lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): Cn1cc(-c2ccc(NC(=O)[C@H](NCCc3ccc(C#N)cc3)c3ccccc3)cc2)cn1
InChIKey: PPUQKDMNCLOBAH-AREMUKBSSA-N
Target: Histone acetyltransferase p300 (SINGLE PROTEIN), Homo sapiens
UniProt: Q09472
Assay: Biochemical Assay: The full length p300 SPA assay was run following the same protocol as p300 HAT SPA assay, but used 6 nM purified full length p300 (purchased from Active Motif) in place of the purified p300-HAT domain.Select compounds were also evaluated in a H3K18Ac MSD cellular assay that measures the ability of compounds to inhibit the the acetylation of chromatin at H3K18, a process catalyzed by p300 and CBP. In a typical experiment the p300 HAT inhibitory activity inside cells of the compounds described herein was determined in accordance with the following experimental method. 20 k HCT-116 cells per well are plated in 75 μL RPMI+10% FBS media the night before treatment. Compounds plated in DMSO at 4× final concentration are resuspended in 30 μL RPMI+10% FBS, then 25 μL is combined with corresponding wells containing cells. Treated cells are incubated for 2 hr at 37° C., then lysed in 500 μL final volume and frozen at −80° C. MSD plates (Meso Scale Discovery) are coated overnight at 4° C. with 60 μL 1:500 α-total histone antibody (Millipore MAB3422) in PBS. Plates are then blocked with 5% BSA in TBST shaking at RT for 1 hr, washed, and 30 μL lysate added to each well for 2 hr shaking at RT. Plates are washed and 25 μL 1:216 α-H3K18ac antibody (CST 9675) in PBS added, then incubated for 1 hr shaking at RT. Plates are washed again, then 25 μL 1:1000 Sulfo-Tag goat α-rabbit antibody (Meso Scale Discovery R32Ab-1) in PBS is added for 1 hr shaking at RT. Plates are washed once more, then 150 μL 1× Read Buffer (MSD #R92TD-3) is added to all wells and read on MSD SECTOR Imager 2400 using the conventional read setup.
Measurement: IC50 = 130 nM (pChEMBL 6.889999866485596)
Descriptors: MW 435.53, ALogP 4.47, HBA 5, HBD 2, PSA 82.74, QED 0.43
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CCC[C@@H](Nc3ncc(CCc4ncc(C(C)(C)C)o4)s3)C2)cc1
InChIKey: NXZXWOASWYOLBZ-HXUWFJFHSA-N
Target: CDK2/Cyclin A1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P78396
Assay: Inhibition of recombinant human full-length N-terminal GST-tagged CDK2/cyclinA1 expressed in baculovirus infected Sf9 insect cells using FRET-labeled Ser/Thr 12 as substrate measured after 1 hr by Z'-lyte assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 507.66, ALogP 5.06, HBA 7, HBD 2, PSA 100.36, QED 0.41
Compound (SMILES): CC(C)(CCc1cccc(O)c1)NCC(O)c1cc(O)cc2c1OCC(=O)N2.Cl
InChIKey: QZZQNYSUVCVWOK-UHFFFAOYSA-N
Target: Beta-1 adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08588
Assay: Agonist activity at human beta1 adrenoreceptor overexpressed in human HEK293 cells assessed as cAMP accumulation incubated for 60 mins by HTRF assay
Measurement: EC50 = 4.169 nM (pChEMBL 8.380000114440918)
Descriptors: MW 386.45, ALogP 2.46, HBA 6, HBD 5, PSA 111.05, QED 0.5
Compound (SMILES): O=C([C@H]1Cc2cc(Cl)cc(-c3ccnc4ccsc34)c2O1)N1CCNCC1
InChIKey: SSIWAASKJNDWDE-QGZVFWFLSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O94782
Assay: Inhibition of His6-tagged human USP1 expressed in insect Sf21 cells coexpressing untagged UAF1 assessed as cleavage of Ubiquitin-Rhodamine110-glycine to Ubiquitin and Rhodamine110-glycine using Ubiquitin-Rhodamine110-glycine as substrate by fluorescence based analysis
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 399.9, ALogP 3.35, HBA 5, HBD 1, PSA 54.46, QED 0.72
Compound (SMILES): O=C(/C=C/c1cccc(-c2ccccc2)c1)C(=O)NCCc1ccccc1
InChIKey: SLLJIOAKGLRQOP-CCEZHUSRSA-N
Target: Phospholipase A and acyltransferase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P53816
Assay: Inhibition of full-length C-terminal FLAG-tagged human PLAAT3 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis
Measurement: IC50 = 3162.28 nM (pChEMBL 5.5)
Descriptors: MW 355.44, ALogP 4.29, HBA 2, HBD 1, PSA 46.17, QED 0.51
Compound (SMILES): CCCCNC(=O)[C@@H]1C[C@H]1[C@]12CN(c3ncccn3)C[C@H]1CSC(N)=N2
InChIKey: QJJBLKYNQOSIHJ-LWGWVAHUSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Inhibition of human BACE2
Measurement: IC50 = 44 nM (pChEMBL 7.360000133514404)
Descriptors: MW 374.51, ALogP 1.27, HBA 7, HBD 2, PSA 96.5, QED 0.73
Compound (SMILES): Cc1c(-c2ccccc2)cccc1-c1nc2c(s1)CNCC2
InChIKey: DISXBCWMOVBSKF-UHFFFAOYSA-N
Target: Programmed cell death protein 1/Programmed cell death 1 ligand 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: Q9NZQ7
Assay: Antagonist activity at human PD1/PD-L1
Measurement: IC50 <= 100 nM (pChEMBL 7)
Descriptors: MW 306.43, ALogP 4.43, HBA 3, HBD 1, PSA 24.92, QED 0.76
Compound (SMILES): CC(C)c1onc(-c2c(Cl)cccc2Cl)c1COc1ccc(COc2ccc(CC(=O)O)cc2)cc1
InChIKey: PBMMUBYHOOPFPQ-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor delta (SINGLE PROTEIN), Homo sapiens
UniProt: Q03181
Assay: Activation of human PPAR-delta LBD expressed in HEK293T cells assessed as induction of receptor activation incubated for 12 to 14 hrs by luciferase reporter gene assay
Measurement: EC50 = 3100 nM (pChEMBL 5.510000228881836)
Descriptors: MW 526.42, ALogP 7.56, HBA 5, HBD 1, PSA 81.79, QED 0.23
Compound (SMILES): C/C=C\Cc1c(NCc2ccccc2N2CCN(C)CC2)cnn(C)c1=O
InChIKey: SDZLXWXQFRHLMT-PLNGDYQASA-N
Target: Peregrin (SINGLE PROTEIN), Homo sapiens
UniProt: P55201
Assay: Binding affinity to human partial length BRPF1 (E627 to G740 residues) expressed in bacterial expression system by BROMOscan assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 367.5, ALogP 2.26, HBA 6, HBD 1, PSA 53.4, QED 0.79
Compound (SMILES): O=C(Nc1ccccc1-c1ccccc1)OCC1CCNCC1
InChIKey: PEOXDNXZHVLPEP-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M1 (SINGLE PROTEIN), Homo sapiens
UniProt: P11229
Assay: Displacement of [3H]N-methylscopolamine from human muscarinic M1 receptor transiently expressed in HEK293T cell membranes incubated for 1 hr by scintillation counting method
Measurement: Ki = 1.8 nM (pChEMBL 8.739999771118164)
Descriptors: MW 310.4, ALogP 3.9, HBA 3, HBD 2, PSA 50.36, QED 0.9
Compound (SMILES): Oc1ccc2c3c1O[C@H]1c4ncc(-c5ccc(F)cc5F)cc4C[C@@]4(OCCCc5ccccc5)[C@@H](C2)N(CC2CC2)CC[C@]314
InChIKey: KZQJKMAPRMFNGT-RJKGWOMYSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Displacement of [3H]-diprenorphine from human delta opioid receptor expressed in CHO cell membranes incubated for 1 hr by competition radioligand binding assay
Measurement: Ki = 53.7 nM (pChEMBL 7.269999980926514)
Descriptors: MW 606.71, ALogP 7.09, HBA 5, HBD 1, PSA 54.82, QED 0.22
Compound (SMILES): COCc1ccncc1-c1ccc2[nH]nc(C(=O)NCC3CCOCC3)c2c1
InChIKey: GTBVWLAMASZLOC-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in CHOK1 cells assessed as reduction in tail current by measuring tail current amplitude measured after deploarization to +20 mV for 2s followed by 1s pulse to -40 mV by whole cell patch clamp assay
Measurement: IC50 = 47100 nM (pChEMBL 4.329999923706055)
Descriptors: MW 380.45, ALogP 2.93, HBA 5, HBD 2, PSA 89.13, QED 0.69
Compound (SMILES): COc1cc(C(=O)N[C@@H]2C[C@H]3CCC[C@@H](C2)N3CC(=O)Nc2c(Cl)cccc2Cl)cc(OC)c1OC
InChIKey: JSLIPMNVBDSXEB-NNZMDNLPSA-N
Target: C-X-C chemokine receptor type 6 (SINGLE PROTEIN), Homo sapiens
UniProt: O00574
Assay: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of forskolin-induced cAMP accumulation by DiscoveRx cell based assay
Measurement: IC50 > 40000 nM (pChEMBL 4.3979997634887695)
Descriptors: MW 536.46, ALogP 4.77, HBA 6, HBD 2, PSA 89.13, QED 0.51
Compound (SMILES): CCCNC(=O)[C@@H]1C[C@H]1[C@]12COC[C@H]1CSC(N)=N2
InChIKey: AZMITPYXDXQIOX-WTBMIXGQSA-N
Target: Beta-secretase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Z0
Assay: Inhibition of human BACE2
Measurement: IC50 = 24600 nM (pChEMBL 4.610000133514404)
Descriptors: MW 283.4, ALogP 0.6, HBA 5, HBD 2, PSA 76.71, QED 0.79
Compound (SMILES): COc1cc2c3c(c1OC1CC1)-c1cc(N)ccc1CC3N(C)CC2
InChIKey: USOMZJJKRPELBV-UHFFFAOYSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Binding affinity to human D1 receptor
Measurement: Ki = 1111 nM (pChEMBL 5.949999809265137)
Descriptors: MW 336.44, ALogP 3.57, HBA 4, HBD 1, PSA 47.72, QED 0.87
Compound (SMILES): O=c1n(CCCCN2CCN(c3cccc4sccc34)CC2)nc2c(Cl)cccn12
InChIKey: INWVSVHMMAMJRR-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Agonist activity at 5HT1A receptor (unknown origin) by calcium-dye based FLIPR assay
Measurement: EC50 = 12.1 nM (pChEMBL 7.920000076293945)
Descriptors: MW 441.99, ALogP 3.97, HBA 7, HBD 0, PSA 45.78, QED 0.42
Compound (SMILES): COc1cccc(-c2ccc(COC3CN(C#N)C3)c(OC)c2)c1
InChIKey: WNEHLKSOWWIADC-UHFFFAOYSA-N
Target: N-acylethanolamine-hydrolyzing acid amidase (SINGLE PROTEIN), Homo sapiens
UniProt: Q02083
Assay: Inhibition Assay: In order to have an assay method more conducive to high-throughput screening than those published for measuring the NAE hydrolyzing activity of NAAA, we developed the fluorogenic PEA analog N-(4-methyl coumarin)palmitamide (PAMCA), which is hydrolyzed to fluorescent 7-amino-4-methyl coumarin (AMC) and palmitic acid. For three point concentration inhibition assays with hNAAA the following procedure is used. Purified activated NAAA (final concentration of 0.25 μg/mL) is incubated in assay buffer (100 mM citrate-phosphate buffer, pH 4.5, 3 mM DTT, 0.1% Triton X-100, 0.05% BSA, and 150 mM NaCl) made up to a total volume of 180 μL, followed by addition of the compound dissolved in 10 μL DMSO (along with DMSO neat for the control sample) with the final concentrations for each compound of 100, 10, and 1 μM, in triplicate on a 96 well plate. These samples are allowed to incubate for 15 min at room temperature and then 10 μL of a PAMCA stock solution in DMSO (final PAMCA concentration [5 μM]) was added. After 5 minutes of agitation on a shaking plate, the reaction is allowed to proceed at 37° C. for 120 minutes, with fluorescence readings taken every 10 minutes at a wavelength of 460 nm (using an excitation wavelength of 360 nm) on a Synergy HT Plate Reader using Gen5 software from Bio-Tek. The enzyme activity is calculated by converting the relative fluorescence units to AMC formed, using a standard curve of AMC. For compounds that inhibit hNAAA in range IC50 <1 μM full inhibition curves using eight different concentrations of inhibitor (8 point assay) are generated. The assay procedure used is the same as the three point assay. For ostensibly covalent compounds (as observed by a significant decrease in the slope of a plot of fluorescence vs. time in three point screen) samples are allowed to incubate for 2 hours at 37° C., instead of 15 minutes, before addition of 10 μL of a PAMCA stock solution in DMSO for a final PAMCA concentration of 5 μM. After 5 minutes of agitation on a shaking plate, the reaction is allowed to proceed at 37° C. for 120 minutes Inhibition constants are calculated using pro Fit software (Quantum Soft, Uetikon am See, Switzerland) and a Levenberg-Marquardt algorithm.
Measurement: IC50 = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 324.38, ALogP 3.05, HBA 5, HBD 0, PSA 54.72, QED 0.76
Compound (SMILES): Cc1cc(F)c(-c2ncc[nH]2)cc1NC(=O)c1ccc(OCc2ccccn2)cc1
InChIKey: PSQRFWCESROCRS-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 402.43, ALogP 4.75, HBA 4, HBD 2, PSA 79.9, QED 0.49
Compound (SMILES): CN(C)c1ccc2c(c1)-c1cccc3c1C(C2)N(C)CC3
InChIKey: KKEZUZPTEQWDCZ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]-Ketanserin from 5-HT2A receptor (unknown origin) incubated for 90 mins by microbeta counting method
Measurement: Ki = 566 nM (pChEMBL 6.25)
Descriptors: MW 278.4, ALogP 3.5, HBA 2, HBD 0, PSA 6.48, QED 0.79
Compound (SMILES): COc1cc(/C=C/C(=O)/C=C(O)/C=C/c2ccc(OC(C)C(N)=O)c(OC)c2)ccc1OC(C)C(N)=O
InChIKey: FRVLZLOAXPRLEG-OEHUVLJNSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of HDAC2 (unknown origin)
Measurement: Ki = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 510.54, ALogP 2.95, HBA 8, HBD 3, PSA 160.4, QED 0.21
Compound (SMILES): C=CC(=O)N1CC=C(c2cccc3nc(NC(=O)C4CC4)nn23)CC1
InChIKey: UTDWZTRWAKZXLC-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of JAK2 (unknown origin) in presence of ATP at Km concentration by caliper assay
Measurement: IC50 = 424 nM (pChEMBL 6.369999885559082)
Descriptors: MW 337.38, ALogP 1.88, HBA 5, HBD 1, PSA 79.6, QED 0.86
Compound (SMILES): OC(Cc1ccc(C(F)(F)F)cc1)CN1CCN(CCSC(c2ccc(F)cc2)c2ccc(F)cc2)CC1
InChIKey: LAEICYGPBHBQPM-UHFFFAOYSA-N
Target: Sodium-dependent serotonin transporter (SINGLE PROTEIN), Rattus norvegicus
UniProt: P31652
Assay: Displacement of [3H]citalopram from SERT in Sprague-Dawley rat midbrain membranes incubated for 60 mins by microbeta scintillation counting method
Measurement: Ki = 4480 nM (pChEMBL 5.349999904632568)
Descriptors: MW 550.64, ALogP 6.03, HBA 4, HBD 1, PSA 26.71, QED 0.31
Compound (SMILES): COc1cc(C(=O)N[C@@H]2C[C@H]3CCC[C@@H](C2)N3Cc2nc3c(OC)cccc3s2)cc(OC)c1OC
InChIKey: DAFZGCMXOSWKOV-LDLYASANSA-N
Target: C-X-C chemokine receptor type 6 (SINGLE PROTEIN), Homo sapiens
UniProt: O00574
Assay: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of forskolin-induced cAMP accumulation by DiscoveRx cell based assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 511.64, ALogP 4.65, HBA 8, HBD 1, PSA 82.15, QED 0.47
Compound (SMILES): NC1=N[C@@]2(c3cc(NC(=O)c4cnc(OCF)cn4)ccc3F)CO[C@@H](CF)C[C@H]2CC1(F)F
InChIKey: YTDOAMKMBQFAAC-SCLGINMFSA-N
Target: Beta-secretase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P56817
Assay: Inhibition of BACE1 (unknown origin) assessed as reduction in Abeta42 level by cell based assay
Measurement: IC50 = 4.8 nM (pChEMBL 8.319999694824219)
Descriptors: MW 485.41, ALogP 3.14, HBA 7, HBD 2, PSA 111.72, QED 0.61
Compound (SMILES): CC(=O)c1c(C)c2cnc(Nc3ccc(N4CCN(CCOCCOCCNC(=O)CNc5cccc6c5C(=O)N(C5CCC(=O)NC5=O)C6=O)CC4)cn3)nc2n(C2CCCC2)c1=O
InChIKey: JWNZXWGMBRXMPK-UHFFFAOYSA-N
Target: CDK6/cyclin D3 (PROTEIN COMPLEX), Homo sapiens
UniProt: P30281
Assay: Inhibition of human CDK6/cyclin-D3 using RB protein as substrate by [gamma-33P]-ATP assay
Measurement: IC50 = 15.85 nM (pChEMBL 7.800000190734863)
Descriptors: MW 891.99, ALogP 2.34, HBA 17, HBD 4, PSA 239.39, QED 0.06
Compound (SMILES): CN(C)c1cc(O)c(C(=O)O)cc1C#Cc1ccc(NC(=O)C(=O)O)cc1
InChIKey: MRLCNUQXWFAUNN-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: Inhibition of SHP2 (unknown origin) expressed in Escherichia coli BL21 using p-nitrophenyl phosphate as substrate measured after 30 mins by UV-vis spectrophotometric method
Measurement: IC50 = 78500 nM (pChEMBL 4.110000133514404)
Descriptors: MW 368.35, ALogP 1.58, HBA 5, HBD 4, PSA 127.17, QED 0.48
Compound (SMILES): CN(C)CCNC(=O)c1ccc(C2=CC(=O)C=CC2=O)cc1
InChIKey: ZTFVFDYLAWDTHB-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase SETD7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8WTS6
Assay: Binding affinity to SET7 (unknown origin) by SPR analysis
Measurement: Kd = 29000 nM (pChEMBL 4.539999961853027)
Descriptors: MW 298.34, ALogP 1.07, HBA 4, HBD 1, PSA 66.48, QED 0.83
Compound (SMILES): COC(=O)Cn1c(-c2ccncc2)nc2c(C(N)=O)cccc21
InChIKey: JZAKGIXPCUQOIV-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase N2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16513
Assay: Displacement of tracer from PKN2 (unknown origin) by TR-FRET assay
Measurement: Ki = 2690 nM (pChEMBL 5.570000171661377)
Descriptors: MW 310.31, ALogP 1.37, HBA 6, HBD 1, PSA 100.1, QED 0.73
Compound (SMILES): Cc1[nH]nc2[nH]c(=O)cc([C@H]3CC[C@H](N)CC3)c12
InChIKey: QWRZJECYUOVWGI-KYZUINATSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of N-terminal His-tagged human JAK2 catalytic domain incubated for 20 mins in presence of TK substrate-biotin by TR-FRET assay
Measurement: IC50 = 18000 nM (pChEMBL 4.75)
Descriptors: MW 246.31, ALogP 1.54, HBA 3, HBD 3, PSA 87.56, QED 0.71
Compound (SMILES): Cc1[nH]nc2[nH]c(=O)cc(C3CCCCC3)c12
InChIKey: JYQPIKLUCRVQRE-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of N-terminal His-tagged human JAK2 catalytic domain incubated for 20 mins in presence of TK substrate-biotin by TR-FRET assay
Measurement: IC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 231.3, ALogP 2.61, HBA 2, HBD 2, PSA 61.54, QED 0.79
Compound (SMILES): COc1ccc(CCNC(=O)C(=O)CCCc2ccccc2)cc1
InChIKey: NBKGQJDOAOVZTL-UHFFFAOYSA-N
Target: Phospholipase A and acyltransferase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P53816
Assay: Inhibition of full-length C-terminal FLAG-tagged human PLAAT3 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis
Measurement: IC50 = 794.33 nM (pChEMBL 6.099999904632568)
Descriptors: MW 325.41, ALogP 2.95, HBA 3, HBD 1, PSA 55.4, QED 0.72
Compound (SMILES): C[C@@H]1COCCN1c1cc(C2CCOCC2)c2ccnc(-c3ccn[nH]3)c2n1
InChIKey: QCOPMJSHRBYTRK-CQSZACIVSA-N
Target: Serine/threonine-protein kinase ATR (SINGLE PROTEIN), Homo sapiens
UniProt: Q13535
Assay: Time-Resolved Fluorescence Energy Transfer (TR-FRET Tracer A): To determine of binding activity of the test compounds, full-length human ATR protein was expressed and purified together with ATRIP as described above. Furthermore, a fluorescently labelled compound (tracer A) was used as a tracer molecule. Detection of the binding event of the tracer was achieved by time-resolved fluorescence energy transfer (TR-FRET). We used an anti-GST-Terbium antibody (CisBio) that binds to the GST-tag at the N-terminus of ATR-kinase. Excitation of Terbium with 337 nm light results in emission of fluorescent light with 545 nm. In case a tetrameric complex has formed (antiGST-Tb+GST-ATR+Strp2-ATRIP+tracer), part of the energy will be transferred from the Terbium to the fluorophore that itself emits light of 570 nm. Displacement of the fluorescent tracer by a test compound leads to a reduction of the TR-FRET-signal.For the assay 50 nl of a 100-fold concentrated solution of the test compound in DMSO was pipetted into a black low volume 384well microtiter plate (MTP, Greiner Bio-One, Frickenhausen, Germany). To prepare the ATR-working solution, ATR/ATRIP stock solution was diluted in assay buffer [50 mM HEPES (pH 7.0), 10 mM MgCl2, 1 mM DTT, 0.01% (w/v) Igepal, 0.01% (w/v) BSA] to 4.2 nM protein concentration (concentration may vary from lot to lot of protein preparation). AntiGST-Tb antibody was diluted to 4.2 nM. The ATR-working solution was incubated for 30 min at 22° C. prior to dispensing to pre-form the complex of antiGST-Tb+GST-ATR+ATRIP. Then, 3 μl of the ATR-working solution were added to the test compound and the mixture was incubated for 10 min at 22° C. to allow pre-binding of the test compounds to ATR/ATRIP. Then, 2 μl of a 100 nM solution of either tracer A or B in assay buffer were added to the ATR-working solution. The resulting mixture was incubated for 30 min at 22° C. The measurement of the TR-FRET signal was performed in a standard HTRF-compatible MTP reader instrument (e.g. BMG Pherastar) by recording the fluorescence emissions at 545 nm and 570 nm after excitation at 337-350 nm. The ratio between emission at 570 nm divided by emission at 545 nm was calculated to give the well ratio. The experimental data (well ratios) were normalised by the following way: positive control contained ATR-working solution plus either tracer A or B solution (=0% inhibition), the negative control contained all components except GST-ATR/ATRIP (=100% inhibition).
Measurement: IC50 = 13.7 nM (pChEMBL 7.860000133514404)
Descriptors: MW 379.46, ALogP 3.14, HBA 6, HBD 1, PSA 76.16, QED 0.75
Compound (SMILES): C=C(c1ncnc2[nH]ccc12)C1CCCCC1
InChIKey: XZABOWPIWJFDDW-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Lck (SINGLE PROTEIN), Homo sapiens
UniProt: P06239
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human Lck using TK-substrate-biotin as substrate incubated for 60 mins in presence of ATP by fluorescence method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 227.31, ALogP 3.55, HBA 2, HBD 1, PSA 41.57, QED 0.85
Compound (SMILES): O=[N+]([O-])C1C(Cc2c[nH]cn2)NC2(c3ccccc3-c3nc4ccccc4nc32)C1c1ccccn1
InChIKey: FJQQUHPZFRBAME-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of BChE (unknown origin)
Measurement: IC50 = 24250 nM (pChEMBL 4.619999885559082)
Descriptors: MW 475.51, ALogP 3.62, HBA 7, HBD 2, PSA 122.52, QED 0.3
Compound (SMILES): CC(=O)N[C@@H]1CCCc2c1cncc2N1C(=O)c2ccc(Cl)cc2[C@@H]1C1CC1
InChIKey: FVQHFNCQANINKL-CTNGQTDRSA-N
Target: Cytochrome P450 11B1, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P15538
Assay: Inhibition of human CYP11B1 expressed in human renal leiomyoblastoma cells harboring FDXR/FDX using 1-deoxycortisol as substrate by HTRF assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 395.89, ALogP 4.36, HBA 3, HBD 1, PSA 62.3, QED 0.84
Compound (SMILES): Cc1ccc(-c2ncnc(Nc3cccc(C#N)c3)c2O)cc1
InChIKey: QRNSWXQJLICAKS-UHFFFAOYSA-N
Target: Coagulation factor X (SINGLE PROTEIN), Homo sapiens
UniProt: P00742
Assay: Inhibition of activated factor X (unknown origin) using CH3O-CO-D-CHG-Gly-Arg-pNA-AcOH as substrate by fluorescence based assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 302.34, ALogP 3.77, HBA 5, HBD 2, PSA 81.83, QED 0.77
Compound (SMILES): Cc1cn([C@H]2C[C@H](n3cc(CN(Cc4cn([C@H]5C[C@H](n6cc(C)c(=O)[nH]c6=O)O[C@@H]5CO)nn4)c4ccc(S(N)(=O)=O)cc4)nn3)[C@@H](CO)O2)c(=O)[nH]c1=O
InChIKey: XKPQGMYSCDURHS-BQXGFVACSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of human CA1 pre-incubated for 15 mins by stopped flow CO2 hydrase assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 782.8, ALogP -1.92, HBA 19, HBD 5, PSA 293.46, QED 0.09
Compound (SMILES): CC(C)(C#N)c1cc(COc2ccccc2CC(=O)O)cc(-c2ccc3c(c2)[C@H](N)CO3)c1
InChIKey: SRKDCGUSWAONMJ-HSZRJFAPSA-N
Target: Complement factor D (SINGLE PROTEIN), Homo sapiens
UniProt: P00746
Assay: Inhibition of human complement FD by TR-FRET assay
Measurement: IC50 = 40 nM (pChEMBL 7.400000095367432)
Descriptors: MW 442.52, ALogP 4.75, HBA 5, HBD 2, PSA 105.57, QED 0.55
Compound (SMILES): COc1cc(/C=C/C(=O)O)ccc1OCc1cn(-c2ccc([N+](=O)[O-])cc2)nn1
InChIKey: YNGUUJMDZWAULM-YCRREMRBSA-N
Target: Carbonic anhydrase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16790
Assay: Inhibition of human carbonic anhydrase 9 using p-nitrophenyl acetate as substrate by UV-VIS spectrophotometric analysis
Measurement: IC50 = 1450 nM (pChEMBL 5.840000152587891)
Descriptors: MW 396.36, ALogP 2.86, HBA 8, HBD 1, PSA 129.61, QED 0.35
Compound (SMILES): CN(C)C(=O)Oc1cccc(C(O)CNC(C)(C)c2ccccc2)c1.Cl
InChIKey: CVGVEFHYHBBASN-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Equus caballus
UniProt: P81908
Assay: Inhibition of equine serum BChE using S-butyrylthiocholine iodide as substrate preincubated for 60 mins followed by substrate addition and measured for 5 mins by Ellman's method
Measurement: IC50 = 303 nM (pChEMBL 6.519999980926514)
Descriptors: MW 342.44, ALogP 3.31, HBA 4, HBD 2, PSA 61.8, QED 0.85
Compound (SMILES): CNc1nccc(-c2cc(-c3nnc[nH]3)c3nc(C)n(-c4ccnc5c(F)ccc(F)c45)c3c2)c1F
InChIKey: MXSPHGKHZVCALT-UHFFFAOYSA-N
Target: PI3-kinase p110-alpha/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: P42336
Assay: Inhibition of human full length p110alpha/p85alpha using PIP2 as substrate after 30 mins in presence of ATP at 2xKm concentration by TR-FRET assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 486.46, ALogP 5.19, HBA 7, HBD 2, PSA 97.2, QED 0.36
Compound (SMILES): O=C(CCCCCONC(=O)c1cc(I)cc(I)c1I)NO
InChIKey: NTYOIGBEMWFXEN-UHFFFAOYSA-N
Target: Histone deacetylase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P56524
Assay: Inhibition of recombinant human HDAC4
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 643.99, ALogP 3.23, HBA 4, HBD 3, PSA 87.66, QED 0.13
Compound (SMILES): O=C1[C@@H]2[C@H]3CC[C@H](C3)[C@@H]2C(=O)N1CCCCCCN1CCN(c2cccc(C(F)(F)F)c2)CC1
InChIKey: ZTEPHOYXWWHRDM-ZIIYYELXSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Displacement of [3H]8-OH-DPAT from human 5HT1A receptor expressed in HEK293 cell membranes measured after 1 hr by microbeta counting method
Measurement: Ki = 22 nM (pChEMBL 7.659999847412109)
Descriptors: MW 477.57, ALogP 4.42, HBA 4, HBD 0, PSA 43.86, QED 0.41
Compound (SMILES): CC(C)OC(=O)[C@H](C)N[P@](=O)(OC[C@H]1O[C@@H](n2ccc(=O)[nH]c2=O)[C@](Cl)(Br)[C@@H]1O)Oc1ccccc1
InChIKey: HLRNDJIUSMTWTG-VUNLHXCISA-N
Target: RNA-directed RNA polymerase (SINGLE PROTEIN), Hepacivirus hominis
UniProt: O39930
Assay: Inhibition of NS5B polymerase in HCV genotype 1b Con1 infected in human HuH7 replicon cells assessed as inhibition of viral replication after 3 days by luciferase reporter gene assay
Measurement: EC50 = 147 nM (pChEMBL 6.829999923706055)
Descriptors: MW 610.78, ALogP 2.26, HBA 10, HBD 3, PSA 158.18, QED 0.21
Compound (SMILES): Cc1ccccc1Nc1nc(Nc2ccccn2)ncc1Cl
InChIKey: KHCVPLHLJMHVPB-UHFFFAOYSA-N
Target: CDK9/Cyclin K (PROTEIN COMPLEX), Homo sapiens
UniProt: O75909
Assay: Inhibition of recombinant human full-length N-terminal GST-tagged CDK9/cyclinK expressed in baculovirus infected Sf9 insect cells using PDKtide as substrate measured after 120 mins by ADP-glo assay
Measurement: IC50 = 8110 nM (pChEMBL 5.090000152587891)
Descriptors: MW 311.78, ALogP 4.32, HBA 5, HBD 2, PSA 62.73, QED 0.75
Compound (SMILES): CC[C@H](NS(=O)(=O)c1ccc(-c2sc(C(=O)NCC(C)(C)O)nc2C(=O)N2CCC(F)(F)CC2)c(Cl)c1Cl)C(F)(F)F
InChIKey: ODLJZSVWTFUBLM-AWEZNQCLSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Binding affinity to human RORgamma LBD by thermofluor thermal shift assay
Measurement: Kd = 0.33 nM (pChEMBL 9.479999542236328)
Descriptors: MW 681.53, ALogP 5.11, HBA 7, HBD 3, PSA 128.7, QED 0.32
Compound (SMILES): CCc1nc(N)nc(N)c1-c1ccc(-c2cn(CCCCCCCC(=O)NO)nn2)cc1
InChIKey: CGKUMULSZZUXMU-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of human recombinant HDAC6 using fluorogenic HDAC substrate 3 preincubated for 30 mins followed by substrate addition and measured after 15 mins by fluorogenic assay
Measurement: IC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 438.54, ALogP 2.97, HBA 9, HBD 4, PSA 157.86, QED 0.2
Compound (SMILES): O=C(CCc1ccc(Cl)cc1)C(=O)NCCCCc1ccccc1
InChIKey: IIKSZZXCTQEEMT-UHFFFAOYSA-N
Target: Phospholipase A and acyltransferase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P53816
Assay: Inhibition of full-length C-terminal FLAG-tagged human PLAAT3 expressed in HEK293T cell lysate preincubated for 30 mins followed by MB064 addition and measured after 20 mins by SDS-PAGE based ABPP analysis
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 343.85, ALogP 3.98, HBA 2, HBD 1, PSA 46.17, QED 0.55
Compound (SMILES): CC(C)NCCc1c[nH]c2c1C(=O)C(c1cccnc1)=CC2=O
InChIKey: ZKAUYXGXHUMEJM-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IFNgamma-stimulated IDO1 in human HeLa cells
Measurement: EC50 = 2600 nM (pChEMBL 5.579999923706055)
Descriptors: MW 309.37, ALogP 2.41, HBA 4, HBD 2, PSA 74.85, QED 0.89
Compound (SMILES): CC[C@H](NS(=O)(=O)c1ccc(-c2sc(C(=O)NCC(C)(C)O)nc2C(=O)N(CC)CC)c(C(F)F)c1Cl)C(F)(F)F
InChIKey: IMIKQYITCVUQTH-AWEZNQCLSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at human RORgammat LBD by M1H cell based assay
Measurement: IC50 = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 649.1, ALogP 5, HBA 7, HBD 3, PSA 128.7, QED 0.28
Compound (SMILES): C[n+]1cn([C@@H]2O[C@H](COP(=O)(O)S)[C@@H](O)[C@H]2O)c2nc(N)nc([O-])c21
InChIKey: IRIAOLOKILXSNT-KQYNXXCUSA-N
Target: Eukaryotic translation initiation factor 4E (SINGLE PROTEIN), Oryctolagus cuniculus
UniProt: P29338
Assay: Inhibition of eIF4E in rabbit reticulocyte lysate system assessed as reduction in ARCA mRNA cap-dependent translation measured after 60 mins by luciferase reporter gene based luminescence assay
Measurement: IC50 = 52000 nM (pChEMBL 4.28000020980835)
Descriptors: MW 393.32, ALogP -2.42, HBA 10, HBD 5, PSA 179.89, QED 0.21
Compound (SMILES): C=C1C(=O)N[C@H](C)C(=O)N[C@@H](Cc2ccc(OCc3cn(-c4cc5ccc(O)cc5oc4=O)nn3)cc2)C(=O)N[C@@H](C(=O)O)[C@H](C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](/C=C/C(C)=C/[C@H](C)[C@H](Cc2ccccc2)OC)[C@H](C)C(=O)N[C@@H](C(=O)O)CCC(=O)N1C
InChIKey: ASUBNTZHTFZCMQ-AYHCWQHMSA-N
Target: Solute carrier organic anion transporter family member 1B1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y6L6
Assay: Substrate activity at OATP1B1 (unknown origin) expressed in HEK293 cells assessed as cytotoxicity incubated for 48 hrs by sulforhodamine B assay
Measurement: EC50 = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 1286.41
Compound (SMILES): COc1cc(NS(C)(=O)=O)ccc1Nc1ncc2c(n1)N(C)c1ccccc1C(=O)N2C
InChIKey: ISCJKSNXTHTNBW-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: Inhibition of recombinant human GST-tagged LRRK2 catalytic domain (970 to 2527 residues) expressed in baculovirus expression system using LRRKtide as substrate measured after 1 hr by Alexa fluor-647 ADP tracer-based ADAPTA assay
Measurement: IC50 = 5.9 nM (pChEMBL 8.229999542236328)
Descriptors: MW 454.51, ALogP 2.96, HBA 8, HBD 2, PSA 116.76, QED 0.6
Compound (SMILES): Cc1cn([C@H]2C[C@H](n3cc(C[Se]c4ccc(NC(=S)Nc5ccc(S(N)(=O)=O)cc5)cc4)nn3)[C@@H](CO)O2)c(=O)[nH]c1=O
InChIKey: NSQRIPKJLSPJRG-YTFSRNRJSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human CA2 pre-incubated for 15 mins by stopped flow CO2 hydrase assay
Measurement: Ki = 5.6 nM (pChEMBL 8.25)
Descriptors: MW 691.65
Compound (SMILES): COCCOc1nc(N)c2nc(O)n(Cc3ccc(C(=O)N[C@H]4[C@H](O)[C@H]5O[C@H]6[C@H](O)[C@@H](O)[C@@H](O[C@H]7[C@H](O)[C@@H](O)[C@@H](O[C@H]8[C@H](O)[C@@H](O)[C@@H](O[C@H]9[C@H](O)[C@@H](O)[C@@H](O[C@H]%10[C@H](O)[C@@H](O)[C@@H](O[C@H]%11[C@H](O)[C@@H](O)[C@@H](O[C@H]%12[C@H](O)[C@@H](O)[C@@H](O[C@@H]4[C@@H](CO)O5)O[C@@H]%12CO)O[C@@H]%11CO)O[C@@H]%10CO)O[C@@H]9CO)O[C@@H]8CO)O[C@@H]7CO)O[C@@H]6CO)cc3)c2n1
InChIKey: HCSRFFOXVPTEDP-IUKBSCCRSA-N
Target: Toll-like receptor 7 (SINGLE PROTEIN), Mus musculus
UniProt: P58681
Assay: Agonist activity at TLR7 in mouse BMDC cells assessed as immunostimulatory activity by measuring increase in IL6 secretion incubated for 18 hrs by ELISA
Measurement: EC50 = 56 nM (pChEMBL 7.25)
Descriptors: MW 1637.47
Compound (SMILES): Cc1ccc2nc(-c3ccc(NC(=O)c4ccccc4)cc3)[nH]c2c1
InChIKey: KCALIQOEAOMMLX-UHFFFAOYSA-N
Target: Neutrophil collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P22894
Assay: Inhibition of recombinant human MMP8 catalytic domain (Phe99 to Gln269 residues) expressed in Escherichia coli cells using Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2/TQ3-GABA-Pro-Cha-Abu-Smc-His-Ala-Dab(6'-TAMRA)-Ala-Lys-NH2 as fluorogenic substrate preincubated for 15 mins followed by substrate addition measured after 2 to 4 hrs by fluorometric assay
Measurement: IC50 = 45300 nM (pChEMBL 4.340000152587891)
Descriptors: MW 327.39, ALogP 4.79, HBA 2, HBD 2, PSA 57.78, QED 0.57
Compound (SMILES): CCC(C)c1c(-c2ccc(OC)c(OC)c2)[nH]c2ccc(C3CCN(CCNC)CC3)cc12
InChIKey: QSNNJQWJYKWBFO-UHFFFAOYSA-N
Target: Toll-like receptor 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NYK1
Assay: Antagonist activity at human TLR7 overexpressed in HEK-Blue cells assessed as inhibition of gardiquimod-induced NFkappaB and AP-1 activation preincubated for 30 mins followed by gardiquimod stimulation measured after 22 hrs by quanti-blue SEAP assay
Measurement: IC50 = 1290 nM (pChEMBL 5.889999866485596)
Descriptors: MW 449.64, ALogP 5.76, HBA 4, HBD 2, PSA 49.52, QED 0.44
Compound (SMILES): Cc1cc(/C=C/C=C/c2ccc(N(C)C)cc2)cc(C)[n+]1CCCc1c[nH]cn1.O=C(O)C(F)(F)F.O=C([O-])C(F)(F)F
InChIKey: AQJCVXSDQBVZED-UHFFFAOYSA-M
Target: Histamine H3 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5N1
Assay: Displacement of [3H]-UR-PI294 from Galphai2/Gbeta1gamma2-coupled human recombinant H3R expressed in baculovirus infected Sf9 insect cell membranes
Measurement: Ki = 11.75 nM (pChEMBL 7.929999828338623)
Descriptors: MW 387.55, ALogP 4.74, HBA 2, HBD 1, PSA 35.8, QED 0.45
Compound (SMILES): c1ccc(-c2cc(N[C@H]3CCCNC3)c3ccncc3c2)cc1
InChIKey: XKVKEBRJQBYODL-SFHVURJKSA-N
Target: Serine/threonine-protein kinase D2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BZL6
Assay: Inhibition of PKD2 (unknown origin)
Measurement: IC50 = 144 nM (pChEMBL 6.840000152587891)
Descriptors: MW 303.41, ALogP 4.07, HBA 3, HBD 2, PSA 36.95, QED 0.77
Compound (SMILES): c1cc(C2CC2)c2c3c1CNCCN3CC2
InChIKey: SUAHZXUTRBZCQE-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Agonist activity at 5HT2B receptor (unknown origin)
Measurement: EC50 = 260 nM (pChEMBL 6.579999923706055)
Descriptors: MW 214.31, ALogP 2.03, HBA 2, HBD 1, PSA 15.27, QED 0.77
Compound (SMILES): CNCCN1CCC(c2ccc3[nH]c(-c4ccc(OC)c(OC)c4)c(C(C)C)c3c2)CC1
InChIKey: UKYUETHIPBXYBQ-UHFFFAOYSA-N
Target: Toll-like receptor 7 (SINGLE PROTEIN), Mus musculus
UniProt: P58681
Assay: In vivo antagonist activity at TLR7 in po dosed C57BL/6 mouse assessed as reduction of gardiquimod-induced IL-6 production pretreated for 30 mins followed by gardiquimod-stimulation and measured after 120 mins by ELISA
Measurement: EC50 = 2.4 nM (pChEMBL 8.619999885559082)
Descriptors: MW 435.61, ALogP 5.37, HBA 4, HBD 2, PSA 49.52, QED 0.5
Compound (SMILES): COc1cccc(Cn2cnc3sc(-c4ccc5[nH]ncc5c4)cc3c2=O)c1
InChIKey: KVTLEWCUMJPLAT-UHFFFAOYSA-N
Target: Rho-associated protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75116
Assay: Inhibition of recombinant human ROCK2 (11 to 552 residues) using KEAKEKRQEQIAKRRRLSSLRASTSKSGGSQK as substrate incubated for 40 mins in presence of [gamma-33P]ATP by radiometric scintillation assay
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 388.45, ALogP 4.06, HBA 6, HBD 1, PSA 72.8, QED 0.5
Compound (SMILES): Cc1ccnc(C(=O)N[C@@H]2CCCc3c2cnn3-c2ccccc2C)c1
InChIKey: MCXYMWBMIJVYML-QGZVFWFLSA-N
Target: Dihydroorotate dehydrogenase (quinone), mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q02127
Assay: Inhibition Assay: Assay B: Example compounds as described herein were dispensed with an acoustic liquid handler, Echo 550 (Labcyte) to a maximum volume of 50 nl per well in a 384 well plate. DHODH enzyme assays were performed with 4 nM recombinant human DHODH (purified essentially as described by Walse et. al., Biochemistry, 47, 8929-8936 (2008)). The reaction mixture consisted of 2 mM DL-dihydroorotic acid (#D7003, Sigma-Aldrich), 100 μM 3,4-dimethoxy-5-methyl-p-benzoquinone (#D9150, Sigma-Aldrich), and 200 μM 2,6-dichlorophenolindophenol sodium salt (DCIP) (#D1878, Sigma-Aldrich) in enzyme buffer (50 mM Tris-HCl pH 8.0, 0.1% Triton X-100, 150 mM KCl) in a final volume of 50 μl per well. A stock solution of 80 mM DCIP was prepared in DMSO just before use. Loss in absorbance by chromogen DCIP was measured at 595 nm at RT every 2 min for an hour with a plate reader (Envision, Perkin Elmer).
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 346.43, ALogP 3.69, HBA 4, HBD 1, PSA 59.81, QED 0.79
Compound (SMILES): CC(C)=CCCC1=CC[C@H](C(=O)NO)[C@@H](c2ccccc2)C1
InChIKey: HVCBSZZKWHLAJI-ZWKOTPCHSA-N
Target: Induced myeloid leukemia cell differentiation protein Mcl-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07820
Assay: Inhibition of Mcl-1 (unknown origin)/Bid interaction preincubated for 5 mins followed by fluorescein-labeled peptide addition and measured after 10 mins by fluorescein-labeled peptide displacement based fluorescence polarization assay
Measurement: Ki = 7300 nM (pChEMBL 5.139999866485596)
Descriptors: MW 299.41, ALogP 4.36, HBA 2, HBD 2, PSA 49.33, QED 0.48
Compound (SMILES): Cc1oc(-c2ccccc2Cl)nc1C(=O)N[C@H]1CN(S(=O)(=O)c2ccccc2)C[C@@H]1C(=O)N[C@H]1CCCNC1
InChIKey: KARCZKAKZQTJTH-HARLFGEKSA-N
Target: Growth hormone secretagogue receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92847
Assay: Agonist activity at human GHSR expressed in HEK293 cells assessed as increase in IP1 accumulation measured after 90 mins in presence of LiCl by HTRF assay
Measurement: EC50 = 0.543 nM (pChEMBL 9.270000457763672)
Descriptors: MW 572.09, ALogP 2.59, HBA 7, HBD 3, PSA 133.64, QED 0.4
Compound (SMILES): COc1nn(-c2ccncc2)cc1C(=O)Nc1cccc(-c2nncn2C(C)C)n1
InChIKey: KVJFGNCSRKLHAJ-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 HEK293T cells assessed as reduction in T848 autophosphorylation incubated for 1 hr by MSD assay
Measurement: IC50 = 1710 nM (pChEMBL 5.769999980926514)
Descriptors: MW 404.43, ALogP 2.76, HBA 9, HBD 1, PSA 112.64, QED 0.53
Compound (SMILES): Cc1[nH]nc2[nH]c(=O)cc([C@H]3CC[C@H](CC(=O)N4CCC(C)(C)CC4)CC3)c12
InChIKey: ZPDYGMNVYLLBBB-WKILWMFISA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of N-terminal His-tagged human JAK2 catalytic domain incubated for 20 mins in presence of TK substrate-biotin by TR-FRET assay
Measurement: IC50 = 32 nM (pChEMBL 7.5)
Descriptors: MW 384.52, ALogP 3.87, HBA 3, HBD 2, PSA 81.85, QED 0.84
Compound (SMILES): C[C@H](NS(=O)(=O)c1ccc(-c2sc(NCCC(C)(C)O)nc2C(=O)N2CCC(F)CC2)c(Cl)c1Cl)C(F)(F)F
InChIKey: YPVQXFDCVBYNDA-LBPRGKRZSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at human RORgammat LBD by M1H cell based assay
Measurement: IC50 = 37 nM (pChEMBL 7.429999828338623)
Descriptors: MW 635.53, ALogP 5.49, HBA 7, HBD 3, PSA 111.63, QED 0.31
Compound (SMILES): CN(C)C(=O)c1ccc(Nc2nccc(N(C)C3CCCCC3)n2)cc1
InChIKey: XCOJWYMCLNBWGL-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Lck (SINGLE PROTEIN), Homo sapiens
UniProt: P06239
Assay: Inhibition of N-terminal His6-tagged recombinant full-length human Lck using TK-substrate-biotin as substrate incubated for 60 mins in presence of ATP by fluorescence method
Measurement: IC50 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 353.47, ALogP 3.69, HBA 5, HBD 1, PSA 61.36, QED 0.89
Compound (SMILES): CCCC(=O)Nc1ccc(-c2ccc(-c3c[nH]c([C@@H]4CCCN4C(=O)[C@H](NC(=O)N4CC[C@H](NC(=O)OCc5ccccc5)C4)c4ccccc4)n3)cc2)cc1
InChIKey: KHJDZSOETVYKLV-WSMIHHHMSA-N
Target: Nonstructural protein 5A (SINGLE PROTEIN), Hepatitis C virus
UniProt: Q5L478
Assay: Inhibition of NS5A in Hepatitis C virus subtype 1b replicon infected in human HuH7 cells assessed as reduction in viral replication
Measurement: EC50 = 0.037 nM (pChEMBL 10.430000305175781)
Descriptors: MW 753.9, ALogP 7.6, HBA 6, HBD 4, PSA 148.76, QED 0.1
Compound (SMILES): CNC(=O)c1cc(C(=O)NCCO)cc2c1O[C@H](C)[C@H]2c1ccccc1
InChIKey: YFWPUPFZVKKKFS-PXAZEXFGSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Displacement of Alexa Fluor 647 labelled ligand from His6-tagged BRD4 BD1 (1 to 477 residues)/BD2 Y390A mutant (unknown origin) after 30 mins by TR-FRET assay
Measurement: IC50 > 50118.72 nM (pChEMBL 4.300000190734863)
Descriptors: MW 354.41, ALogP 1.68, HBA 4, HBD 3, PSA 87.66, QED 0.76
Compound (SMILES): COc1cccc2c1N(C(C)=O)C(C(=O)O)C1CC=CC21
InChIKey: IYUKESXEKWSMOY-UHFFFAOYSA-N
Target: Protein fosB/Transcription factor jun-D (PROTEIN COMPLEX), Homo sapiens
UniProt: P17535
Assay: Inhibition of recombinant Hi6-tagged deltaFOSB (unknown origin)/His6-tagged JUND (unknown origin) expressed in insect cells interaction with TAMRA labeled 5'-GTCGGTGACTCAAAACA-3' AP1 oligonucleotide measured after 15 mins by fluorescence polarization assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 287.31, ALogP 2.17, HBA 3, HBD 1, PSA 66.84, QED 0.85
Compound (SMILES): CCCCCn1c(=O)c(C(=O)NC23CC4CC(CC(C4)C2)C3)c(O)c2nn(CCO)cc21
InChIKey: NOTNAUPLTQNICZ-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]-CP-55,940 from recombinant human CB2R expressed in HEK293 cell membranes
Measurement: Ki = 4.8 nM (pChEMBL 8.319999694824219)
Descriptors: MW 442.56, ALogP 2.78, HBA 7, HBD 3, PSA 109.38, QED 0.54
Compound (SMILES): O=C(CCCCCCC(=O)NCCCN1c2ccccc2CCc2ccc(Cl)cc21)NO
InChIKey: QJAVVKUFLLJMRG-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of recombinant C-terminal His-tagged and N-terminal Streptavidin2-tagged human HDAC8 (1 to 377 residues) expressed in baculovirus infected insect cells using RHK-K(Ac)-AMC as substrate after 60 mins by fluorescence assay
Measurement: IC50 = 2330 nM (pChEMBL 5.630000114440918)
Descriptors: MW 458, ALogP 4.93, HBA 4, HBD 3, PSA 81.67, QED 0.25
Compound (SMILES): O=C(Nc1ccc(F)cc1-c1ccc(F)c(Cl)c1)OCC1CCNCC1
InChIKey: GUWDPEQJYFKDCE-UHFFFAOYSA-N
Target: Muscarinic acetylcholine receptor M2 (SINGLE PROTEIN), Homo sapiens
UniProt: P08172
Assay: Displacement of [3H]N-methylscopolamine from human muscarinic M2 receptor transiently expressed in HEK293T cell membranes incubated for 1 hr by scintillation counting method
Measurement: Ki = 3.4 nM (pChEMBL 8.470000267028809)
Descriptors: MW 380.82, ALogP 4.83, HBA 3, HBD 2, PSA 50.36, QED 0.8
Compound (SMILES): N[C@@H](CCCCCC(=O)c1cocn1)c1ncc(-c2ccccc2F)[nH]1
InChIKey: UTQMWCHHCIKOKP-HNNXBMFYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of full length human recombinant FLAG-tagged HDAC2 expressed in baculovirus infected Sf9 cells using FLUOR DE LYS as substrate preincubated for 3 hrs followed by substrate addition and measured after 60 mins by fluorescence based assay
Measurement: IC50 = 740 nM (pChEMBL 6.130000114440918)
Descriptors: MW 356.4, ALogP 4.04, HBA 5, HBD 2, PSA 97.8, QED 0.45
Compound (SMILES): O=C(NO)c1ccc(Oc2ccc(CN3CCCC3c3cccc(F)c3)cc2)c(F)c1
InChIKey: PKXVPXZZPYISNC-UHFFFAOYSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41145
Assay: Displacement of [3H]-U69593 from human kappa opiod receptor expressed in CHO cells incubated for 60 mins by liquid scintillation counting method
Measurement: Ki = 497.6 nM (pChEMBL 6.300000190734863)
Descriptors: MW 424.45, ALogP 5.21, HBA 4, HBD 2, PSA 61.8, QED 0.42
Compound (SMILES): O=C(Nc1nc2ccc(Cl)cc2s1)c1ccc([N+](=O)[O-])cc1
InChIKey: KOSDVCPJQROWRP-UHFFFAOYSA-N
Target: Neutrophil collagenase (SINGLE PROTEIN), Homo sapiens
UniProt: P22894
Assay: Inhibition of recombinant human MMP8 catalytic domain (Phe99 to Gln269 residues) expressed in Escherichia coli cells using Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2/TQ3-GABA-Pro-Cha-Abu-Smc-His-Ala-Dab(6'-TAMRA)-Ala-Lys-NH2 as fluorogenic substrate preincubated for 15 mins followed by substrate addition measured after 2 to 4 hrs by fluorometric assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 333.76, ALogP 4.11, HBA 5, HBD 1, PSA 85.13, QED 0.58
Compound (SMILES): COc1cccc(OC)c1-c1ccc(COC2CN(C#N)C2)cc1
InChIKey: JVHSHNQOEIYBPM-UHFFFAOYSA-N
Target: N-acylethanolamine-hydrolyzing acid amidase (SINGLE PROTEIN), Homo sapiens
UniProt: Q02083
Assay: Inhibition Assay: In order to have an assay method more conducive to high-throughput screening than those published for measuring the NAE hydrolyzing activity of NAAA, we developed the fluorogenic PEA analog N-(4-methyl coumarin)palmitamide (PAMCA), which is hydrolyzed to fluorescent 7-amino-4-methyl coumarin (AMC) and palmitic acid. For three point concentration inhibition assays with hNAAA the following procedure is used. Purified activated NAAA (final concentration of 0.25 μg/mL) is incubated in assay buffer (100 mM citrate-phosphate buffer, pH 4.5, 3 mM DTT, 0.1% Triton X-100, 0.05% BSA, and 150 mM NaCl) made up to a total volume of 180 μL, followed by addition of the compound dissolved in 10 μL DMSO (along with DMSO neat for the control sample) with the final concentrations for each compound of 100, 10, and 1 μM, in triplicate on a 96 well plate. These samples are allowed to incubate for 15 min at room temperature and then 10 μL of a PAMCA stock solution in DMSO (final PAMCA concentration [5 μM]) was added. After 5 minutes of agitation on a shaking plate, the reaction is allowed to proceed at 37° C. for 120 minutes, with fluorescence readings taken every 10 minutes at a wavelength of 460 nm (using an excitation wavelength of 360 nm) on a Synergy HT Plate Reader using Gen5 software from Bio-Tek. The enzyme activity is calculated by converting the relative fluorescence units to AMC formed, using a standard curve of AMC. For compounds that inhibit hNAAA in range IC50 <1 μM full inhibition curves using eight different concentrations of inhibitor (8 point assay) are generated. The assay procedure used is the same as the three point assay. For ostensibly covalent compounds (as observed by a significant decrease in the slope of a plot of fluorescence vs. time in three point screen) samples are allowed to incubate for 2 hours at 37° C., instead of 15 minutes, before addition of 10 μL of a PAMCA stock solution in DMSO for a final PAMCA concentration of 5 μM. After 5 minutes of agitation on a shaking plate, the reaction is allowed to proceed at 37° C. for 120 minutes Inhibition constants are calculated using pro Fit software (Quantum Soft, Uetikon am See, Switzerland) and a Levenberg-Marquardt algorithm.
Measurement: IC50 = 55 nM (pChEMBL 7.260000228881836)
Descriptors: MW 324.38, ALogP 3.05, HBA 5, HBD 0, PSA 54.72, QED 0.76
Compound (SMILES): COC(=O)c1ccc(C#Cc2ccc(NC(=O)C(=O)O)cc2)cc1O
InChIKey: FDRGEQQVYZZVAM-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: Inhibition of SHP2 (unknown origin) expressed in Escherichia coli BL21 using p-nitrophenyl phosphate as substrate measured after 30 mins by UV-vis spectrophotometric method
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 339.3, ALogP 1.6, HBA 5, HBD 3, PSA 112.93, QED 0.44
Compound (SMILES): Cc1cc(Br)c(NC2=NCCN2)c2ccccc12
InChIKey: UYAOIRISFNRFCT-UHFFFAOYSA-N
Target: Complement factor B (SINGLE PROTEIN), Homo sapiens
UniProt: P00751
Assay: Binding affinity to human serine protease factor B by SPR assay
Measurement: Kd = 10000 nM (pChEMBL 5)
Descriptors: MW 304.19, ALogP 3.28, HBA 3, HBD 2, PSA 36.42, QED 0.85
Compound (SMILES): CCCn1c(=O)c(C(=O)NC23CC4CC(CC(C4)C2)C3)c(O)c2nn(CCOC(C)=O)cc21
InChIKey: LHQLBIIVVJMZCQ-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]-CP-55,940 from recombinant human CB2R expressed in HEK293 cell membranes
Measurement: Ki = 186 nM (pChEMBL 6.730000019073486)
Descriptors: MW 456.54, ALogP 2.58, HBA 8, HBD 2, PSA 115.45, QED 0.62
Compound (SMILES): Cc1c(Cc2ccc(C(F)(F)F)nc2)c[nH]c1C(=O)N1CC(F)(F)C1
InChIKey: CTQHCGSVDQJGCJ-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (quinone), mitochondrial (SINGLE PROTEIN), Mus musculus
UniProt: O35435
Assay: Inhibition of C-terminal His6-tagged mouse DHODH expressed in Escherichia coli BL21(DE3) cells using L-DHO as substrate by DCIP dye based assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 359.3, ALogP 3.42, HBA 2, HBD 1, PSA 48.99, QED 0.85
Compound (SMILES): COc1ccc2nc(NC(=O)c3ccc([C@@H](N)c4ccccc4)cc3)sc2c1
InChIKey: BHOBUXPHKZSABC-FQEVSTJZSA-N
Target: Stearoyl-CoA desaturase (SINGLE PROTEIN), Homo sapiens
UniProt: O00767
Assay: Inhibition of SCD in human H2009 cells non-expressing CYP4F11 assessed as reduction in cell viability incubated for 96 hrs by cell titer Glo reagent based assay
Measurement: IC50 = 5700 nM (pChEMBL 5.239999771118164)
Descriptors: MW 389.48, ALogP 4.61, HBA 5, HBD 2, PSA 77.24, QED 0.52