lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): NC(=O)c1cccc2c1O/C(=C\c1ccc(C(=O)N3CCn4c(CC5CC5)nnc4C3)cc1)C2=O
InChIKey: PGGOMVDSVVGTHN-NDENLUEZSA-N
Target: Poly [ADP-ribose] polymerase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGN5
Assay: Inhibition of human N-terminal GST-tagged PARP2 (2 to 583 residues) expressed in baculovirus infected Sf9 insect cells using histone as substrate measured after 1 hr by horseradish peroxidase-coupled chemiluminescence assay
Measurement: IC50 = 3.5 nM (pChEMBL 8.460000038146973)
Descriptors: MW 469.5, ALogP 2.6, HBA 7, HBD 1, PSA 120.41, QED 0.57
Compound (SMILES): Cc1cc(Cl)cnc1C(=O)Nc1ccc2c(c1)[C@@]1(C)N=C(N)C(C)(C)S(=O)(=O)[C@@H]1CCO2
InChIKey: GPTXVAMKJRVWAD-VGOFRKELSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of BACE1 (unknown origin) preincubated for 1 hr followed by substrate addition and measured after 1 hr by FRET assay
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 476.99, ALogP 3.23, HBA 7, HBD 2, PSA 123.74, QED 0.69
Compound (SMILES): O=C1NCCc2cc(-c3cccc(Cl)c3)ccc21
InChIKey: VYSHKUXCRTVUNN-UHFFFAOYSA-N
Target: Protein mono-ADP-ribosyltransferase PARP11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR21
Assay: Inhibition of full length human His-SUMO-tagged PARP11 expressed in Escherichia coli BL21 assessed as reduction in MARylation of His6-tagged SRPK2 substrate after 60 mins in presence of NAD+ by chemifluorescence assay
Measurement: IC50 = 5800 nM (pChEMBL 5.239999771118164)
Descriptors: MW 257.72, ALogP 3.29, HBA 1, HBD 1, PSA 29.1, QED 0.83
Compound (SMILES): NCc1ccc(S(=O)(=O)c2ccccc2)s1
InChIKey: ORJXSVLLDNVYIZ-UHFFFAOYSA-N
Target: Lysyl oxidase homolog 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y4K0
Assay: Inhibition of LOXL2 (unknown origin) using H2O2 substrate incubated for 20 mins by luminescence based assay
Measurement: IC50 = 2200 nM (pChEMBL 5.659999847412109)
Descriptors: MW 253.35, ALogP 2.04, HBA 4, HBD 1, PSA 60.16, QED 0.91
Compound (SMILES): CCCN1C(=O)/C(=N\Nc2ccc(S(N)(=O)=O)cc2)c2cc(Br)ccc21
InChIKey: JFPKXQQUUHSPLW-PGMHBOJBSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of recombinant human carbonic anhydrase 9 preincubated for 15 mins by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 55.8 nM (pChEMBL 7.25)
Descriptors: MW 437.32, ALogP 2.67, HBA 5, HBD 2, PSA 104.86, QED 0.7
Compound (SMILES): CCn1c(CCc2ccc(NC(=O)Nc3cc(OC)cc(OC)c3)cc2)nc2ccccc21
InChIKey: DFGRUOZUEZDKAO-UHFFFAOYSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: Inhibition of His-tagged recombinant human ATP-activated TRKA kinase domain (441 to 796 residues) expressed in baculovirus expression system preincubated with enzyme/ATP mixture for 20 mins followed by TK substrate-biotin addition followed by further incubation for 15 mins in presence of ATP by HTRF assay
Measurement: IC50 = 41.2 nM (pChEMBL 7.380000114440918)
Descriptors: MW 444.54, ALogP 5.5, HBA 5, HBD 2, PSA 77.41, QED 0.38
Compound (SMILES): O=C(OC(C(F)(F)F)C(F)(F)F)N1CCN(Cc2c(Cl)cccc2N2CCOCC2)CC1
InChIKey: MMEDAUQDZWXSPI-UHFFFAOYSA-N
Target: Monoglyceride lipase (SINGLE PROTEIN), Homo sapiens
UniProt: Q99685
Assay: Inhibition of MGLL derived from human PC3 cell lysates preincubated for 30 mins followed by JW912 addition after 30 mins by gel-based ABPP assay
Measurement: IC50 = 1100 nM (pChEMBL 5.960000038146973)
Descriptors: MW 489.84, ALogP 3.92, HBA 5, HBD 0, PSA 45.25, QED 0.6
Compound (SMILES): Cc1ccc(CNC(=O)CN(CCCCCC(=O)Nc2ccccc2N)C(=O)c2cc(C)cc(C)c2)cc1
InChIKey: TUQZMESLDYEUSM-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 Sf9 insect cells using Boc-Lys(epsilon-acetyl)-AMC as substrate incubated for 90 mins by fluorescence assay
Measurement: IC50 = 478 nM (pChEMBL 6.320000171661377)
Descriptors: MW 514.67, ALogP 5.15, HBA 4, HBD 3, PSA 104.53, QED 0.23
Compound (SMILES): N/C(=N\O)c1cccc(/C=C/c2ccnc(-c3ccccc3O)c2)c1
InChIKey: LSNJXCLQOPXVDI-CMDGGOBGSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of MAO-B (unknown origin) using (4S)-4,5-dihydro-2-(6-hydroxybenzothiazolyl)-4-thiazolecarboxylic acid as substrate by MAO-Glo assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 331.38, ALogP 3.72, HBA 4, HBD 3, PSA 91.73, QED 0.29
Compound (SMILES): COc1n[nH]c2ncc(-c3cn(-c4c(F)ccc(NS(=O)(=O)c5cccc(-c6ccccc6)c5)c4F)nn3)cc12
InChIKey: QRDCOOSKIFYKIQ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Binding affinity to human ABL1
Measurement: Kd = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 559.56, ALogP 4.96, HBA 8, HBD 2, PSA 127.68, QED 0.28
Compound (SMILES): O=C(O)C1CCCN(C/C=C\CC(c2ccccc2)(c2ccccc2)c2ccccc2)C1
InChIKey: KZOXHIOCUVUEIW-KHPPLWFESA-N
Target: GABA transporter 4 (SINGLE PROTEIN), Mus musculus
UniProt: P31650
Assay: Inhibition of mouse GAT4 expressed in HEK293 cells assessed as reduction in [3H]GABA uptake preincubated for 25 mins followed by [3H]GABA addition and measured after 4 mins by microbeta liquid scintillation counting method
Measurement: IC50 = 15135.61 nM (pChEMBL 4.820000171661377)
Descriptors: MW 425.57, ALogP 5.76, HBA 2, HBD 1, PSA 40.54, QED 0.37
Compound (SMILES): Cc1cc(-c2ccc(C(=O)[C@@H]3CCCC[C@H]3C(=O)Nc3cn(C)nc3C(N)=O)cc2)[nH]n1
InChIKey: WKKFDAKDVQTOTA-IAGOWNOFSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of recombinant human CYP2C9 expressed in Escherichia coli assessed as maximum reduction in metabolite formation using coumarin based substrate by fluorescence assay
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 434.5, ALogP 2.85, HBA 6, HBD 3, PSA 135.76, QED 0.51
Compound (SMILES): O=C(O)CC[C@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](Cc1ccc2ccccc2c1)NC(=O)c1cc2cc(Cl)ccc2[nH]1)C(=O)Nc1ccc(OC(F)(F)F)cc1
InChIKey: MLLGKYJIOWULMN-QMOZSOIISA-N
Target: Catenin beta-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P35222
Assay: Binding affinity to beta catenin (unknown origin) assessed as dissociation constant by VP-ITC method
Measurement: Kd = 420 nM (pChEMBL 6.380000114440918)
Descriptors: MW 796.16, ALogP 5.16, HBA 7, HBD 7, PSA 216.02, QED 0.07
Compound (SMILES): COc1ccc(Cc2ccccc2)cc1[C@@H](C)NC(=O)[C@@H](N)Cc1c(C)cc(O)cc1C.O=C(O)C(F)(F)F
InChIKey: VXVOIJWYOSWGEA-UFABNHQSSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Displacement of [3H]-diprenorphine from human kappa-type opioid receptor expressed in CHO cell membranes incubated for 1 hr in shaker by liquid scintillation counting method
Measurement: Ki = 330 nM (pChEMBL 6.480000019073486)
Descriptors: MW 432.56, ALogP 4.36, HBA 4, HBD 3, PSA 84.58, QED 0.49
Compound (SMILES): CCCn1c(=O)[nH]c2nc(-c3ccc(S(=O)(=O)N4CCN(c5ccccc5Br)CC4)cc3)[nH]c2c1=O
InChIKey: JNKPRJLGQDTUBK-UHFFFAOYSA-N
Target: Adenosine receptor A1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30542
Assay: Displacement of [3H]CCPA from recombinant human A1 adenosine receptor expressed in CHO cell membranes measured after 90 mins in presence of adenosine deaminase by liquid scintillation counting method
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 573.47, ALogP 2.76, HBA 7, HBD 2, PSA 124.16, QED 0.37
Compound (SMILES): O=C(Nc1ccc(Cl)cc1)Nc1ccc(-c2ccc(Cl)c(Cl)c2)s1
InChIKey: OLULDLCUJJCASL-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Antagonist activity at human CB2 receptor expressed in CHO cells co-expressing Galpha16 assessed as inhibition of EC80 CP55,940-induced calcium mobilization preincubated for 15 mins followed by CP55,490 addition measured at 1 sec interval for 90 secs by calcium-5 dye based FLIPR assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 397.71, ALogP 7.02, HBA 2, HBD 2, PSA 41.13, QED 0.49
Compound (SMILES): N#Cc1cnc(N2CCC(C(=O)N3N=CC[C@H]3c3cc(F)cc(F)c3)CC2)cn1
InChIKey: LPURNEQRSBXUFH-SFHVURJKSA-N
Target: Receptor-interacting serine/threonine-protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13546
Assay: Inhibition of RIP1 in human U937 cells assessed as reduction in TNFalpha/QVD-Oph-induced necroptosis measured after 24 hrs by cell titer-glo luminescent cell viability assay
Measurement: IC50 = 7.9 nM (pChEMBL 8.100000381469727)
Descriptors: MW 396.4, ALogP 2.8, HBA 6, HBD 0, PSA 85.48, QED 0.8
Compound (SMILES): Cc1cc(N)nc(CCc2cc(CC[C@@H]3CCCN3C)cc(F)c2F)c1
InChIKey: DWIFPRVVASXUJK-SFHVURJKSA-N
Target: Nitric oxide synthase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P29475
Assay: Inhibition of human neuronal NOS expressed in Escherichia coli using L-arginine as substrate in presence of human oxyhemoglobin after 6 mins by hemoglobin NO capture assay
Measurement: Ki = 37 nM (pChEMBL 7.429999828338623)
Descriptors: MW 359.46, ALogP 4.06, HBA 3, HBD 1, PSA 42.15, QED 0.85
Compound (SMILES): COC1CCN(c2ccc(C3(c4ccsc4)CC(O)=C(Sc4ccccc4Cl)C(=O)N3)cc2)CC1
InChIKey: XYENCVBPSGNPKA-UHFFFAOYSA-N
Target: L-lactate dehydrogenase A chain (SINGLE PROTEIN), Homo sapiens
UniProt: P00338
Assay: Inhibition of LDHA in human MiPaca2 cells assessed as inhibition of lactate production
Measurement: IC50 = 2900 nM (pChEMBL 5.539999961853027)
Descriptors: MW 527.11, ALogP 6.34, HBA 6, HBD 2, PSA 61.8, QED 0.39
Compound (SMILES): N#CN1CC[C@@H](NC(=O)c2ccnc(N3Cc4ccccc4C3)c2)C1
InChIKey: DMBLCGWOYRADPE-QGZVFWFLSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 30 (SINGLE PROTEIN), Homo sapiens
UniProt: Q70CQ3
Assay: Inhibition of human USP30 catalytic domain (57 to 517 residues) using ubiquitin-rhodamine 110 as substrate preincubated for 30 min followed by substrate addition and measured after 2 hrs by fluorescence intensity kinetic assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 333.4, ALogP 1.89, HBA 5, HBD 1, PSA 72.26, QED 0.87
Compound (SMILES): COc1ncc(-c2ccc3c(c2)N(C2CC2)C(=O)CO3)cc1NS(=O)(=O)c1ccc(F)cc1
InChIKey: CJHYEYVPXSNZNX-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Inhibition of recombinant human N-terminal FLAG-tagged mTOR (1362 to end residues) using Ulight-4E-BP1 as substrate incubated for 30 mins by fluorescence assay
Measurement: IC50 = 253 nM (pChEMBL 6.599999904632568)
Descriptors: MW 469.49, ALogP 3.58, HBA 6, HBD 1, PSA 97.83, QED 0.59
Compound (SMILES): Cl.Nc1ncc(-c2cccc3c2ccn3S(=O)(=O)c2ccccc2)[nH]1
InChIKey: UBKRXEJMPVIJAB-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H]LSD from human 5HT6 receptor expressed in HEK293 cells measured after 1 hr by liquid scintillation counter method
Measurement: Ki = 34 nM (pChEMBL 7.46999979019165)
Descriptors: MW 338.39, ALogP 2.85, HBA 5, HBD 2, PSA 93.77, QED 0.6
Compound (SMILES): CCSC1=C(C)C(=O)c2ccccc2C1=O
InChIKey: AAPLOQZFUUYECE-UHFFFAOYSA-N
Target: M-phase inducer phosphatase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P30304
Assay: Inhibition of recombinant Cdc25A (unknown origin) using OMFP as substrate measured every 30 sec for 10 mins by fluorometric assay
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 232.3, ALogP 3.09, HBA 3, HBD 0, PSA 34.14, QED 0.79
Compound (SMILES): COc1cc(C(CC(=O)O)c2ccc(C)c(CN3C[C@@H](C)Oc4ccccc4S3(=O)=O)c2)cc2nnn(C)c12
InChIKey: ZDNGJXBUEQNFBQ-ZZWBGTBQSA-N
Target: Nuclear factor erythroid 2-related factor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16236
Assay: BEAS-2B NQO1 MTT Assay: NAD(P)H:quinone oxidoreductase 1 (NQO1), also called DT diaphorase, is a homodimeric FAD-containing enzyme that catalyzes obligatory NAD(P)H-dependent two-electron reductions of quinones and protects cells against the toxic and neoplastic effects of free radicals and reactive oxygen species arising from one-electron reductions. The transcription of NQO1 is finely regulated by Nrf2, and thus NQO1 activity is a good marker for Nrf2 activation. On day one, frozen BEAS-2B cells (ATCC) are thawed in a water bath, counted, and re-suspended at a concentration of 250,000 cells/mL. Fifty microliters of cells are plated in 384 well black clear-bottomed plates. Plates are incubated at 37° C., 5% CO2 overnight. On day two, plates are centrifuged and 50 nL of compound or controls are added to the cells. Plates are then incubated at 37° C., 5% CO2 for 48 h. On day four, medium is aspirated from the plate and crude cell lysates are made by adding 13 μL of 1× Cell Signaling Technologies lysis buffer with 1 Complete, Mini, EDTA-free Protease Inhibitor Tablet (Roche) for each 10 mL of lysis buffer. After lysis plates are incubated for 20 min at room temperature. Two microliters of lysate are removed for use in Cell Titer Glo assay (Promega) and MTT cocktail is prepared (Prochaska et. al. 1998) for measurement of NQO1 activity. Fifty microliters of MTT cocktail is added to each well, plate is centrifuged, and analyzed on an Envision plate reader (Perkin Elmer) using Absorbance 570 nm label for 30 min. Product formation is measured kinetically and the pEC50 of NQO1 specific activity induction is calculated by plotting the change in absorbance (Delta OD/min) versus the log of compound concentration followed by 3-parameter fitting.
Measurement: EC50 = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 550.64, ALogP 3.86, HBA 8, HBD 1, PSA 123.85, QED 0.37
Compound (SMILES): O=[N+]([O-])CC(c1ccccc1)c1c(-c2ccccc2)[nH]c2ccccc12
InChIKey: OHZDCJJHWPHZJD-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Positive allosteric modulation at human CB1 receptor expressed in CHO cells assessed as inhibition of forskolin-induced cAMP production incubated for 90 mins in presence of FM6b by HitHunter assay
Measurement: EC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 342.4, ALogP 5.24, HBA 2, HBD 1, PSA 58.93, QED 0.4
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@H](CSSC[C@H](NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](NC(C)=O)[C@H](C)O)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O)[C@@H](C)CC)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](NC(C)=O)[C@H](C)O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](Cc1ccc(O)cc1)C(N)=O
InChIKey: YLYJVGXDVMNHOS-CTBXZIEYSA-N
Target: Frizzled-7 (SINGLE PROTEIN), Homo sapiens
UniProt: O75084
Assay: Inhibition of Frizzled-7 in HEK293 cells expressing Wnt assessed as reduction in Wnt signaling by firefly luciferase reporter gene assay
Measurement: IC50 = 9.2 nM (pChEMBL 8.039999961853027)
Descriptors: MW 3157.63
Compound (SMILES): CCC(=O)N1CCC[C@@H](n2c(=O)c(-c3ccc(F)cc3Cl)c(C)c3cnc(Nc4ccc(N5CCN(C)CC5)c(C)c4)nc32)C1
InChIKey: IWUQOYKCIWQLQI-RUZDIDTESA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of human C-terminal His-tagged and N-terminal GST-tagged EGFR L858R/T790M/C797S triple mutant ( 668 to 1210 amino acids) expressed in baculovirus infected Sf9 insect cells using Poly(Glu,Tyr) 4:1 as substrate after 60 mins by ELISA
Measurement: IC50 = 224.1 nM (pChEMBL 6.650000095367432)
Descriptors: MW 632.18, ALogP 5.94, HBA 8, HBD 1, PSA 86.6, QED 0.28
Compound (SMILES): O=C(NC1=NN(c2ccc(Cl)c(Cl)c2)CC1)c1cccnn1
InChIKey: DFVAHUXIKJKRTM-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Induction of human c-ABL phosphorylation at Y245/Y412 residues in bacmam-induced HEK-MSR2 cell lysates by in-cell Western blot analysis
Measurement: EC50 > 50118.72 nM (pChEMBL 4.300000190734863)
Descriptors: MW 336.18, ALogP 2.74, HBA 5, HBD 1, PSA 70.48, QED 0.92
Compound (SMILES): CCC(=O)N1N=C(c2c(-c3ccccc3)c3cc(Cl)ccc3[nH]c2=O)CC1c1ccc(OC)cc1
InChIKey: LAVOKBSCOSIGER-UHFFFAOYSA-N
Target: DNA repair protein RAD51 homolog 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06609
Assay: Inhibition of RAD51 in human BxPC3 cells assessed as reduction in homologous recombination incubated for 5 hrs by RT-PCR analysis
Measurement: EC50 = 18400 nM (pChEMBL 4.739999771118164)
Descriptors: MW 485.97, ALogP 5.94, HBA 4, HBD 1, PSA 74.76, QED 0.38
Compound (SMILES): COc1nn(C)cc1Nc1ncc(C)c(-c2c[nH]c3c(NC(=O)[C@@H](C)N4CCN(C)CC4)cccc23)n1
InChIKey: DZGZZYZUXFBJLY-QGZVFWFLSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
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 = 10 nM (pChEMBL 8)
Descriptors: MW 503.61, ALogP 2.99, HBA 9, HBD 3, PSA 116.23, QED 0.35
Compound (SMILES): Cc1cc(-c2cccnc2)nn(-c2ccc(S(N)(=O)=O)cc2)c1=O
InChIKey: CXRDMENMZMEEEV-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human cytosolic CA 2 preincubated for 15 mins by phenol red dye-based stopped-flow CO2 hydration assay
Measurement: Ki = 2.9 nM (pChEMBL 8.539999961853027)
Descriptors: MW 342.38, ALogP 1.25, HBA 6, HBD 1, PSA 107.94, QED 0.77
Compound (SMILES): O=C(NC1CCCc2ccccc21)c1nc2ccccc2s1
InChIKey: IUAGYYVENJFHQP-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Agonist activity at N-terminal Flag epitope tagged CB2 (unknown origin) expressed in HTLA cells assessed as increase of beta-arrestin recruitment by Tango assay
Measurement: EC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 308.41, ALogP 4.1, HBA 3, HBD 1, PSA 41.99, QED 0.77
Compound (SMILES): CN1CCC(Nc2cc(Cl)nn3c(-c4ccc5[nH]c(Nc6ccccc6)nc5c4)cnc23)CC1
InChIKey: JRIQEMVMALSXHW-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase/endoribonuclease IRE1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75460
Assay: Inhibition of dephosphorylated IRE1alpha (G547 to L977 residues) (unknown origin) autophosphorylation at S724 after 25 mins in presence of ATP by dissociation-enhanced lanthanide fluorescence immunoassay
Measurement: IC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 472.98, ALogP 5.18, HBA 7, HBD 3, PSA 86.17, QED 0.33
Compound (SMILES): O=c1oc2ccccc2c2nn(S(=O)(=O)c3ccc(C(F)(F)F)cc3)cc12
InChIKey: QKAAKWXFXXSWER-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3Kgamma (unknown origin) using diC8-PI(4,5)P2 as substrate incubated for 3 hrs by fluorescence polarization assay
Measurement: IC50 = 3480 nM (pChEMBL 5.460000038146973)
Descriptors: MW 394.33, ALogP 3.4, HBA 6, HBD 0, PSA 82.17, QED 0.49
Compound (SMILES): CCCn1nc(O)c(CC(N)C(=O)O)n1
InChIKey: FGCRXYQHIDORDD-UHFFFAOYSA-N
Target: Glutamate receptor 3 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P19492
Assay: Displacement of (RS)-[3H]AMPA from recombinant rat GluA3 expressed in baculovirus infected Sf9 insect cell membranes
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 214.22, ALogP -0.65, HBA 6, HBD 3, PSA 114.26, QED 0.6
Compound (SMILES): N#Cc1ccc(C2Cn3c(=O)c(C(=O)NCC(=O)O)c(O)c4cc(OC(F)(F)F)cc(c43)O2)cc1
InChIKey: WKLDLAIFXJRTMG-UHFFFAOYSA-N
Target: Prolyl hydroxylase EGLN2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96KS0
Assay: Inhibition of recombinant human HIF-PHD1 expressed in baculovirus-infected Sf9 cells using biotin labelled DLDLEMLAPYIPMDDDFQL and 2-oxoglutarate as substrates preincubated for 30 mins followed by substrates addition and measured after 2 hrs by TR-FRET assay
Measurement: IC50 = 1.4 nM (pChEMBL 8.850000381469727)
Descriptors: MW 489.36, ALogP 2.43, HBA 8, HBD 3, PSA 150.88, QED 0.49
Compound (SMILES): CC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(=N)N)C(=O)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: BYLQOZZYBZTSIB-GIHRPWDCSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Antagonist activity at human muscarinic M2 receptor expressed in HEK293 cells co-expressing HA-Galphaq/i5 assessed as inhibition of carbachol-induced IP1 accumulation pre-incubated for 30 mins followed by carbachol addition and measured after 1 hr by HTRF assay
Measurement: IC50 = 93.33 nM (pChEMBL 7.03000020980835)
Descriptors: MW 732.93, ALogP 2.3, HBA 8, HBD 8, PSA 227.87, QED 0.06
Compound (SMILES): COc1ncc(-c2ccc3c(c2)N(c2ccc(F)cc2)C(=O)CO3)cc1NS(=O)(=O)c1ccc(F)cc1
InChIKey: QSTSTVHFXANQAG-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Inhibition of recombinant human N-terminal FLAG-tagged mTOR (1362 to end residues) using Ulight-4E-BP1 as substrate incubated for 30 mins by fluorescence assay
Measurement: IC50 = 34.9 nM (pChEMBL 7.460000038146973)
Descriptors: MW 523.52, ALogP 4.89, HBA 6, HBD 1, PSA 97.83, QED 0.39
Compound (SMILES): Cc1ccc(C[C@H](N)/C(F)=C/CC(=O)NCC(=O)N[C@@H](Cc2ccccc2)C(=O)N[C@@H](CC(C)C)C(=O)O)cc1
InChIKey: DFWIXKCWCXEEET-MFMYLMPHSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at delta opioid receptor (unknown origin) expressed in CHO cells
Measurement: EC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 554.66, ALogP 2.57, HBA 5, HBD 5, PSA 150.62, QED 0.23
Compound (SMILES): COc1ccccc1C(C(=O)NC1CCCCC1)N(C(=O)/C=C/C(=O)c1ccc(C)cc1)C1CCCCC1
InChIKey: GAIRAQHWWXYQQO-QURGRASLSA-N
Target: Thioredoxin reductase 1, cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: Q16881
Assay: Inhibition of TrxR1 (unknown origin) using DTNB as substrate preincubated for 30 mins in presence of insulin followed by substrate addition by colorimetry
Measurement: IC50 = 5280 nM (pChEMBL 5.28000020980835)
Descriptors: MW 516.68, ALogP 6.09, HBA 4, HBD 1, PSA 75.71, QED 0.32
Compound (SMILES): CC(C)CNC(=O)n1c(=O)oc2cc(C3CCN(C)CC3)ccc21
InChIKey: AYXQGWOLRJUITD-UHFFFAOYSA-N
Target: Fatty-acid amide hydrolase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O00519
Assay: Inhibition of human FAAH expressed in HEK293 cells using AMC arachidonyl amide as fluorogenic substrate preincubated for 50 mins followed by substrate addition and measured after 45 mins by fluorescence based assay
Measurement: IC50 = 70 nM (pChEMBL 7.159999847412109)
Descriptors: MW 331.42, ALogP 2.62, HBA 5, HBD 1, PSA 67.48, QED 0.94
Compound (SMILES): C[C@H]1CO[C@H](c2ccc(N)nc2)CN1CC1CC1CNC(=O)c1cc2ccccc2[nH]1
InChIKey: QKMCUEOKZNEZFG-FIHHNCHPSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-(R)-(+)-7-OH-DPAT from recombinant human D2L receptor expressed in HEK293 cell membranes measured after 90 mins by microbeta scintillation counting analysis
Measurement: Ki = 7730 nM (pChEMBL 5.110000133514404)
Descriptors: MW 419.53, ALogP 2.97, HBA 5, HBD 3, PSA 96.27, QED 0.57
Compound (SMILES): CCOc1cc(C2CCN(C)CC2)ccc1Nc1ncc2c(n1)N(Cc1cccc(Br)c1)[C@H](CC)C(=O)N2C
InChIKey: KPXMSUZHJCHOTN-RUZDIDTESA-N
Target: Serine/threonine-protein kinase PLK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P53350
Assay: Inhibition of PLK1 (unknown origin) using Ser/Thr 16 as substrate after 60 mins by Z-LYTE activity assay
Measurement: IC50 = 540 nM (pChEMBL 6.269999980926514)
Descriptors: MW 593.57, ALogP 5.95, HBA 7, HBD 1, PSA 73.83, QED 0.35
Compound (SMILES): CC(C)[C@H]1CC[C@@H](N2CCC(n3cc(CCCN)c4ccccc43)CC2)CC1.Cl.Cl
InChIKey: DSHIIQHRAOIFQU-DBEIMXIDSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Displacement of [3H]DPDPE from human DOP expressed in CHO cell membrane incubated for 60 mins by liquid scintillation counting method
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 381.61, ALogP 5.38, HBA 3, HBD 1, PSA 34.19, QED 0.73
Compound (SMILES): Cn1c(=O)n(CCCO)c(=O)c2c(Cc3ccccc3)c(-c3cccc(OC(F)(F)F)c3)ccc21
InChIKey: XGQMAQHQMRPRKK-UHFFFAOYSA-N
Target: Short transient receptor potential channel 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UL62
Assay: Inhibition of TRPC5 (unknown origin) transfected in HEK293/TREx cells assessed as blocking of inward/outward currents after 20 to 48 hrs in presence of LaCl3 by patch clamp assay
Measurement: IC50 = 5.3 nM (pChEMBL 8.279999732971191)
Descriptors: MW 484.47, ALogP 4.24, HBA 6, HBD 1, PSA 73.46, QED 0.43
Compound (SMILES): CCCNNC(=O)CCCCCCC(=O)Nc1ccccc1
InChIKey: QDBUPYIRFBUJSV-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of HDAC3 (unknown origin)
Measurement: IC50 = 20.26 nM (pChEMBL 7.690000057220459)
Descriptors: MW 305.42, ALogP 3, HBA 3, HBD 3, PSA 70.23, QED 0.43
Compound (SMILES): CN(C)c1ncc(-c2ccc(O)cc2)cc1-c1ccc(S(C)(=O)=O)cc1
InChIKey: JUSSLCLDOMYWPZ-UHFFFAOYSA-N
Target: Misshapen-like kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N4C8
Assay: Inhibition of human 6His-TEV-Avi-MINK1(1 to 328)-GNS expressed in baculovirus-infected sf21 cells using LRRKtide as substrate preincubated for 30 mins followed by substrate addition and measured after 75 to 90 mins by ADP-Glo Reagent based method
Measurement: IC50 = 19952.62 nM (pChEMBL 4.699999809265137)
Descriptors: MW 368.46, ALogP 3.59, HBA 5, HBD 1, PSA 70.5, QED 0.76
Compound (SMILES): CN(C)C(=O)Cn1ccc2ncc(-c3cccc(Cl)c3)cc21
InChIKey: VGTGGHWSTHBVTR-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 313.79, ALogP 3.44, HBA 3, HBD 0, PSA 38.13, QED 0.74
Compound (SMILES): CC(C)c1ccc(S(=O)(=O)N2C(=O)NC(=O)C23CCCc2ccccc23)cc1
InChIKey: XSTOJSNXCJOZLO-UHFFFAOYSA-N
Target: Aldo-keto reductase family 1 member B1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P07943
Assay: Inhibition of ALR2 in rat erythrocytes assessed as reduction in sorbitol accumulation incubated for 3 hrs in presence of 28 mM glucose by gas chromatographic analysis relative to control
Measurement: IC50 = 850 nM (pChEMBL 6.070000171661377)
Descriptors: MW 398.48, ALogP 3.28, HBA 4, HBD 1, PSA 83.55, QED 0.8
Compound (SMILES): CC(C)n1cnnc1-c1cccc(NC(=O)c2ccccc2F)n1
InChIKey: IUQZTKCWPJKKDY-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99683
Assay: Inhibition of V5 tagged human ASK1 expressed in HEK-293T cells assessed as reduction in T838 autophosphorylation incubated for 1 hr
Measurement: IC50 = 8164 nM (pChEMBL 5.090000152587891)
Descriptors: MW 325.35, ALogP 3.31, HBA 5, HBD 1, PSA 72.7, QED 0.8
Compound (SMILES): CO[C@H]1CSC(N)=N[C@]1(C)c1cc(NC(=O)c2cnc(OCF)cn2)ccc1F
InChIKey: MUPBDTQMTBLIBE-KBXCAEBGSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of BACE1 in human SKNBE2 cells expressing APP695 assessed as reduction in Abeta42 level measured after 18 hrs by sandwich ELISA
Measurement: IC50 = 4.5 nM (pChEMBL 8.350000381469727)
Descriptors: MW 423.45, ALogP 2.47, HBA 8, HBD 2, PSA 111.72, QED 0.73
Compound (SMILES): CCCOc1ccc(Cc2ccccc2)cc1CNC(=O)[C@@H](N)Cc1c(C)cc(O)cc1C.O=C(O)C(F)(F)F
InChIKey: FZLOLDICIGXTSC-SNYZSRNZSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Displacement of [3H]-diprenorphine from human kappa-type opioid receptor expressed in CHO cell membranes incubated for 1 hr in shaker by liquid scintillation counting method
Measurement: Ki = 390 nM (pChEMBL 6.409999847412109)
Descriptors: MW 446.59, ALogP 4.57, HBA 4, HBD 3, PSA 84.58, QED 0.43
Compound (SMILES): CSCC[C@H](NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)CNC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@@H]1CCCN1C(=O)CNC(=O)[C@@H]1CCC(=O)N1)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](Cc1ccccc1)C(N)=O
InChIKey: GKDWRERMBNGKCZ-RNXBIMIWSA-N
Target: Cholecystokinin receptor type A (SINGLE PROTEIN), Homo sapiens
UniProt: P32238
Assay: Agonist activity at human CCK1R expressed in human 1321N1 cells assessed as IP1 accumulation after 1 hr by HTRF assay
Measurement: EC50 = 269.15 nM (pChEMBL 6.570000171661377)
Descriptors: MW 2098.24
Compound (SMILES): O=C1NC(=O)C2(CCCc3ccccc32)N1S(=O)(=O)c1ccc(F)cc1
InChIKey: HFXHDSJNJKVJNB-UHFFFAOYSA-N
Target: Aldo-keto reductase family 1 member B1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P07943
Assay: Inhibition of ALR2 in rat sciatic nerve assessed as reduction in sorbitol accumulation incubated for 3 hrs in presence of 28 mM glucose by gas chromatographic analysis
Measurement: IC50 = 7370 nM (pChEMBL 5.130000114440918)
Descriptors: MW 374.39, ALogP 2.3, HBA 4, HBD 1, PSA 83.55, QED 0.82
Compound (SMILES): COc1ccc2c3c1O[C@H]1[C@@]4(OC)CC[C@@]5(C[C@@H]4c4ccc(N)cc4)[C@@H](C2)N(CC2CC2)CC[C@]315
InChIKey: XNIHSNZTKXNOGK-CLRRHZRJSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Displacement of [3H]U69593 from human KOR expressed in CHO cell membranes incubated for 30 mins by liquid scintillation counting
Measurement: Ki = 6.4 nM (pChEMBL 8.1899995803833)
Descriptors: MW 472.63, ALogP 4.67, HBA 5, HBD 1, PSA 56.95, QED 0.64
Compound (SMILES): N#CN1CC[C@@H](NC(=O)c2ccc(-c3ccccn3)cn2)C1
InChIKey: FJAKNGKONIPPPQ-CYBMUJFWSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 30 (SINGLE PROTEIN), Homo sapiens
UniProt: Q70CQ3
Assay: Biochemical Fluorescence Intensity Assay: Dilution plates were prepared at 21 times the final concentration (2100 μM for a final concentration of 100 μM) in 50% DMSO in a 96-well polypropylene V-bottom plate (Greiner #651201). A typical 8-point dilution series would be 100, 30, 10, 3, 1, 0.3, 0.1, 0.03 μM final. Reactions were performed in duplicate in black 384 well plates (small volume, Greiner 784076) in a final reaction volume of 21 μl.Either 1 μl of 50% DMSO or diluted compound was added to the plate. USP30 was diluted in reaction buffer (40 mM Tris, pH 7.5, 0.005% Tween 20, 0.5 mg/ml BSA, 5 mMbeta-mercaptoethanol) to the equivalent of 0.001 μl/well and 10 μl of diluted USP30 was added to the compound. Enzyme and compound were incubated for 30 min at room temp. Reactions were initiated by the addition of Ubiquitin-Rhodamine 110 (U-555; Boston Biochem) at a final concentration of 100 nM. Reactions were read immediately after addition of substrate and following a 2 h incubation at room temperature. Readings were performed on a Pherastar Plus (BMG Labtech). λ Excitation 487 nm; λ Emission 535 nm.
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 293.33, ALogP 1.43, HBA 5, HBD 1, PSA 81.91, QED 0.87
Compound (SMILES): Cc1cc(OCCCc2c3n(c4c(-c5c(C)nn(C)c5C)c(Cl)ccc24)[C@@H](C)CN(Cc2ccc(C(=O)O)cc2)C3=O)cc(C)c1Cl
InChIKey: LGHFURZJMBZNQG-QFIPXVFZSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Fluorescence Polarization Anisotropy Competition Assay: Compound affinity was measured using a fluorescence polarization anisotropy competition assay. Anisotropy measurements were carried out in 384-well, black, flat-bottom plates (Greiner Bio-one, Monroe, N.C., USA). The assay was run using either a fluorescein isothiocyanate-labeled BH3 peptide derived from Bak (FITC-AHx-GQVGRQLAIIGDDINR-NH2) or a fluorescein isothiocyanate-labeled BH3 peptide derived from Bim (FITC-AHx-EARIAQELRRIGDEFNETYTR-NH2) that were purchased from GenScript (Piscataway, N.J.) at >95% purity and used without further purification. 10 nM FITC-Bak peptide and 15 nM recombinant Mcl-1 (residues 172-327) were added to assay buffer (3 mM dithiothreitol, 50 mM NaCl, 20 mM Tris, pH 7.5). The Bim based assay was run with 1 nM FITC-Bim peptide and 1.5 nM recombinant Mcl-1 (residues 172-327) added to assay buffer (20 mM TRIS pH 7.5, 50 mM NaCl, 3 mM DTT, 0.01% CHAPS). For selectivity assays, 40 nM Bcl-2 (residues 1-207A96T,G110R, Î35-91, replaced with Bcl-xL35-50) or 4 nM Bcl-xL (residues 1-209, loop 45-86 deleted) were incubated with 10 nM FITC-Bak in assay buffer.
Measurement: Ki < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 673.64, ALogP 8.51, HBA 6, HBD 1, PSA 89.59, QED 0.16
Compound (SMILES): Cc1nc(-c2ccccc2)sc1C(=O)N1CCOCC1
InChIKey: JLBMVGMULMUXNW-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Agonist activity at N-terminal Flag epitope tagged CB2 (unknown origin) expressed in HTLA cells assessed as increase of beta-arrestin recruitment by Tango assay
Measurement: EC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 288.37, ALogP 2.59, HBA 4, HBD 0, PSA 42.43, QED 0.85
Compound (SMILES): O=c1c(-c2ccccc2)c2ccccn2c(=O)n1CCCCN1CCCC(c2c[nH]c3ccccc23)C1
InChIKey: BLVMGNGXAWHZQW-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H]-LSD from recombinant human 5HT6 receptor expressed in HEK293 cells measured after 1 hr by microbeta scintillation counting analysis
Measurement: Ki = 435 nM (pChEMBL 6.360000133514404)
Descriptors: MW 492.62, ALogP 5.27, HBA 5, HBD 1, PSA 62.51, QED 0.32
Compound (SMILES): CCOC(=O)N1CCN(C(=O)[C@H](Cc2cccc(C(=N)N)c2)NS(=O)(=O)c2c(C(C)C)cc(C(C)C)cc2C(C)C)CC1.Cl
InChIKey: FMHIVIJVVYYSRN-JCOPYZAKSA-N
Target: Coagulation factor X (SINGLE PROTEIN), Homo sapiens
UniProt: P00742
Assay: Inhibition of factor 10a (unknown origin)
Measurement: Ki = 980 nM (pChEMBL 6.010000228881836)
Descriptors: MW 613.83, ALogP 4.53, HBA 6, HBD 3, PSA 145.89, QED 0.25
Compound (SMILES): CCC[C@@H]1NC[C@@H](O)[C@H](O)[C@H]1C(=O)O
InChIKey: FBBVTGIVZAYALR-YWIQKCBGSA-N
Target: Beta-glucuronidase (SINGLE PROTEIN), Escherichia coli (strain K12)
UniProt: P05804
Assay: Inhibition of Escherichia coli GUS pre-incubated for 5 to 30 mins before 4-methylumbelliferone beta-D-glucuronide substrate addition at pH 6.7
Measurement: Ki = 73.7 nM (pChEMBL 7.130000114440918)
Descriptors: MW 203.24, ALogP -0.82, HBA 4, HBD 4, PSA 89.79, QED 0.48
Compound (SMILES): C[C@@H]1O[C@H](CNC(=O)/C=C/c2ccccc2)[C@@H](O)[C@H](O)[C@@H]1O
InChIKey: NJLORPYFUUWZNP-NPLZYVICSA-N
Target: Fucose-binding lectin PA-IIL (SINGLE PROTEIN), Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM14847 / LMG 12228 / 1C / PRS 101 / PAO1)
UniProt: Q9HYN5
Assay: Binding affinity to Pseudomonas aeruginosa PAO1 LecB assessed as dissociation constant by isothermal titration calorimetry
Measurement: Kd = 3090 nM (pChEMBL 5.510000228881836)
Descriptors: MW 307.35, ALogP -0.31, HBA 5, HBD 4, PSA 99.02, QED 0.57
Compound (SMILES): O=C(Nc1cc2cc[nH]c2cn1)c1ccc(Cl)c(F)c1
InChIKey: VBEFQDCTDAFHBI-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Rattus norvegicus
UniProt: P19643
Assay: Inhibition of Sprague-Dawley rat liver MAO-B using p-tyramine as substrate preincubated for 15 mins and measured after 45 mins by resorufin-based fluorescence assay
Measurement: IC50 = 574 nM (pChEMBL 6.239999771118164)
Descriptors: MW 289.7, ALogP 3.61, HBA 2, HBD 2, PSA 57.78, QED 0.76
Compound (SMILES): COc1ccccc1N1CCN(C[C@H]2OCCO[C@@H]2c2ccccc2)CC1
InChIKey: GWNABLDNNOYTMC-FGZHOGPDSA-N
Target: Alpha-1D adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P25100
Assay: Displacement of [3H]Prazosin from human recombinant alpha 1D adrenergic receptor expressed in CHO cells incubated for 30 mins by radioligand competition binding assay
Measurement: Ki = 53.7 nM (pChEMBL 7.269999980926514)
Descriptors: MW 368.48, ALogP 2.97, HBA 5, HBD 0, PSA 34.17, QED 0.81
Compound (SMILES): Cc1cnc2c(N)c(C(=O)NCCc3c(F)cc(N4CC5CCC(C4)N5)cc3F)sc2n1
InChIKey: MQLOUMARQGGGQC-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 28 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RU2
Assay: Inhibition of TEV-cleavable hexa-histidine tagged USP28 (1 to 1077 residues) (unknown origin) using ubiquitin-rhodamine 110 as substrate preincubated for 30 mins followed by substrate addition and measured after 20 mins by fluorescence based assay
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 458.54, ALogP 2.77, HBA 7, HBD 3, PSA 96.17, QED 0.54
Compound (SMILES): CNc1nc(Nc2cnn(CCCCCCC(=O)NO)c2)ncc1Cl
InChIKey: YCNKBPYTVIXQKU-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of HDAC6 (unknown origin) using Boc-Lys(acetyl)-AMC as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by fluorescence assay
Measurement: IC50 = 29 nM (pChEMBL 7.539999961853027)
Descriptors: MW 367.84, ALogP 2.57, HBA 8, HBD 4, PSA 116.99, QED 0.29
Compound (SMILES): NC1=NN(c2ccc(Cl)c(Cl)c2)CC1
InChIKey: CRLRIZCQVMRUTK-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ABL1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00519
Assay: Induction of human c-ABL phosphorylation at Y245/Y412 residues in bacmam-induced HEK-MSR2 cell lysates by in-cell Western blot analysis
Measurement: EC50 = 12589.25 nM (pChEMBL 4.900000095367432)
Descriptors: MW 230.1, ALogP 2.48, HBA 3, HBD 1, PSA 41.62, QED 0.8
Compound (SMILES): Cn1c(=O)c2c(nc3n2CCN([C@@H]2CCCc4ccccc42)C3)n(C)c1=O
InChIKey: GEMWFQCNZGPNFF-OAHLLOKOSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of recombinant human MAO-A expressed in baculovirus infected BTI insect cells preincubated for 30 mins followed by addition of p-tyramine as substrate measured over 45 mins by Amplex Red MAO assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 365.44, ALogP 1.33, HBA 7, HBD 0, PSA 65.06, QED 0.65
Compound (SMILES): CC(C)N1CCN(c2ccc(/C(=C(/CCCO)c3ccccc3)c3cccc(O)c3)cc2)CC1.Cl.Cl
InChIKey: VREKGOHYUPVQSX-NFOZGECASA-N
Target: Estrogen-related receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P62508
Assay: Binding affinity to GST-tagged ERRgamma LBD (unknown origin) using fluorescein-conjugated coactivator PGC-1alpha incubated for 1 hr by TR-FRET assay
Measurement: IC50 = 35 nM (pChEMBL 7.460000038146973)
Descriptors: MW 456.63, ALogP 5.65, HBA 4, HBD 2, PSA 46.94, QED 0.43
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](C)N)[C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(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)N[C@@H](CCCCNC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCCCCCC(=O)O)C(=O)O)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)[C@@H](C)O
InChIKey: XYWRQGXTNVPXDN-FLAUDIHOSA-N
Target: Amylin receptor AMY3; CALCR/RAMP3 (PROTEIN COMPLEX), Homo sapiens
UniProt: O60896
Assay: Agonist activity at human amylin receptor expressed in BHK570 cells co-expressing RAMP3 assessed as increase in intracellular cAMP concentration incubated for 3 hrs in presence of 10% FBS by CRE luciferase reporter gene assay
Measurement: EC50 = 0.14 nM (pChEMBL 9.850000381469727)
Descriptors: MW 3675.25
Compound (SMILES): Cc1cc(OCCCc2c3n(c4c(-c5c(C)nn(C)c5C)c(Cl)ccc24)[C@@H](C)CNC3=O)cc(C)c1Cl
InChIKey: QEURJQLBXNSJGE-KRWDZBQOSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Fluorescence Polarization Anisotropy Competition Assay: Compound affinity was measured using a fluorescence polarization anisotropy competition assay. Anisotropy measurements were carried out in 384-well, black, flat-bottom plates (Greiner Bio-one, Monroe, N.C., USA). The assay was run using either a fluorescein isothiocyanate-labeled BH3 peptide derived from Bak (FITC-AHx-GQVGRQLAIIGDDINR-NH2) or a fluorescein isothiocyanate-labeled BH3 peptide derived from Bim (FITC-AHx-EARIAQELRRIGDEFNETYTR-NH2) that were purchased from GenScript (Piscataway, N.J.) at >95% purity and used without further purification. 10 nM FITC-Bak peptide and 15 nM recombinant Mcl-1 (residues 172-327) were added to assay buffer (3 mM dithiothreitol, 50 mM NaCl, 20 mM Tris, pH 7.5). The Bim based assay was run with 1 nM FITC-Bim peptide and 1.5 nM recombinant Mcl-1 (residues 172-327) added to assay buffer (20 mM TRIS pH 7.5, 50 mM NaCl, 3 mM DTT, 0.01% CHAPS). For selectivity assays, 40 nM Bcl-2 (residues 1-207A96T,G110R, Î35-91, replaced with Bcl-xL35-50) or 4 nM Bcl-xL (residues 1-209, loop 45-86 deleted) were incubated with 10 nM FITC-Bak in assay buffer.
Measurement: Ki < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 539.51, ALogP 6.9, HBA 5, HBD 1, PSA 61.08, QED 0.27
Compound (SMILES): CCc1sc2ncnc(N[C@H](Cc3ccccc3)C(=O)O)c2c1-c1ccc(OCCN2CCN(C)CC2)c(Cl)c1C
InChIKey: IYVGNFZJSMBRMP-HSZRJFAPSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of human CYP2D6
Measurement: IC50 >= 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 594.18, ALogP 5.62, HBA 8, HBD 2, PSA 90.82, QED 0.23
Compound (SMILES): Cc1c(C#N)cccc1[C@@H]1CN2CCN(C(=O)Cc3ccc(-n4cnnn4)cc3)C[C@H]2CO1
InChIKey: VRAKMPVBHWYNGD-GMAHTHKFSA-N
Target: ATP-sensitive inward rectifier potassium channel 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P48048
Assay: Electrophysiology Assay: Block of Kir1.1 (ROMK1) currents was examined by whole cell voltage clamp (Hamill et. al. Pfluegers Archives 391:85-100 (1981)) using the IonWorks Quattro automated electrophysiology platform (Molecular Devices, Sunnyvale, Calif.). Chinese hamster ovary cells stably expressing Kir1.1 channels were maintained in T-75 flasks in cell culture media in a humidified 10% CO2 incubator at 37° C. Prior to an experiment, Kir1.1 expression was induced by overnight incubation with 1 mM sodium butyrate. On the day of the experiment, cells were dissociated with 2.5 mL of Versene (Invitrogen 15040-066) for approximately 6 min at 37° C. and suspended in 10 mL of bath solution containing (in mM): 150 NaCl, 10 KCl, 2.7 CaCl2, 0.5 MgCl2, 5 HEPES, pH 7.4. After centrifugation, the cell pellet was resuspended in approximately 4.0 mL of bath solution and placed in the IonWorks instrument. The intracellular solution consisted of (in mM): 80 K gluconate, 40 KCl, 20 KF, 3.2 MgCl2, 3 EGTA, 5 Hepes, pH 7.4. Electrical access to the cytoplasm was achieved by perforation in 0.13 mg/mL amphotericin B for 4 min. Amphotericin B (Sigma A-4888) was prepared as a 40 mg/mL solution in DMSO. Voltage protocols and current recordings were performed using the IonWorks HT software/hardware system. Currents were sampled at 1 kHz. No correction for liquid junction potentials was used. The test pulse, consisting of a 100 ms step to 0 mV from a holding potential of −70 mV, followed by a 100 ms voltage ramp from −70 mV to +70 mV, was applied before and after a 6 min compound incubation period. Test compounds were prepared by diluting DMSO stock solutions into the bath solution at 3× the final concentration and placed in the instrument in 96-well polypropylene plates.
Measurement: IC50 = 90 nM (pChEMBL 7.050000190734863)
Descriptors: MW 443.51, ALogP 1.67, HBA 8, HBD 0, PSA 100.17, QED 0.6
Compound (SMILES): Cc1ccc(-n2nc(C(=O)N3C[C@@H](C)N[C@@H](C)C3)nc2-c2ccc3c(c2)N(C2CCCC2)[C@H](C)C(=O)N3C)cc1
InChIKey: RCVYHIHRLZXFNV-BHIFYINESA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to His6-tagged human BRD4 bromodomain 1 expressed in Escherichia coli BL21(DE3) )-codon plus-RIL cells by isothermal titration calorimetric method
Measurement: Kd = 15.2 nM (pChEMBL 7.820000171661377)
Descriptors: MW 541.7, ALogP 4.18, HBA 7, HBD 1, PSA 86.6, QED 0.53
Compound (SMILES): Cc1ccc2nc(CSc3nnc(NC(=O)Nc4cccc(C)c4C)s3)cc(=O)n2c1
InChIKey: LXDDVLXCLMFJMU-UHFFFAOYSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: Inhibition of human full length TRKA expressed in CHO cells assessed as decrease in NGF-induced Ca2+ flux by Calcium 4 dye-based FLIPR TETRA assay
Measurement: IC50 = 20000 nM (pChEMBL 4.699999809265137)
Descriptors: MW 452.57, ALogP 4.41, HBA 8, HBD 2, PSA 101.28, QED 0.34
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1ccc(-c2ccccc2)o1)[C@@H](CC)N(C=O)OC(=O)C(C)(C)C
InChIKey: NIWQGPFLQLKRNR-FGZHOGPDSA-N
Target: Tolloid-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43897
Assay: Inhibition of recombinant human TLL1 I156V/N221S/V284A mutant expressed in CHOE1A cells pre-incubated for 10 mins before promyostatin peptide substrate addition and measured after 60 mins by FRET based assay
Measurement: IC50 < 398.11 nM (pChEMBL 6.400000095367432)
Descriptors: MW 513.64, ALogP 4.69, HBA 6, HBD 2, PSA 117.95, QED 0.16
Compound (SMILES): CN(C)c1ccc(C(=O)N(CCCCCC(=O)Nc2cc(F)ccc2N)CC(=O)NCc2ccccc2)cc1
InChIKey: ATAYIUXFFSKHFW-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 Sf9 insect cells using Boc-Lys(epsilon-acetyl)-AMC as substrate incubated for 90 mins by fluorescence assay
Measurement: IC50 = 369 nM (pChEMBL 6.429999828338623)
Descriptors: MW 533.65, ALogP 4.43, HBA 5, HBD 3, PSA 107.77, QED 0.22
Compound (SMILES): CC(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CCCCN)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
InChIKey: ZLAXGRCKZJJOJF-FLJNZOMCSA-N
Target: Muscarinic acetylcholine receptor M3 (SINGLE PROTEIN), Homo sapiens
UniProt: P20309
Assay: Displacement of [3H]-NMS from human muscarinic M3 receptor expressed in CHO-K9 cells after 3 hrs by microbeta2 scintillation counting method
Measurement: Ki = 16.22 nM (pChEMBL 7.789999961853027)
Descriptors: MW 852.09, ALogP 3.6, HBA 10, HBD 6, PSA 192.68, QED 0.09
Compound (SMILES): Cl.NOC(c1ccccc1)c1ccccc1Br
InChIKey: DRBUKXMGMFEVHA-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 2 (SINGLE PROTEIN), Mus musculus
UniProt: Q8R0V5
Assay: Inhibition of mouse IDO2 expressed in human T-REx cells using L-tryptophan as substrate after 20 hrs
Measurement: IC50 = 12300 nM (pChEMBL 4.909999847412109)
Descriptors: MW 278.15, ALogP 3.43, HBA 2, HBD 1, PSA 35.25, QED 0.87
Compound (SMILES): O=C(NCc1cc(F)cc(F)c1)[C@@]1(O)CCN(c2cnc3[nH]ccc3c2)C1=O
InChIKey: DCPZWZZBXOFMHX-IBGZPJMESA-N
Target: Methionine aminopeptidase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P50579
Assay: Inhibition of 5-[(S)-3-(3-Chloro-5-fluoro-benzylcarbamoyl)-3-hydroxy-2-oxopyrrolidin-1-yl]-1H-indole-2-carboxylic Acid (3-Amino-propyl)-amide-Dy647 binding to recombinant full length N-terminal GFP-fused MetAP2 (unknown origin) expressed in HEK293 cells by Cheng-Prusoff equation analysis
Measurement: Ki = 0.9 nM (pChEMBL 9.050000190734863)
Descriptors: MW 386.36, ALogP 1.63, HBA 4, HBD 3, PSA 98.32, QED 0.59