lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1ncc(-c2ccc3ncnc(N[C@H]4CCN(C(=O)C5CCOCC5)C4)c3c2)cc1NS(C)(=O)=O
InChIKey: ALLABKANEWPTJO-IBGZPJMESA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (SINGLE PROTEIN), Homo sapiens
UniProt: O00329
Assay: Inhibition of PI3K delta (unknown origin) using lipid substrate measured after 40 mins in presence of ATP by Kinase-Glo plus reagent based luminescence assay
Measurement: IC50 = 7.4 nM (pChEMBL 8.130000114440918)
Descriptors: MW 526.62, ALogP 2.51, HBA 9, HBD 2, PSA 135.64, QED 0.48
Compound (SMILES): Cc1nn(C)c(C)c1S(=O)(=O)N1CCC2(CC1)OCCS2
InChIKey: SDOGILAPEUUMEN-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M5 (SINGLE PROTEIN), Homo sapiens
UniProt: P08912
Assay: Displacement of [3H]NMS from human muscarinic M5 receptor
Measurement: Ki = 2700 nM (pChEMBL 5.570000171661377)
Descriptors: MW 331.46, ALogP 1.28, HBA 6, HBD 0, PSA 64.43, QED 0.82
Compound (SMILES): CC(=O)N1N=C(c2ccc(OS(N)(=O)=O)cc2)CC1c1ccccc1
InChIKey: ZTFVAXOMFNDDQF-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human recombinant CA2
Measurement: Ki = 0.4 nM (pChEMBL 9.399999618530273)
Descriptors: MW 359.41, ALogP 1.97, HBA 5, HBD 1, PSA 102.06, QED 0.9
Compound (SMILES): CC(=O)N1CCC(c2ccc(C(=O)NC3=NCCN3)cc2C(F)(F)F)CC1
InChIKey: UPJRPOWMFLBSKZ-UHFFFAOYSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q01959
Assay: GPCRScan assay: inhibition of DAT
Measurement: Ki = 825 nM (pChEMBL 6.079999923706055)
Descriptors: MW 382.39, ALogP 2.12, HBA 4, HBD 2, PSA 73.8, QED 0.82
Compound (SMILES): Cn1c(=O)c2c(nc3n2CCCN3Cc2ccccc2F)n(C)c1=O
InChIKey: USJJUXVFLOLHIY-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of recombinant human MAOA expressed in baculovirus infected BTI insect cells using p-tyramine as substrate preincubated for 30 mins followed by substrate addition and measured over 45 mins by horseradish peroxidase-Amplex Red-coupled fluorometric assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 343.36, ALogP 0.98, HBA 7, HBD 0, PSA 65.06, QED 0.7
Compound (SMILES): CNc1[nH]c(Nc2ccc(C(=O)N3CCOCC3)cc2OC)nc2ncc(Cl)c1-2
InChIKey: HUEKBQXFNHWTQQ-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Enzyme Assay: Active GST-LRRK2 (1326-2527), GST-LRRK2[G2019S] (1326-2527), GST-LRRK2[A2016T] (1326-2527) and GST-LRRK2[A2016T+G2019S] (1326-2527) enzyme was purified with glutathione sepharose from HEK293 cell lysate 36 h following transient transfection of the appropriate cDNA constructs. Peptide kinase assays, performed in triplicate, were set up in a total volume of 40 μl containing 0.5 μg LRRK2 kinase (which at approximately 10% purity gives a final concentration of 8 nM) in 50 mM Tris/HCl, pH 7.5, 0.1 mM EGTA, 10 mM MgCl2, 20 μM Nictide, 0.1 μM [γ-32P]ATP (500 cpm/pmol) and the indicated concentrations of inhibitor dissolved in DMSO. After incubation for 15 min at 30° C., reactions were terminated by spotting 35 μl of the reaction mix onto P81 phosphocellulose paper and immersion in 50 mM phosphoric acid. Samples were washed extensively and the incorporation of [γ-32P]ATP into Nictide was quantified by Cerenkov counting. IC50 values were calculated with GraphPad Prism using non-linear regression analysis.
Measurement: IC50 = 47.7 nM (pChEMBL 7.320000171661377)
Descriptors: MW 416.87, ALogP 2.83, HBA 7, HBD 3, PSA 104.4, QED 0.59
Compound (SMILES): CN(C)C(=O)c1ccc(N(Cc2ccc(O)cc2)C(=O)c2ccc(O)cc2O)cc1
InChIKey: TYTXGPAMIGYEGN-UHFFFAOYSA-N
Target: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q15119
Assay: Inhibition of PDHK2 (unknown origin) assessed as reduction in NAD measured for 30 mins
Measurement: IC50 = 1455 nM (pChEMBL 5.840000152587891)
Descriptors: MW 406.44, ALogP 3.35, HBA 5, HBD 3, PSA 101.31, QED 0.6
Compound (SMILES): O=P(O)(Cc1cc2c(O)c(c1)Sc1cc(CP(=O)(O)c3ccccc3)cc(c1O)Sc1cc(CP(=O)(O)c3ccccc3)cc(c1O)Sc1cc(CP(=O)(O)c3ccccc3)cc(c1O)S2)c1ccccc1
InChIKey: RHGDRBPQTMCKHX-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: Inhibition of recombinant human SHP2 expressed in Escherichia coli using p-nitrophenol as substrate preincubated with substrate for 5 mins followed by enzyme addition
Measurement: IC50 = 3700 nM (pChEMBL 5.429999828338623)
Descriptors: MW 1113.08
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@@H]1CCCN1C(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]1CCCN1C(=O)[C@H](C)N)C(C)C)[C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O)[C@@H](C)O
InChIKey: HFDKKNHCYWNNNQ-YOGANYHLSA-N
Target: Neuropeptide Y receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P50391
Assay: Displacement of [3H]UR-KK200 from human Y4 receptor expressed in CHO cells co-expressing Gqi5-mtAEQ measured after 90 mins by scintillation counting analysis
Measurement: Ki = 0.6918 nM (pChEMBL 9.15999984741211)
Descriptors: MW 4181.78
Compound (SMILES): O=C(O)C(=O)O.c1ccc(-c2ccc(OCCCCCN3CCCCC3)cc2)cc1
InChIKey: PHZSQKZXVYUBRJ-UHFFFAOYSA-N
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of [3H]-N-alpha-methylhistamine from human recombinant full length H3R expressed in HEK293 cell membranes incubated for 90 mins by liquid scintillation counting method
Measurement: Ki = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 323.48, ALogP 5.39, HBA 2, HBD 0, PSA 12.47, QED 0.6
Compound (SMILES): CCCC[C@H](N)C(=O)NNc1cccc(C(=O)N[C@@H](Cc2c[nH]c3ccccc23)C(=O)OCc2ccccc2)c1
InChIKey: HSUTVEOJRBSEAV-XCZPVHLTSA-N
Target: Interleukin-1 receptor antagonist protein (SINGLE PROTEIN), Homo sapiens
UniProt: P18510
Assay: Competitive inhibition of human recombinant IRAP expressed in baculovirus infected sf9 cells using L-AMC as substrate incubated for 5 to 10 mins by Michaelis-Menten analysis
Measurement: Ki = 3800 nM (pChEMBL 5.420000076293945)
Descriptors: MW 541.65, ALogP 4.21, HBA 6, HBD 5, PSA 138.34, QED 0.13
Compound (SMILES): Cc1ccc(-c2cc3cccc(C)c3oc2=O)cc1
InChIKey: HPKMVGQGAIWEID-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Displacement of radioligand from human adenosine receptor A2B expressed in CHO cell membranes by radioligand competition assay
Measurement: Ki > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 250.3, ALogP 4.08, HBA 2, HBD 0, PSA 30.21, QED 0.61
Compound (SMILES): C=CC(=O)Nc1cc(Oc2nc(Nc3ccc(N4CCN(C)CC4)cc3OC)ccc2N2CCCCC2)ccc1C
InChIKey: ZFRMQNBHXVYHCH-UHFFFAOYSA-N
Target: Procathepsin L (SINGLE PROTEIN), Homo sapiens
UniProt: P07711
Assay: Inhibition of recombinant human C-terminal His6-tagged cathepsin L (Glu113 to Val333 and Ala114 to Val333 residues) expressed in mouse myeloma cells using Z-Leu-Arg-AMC as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins
Measurement: IC50 = 3000 nM (pChEMBL 5.519999980926514)
Descriptors: MW 556.71, ALogP 5.8, HBA 8, HBD 2, PSA 82.2, QED 0.32
Compound (SMILES): CC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(=N)N)C(=O)NCCN1CCN(CCCCC2CCN(CC(=O)N3c4ccccc4NC(=O)c4ccccc43)CC2)CC1.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
InChIKey: FPYAQRXRBVHTRN-NAVQYVAVSA-N
Target: Muscarinic acetylcholine receptor M5 (SINGLE PROTEIN), Homo sapiens
UniProt: P08912
Assay: Displacement of [3H]-NMS from human muscarinic M5 receptor expressed in CHO-K9 cells after 3 hrs by microbeta2 scintillation counting method
Measurement: Ki = 112.2 nM (pChEMBL 6.949999809265137)
Descriptors: MW 845.11, ALogP 1.91, HBA 10, HBD 8, PSA 234.35, QED 0.05
Compound (SMILES): CC(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)c1nc2ccccc2s1
InChIKey: BLOFNYQHKSGSGE-MLCQCVOFSA-N
Target: Suppressor of tumorigenicity 14 protein (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Y6
Assay: Inhibition of recombinant human N-terminal met-His6-tagged matriptase catalytic domain (Gly596 to Val855 residues) expressed in Escherichia coli using Boc-QAR-AMC as substrate preincubated for 30 mins followed by substrate addition by fluorescence based assay
Measurement: IC50 = 6.1 nM (pChEMBL 8.210000038146973)
Descriptors: MW 661.83, ALogP -0.13, HBA 10, HBD 9, PSA 254.51, QED 0.04
Compound (SMILES): OB1OCc2ccc(/N=C/c3ccc(/C=N/c4ccc5c(c4)B(O)OC5)s3)cc21
InChIKey: ZIDJLFURKBSKJY-WDBPGAOMSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human carbonic anhydrase 12 assessed as reduction in CO2 hydration preincubated for 15 mins to 2 hrs by phenol red dye based stopped flow CO2 hydrase assay
Measurement: Ki = 181 nM (pChEMBL 6.739999771118164)
Descriptors: MW 402.05
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCCCC(=O)O)C(=O)O)[C@@H](C)O)[C@@H](C)O)C(C)C)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CO)C(=O)N1CCC[C@H]1C(N)=O)[C@@H](C)O)[C@@H](C)O
InChIKey: NCNNIHNSLHNRQP-BQXNAASMSA-N
Target: Calcitonin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30988
Assay: Displacement of [125I]-labeled human calcitonin from human calcitonin receptor expressed in BHK tkts13 whole cells incubated for 60 mins by scintillation proximity assay
Measurement: IC50 = 0.821 nM (pChEMBL 9.09000015258789)
Descriptors: MW 3459.99
Compound (SMILES): O[C@@H]1[C@H](O)[C@@H](CCl)O[C@H]1n1cnc2c(N[C@H]3C[C@H]4CC[C@@H]3C4)ncnc21
InChIKey: PVJGDYDNVNCGBT-XSMNFLGNSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: Inhibition of sigma receptor 2 (unknown origin)
Measurement: Ki = 432 nM (pChEMBL 6.369999885559082)
Descriptors: MW 379.85, ALogP 1.28, HBA 8, HBD 3, PSA 105.32, QED 0.69
Compound (SMILES): CC[C@H](C)[C@@H]1NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)CCSSC[C@@H](C(=O)N2CCC[C@H]2C(=O)N[C@@H](CCCCNC(=O)CCCCCCCCC(=O)NCCCC[C@H](NC(=O)[C@@H]2CCCN2C(=O)[C@@H]2CSSCCC(=O)N[C@@H](Cc3ccc(O)cc3)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N2)C(=O)NCC(N)=O)C(=O)NCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC1=O
InChIKey: JTYYTRAVGLFARZ-KOFKWYMHSA-N
Target: Oxytocin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P30559
Assay: Agonist activity at human oxytocin receptor expressed in HEK293 cells coexpressing Rluc8-tagged Galphaq, N-terminal GFP-tagged Ggamma2 and Gbeta1 protein incubated for 2 mins in presence of TMH1-TAT peptide by Gq protein activation based BRET assay
Measurement: EC50 = 17.3 nM (pChEMBL 7.760000228881836)
Descriptors: MW 2180.63
Compound (SMILES): CCc1cc(NC(=O)c2ccc3c(c2)C[C@H](N(C)c2cncnc2)C3)cc(-n2cnc(C)c2)c1
InChIKey: SBGAHKXLTGCPRN-XMMPIXPASA-N
Target: NT-3 growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16288
Assay: Inhibition of His-tagged human TrkC expressed in baculovirus expression system using Tyr1 peptide as substrate after 1.5 hrs by FRET-based Z-LYTE assay
Measurement: IC50 = 364.2 nM (pChEMBL 6.440000057220459)
Descriptors: MW 452.56, ALogP 4.39, HBA 6, HBD 1, PSA 75.94, QED 0.47
Compound (SMILES): COC(=O)C1=C(CN2CC(F)(F)C[C@H]2C(=O)O)NC(c2nccs2)=N[C@@]1(C)c1ccc(F)cc1
InChIKey: ZUNJWALIUFZGCH-BTYIYWSLSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes using substrate preincubated for 10 mins followed by NADPH addition measured after 30 mins by LC-MS/MS analysis
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 494.5, ALogP 2.77, HBA 8, HBD 2, PSA 104.12, QED 0.6
Compound (SMILES): COc1ccc(Cl)cc1NCC1C(c2ccc(S(N)(=O)=O)cc2)C1(C)C
InChIKey: LWWDCTBUJUEFDE-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 394.92, ALogP 3.85, HBA 4, HBD 2, PSA 81.42, QED 0.78
Compound (SMILES): C=CC(=O)NCc1ccc(-n2nc3c(=O)[nH]nc(N)c3c2-c2oc3ccc(C)cc3c2C)cc1
InChIKey: GXIHBWCRCZNSHX-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of human VEGFR2 using poly (Glu, Tyr)4:1 as substrate measured after 60 mins by ELISA
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 454.49, ALogP 3.52, HBA 7, HBD 3, PSA 131.83, QED 0.35
Compound (SMILES): CC(C)[C@H]1CC[C@@H](N2CCC(n3cc(CN4CCCC4)c4ccccc43)CC2)CC1
InChIKey: NGKDULCWDLWYAO-QUPDYRNUSA-N
Target: Nociceptin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41146
Assay: Agonist activity at human NOP expressed in CHO cell membrane incubated for 60 mins by [35S]GTPgammaS binding assay
Measurement: EC50 = 97.4 nM (pChEMBL 7.010000228881836)
Descriptors: MW 407.65, ALogP 6.09, HBA 3, HBD 0, PSA 11.41, QED 0.59
Compound (SMILES): C[C@@H]1NC(=O)[C@H](CN)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CS)NC(=O)[C@@H]2CCCN2C(=O)[C@H]2CCCN2C(=O)[C@H](Cc2ccccc2)NC1=O
InChIKey: DKTHXDHZNKFNNS-PLUWKHBFSA-N
Target: Melanocortin receptor 5 (SINGLE PROTEIN), Mus musculus
UniProt: P41149
Assay: Agonist activity at mouse melanocortin receptor 5 expressed in HEK293 cells assessed as stimulation of cAMP accumulation incubated for 2 hrs by cAMP Alpha-screen assay
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 896.08, ALogP -0.47, HBA 10, HBD 8, PSA 241.24, QED 0.14
Compound (SMILES): Cn1cncc1-c1c[nH]c2ccc(I)cc12
InChIKey: UZRMRNOPEVQTSO-UHFFFAOYSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H] raclopride from human recombinant D2L receptor expressed in HEK293 cells measured after 1 hr by microbeta scintillation counting method
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 323.14, ALogP 3.17, HBA 2, HBD 1, PSA 33.61, QED 0.69
Compound (SMILES): Cc1nn(-c2ccccn2)c2c1C(c1ccccc1Cl)C1=C(N2)c2ccccc2C1=O
InChIKey: ZUWTUMOFLHZZRE-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Mus musculus
UniProt: P51450
Assay: PUBCHEM_BIOASSAY: qHTS for inhibitors of ROR gamma transcriptional activity. (Class of assay: confirmatory) 
Measurement: Potency = 2818.4 nM (pChEMBL 5.550000190734863)
Descriptors: MW 424.89, ALogP 5.39, HBA 5, HBD 1, PSA 59.81, QED 0.47
Compound (SMILES): CNCc1ccc(-c2cc(-c3nc(-c4ccc(S(=O)(=O)C(C)C)cc4)cnc3N)on2)cc1Cl
InChIKey: WEOFJQBDUVLXHQ-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase ATR (SINGLE PROTEIN), Homo sapiens
UniProt: Q13535
Assay: Inhibition Assay: Compounds were screened for their ability to inhibit ATR kinase using a radioactive-phosphate incorporation assay. Assays were carried out in a mixture of 50 mM Tris/HCl (pH 7.5), 10 mM MgCl2 and 1 mM DTT. Final substrate concentrations were 10 M [γ-33P]ATP (3mCi 33P ATP/mmol ATP, Perkin Elmer) and 800 μM target peptide (ASELPASQPQPFSAKKK).Assays were carried out at 25° C. in the presence of 5 nM full-length ATR. An assay stock buffer solution was prepared containing all of the reagents listed above, with the exception of ATP and the test compound of interest. 13.5 μL of the stock solution was placed in a 96 well plate followed by addition of 2 μL of DMSO stock containing serial dilutions of the test compound (typically starting from a final concentration of 15 μM with 3-fold serial dilutions) in duplicate (final DMSO concentration 7%). The plate was pre-incubated for 10 minutes at 25° C. and the reaction initiated by addition of 15 μL [γ-33P]ATP (final concentration 10 μM).The reaction was stopped after 24 hours by the addition of 30 μL 0.1M phosphoric acid containing 2 mM ATP. A multiscreen phosphocellulose filter 96-well plate (Millipore, Cat no. MAPHN0B50) was pretreated with 100 μL 0.2M phosphoric acid prior to the addition of 45 μL of the stopped assay mixture. The plate was washed with 5×200 μL 0.2M phosphoric acid. After drying, 100 μL Optiphase SuperMix liquid scintillation cocktail (Perkin Elmer) was added to the well prior to scintillation counting (1450 Microbeta Liquid Scintillation Counter, Wallac).
Measurement: Ki < 10 nM (pChEMBL 8)
Descriptors: MW 498.01, ALogP 4.6, HBA 8, HBD 2, PSA 124, QED 0.38
Compound (SMILES): CC(C)N1CCN(c2ccc(/C(=C(/CCCO)c3ccccc3)c3ccc(Br)cc3)cc2)CC1.Cl.Cl
InChIKey: KQOSLTWWFIOWBQ-JYOLQUMFSA-N
Target: Estrogen-related receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P62508
Assay: Inverse agonist activity at CMX-gal4-fused ERRgamma (unknown origin) transfected in human AD293 cells co-expressing CMV-beta galactosidase assessed as effect on beta-galactosidase activity after 24 hrs by luciferase reporter gene assay
Measurement: IC50 = 64 nM (pChEMBL 7.190000057220459)
Descriptors: MW 519.53, ALogP 6.71, HBA 3, HBD 1, PSA 26.71, QED 0.34
Compound (SMILES): Cl.O=C1c2cccc3cccc(c23)N1CCCCCCN1CCN(c2ccccc2F)CC1
InChIKey: KUWVCFQZKSJXPD-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P34969
Assay: Displacement of [3H]5-CT from human 5HT7B receptor expressed in HEK293 cell membranes after 1 hr by microbeta plate reader method
Measurement: Ki = 420 nM (pChEMBL 6.380000114440918)
Descriptors: MW 431.56, ALogP 5.32, HBA 3, HBD 0, PSA 26.79, QED 0.45
Compound (SMILES): COc1ccccc1CNCC1CC1(F)c1cc(F)ccc1OC.Cl
InChIKey: BIRIRFXEYPAVNI-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Agonist activity at recombinant human 5HT2B receptor expressed in Flp-In-293 cells assessed as increase in calcium influx measured for 300 secs by Fluo-4 dye based FLIPR assay
Measurement: EC50 = 285 nM (pChEMBL 6.539999961853027)
Descriptors: MW 333.38, ALogP 3.82, HBA 3, HBD 1, PSA 30.49, QED 0.84
Compound (SMILES): COc1nn(C)cc1Nc1ncc(F)c(-c2c[nH]c3c(NC(=O)[C@@H](C)N4CCN(C)CC4)cccc23)n1
InChIKey: OEONIHQPMGEGIL-OAHLLOKOSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: JAK Enzymatic Assay: Enzyme inhibition studies were performed using recombinant JAK1 (amino acids 866-1154, Life Technologies, #PV4774, Carlsbad, Calif.), JAK2 (amino acids 831-1132), or JAK3 (amino acids 781-1124) under buffer conditions of 50 mM HEPES pH 7.3, 1 mM DTT, 0.01% Tween® 20, 50 μg/mL BSA, and 10 mM MgCl2. JAK enzyme was expressed as an N-terminal GST fusion in insect cells and purified by glutathione-affinity and size-exclusion chromatographies. Enzymes were assayed both at their respective ATP Km (JAK1: 55 μM, JAK2: 15 μM, JAK3: 3 μM) and the approximated high end of physiological ATP concentration of 5 mM, in the presence of inhibitor dosed at 30, 3, 0.3, 0.03, 0.003 and 0 μM final test concentrations. For JAK1, 6 nM of enzyme (for Km ATP assay) or 4 nM enzyme (for high ATP assay) was incubated with 1.5 μM peptide substrate (FITC-C6-KKHTDDGYMPMSPGVA-NH2 (SEQ ID NO:1), Intonation, Boston, Mass.). For JAK2, 0.8 nM of enzyme (for Km ATP assay) or 0.3 nM enzyme (for high ATP assay) was incubated with 1.5 μM peptide substrate (5FAM-GEEPLYWSFPAKKK-NH2 (SEQ ID NO:2), Intonation, Boston, Mass.). For JAK3, 0.2 nM of enzyme (for Km ATP assay) or 0.1 nM enzyme (for high ATP assay) was incubated with 1.5 μM peptide substrate (5FAM-GEEPLYWSFPAKKK-NH2 (SEQ ID NO:2), Intonation, Boston, Mass.). Phosphorylated and unphosphorylated peptides were separated and quantified by a Caliper LC3000 system (Caliper Life Sciences, MA) for calculating percent inhibition. The results of this assay are shown in Table 16 and indicate that the compounds of Formula (I), (Ia), (Ib) and Table 1 exhibit preferential inhibition of JAK1 over JAK2 (in many cases demonstrating over 100 times selectivity for inhibition of JAK1 vs. JAK2).
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 507.57, ALogP 2.82, HBA 9, HBD 3, PSA 116.23, QED 0.35
Compound (SMILES): NS(=O)(=O)c1ccc(NC(=O)CN2C(=O)NC3(CCCCC3)C2=O)cc1
InChIKey: KZSVRJBEJFDDMB-UHFFFAOYSA-N
Target: Carbonic anhydrase 5A, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P35218
Assay: Inhibition of human carbonic anhydrase 5A incubated for 15 mins prior to testing by stopped-flow CO2 hydration assay
Measurement: Ki = 727.4 nM (pChEMBL 6.139999866485596)
Descriptors: MW 380.43, ALogP 0.53, HBA 5, HBD 3, PSA 138.67, QED 0.65
Compound (SMILES): CC(C)CC(NC(=O)c1ccc(-c2ccc(S(C)(=O)=O)cc2)cc1)C(=O)N(C)N(C)C#N
InChIKey: XHBRHGRXSUUCGR-UHFFFAOYSA-N
Target: Cathepsin B (SINGLE PROTEIN), Homo sapiens
UniProt: P07858
Assay: Inhibition of human liver cathepsin B
Measurement: IC50 = 915 nM (pChEMBL 6.039999961853027)
Descriptors: MW 456.57, ALogP 2.69, HBA 6, HBD 1, PSA 110.58, QED 0.37
Compound (SMILES): Cn1cncc1-c1cn(Cc2ccc(C(=O)NO)cc2)c2ccccc12
InChIKey: ANMZNMDSWZJYNP-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of recombinant full-length C-terminal His-tagged human HDAC2 expressed in baculovirus infected Sf9 insect cells measured after 40 mins by HDAC-Glo1/2 luminescent assay
Measurement: IC50 = 3162.28 nM (pChEMBL 5.5)
Descriptors: MW 346.39, ALogP 3.21, HBA 5, HBD 2, PSA 72.08, QED 0.44
Compound (SMILES): Nc1n[nH]c(N2CCC(N(CCc3ccc(Cl)cc3)CC3CCCO3)CC2)n1
InChIKey: YWLYLZBGUFBPHR-UHFFFAOYSA-N
Target: Acidic mammalian chitinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BZP6
Assay: Inhibition of full-length C-terminal his-tagged human acidic mammalian chitinase expressed in CHOK1 cells assessed as reduction in chitinolytic activity using 4-methylumbelliferyl-beta-D-N,N-diacetylchitobioside hydrate as substrate after 60 mins by fluorometric assay
Measurement: IC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 404.95, ALogP 2.73, HBA 6, HBD 2, PSA 83.3, QED 0.74
Compound (SMILES): CCN(CCCCNC(=O)c1ccc2ccccc2c1)CC1CC1c1cc(Cl)ccc1OC.Cl
InChIKey: WQFHHKMPQVRCRI-UHFFFAOYSA-N
Target: D(1B) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21918
Assay: Displacement of [3H]-SCH23390 from recombinant human D5 receptor transiently expressed in HEKT cell membranes measured after 90 mins by microbeta scintillation counting method
Measurement: Ki = 571 nM (pChEMBL 6.239999771118164)
Descriptors: MW 465.04, ALogP 6.14, HBA 3, HBD 1, PSA 41.57, QED 0.35
Compound (SMILES): O=C(O)Cc1ccc(Cc2cc(-c3cccc(Cl)c3)nc(C(F)(F)F)c2)cc1
InChIKey: LTSUMTMGJHPGFX-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin) by fluorescence-based assay
Measurement: IC50 > 51000 nM (pChEMBL 4.291999816894531)
Descriptors: MW 405.8, ALogP 5.64, HBA 2, HBD 1, PSA 50.19, QED 0.6
Compound (SMILES): O=S(=O)(Nc1ccc(-c2nc3ccccc3o2)cc1)c1ccccc1F
InChIKey: KZSXXKOXHVIXPZ-UHFFFAOYSA-N
Target: Malate dehydrogenase, mitochondrial (SINGLE PROTEIN), Sus scrofa
UniProt: P00346
Assay: Inhibition of refolded pig heart mitochondrial MDH preincubated with Escherichia coli GroEL/GroES for 45 mins using sodium mesoxalate as substrate followed by compound addition and measured after 20 to 30 mins by spectrometric analysis
Measurement: IC50 > 63000 nM (pChEMBL 4.201000213623047)
Descriptors: MW 368.39, ALogP 4.43, HBA 4, HBD 1, PSA 72.2, QED 0.58
Compound (SMILES): Cc1ccc(CNC(=O)[C@@H]2COCCCCCCCc3c(cnn3C)C(=O)N[C@@H](CC(=O)NCC(C)(C)C)C(=O)N2)cc1
InChIKey: VYZYAEPKILNKBY-UIOOFZCWSA-N
Target: Proteasome component C5 (SINGLE PROTEIN), Homo sapiens
UniProt: P20618
Assay: Inhibition of human hepatic cell derived 20s constitutive proteasome beta1 caspase-like activity using Suc-LLE-AMC as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by fluorescence assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 596.77, ALogP 2.7, HBA 7, HBD 4, PSA 143.45, QED 0.4
Compound (SMILES): Nc1n[nH]c(N2CCC(N(CCc3ccc(Cl)cc3)CC(=O)O)CC2)n1
InChIKey: WNAJLDWZFORROB-UHFFFAOYSA-N
Target: Acidic mammalian chitinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BZP6
Assay: Inhibition of full-length C-terminal his-tagged human acidic mammalian chitinase expressed in CHOK1 cells assessed as reduction in chitinolytic activity using 4-methylumbelliferyl-beta-D-N,N-diacetylchitobioside hydrate as substrate after 60 mins by fluorometric assay
Measurement: IC50 = 1040 nM (pChEMBL 5.980000019073486)
Descriptors: MW 378.86, ALogP 1.64, HBA 6, HBD 3, PSA 111.37, QED 0.67
Compound (SMILES): Nc1ncnc2c1c(OC(F)F)nn2[C@@H]1O[C@H](COS(N)(=O)=O)[C@@H](O)[C@H]1O
InChIKey: DCMDVFZIMQIMKS-BHBWVORQSA-N
Target: Ubiquitin-like modifier-activating enzyme ATG7 (SINGLE PROTEIN), Homo sapiens
UniProt: O95352
Assay: Enzyme Assay: The total volume of the ATG7 enzymatic assay is 50 μL and contains 50 mM HEPES Hemisodium (pH 7.5), 0.05% BSA, 0.01% Tween-20, 25 mM NaCl, 5 mM MgCl2, 10 μM ATP, 250 μM GSH, 5 nM ATG3-GST, 5 nM Flag-Gabarap, 100 μM TCEP and 0.15 nM recombinant human His-ATG7 enzyme. The enzymatic reaction mixture, with and without inhibitor, was incubated at 24° C. for 105 min in a 384-well plate before termination with 25 μM of Stop/Detection buffer (0.1M HEPES Hemisodium pH 7.5, 0.05% Tween20, 20 mM EDTA, 410 mM KF, 0.53 nM Europium-Cryptate labeled monoclonal anti-Flag M2 Antibody (CisBio International) and 8.125 μg/ml PHYCOLINK goat anti-GST allophycocyanin (XL-APC) antibody (Prozyme)). After incubation for 2 hours at 24° C., quantification of FRET is performed on the Pherostar (BMG Labtech). Percentage inhibition values at a single concentration or enzyme inhibition (IC50) values are determined from those curves. One skilled in the art will appreciate that the values generated either as percentage inhibition at a single concentration or IC50 values are subject to experimental variation.
Measurement: IC50 = 35 nM (pChEMBL 7.460000038146973)
Descriptors: MW 412.33, ALogP -2.15, HBA 12, HBD 4, PSA 197.93, QED 0.4
Compound (SMILES): O=C1Nc2c(Br)cccc2S(=O)(=O)N1
InChIKey: UNWFVIMGKIDJKB-UHFFFAOYSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 incubated for 1 hr prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 73.3 nM (pChEMBL 7.130000114440918)
Descriptors: MW 277.1, ALogP 1.27, HBA 3, HBD 2, PSA 75.27, QED 0.75
Compound (SMILES): O=c1[nH]c(=O)n(-c2ccc(Oc3ccccc3)cc2)c(=O)n1-c1ccccc1
InChIKey: CFKWJKZXGVUURM-UHFFFAOYSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: Agonist activity at TrkA (unknown origin) in expressed in U2OS cells incubated for 3 hrs and measured after 60 hrs in presence of NGF by fluorescence complementation assay
Measurement: EC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 373.37, ALogP 2.47, HBA 6, HBD 1, PSA 86.09, QED 0.6
Compound (SMILES): O=C(Cc1ccc(F)cc1)N1CCC(C(O)CC2c3ccccc3-c3cncn32)CC1
InChIKey: GCUYSCRDNLRJNF-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 = 4800 nM (pChEMBL 5.320000171661377)
Descriptors: MW 419.5, ALogP 3.82, HBA 4, HBD 1, PSA 58.36, QED 0.68
Compound (SMILES): Cc1nc2c(F)cc(-c3nc(Nc4ccc5c(n4)CCN(CCN(C)C)C5)ncc3F)cc2n1C1(C)CC1
InChIKey: SPKWRLBKVPRPMT-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00535
Assay: LANCE Ultra ULight Assay: 1. Take 10 mM stock solution of the test compound, in 96-well compound plate, DMSO was used to dilute the compound to an initial concentration of 100x, then this concentration was used as the first concentration, 3-fold diluted to make 10 serial concentrations; 1 μL each serial dilution was then added to 19 μL 1x reaction buffer to prepare 5x compound for use; 2 μL 5x compound was transferred from 96-well plate to 384-well plate; compound-free control well was added with 2 μL the following liquid: 1x reaction buffer with the addition of 1 μL DMSO; 2 μL 250 mM EDTA was added to the Min control well.2.1x reaction buffer was used to formulate the kinase, substrate and ATP into a 2.5xenzyme/substrate mixture and 2.5xATP solution respectively. In the experiment, the final concentration of CDK4/CycD3 kinase is 0.76 ng/μL, the final concentration of ATP is 8 μM; the final concentration of CDK6/CycD3 kinase is 0.5 ng/μL, the final concentration of ATP is 50M; the final concentration of CDK2/CycA2 kinase is 0.86 ng/μL, the final concentration of ATP is 1 μM; the final concentration of CDK2/CycE1 kinase is 1.016 ng/μL, the final concentration of ATP is 20M; 2.5xenzyme/substrate mixture was added to a 384-well plate, incubated at room temperature for 5 minutes; then added with 2.5xATP solution, reacted at room temperature for 30 minutes.3. LANCE Detection Buffer was used, 1xto prepare 2xLANCE Ultra Europium-anti-phospho-eIF4E-binding protein 1 (Thr37/46) for use. After the enzymatic reaction was continued for 30 minutes, 10 mM EDTA was added to 384-well plate and the mixture was reacted at room temperature for 5 minutes. Then LANCE Ultra Europium-anti-phospho-eIF4E-binding protein 1 (Thr37/46) was added, reacted at room temperature for 1 hour.4. The 384-well plate was placed in HERAEUS Multifuge X1R centrifuge, centrifuged at 2000 rpm for 2 minutes; data were measured on EnVision, 337 nM wavelength laser was used as the excitation light, test at RFU665 nM and RFU615 nM, and RFU665 nM/RFU615 nM x10000 was used as the final data for analysis.
Measurement: IC50 = 33.3 nM (pChEMBL 7.480000019073486)
Descriptors: MW 518.62, ALogP 4.65, HBA 8, HBD 1, PSA 75, QED 0.38
Compound (SMILES): Cc1cc(-c2ccc(C(=O)[C@@H]3CCCC[C@H]3C(=O)Nc3cnn4c3C(=O)NCC4)cc2)n[nH]1
InChIKey: ROTWSDMXHVGAHZ-QZTJIDSGSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of recombinant human CYP2C19 expressed in Escherichia coli using CEC as substrate by fluorescence assay
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 446.51, ALogP 2.95, HBA 6, HBD 3, PSA 121.77, QED 0.52
Compound (SMILES): COc1ccccc1NC(=O)COc1ccc(-c2nc3ccccc3c(=O)[nH]2)cc1OC
InChIKey: XXSREMXIMKCNHF-UHFFFAOYSA-N
Target: CDK6/cyclin D1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P24385
Assay: Inhibition of CDK6/cyclin D1 (unknown origin) using RBER-CHKtide as substrate measured after 1 hr by ADP-glo luminescence assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 431.45, ALogP 3.62, HBA 6, HBD 2, PSA 102.54, QED 0.46
Compound (SMILES): CCO[C@H]1C[C@@H](c2nc3ccc4cc5c(cc4c3[nH]2)OCc2cc(-c3cnc([C@@H]4CCCN4C(=O)[C@@H](NC(=O)OC)C(C)C)[nH]3)ccc2-5)N(C(=O)[C@@H](NC(=O)OC)C(C)C)C1
InChIKey: YTWJMIVKVBIOJL-OZAMDKPCSA-N
Target: Nonstructural protein 5A (SINGLE PROTEIN), Hepatitis C virus
UniProt: Q5L478
Assay: Inhibition of NS5A in HCV genotype 3a S52 infected in human HuH7 transient chimeric replicon cells assessed as reduction in viral replication after 3 days by luciferase reporter gene assay
Measurement: EC50 = 0.048 nM (pChEMBL 10.319999694824219)
Descriptors: MW 834.97, ALogP 6.77, HBA 10, HBD 4, PSA 193.1, QED 0.11
Compound (SMILES): O=C(NC[C@H](O)CN1CCc2ccccc2C1)c1ccnc(NC2CCC2)c1
InChIKey: TWKYXZSXXXKKJU-FQEVSTJZSA-N
Target: PRMT5/MEP50 complex (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9BQA1
Assay: Inhibition of Flag-tagged human PRMT5/his-tagged MEP50 (unknown origin) expressed in baculovirus expression system using HNRNPH1 as substrate preincubated for 60 mins followed by substrate addition and measured after 30 mins by Cheng-Prusoff plot analysis
Measurement: IC50 = 19.6 nM (pChEMBL 7.710000038146973)
Descriptors: MW 380.49, ALogP 2.19, HBA 5, HBD 3, PSA 77.49, QED 0.69
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCSC)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)CNC(=O)[C@H](CCCNC(=N)N)NC(=O)CCCC(=O)NCCCO[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O)[C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CC(C)C)C(=O)O
InChIKey: SAICHWHCFQOCAR-MLPJQUDWSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11166
Assay: Binding affinity to GLUT1 in human NCI-H1437 cells assessed as cytotoxicity by measuring reduction in cell viability measured after 24 hrs by CCK8 assay
Measurement: IC50 = 5300 nM (pChEMBL 5.28000020980835)
Descriptors: MW 3261.82
Compound (SMILES): O=C(Nc1n[nH]c2cc(-c3cccc(CNS(=O)(=O)CC4CC4)c3)ccc12)C1CC1
InChIKey: DPCPNRYPXUUJCP-UHFFFAOYSA-N
Target: AP2-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q2M2I8
Assay: Inhibition of tracer K5 binding to N-terminal nano luciferase-fused AAK1 (unknown origin) expressed in HEK293 cells incubated for 2 hrs followed by NanoBRET NanoGlo Substrate addition and measured within 10 mins by NanoBRET assay
Measurement: IC50 = 1260 nM (pChEMBL 5.900000095367432)
Descriptors: MW 424.53, ALogP 3.41, HBA 4, HBD 3, PSA 103.95, QED 0.52
Compound (SMILES): CC(C)(C)OC(=O)Nc1cccc(C(=O)/C=C/c2ccc(/C=C/C(=O)NO)cc2)c1
InChIKey: XDLZZHYUUVQYDU-PHEQNACWSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of HDAC3 (unknown origin)
Measurement: IC50 = 10800 nM (pChEMBL 4.96999979019165)
Descriptors: MW 408.45, ALogP 4.45, HBA 5, HBD 3, PSA 104.73, QED 0.28
Compound (SMILES): Cc1ccc2[nH]c(-c3ccc(-c4ccc(O[C@H]5CC[C@@H](CC(=O)O)CC5)nc4)nc3)nc2n1
InChIKey: FNWZYYCFELRHJC-UWUNEBHHSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Activity against human A2AR assessed as inhibition of cAMP accumulation by cAMP functional assay
Measurement: IC50 = 490 nM (pChEMBL 6.309999942779541)
Descriptors: MW 443.51, ALogP 4.8, HBA 6, HBD 2, PSA 113.88, QED 0.44
Compound (SMILES): CCCCCCCCCCCCSP(=O)(Oc1ccc(S(N)(=O)=O)cc1)c1ccccc1
InChIKey: FLKUIPIWTDVAMV-UHFFFAOYSA-N
Target: Carbonic anhydrase 5B, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2D0
Assay: Inhibition of human recombinant carbonic anhydrase 5B preincubated with enzyme for 1 hr prior to testing by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 224.6 nM (pChEMBL 6.650000095367432)
Descriptors: MW 497.66, ALogP 6.89, HBA 5, HBD 1, PSA 86.46, QED 0.2
Compound (SMILES): Cc1nn(C)c(C)c1S(=O)(=O)N1CCC2(CC1)OCCS2
InChIKey: SDOGILAPEUUMEN-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: Antagonist activity at human muscarinic M1 receptor assessed as inhibition of acetylcholine-induced calcium response
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 331.46, ALogP 1.28, HBA 6, HBD 0, PSA 64.43, QED 0.82
Compound (SMILES): CC(=O)N1N=C(c2ccc(OS(N)(=O)=O)cc2)CC1c1ccccc1
InChIKey: ZTFVAXOMFNDDQF-UHFFFAOYSA-N
Target: Carbonic anhydrase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P22748
Assay: Inhibition of human recombinant CA4
Measurement: Ki = 17.7 nM (pChEMBL 7.75)
Descriptors: MW 359.41, ALogP 1.97, HBA 5, HBD 1, PSA 102.06, QED 0.9
Compound (SMILES): CC(=O)N1CCC(c2ccc(C(=O)NC3=NCCN3)cc2C(F)(F)F)CC1
InChIKey: UPJRPOWMFLBSKZ-UHFFFAOYSA-N
Target: Sodium-dependent dopamine transporter (SINGLE PROTEIN), Homo sapiens
UniProt: Q01959
Assay: GPCRScan assay: inhibition of DAT
Measurement: Ki = 794.33 nM (pChEMBL 6.099999904632568)
Descriptors: MW 382.39, ALogP 2.12, HBA 4, HBD 2, PSA 73.8, QED 0.82
Compound (SMILES): Cn1c(=O)c2c(nc3n2CCCN3Cc2ccccc2F)n(C)c1=O
InChIKey: USJJUXVFLOLHIY-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of recombinant human MAOB expressed in baculovirus infected BTI insect cells using p-tyramine as substrate preincubated for 30 mins followed by substrate addition and measured over 45 mins by horseradish peroxidase-Amplex Red-coupled fluorometric assay
Measurement: IC50 = 583 nM (pChEMBL 6.230000019073486)
Descriptors: MW 343.36, ALogP 0.98, HBA 7, HBD 0, PSA 65.06, QED 0.7
Compound (SMILES): CNc1[nH]c(Nc2ccc(C(=O)N3CCOCC3)cc2OC)nc2ncc(Cl)c1-2
InChIKey: HUEKBQXFNHWTQQ-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Enzyme Assay: Active GST-LRRK2 (1326-2527), GST-LRRK2[G2019S] (1326-2527), GST-LRRK2[A2016T] (1326-2527) and GST-LRRK2[A2016T+G2019S] (1326-2527) enzyme was purified with glutathione sepharose from HEK293 cell lysate 36 h following transient transfection of the appropriate cDNA constructs. Peptide kinase assays, performed in triplicate, were set up in a total volume of 40 μl containing 0.5 μg LRRK2 kinase (which at approximately 10% purity gives a final concentration of 8 nM) in 50 mM Tris/HCl, pH 7.5, 0.1 mM EGTA, 10 mM MgCl2, 20 μM Nictide, 0.1 μM [γ-32P]ATP (500 cpm/pmol) and the indicated concentrations of inhibitor dissolved in DMSO. After incubation for 15 min at 30° C., reactions were terminated by spotting 35 μl of the reaction mix onto P81 phosphocellulose paper and immersion in 50 mM phosphoric acid. Samples were washed extensively and the incorporation of [γ-32P]ATP into Nictide was quantified by Cerenkov counting. IC50 values were calculated with GraphPad Prism using non-linear regression analysis.
Measurement: IC50 = 19.8 nM (pChEMBL 7.699999809265137)
Descriptors: MW 416.87, ALogP 2.83, HBA 7, HBD 3, PSA 104.4, QED 0.59
Compound (SMILES): CN(C)C(=O)c1ccc(N(Cc2ccc(O)cc2)C(=O)c2ccc(O)cc2O)cc1
InChIKey: TYTXGPAMIGYEGN-UHFFFAOYSA-N
Target: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 4, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q16654
Assay: Inhibition of PDHK4 (unknown origin) assessed as reduction in NAD measured for 30 mins
Measurement: IC50 = 1311 nM (pChEMBL 5.880000114440918)
Descriptors: MW 406.44, ALogP 3.35, HBA 5, HBD 3, PSA 101.31, QED 0.6
Compound (SMILES): O=P(O)(Cc1cc2c(O)c(c1)Sc1cc(CP(=O)(O)c3ccccc3)cc(c1O)Sc1cc(CP(=O)(O)c3ccccc3)cc(c1O)Sc1cc(CP(=O)(O)c3ccccc3)cc(c1O)S2)c1ccccc1
InChIKey: RHGDRBPQTMCKHX-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P29074
Assay: Inhibition of recombinant human N-terminal GST-tagged MEG1 catalytic domain (637 to 926 residues) expressed in Escherichia coli using p-nitrophenol as substrate preincubated with substrate for 5 mins followed by enzyme addition
Measurement: IC50 = 5400 nM (pChEMBL 5.269999980926514)
Descriptors: MW 1113.08
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@@H]1CCCN1C(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]1CCCN1C(=O)[C@H](C)N)C(C)C)[C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O)[C@@H](C)O
InChIKey: HFDKKNHCYWNNNQ-YOGANYHLSA-N
Target: Neuropeptide Y receptor type 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P50391
Assay: Displacement of [3H]UR-KK200 from human Y4 receptor expressed in CHO cells co-expressing Gqi5-mtAEQ measured after 90 mins by scintillation counting analysis
Measurement: Ki = 0.68 nM (pChEMBL 9.170000076293945)
Descriptors: MW 4181.78
Compound (SMILES): C=CC(=O)Nc1cc(Oc2nc(Nc3ccc(N4CCN(C)CC4)cc3OC)ccc2N2CCCCC2)ccc1C
InChIKey: ZFRMQNBHXVYHCH-UHFFFAOYSA-N
Target: Cathepsin S (SINGLE PROTEIN), Homo sapiens
UniProt: P25774
Assay: Inhibition of recombinant human C-terminal polyhistidine-tagged cathepsin S (Met1 to Ile331 residues) expressed in HEK293 cells using MCA-Arg-Pro-Lys-Pro-Val-Glu-NVAL-Trp-Arg-Lys(DNP)-NH2 as substrate preincubated for 30 mins followed by substrate addition and measured after 30 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 556.71, ALogP 5.8, HBA 8, HBD 2, PSA 82.2, QED 0.32
Compound (SMILES): CC(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)c1nc2ccccc2s1
InChIKey: BLOFNYQHKSGSGE-MLCQCVOFSA-N
Target: Serine protease hepsin (SINGLE PROTEIN), Homo sapiens
UniProt: P05981
Assay: Inhibition of recombinant human C-terminal His10-tagged hepsin catalytic domain preincubated for 30 mins followed by Boc-QAR-AMC substrate addition and measured for 1 hr by fluorescence assay
Measurement: Ki = 0.16 nM (pChEMBL 9.800000190734863)
Descriptors: MW 661.83, ALogP -0.13, HBA 10, HBD 9, PSA 254.51, QED 0.04
Compound (SMILES): O[C@@H]1[C@H](O)[C@@H](CCl)O[C@H]1n1cnc2c(N[C@H]3C[C@H]4CC[C@@H]3C4)ncnc21
InChIKey: PVJGDYDNVNCGBT-XSMNFLGNSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99720
Assay: Inhibition of sigma receptor 1 (unknown origin)
Measurement: Ki = 484 nM (pChEMBL 6.320000171661377)
Descriptors: MW 379.85, ALogP 1.28, HBA 8, HBD 3, PSA 105.32, QED 0.69
Compound (SMILES): COc1ccc(Cl)cc1NCC1C(c2ccc(S(N)(=O)=O)cc2)C1(C)C
InChIKey: LWWDCTBUJUEFDE-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 394.92, ALogP 3.85, HBA 4, HBD 2, PSA 81.42, QED 0.78
Compound (SMILES): C=CC(=O)NCc1ccc(-n2nc3c(=O)[nH]nc(N)c3c2-c2oc3ccc(C)cc3c2C)cc1
InChIKey: GXIHBWCRCZNSHX-UHFFFAOYSA-N
Target: Proto-oncogene tyrosine-protein kinase Src (SINGLE PROTEIN), Homo sapiens
UniProt: P12931
Assay: Inhibition of human c-Src using poly (Glu, Tyr)4:1 as substrate measured after 60 mins by ELISA relative to control
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 454.49, ALogP 3.52, HBA 7, HBD 3, PSA 131.83, QED 0.35
Compound (SMILES): C[C@@H]1NC(=O)[C@H](CN)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CS)NC(=O)[C@@H]2CCCN2C(=O)[C@H]2CCCN2C(=O)[C@H](Cc2ccccc2)NC1=O
InChIKey: DKTHXDHZNKFNNS-PLUWKHBFSA-N
Target: Melanocyte-stimulating hormone receptor (SINGLE PROTEIN), Mus musculus
UniProt: Q01727
Assay: Displacement of [125I]-NDP-MSH from mouse melanocortin receptor 1 expressed in HEK293 cell mebranes incubated for 1 hr by automatic gamma counting method
Measurement: IC50 = 33000 nM (pChEMBL 4.480000019073486)
Descriptors: MW 896.08, ALogP -0.47, HBA 10, HBD 8, PSA 241.24, QED 0.14
Compound (SMILES): Cc1nn(-c2ccccn2)c2c1C(c1ccccc1Cl)C1=C(N2)c2ccccc2C1=O
InChIKey: ZUWTUMOFLHZZRE-UHFFFAOYSA-N
Target: Lethal(3)malignant brain tumor-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y468
Assay: PUBCHEM_BIOASSAY: qHTS Assay for the Inhibitors of L3MBTL1. (Class of assay: confirmatory) [Related pubchem assays: 485292 (Probe Development Summary for Inhibitors of L3MBTL1)]
Measurement: Potency = 39810.7 nM (pChEMBL 4.400000095367432)
Descriptors: MW 424.89, ALogP 5.39, HBA 5, HBD 1, PSA 59.81, QED 0.47
Compound (SMILES): CC(C)N1CCN(c2ccc(/C(=C(/CCCO)c3ccccc3)c3ccc(Br)cc3)cc2)CC1.Cl.Cl
InChIKey: KQOSLTWWFIOWBQ-JYOLQUMFSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG after 4 hrs by fluorescence polarization assay
Measurement: IC50 = 15300 nM (pChEMBL 4.820000171661377)
Descriptors: MW 519.53, ALogP 6.71, HBA 3, HBD 1, PSA 26.71, QED 0.34
Compound (SMILES): COc1ccccc1CNCC1CC1(F)c1cc(F)ccc1OC.Cl
InChIKey: BIRIRFXEYPAVNI-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Agonist activity at recombinant human 5HT2A receptor expressed in Flp-In-293 cells assessed as increase in calcium influx measured for 300 secs by Fluo-4 dye based FLIPR assay
Measurement: EC50 = 31 nM (pChEMBL 7.510000228881836)
Descriptors: MW 333.38, ALogP 3.82, HBA 3, HBD 1, PSA 30.49, QED 0.84
Compound (SMILES): NS(=O)(=O)c1ccc(NC(=O)CN2C(=O)NC3(CCCCC3)C2=O)cc1
InChIKey: KZSVRJBEJFDDMB-UHFFFAOYSA-N
Target: Carbonic anhydrase 5B, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2D0
Assay: Inhibition of human carbonic anhydrase 5B incubated for 15 mins prior to testing by stopped-flow CO2 hydration assay
Measurement: Ki = 4292 nM (pChEMBL 5.369999885559082)
Descriptors: MW 380.43, ALogP 0.53, HBA 5, HBD 3, PSA 138.67, QED 0.65
Compound (SMILES): CC(C)CC(NC(=O)c1ccc(-c2ccc(S(C)(=O)=O)cc2)cc1)C(=O)N(C)N(C)C#N
InChIKey: XHBRHGRXSUUCGR-UHFFFAOYSA-N
Target: Cathepsin S (SINGLE PROTEIN), Homo sapiens
UniProt: P25774
Assay: Inhibition of recombinant human cathepsin S expressed in Escherichia coli
Measurement: IC50 = 332 nM (pChEMBL 6.480000019073486)
Descriptors: MW 456.57, ALogP 2.69, HBA 6, HBD 1, PSA 110.58, QED 0.37
Compound (SMILES): Cn1cncc1-c1cn(Cc2ccc(C(=O)NO)cc2)c2ccccc12
InChIKey: ANMZNMDSWZJYNP-UHFFFAOYSA-N
Target: Histone deacetylase 3/Nuclear receptor corepressor 2 (HDAC3/NCoR2) (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9Y618
Assay: Inhibition of human recombinant full length C-terminal His-tagged HDAC3 (1 to 428 residues)/N-terminal GST-tagged NCOR2 (395 to 489 residues) expressed in baculovirus infected insect cells measured after 40 mins by HDAC-Glo1/2 luminescent assay
Measurement: IC50 = 501.19 nM (pChEMBL 6.300000190734863)
Descriptors: MW 346.39, ALogP 3.21, HBA 5, HBD 2, PSA 72.08, QED 0.44
Compound (SMILES): CCN(CCCCNC(=O)c1ccc2ccccc2c1)CC1CC1c1cc(Cl)ccc1OC.Cl
InChIKey: WQFHHKMPQVRCRI-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2C (SINGLE PROTEIN), Homo sapiens
UniProt: P28335
Assay: Displacement of [3H]-Mesulergine from recombinant human 5HT2C receptor expressed in HEKT cell membranes measured after 90 mins by microbeta scintillation counting method
Measurement: Ki = 49 nM (pChEMBL 7.309999942779541)
Descriptors: MW 465.04, ALogP 6.14, HBA 3, HBD 1, PSA 41.57, QED 0.35
Compound (SMILES): O=C(O)Cc1ccc(Cc2cc(-c3cccc(Cl)c3)nc(C(F)(F)F)c2)cc1
InChIKey: LTSUMTMGJHPGFX-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4D (SINGLE PROTEIN), Homo sapiens
UniProt: Q08499
Assay: Inhibition of recombinant human His6-tagged PDE4D2 expressed in baculovirus infected Sf9 insect cells using cAMP as substrate preincubated for 5 to 10 mins followed by substrate addition and measured for 10 mins by yeast myokinase/pyruvate kinase/lactate dehydrogenase-coupled fluorescence assay
Measurement: IC50 = 127 nM (pChEMBL 6.900000095367432)
Descriptors: MW 405.8, ALogP 5.64, HBA 2, HBD 1, PSA 50.19, QED 0.6
Compound (SMILES): O=S(=O)(Nc1ccc(-c2nc3ccccc3o2)cc1)c1ccccc1F
InChIKey: KZSXXKOXHVIXPZ-UHFFFAOYSA-N
Target: GroEL/GroES (PROTEIN COMPLEX), Escherichia coli
UniProt: Q7BGE6
Assay: Inhibition of Escherichia coli GroEL expressed in Escherichia coliDH5alpha/Escherichia coli GroES expressed in Escherichia coli BL21 (DE3) assessed as reduction in GroEL/GroES-mediated denatured pig heart mitochondrial MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 20 to 40 mins by spectrometric analysis
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 368.39, ALogP 4.43, HBA 4, HBD 1, PSA 72.2, QED 0.58
Compound (SMILES): O=C1Nc2c(Br)cccc2S(=O)(=O)N1
InChIKey: UNWFVIMGKIDJKB-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of recombinant human carbonic anhydrase 12 incubated for 1 hr prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 75.8 nM (pChEMBL 7.119999885559082)
Descriptors: MW 277.1, ALogP 1.27, HBA 3, HBD 2, PSA 75.27, QED 0.75
Compound (SMILES): O=C(Cc1ccc(F)cc1)N1CCC(C(O)CC2c3ccccc3-c3cncn32)CC1
InChIKey: GCUYSCRDNLRJNF-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 (unknown origin)
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 419.5, ALogP 3.82, HBA 4, HBD 1, PSA 58.36, QED 0.68