assessed as induction of beta-arrestin recruitment incubated for 10 mins measured followed by addition of D-luciferin by firefly-luciferase complementation assay
Measurement: EC50 = 8511.38 nM (pChEMBL 5.070000171661377)
Descriptors: MW 402.48, ALogP 4.89, HBA 3, HBD 2, PSA 75.27, QED 0.5
Compound (SMILES): CCN(CCCCOc1ccc(C(=O)/C=C/c2ccc(N(C)C)cc2)c(O)c1)Cc1ccccc1OC
InChIKey: CIZLBNISCSSNJN-XMHGGMMESA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Inhibition of self-induced amyloid beta (1 to 42) (unknown origin) aggregation by T-fluorescence assay relative to control
Measurement: IC50 = 1480 nM (pChEMBL 5.829999923706055)
Descriptors: MW 502.66, ALogP 6.04, HBA 6, HBD 1, PSA 62.24, QED 0.16
Compound (SMILES): Oc1cc(Nc2ccnc3cc(-c4ccccc4)ccc23)ccc1Cl
InChIKey: NLJVTJDPRBIFFV-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of VEGFR2 (unknown origin)
Measurement: IC50 < 1 nM (pChEMBL 9)
Descriptors: MW 346.82, ALogP 6, HBA 3, HBD 2, PSA 45.15, QED 0.48
Compound (SMILES): COc1ccc(C[C@H](NC(=O)[C@@H](C)NC(=O)N2CCCC2)C(=O)N[C@@H](Cc2ccccc2)C(=O)[C@@]2(C)CO2)cc1
InChIKey: NUNIZFZGKPNEMD-OCOQMYJFSA-N
Target: Proteasome subunit beta type-8 (SINGLE PROTEIN), Homo sapiens
UniProt: P28062
Assay: Inhibition of human proteasome subunit beta-5i chymotrypsin like activity using SUC-ANW-AMC as flurogenic substrate preincubated for 15 mins followed by substrate addition and measured after 1 hr by fluorescence assay
Measurement: IC50 = 62.9 nM (pChEMBL 7.199999809265137)
Descriptors: MW 550.66, ALogP 2, HBA 6, HBD 3, PSA 129.37, QED 0.35
Compound (SMILES): CC(C)NC(=O)c1cccc(COc2ccc(C(F)(F)F)cc2Cl)c1
InChIKey: OZJCWDQQDGHUTN-UHFFFAOYSA-N
Target: Mas-related G-protein coupled receptor member X4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96LA9
Assay: Antagonist activity at human MRGPRX4 expressed in HEK cells incubated in dark for 1 hr at 37 degree C and then incubated for 30 mins at room temperature in presence of 10 pM of bilirubin by HTRF assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 371.79, ALogP 5.08, HBA 2, HBD 1, PSA 38.33, QED 0.8
Compound (SMILES): O=C1CCCc2cc(Nc3nccc(Oc4ccc(NC(=O)C5(C(=O)Nc6ccc(F)cc6)CC5)cc4)n3)ccc2N1
InChIKey: OMQNZKRSDWNBHH-UHFFFAOYSA-N
Target: Hepatocyte growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08581
Assay: Inhibition of c-MET kinase (unknown origin) using poly(Glu:Tyr)(4:1) as substrate by ELISA
Measurement: IC50 = 112.9 nM (pChEMBL 6.949999809265137)
Descriptors: MW 566.59, ALogP 5.78, HBA 7, HBD 4, PSA 134.34, QED 0.2
Compound (SMILES): CCCc1ccc2c(c1)CCC(=O)N2Cc1ccc(C(=O)NO)cc1
InChIKey: QXGDTBMYGOOZOG-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of recombinant human HDAC6 using Ac-GAK(Ac)-AMC as substrate preincubated for 10 mins followed by substrate addition and measured after 30 mins by fluorescence-based assay
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 338.41, ALogP 3.24, HBA 3, HBD 2, PSA 69.64, QED 0.65
Compound (SMILES): C[C@H](n1cnnc1-c1cccc(NC(=O)c2cccn(C)c2=O)n1)C(F)(F)F
InChIKey: AOYMSJGLPMXFDW-JTQLQIEISA-N
Target: Mitogen-activated protein kinase kinase kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99683
Assay: Inhibition of ASK1 (unknown origin) using myelin basic protein as substrate preincubated for 20 mins followed by 33P-ATP addition and measured after 2 hrs
Measurement: IC50 = 18 nM (pChEMBL 7.75)
Descriptors: MW 392.34, ALogP 2.41, HBA 7, HBD 1, PSA 94.7, QED 0.74
Compound (SMILES): CC1(C)CCN(Cc2ccc(C(=O)NO)cc2)c2ccc(Cl)cc21
InChIKey: QHQCFPSGXOOKAL-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13547
Assay: HDAC Enzyme Activity Inhibition Assay (In Vitro): The effectiveness, or potency, of a present HDACI with respect to inhibiting the activity of an HDAC is measured by an IC50 value. The quantitative IC50 value indicates the concentration of a particular compound that is needed to inhibit the activity of an enzyme by 50% in vitro. Stated alternatively, the IC50 value is the half maximal (50%) inhibitory concentration of a compound tested using a specific enzyme, e.g., HDAC, of interest. The smaller the IC50 value, the more potent the inhibiting action of the compound because a lower concentration of the compound is needed to inhibit enzyme activity by 50%.In preferred embodiments, a present HDACI inhibits HDAC enzymatic activity by about at least 50%, preferably at least about 75%, at least 90%, at least 95%, or at least 99%.Compounds of the present invention were tested for IC50 values against both HDAC6 and HDAC1. In some embodiments, a present compound also was tested against HDAC1, 2, 3, 4, 5, 8, 10, and 11. The tested compounds showed a range of IC50 values vs. HDAC6 of about 1 nm to greater than 30 μm, and a range of IC50 values vs. HDAC1 of about 91 nm to greater than 30 μm. Therefore, in some embodiments, a present HDACI is a selective HDAC6 inhibitor which, because of a low affinity for other HDAC isozymes, e.g., HDAC1, give rise to fewer side effects than compounds that are non-selective HDAC inhibitors.In some embodiments, the present HDACIs interact with and reduce the activity of all histone deacetylases in a cell. In some preferred embodiments, the present HDACIs interact with and reduce the activity of fewer than all histone deacetylases in the cell. In certain preferred embodiments, the present HDACIs interact with and reduce the activity of one histone deacetylase (e.g., HDAC-6), but do not substantially interact with or reduce the activities of other histone deacetylases (e.g., HDAC-1, HDAC-2, HDAC-3, HDAC-4, HDAC-5, HDAC-7, HDAC-8, HDAC-9, HDAC-10, and HDAC-11).
Measurement: IC50 = 19500 nM (pChEMBL 4.710000038146973)
Descriptors: MW 344.84, ALogP 4.15, HBA 3, HBD 2, PSA 52.57, QED 0.65
Compound (SMILES): C/C(=C\c1ccc2c(c1)N(S(=O)(=O)c1ccc(F)c(C3CC3)c1)C[C@H](CCC(=O)O)O2)c1c(F)cccc1Cl
InChIKey: GWWYZVGKIYDKCQ-NXNYUAIASA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Agonist activity at human His-tagged RORgamma-LBD expressed in Sf9 cells assessed as inhibition of N-terminal biotinylated co-activator SRC1 recruitment in presence of ursolic acid measured after 60 mins by FRET assay
Measurement: EC50 = 269 nM (pChEMBL 6.570000171661377)
Descriptors: MW 574.05, ALogP 6.88, HBA 4, HBD 1, PSA 83.91, QED 0.3
Compound (SMILES): COc1cc([C@H]2C[C@@H]2C(=O)N2CCCCC2)ccc1OCc1ccccc1
InChIKey: AGOOVYOKDKIMTM-UXHICEINSA-N
Target: Amyloid-beta precursor protein (SINGLE PROTEIN), Homo sapiens
UniProt: P05067
Assay: Inhibition of human biotinylated amyloid beta (1 to 42) oligomerization assessed as decrease in oligomer abundance measured after 1 hr by ELISA
Measurement: IC50 = 18650 nM (pChEMBL 4.730000019073486)
Descriptors: MW 365.47, ALogP 4.39, HBA 3, HBD 0, PSA 38.77, QED 0.76
Compound (SMILES): CC1(C)CC(=O)c2ccc(Oc3ccc4c(c3)COB4O)cc2O1
InChIKey: RGQFVDHWNYWFLG-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4B (SINGLE PROTEIN), Homo sapiens
UniProt: Q07343
Assay: Inhibition of PDE4B (unknown origin) assessed as hydrolysis of [3H]-cGMP into [3H]-GMP incubated for 30 mins by scintillation of proximity assay
Measurement: IC50 = 65.5 nM (pChEMBL 7.179999828338623)
Descriptors: MW 324.14
Compound (SMILES): C[C@@H](O)[C@@H]1NC(=O)[C@@H]2CSC(=N2)c2cc(ccn2)C[C@@H](C(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC2CC2)NC(=O)[C@H]([C@@H](C)O)NC1=O
InChIKey: BFTKNUUHDKBVIB-AOQLKAHTSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of SARS CoV-2 main protease using DABCYL-KTSAVLQ1SGFRKM-E(EDANS)-NH2 as substrate by FRET based assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 717.81, ALogP -3.76, HBA 12, HBD 9, PSA 297.39, QED 0.13
Compound (SMILES): COc1cc2c(cc1F)CC(CC1(F)CCN(Cc3ccccc3F)CC1)C2=O
InChIKey: OVDJQIGTOXGHIX-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Rattus norvegicus
UniProt: P37136
Assay: Inhibition of rat cortex homogenate acetylcholinesterase using acetylthiocholine iodide as substrate incubated for 20 mins by Ellman's method
Measurement: IC50 = 22.5 nM (pChEMBL 7.650000095367432)
Descriptors: MW 403.44, ALogP 4.72, HBA 3, HBD 0, PSA 29.54, QED 0.72
Compound (SMILES): COc1cc(OC)c(F)c(N2Cc3cnc4[nH]ccc4c3N([C@@H]3CCC[C@H]3O)C2=O)c1F
InChIKey: ILNCSRUGKNZIBY-ZIAGYGMSSA-N
Target: Fibroblast growth factor receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11362
Assay: Enzymatic Assay: The inhibitor potency of the exemplified compounds was measured in an enzyme assay that measures peptide phosphorylation using FRET measurements to detect product formation. Inhibitors were serially diluted in DMSO and a volume of 0.5 μL was transferred to the wells of a 384-well plate. For FGFR3, a 10 μL volume of FGFR3 enzyme (Millipore) diluted in assay buffer (50 mM HEPES, 10 mM MgCl2, 1 mM EGTA, 0.01% Tween-20, 5 mM DTT, pH 7.5) was added to the plate and pre-incubated for 5-10 minutes. Appropriate controls (enzyme blank and enzyme with no inhibitor) were included on the plate. The assay was initiated by the addition of a 10 μL solution containing biotinylated EQEDEPEGDYFEWLE peptide substrate (SEQ ID NO: 1) and ATP (final concentrations of 500 nM and 140 μM respectively) in assay buffer to the wells. The plate was incubated at 25° C. for 1 hr. The reactions were ended with the addition of 10 μL/well of quench solution (50 mM Tris, 150 mM NaCl, 0.5 mg/mL BSA, pH 7.8; 30 mM EDTA with Perkin Elmer Lance Reagents at 3.75 nM Eu-antibody PY20 and 180 nM APC-Streptavidin). The plate was allowed to equilibrate for 1 hr before scanning the wells on a PheraStar plate reader (BMG Labtech).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 444.44, ALogP 3.72, HBA 5, HBD 2, PSA 90.92, QED 0.64
Compound (SMILES): COC(=O)c1ccc2nc(Oc3ccc4c(c3)COB4O)ccc2c1
InChIKey: CIYIXDQCBMUIBI-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4B (SINGLE PROTEIN), Homo sapiens
UniProt: Q07343
Assay: Inhibition of PDE4B (unknown origin) assessed as hydrolysis of [3H]-cGMP into [3H]-GMP incubated for 30 mins by scintillation of proximity assay
Measurement: IC50 = 10.79 nM (pChEMBL 7.96999979019165)
Descriptors: MW 335.12
Compound (SMILES): C[C@H]1CCOc2c(N3CC[C@@H](C4(N)CC4)C3)c(F)cc3cc(C(=O)O)c(=O)n1c23
InChIKey: TVCFBOWWEJUJPT-WCQYABFASA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in CHO-K1 cells by Qpatch clamp method
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 401.44, ALogP 2.5, HBA 6, HBD 2, PSA 97.79, QED 0.82
Compound (SMILES): Fc1cc2[nH]ncc2c2c3c(c(-c4cn[nH]c4)nc12)CCCC3
InChIKey: QAWBPBLABQUSRL-UHFFFAOYSA-N
Target: CDK2/Cyclin A1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P78396
Assay: Inhibition of CDK2/Cyclin A1 (unknown origin) at 1 uM using histone H1 as substrate preincubated for 20 mins followed by 33P-ATP addition and measured after 2 hrs by filter binding method
Measurement: IC50 = 39 nM (pChEMBL 7.409999847412109)
Descriptors: MW 307.33, ALogP 3.52, HBA 3, HBD 2, PSA 70.25, QED 0.57
Compound (SMILES): COc1ccc(Cc2cc(N3CCc4c(C(=O)NC[C@H](O)CF)cccc43)ccn2)cc1F
InChIKey: VMVRQCKICQAQFI-LJQANCHMSA-N
Target: G-protein coupled receptor 52 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2T5
Assay: Agonist activity at GPR52 (unknown origin) expressed in CHO-K1 or HEK293 cells assessed as intracellular cAMP accumulation incubated for 1 hr by HTRF assay
Measurement: EC50 = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 453.49, ALogP 3.57, HBA 5, HBD 2, PSA 74.69, QED 0.55
Compound (SMILES): CCC(NC(=O)c1ccc(Cl)cc1)[C@H]1[C@@H]2C[C@@H](n3cnc4c(F)cccc43)C[C@@H]21
InChIKey: OZPVWUDGSNMDJF-PXFYCIBDSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in human HeLa cells using tryptophan as substrate incubated for 24 hrs by RFMS assay
Measurement: IC50 = 7 nM (pChEMBL 8.149999618530273)
Descriptors: MW 411.91, ALogP 5.23, HBA 3, HBD 1, PSA 46.92, QED 0.62
Compound (SMILES): CCCCCCCC[C@]1(CO)NC[C@H](O)[C@@H](O)[C@@H]1O.Cl
InChIKey: YPDQPTJXUBBYFN-BHARVXRSSA-N
Target: Sucrase-isomaltase, intestinal (SINGLE PROTEIN), Rattus norvegicus
UniProt: P23739
Assay: Inhibition of rat intestinal sucrase using p-nitrophenyl glycoside as substrate assessed as release of p-nitrophenol measured by spectrometric assay
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 275.39, ALogP 0.15, HBA 5, HBD 5, PSA 92.95, QED 0.41
Compound (SMILES): O=C(NCCO)c1cccc2c1CCN2c1ccnc(Cc2cccc(C(F)(F)F)c2)c1
InChIKey: FAVJVWJYEPNXCJ-UHFFFAOYSA-N
Target: G-protein coupled receptor 52 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2T5
Assay: Agonist activity at GPR52 (unknown origin) expressed in CHO-K1 or HEK293 cells assessed as intracellular cAMP accumulation incubated for 1 hr by HTRF assay
Measurement: EC50 = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 441.45, ALogP 4.11, HBA 4, HBD 2, PSA 65.46, QED 0.6
Compound (SMILES): CC(=O)c1sccc1-c1cncc(Cl)c1N1CCC2(CCNC2=O)CC1
InChIKey: ZFQAGIWUUSFHJZ-UHFFFAOYSA-N
Target: CDK8/Cyclin C (PROTEIN COMPLEX), Homo sapiens
UniProt: P24863
Assay: Inhibition of CDK8/Cyclin C (unknown origin) using RBER-CHKtide as substrate in presence of [32P]gammaATP incubated for 60 mins by microplate scintillation counter analysis
Measurement: Ki = 4655 nM (pChEMBL 5.329999923706055)
Descriptors: MW 389.91, ALogP 3.77, HBA 5, HBD 1, PSA 62.3, QED 0.81
Compound (SMILES): CN1CCN(c2nc(-c3ccc(C(=O)NO)cc3)nc3cc(Cl)ccc23)CC1
InChIKey: DYZSQWJEPPEPAQ-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Inhibition of mTOR (unknown origin)
Measurement: IC50 = 133.7 nM (pChEMBL 6.869999885559082)
Descriptors: MW 397.87, ALogP 2.82, HBA 6, HBD 2, PSA 81.59, QED 0.52
Compound (SMILES): CC1(C)[C@@H](Nc2nc(NCc3cnccc3C(F)(F)F)ncc2C#N)C[C@@H]1O
InChIKey: QHLWNCNFYOUHJB-KBPBESRZSA-N
Target: Protein kinase C theta type (SINGLE PROTEIN), Homo sapiens
UniProt: Q04759
Assay: Inhibition of PKA-theta (unknown origin) using Fam-labelled S6-derived peptide incubated for 2 hrs by TR-FRET assay
Measurement: IC50 = 170 nM (pChEMBL 6.769999980926514)
Descriptors: MW 392.39, ALogP 2.95, HBA 7, HBD 3, PSA 106.75, QED 0.72