lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC(C)C[C@](C)(N)COc1ccc(-c2ccnc(C(F)F)c2)nc1Cl
InChIKey: OAWXJOFGASPGQX-SFHVURJKSA-N
Target: AP2-associated protein kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q2M2I8
Assay: Kinase Assay: The assays were performed in U-bottom 384-well plates. The final assay volume was 30 μl prepared from 15 μl additions of enzyme and substrates (fluoresceinated peptide (5-FAM)-Aha-KEEQSQITSQVTGQIGWR-NH2 and ATP) and test compounds in assay buffer (10 mM Tris-HCL pH 7.4, 10 mM MgCl2, 0.01% Tween-20 and 1.0 mM DTT). The reactions were initiated by the combination of bacterially expressed, GST-Xa-hAAK1 with substrates and test compounds. The reactions were incubated at room temperature for 3 hours and terminated by adding 60 μl of 35 mM EDTA buffer to each sample. The reactions were analyzed on the Caliper LabChip 3000 (Caliper, Hopkinton, Mass.) by electrophoretic separation of the fluorescent substrate and phosphorylated product Inhibition data were calculated by comparison to EDTA quenched control reactions for 100% inhibition and vehicle-only reactions for 0% inhibition. The final concentration of reagents in the assays are ATP, 22 μM; (5-FAM)-Aha-KEEQSQITSQVTGQIGWR-NH2, 1.5 μM; GST-Xa-hAAK1, 3.5 nM; and DMSO, 1.6%. Dose response curves were generated to determine the concentration required inhibiting 50% of kinase activity (IC50). Compounds were dissolved at 10 mM in dimethylsulfoxide (DMSO) and evaluated at eleven concentrations.
Measurement: IC50 = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 369.84, ALogP 4.88, HBA 4, HBD 1, PSA 61.03, QED 0.71
Compound (SMILES): Cn1cc(C(=O)N2[C@H]3Cc4ccccc4[C@@H]2CNC3=O)cc(N)c1=O
InChIKey: KYNLKRBYUMMJKS-GJZGRUSLSA-N
Target: ATPase family AAA domain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6PL18
Assay: Inhibition of GST-ATAD2 BD (951 to 1132 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) and biotinylated tetra-acetylated histone H4 peptides as substrate incubated for 30 mins by TR-FRET assay
Measurement: IC50 = 34300 nM (pChEMBL 4.460000038146973)
Descriptors: MW 338.37, ALogP 0.21, HBA 5, HBD 2, PSA 97.43, QED 0.78
Compound (SMILES): CNc1ccc2ccc(OCc3cc(C#N)cc(-n4ccc5c(N)ncnc54)c3)cc2n1
InChIKey: DGAGXNBFXHTCJY-UHFFFAOYSA-N
Target: N6-adenosine-methyltransferase catalytic subunit (SINGLE PROTEIN), Homo sapiens
UniProt: Q86U44
Assay: Inhibition of METTL3 (unknown origin) using UCUGGACUAAA-biotin and 3H-SAM as substrates preincubated for 5 mins followed by substrate addition incubated for 30 mins by TopCount scintillation counting method
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 421.46, ALogP 4.04, HBA 8, HBD 2, PSA 114.67, QED 0.44
Compound (SMILES): CCS(=O)(=O)NC1CCCN(C(C)=O)C1COC1CCC(C(C)C)CC1
InChIKey: BXCHBUYDFXKLTP-UHFFFAOYSA-N
Target: Orexin/Hypocretin receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O43613
Assay: Agonist activity at human OX1R expressed in CHO-K1 cells by FLIPR calcium flux assay
Measurement: EC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 388.57, ALogP 2.54, HBA 4, HBD 1, PSA 75.71, QED 0.73
Compound (SMILES): N#Cc1ccc(C(NC(=O)c2ccc(C(F)(F)F)[nH]c2=O)c2ccccc2)cc1
InChIKey: BZHYJZGIMXZIMK-UHFFFAOYSA-N
Target: 17-beta-hydroxysteroid dehydrogenase type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P37059
Assay: Inhibition of HSD17B2 (unknown origin) using estradiol as substrate incubated for 45 mins and measured after 1 hr by NADH Glo luminescence assay
Measurement: IC50 = 23670 nM (pChEMBL 4.630000114440918)
Descriptors: MW 397.36, ALogP 3.78, HBA 3, HBD 2, PSA 85.75, QED 0.7
Compound (SMILES): C[C@H](CC1CCCCC1)C(=O)N1CC[C@](O)(Cn2cc(C(=O)N3CCNCC3)c(-c3ccccc3)cc2=O)C2(CCCC2)C1
InChIKey: XWIQOVNJMQOLQO-YHZWMNSLSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 19 (SINGLE PROTEIN), Homo sapiens
UniProt: O94966
Assay: Inhibition of C-terminal His6-tagged recombinant human USP19 using iso-peptide ubiquitin-Lys-TAMRA as substrate incubated for 30 mins and measured after 90 mins by fluorescent polarization assay
Measurement: IC50 = 5000 nM (pChEMBL 5.300000190734863)
Descriptors: MW 602.82, ALogP 4.69, HBA 6, HBD 2, PSA 94.88, QED 0.48
Compound (SMILES): COc1ccc([C@H](NC(=O)[C@H](Cc2ccccc2C#N)NC(=O)c2ccccn2)C(=O)N[C@H](C(=O)C(F)(F)F)C(C)C)cc1
InChIKey: GCPVZBQKNVCOHO-GSDHBNRESA-N
Target: Serine protease HTRA1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92743
Assay: Enzyme Inhibition Assay: Enzyme activity is measured by observing the increase in fluorescence intensity caused by cleavage of a peptide substrate containing a fluorophore, whose emission is quenched in the intact peptide.Assay buffer: 500 mM Tris pH 8.0, 200 mM NaCl, 0.025% CHAPS, 0.005% BSGEnzyme: human HtrA1 Cat-PDZ, final concentration 1 nMSubstrate: Mca-Ile-Arg-Arg-Val-Ser-Tyr-Ser-Phe-Lys(Dnp)-Lys, final concentration 500 nM (from Innovagen Cat: SP-5076-1, Lot: 89584.02)Mca=(7-Methoxycoumarin-4-yl)acetylDnp=2,4-DinitrophenylFinal volume: 51 μl
Measurement: IC50 = 1.1 nM (pChEMBL 8.960000038146973)
Descriptors: MW 609.61, ALogP 3.43, HBA 7, HBD 3, PSA 150.28, QED 0.28
Compound (SMILES): O=C(C(O)c1ccnc(N2CCOCC2)c1)N1CC2=C(C1)CN(S(=O)(=O)c1ccc3c(c1)OCCO3)C2
InChIKey: OVPFVGMPBJDRHG-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 9X (SINGLE PROTEIN), Homo sapiens
UniProt: Q93008
Assay: Inhibition of USP9X (unknown origin) using Ubiquitin-Rhoadmine 110 as substrate preincubated for 30 mins followed by substrate addition and measured after 11 mins by fluorescence assay
Measurement: IC50 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 528.59, ALogP 0.57, HBA 9, HBD 1, PSA 121.74, QED 0.56
Compound (SMILES): CNCC(C(=O)N1CC2=C(C1)CN(S(=O)(=O)c1ccc3c(c1)OCCO3)C2)c1cc(C)c(OC)cc1F
InChIKey: CVYCNXUWMQZEBN-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 9X (SINGLE PROTEIN), Homo sapiens
UniProt: Q93008
Assay: Inhibition of USP9X (unknown origin) using Ubiquitin-Rhoadmine 110 as substrate preincubated for 30 mins followed by substrate addition and measured after 11 mins by fluorescence assay
Measurement: IC50 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 531.61, ALogP 2.06, HBA 7, HBD 1, PSA 97.41, QED 0.55
Compound (SMILES): COc1ccc(-c2cccc(C(=O)N(C)Cc3ccccc3)c2)cc1S(=O)(=O)Nc1cccc(NCCNC(=O)c2cccc(C)c2)c1
InChIKey: LCCDICCIIOWTER-UHFFFAOYSA-N
Target: Orexin receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O43614
Assay: Agonist activity at human OX2R stably expressed in CHO RD-HGA16 cells assessed as fluorescence changes measured after 30 mins by calcium mobilization assay
Measurement: EC50 = 532 nM (pChEMBL 6.269999980926514)
Descriptors: MW 662.81, ALogP 6.59, HBA 6, HBD 3, PSA 116.84, QED 0.12
Compound (SMILES): C#Cc1ccc2c(c1)[nH]c1ncnc(N(C)C3CCCN(CCC#N)C3)c12
InChIKey: VYWVFPWNSYBICQ-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of recombinant human GSK-3-beta using YRRAAVPPSPSLSRHSSPHQ(pS)EDEEE as substrate preincubated for 10 mins followed by substrate addition and measured after 1 hr in presence of ATP by ADP Glo kinase assay
Measurement: IC50 = 25.12 nM (pChEMBL 7.599999904632568)
Descriptors: MW 358.45, ALogP 2.91, HBA 5, HBD 1, PSA 71.84, QED 0.73
Compound (SMILES): Cn1cnnc1CC1(c2cccc(NC(=O)c3cc(Cn4ccnn4)nc(C4CC4)n3)c2)COC1
InChIKey: QAQAAXWNWSLMLT-UHFFFAOYSA-N
Target: E3 ubiquitin-protein ligase CBL-B (SINGLE PROTEIN), Homo sapiens
UniProt: Q13191
Assay: Binding affinity towards N-terminal biotinylated Avi-tagged human CBL-B (36 to 427 residues) measured by surface plasmon resonance assay
Measurement: Kd < 100 nM (pChEMBL 7)
Descriptors: MW 471.53, ALogP 1.89, HBA 10, HBD 1, PSA 125.53, QED 0.41
Compound (SMILES): CCCCSc1nc(N)nc2ccc(Cc3ccccc3)nc12
InChIKey: RGGDASQQFBMXST-UHFFFAOYSA-N
Target: Toll-like receptor 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR97
Assay: Agonist activity at human TLR8 expressed in HEK293 cells incubated for 6 to 16 hrs by SEAP reporter gene assay
Measurement: EC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 324.45, ALogP 4.09, HBA 5, HBD 1, PSA 64.69, QED 0.42
Compound (SMILES): Cc1cccc(-c2cc(=O)n(CC3(O)CCN(C(=O)C[C@@H](C)c4ccccc4)CC3)cc2C(=O)N(C)C(C)C)c1
InChIKey: INBOFXODFCGVCP-RUZDIDTESA-N
Target: Ubiquitin carboxyl-terminal hydrolase 19 (SINGLE PROTEIN), Homo sapiens
UniProt: O94966
Assay: USP19 Activity Assay: USP19 activity was monitored in a fluorescence polarisation (FP) homogeneous assay using the isopeptide Ubiquitin-Lys-TAMRA substrate (either AUB-101, Almac Sciences Scotland Limited, or U-558, Boston Biochem, both of which gave identical results). Full-length USP19 was purchased from Boston Biochem (E-576). Unless otherwise stated, all other reagents were purchased from Sigma. Enzymatic reactions were conducted in black flat bottom polystyrene 384-well plates (Nunc) and 30 μL total volume. USP19 (2.5 nM, 10 μL) was incubated in assay buffer (50 mM HEPES (pH 7.4), 150 mM NaCl, 5 mM DTT, 0.05% BSA (w/v), 0.05% CHAPS) in the presence or absence of inhibitor (10 μL). Inhibitors were stored as 10 mM DMSO stocks in an inert environment (low humidity, dark, low oxygen, room temperature) using the Storage Pod System and serial dilutions were prepared in buffer just prior to the assay (from 200 μM to 2 pM, 8-18 data point curve). Following incubation at RT for 30 min, the enzymatic reactions were initiated by dispensing the Ub substrate (500 nM, 10 μL). FP was measured every 15 min over a period of 90 min (within the linear range of the assay) using a Synergy 4 plate reader (BioTek) exciting at 530 nm and measuring the amount of parallel and perpendicular light at 575 nm. The FP signal was subsequently normalised to the no compound control. Data were plotted and fitted, and the concentrations resulting in 50% inhibition (IC50) were calculated using the non-linear regression curve fitting model using GraphPad (Prism).
Measurement: IC50 = 2750 nM (pChEMBL 5.559999942779541)
Descriptors: MW 543.71, ALogP 4.85, HBA 5, HBD 1, PSA 82.85, QED 0.44
Compound (SMILES): CCOCC(Sc1nncn1C)c1cccc(NC(=O)c2cccc(C(F)(F)F)n2)c1
InChIKey: JZXJPYWZTSLTJJ-UHFFFAOYSA-N
Target: E3 ubiquitin-protein ligase CBL-B (SINGLE PROTEIN), Homo sapiens
UniProt: Q13191
Assay: Binding affinity towards N-terminal biotinylated Avi-tagged human CBL-B (36 to 427 residues) measured by surface plasmon resonance assay
Measurement: Kd = 3001 nM (pChEMBL 5.519999980926514)
Descriptors: MW 451.47, ALogP 4.35, HBA 7, HBD 1, PSA 81.93, QED 0.51
Compound (SMILES): Nc1ncnc2c1ccn2[C@@H]1C[C@H](CCc2ccc3c(OCc4ccccc4)ccnc3c2)[C@@H](O)[C@H]1O
InChIKey: DPMSWDOKPMTFIY-AUTMPROSSA-N
Target: Protein arginine N-methyltransferase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: O14744
Assay: Inhibition of PRMT5 (unknown origin) using Ac-SGRGKGGKGLGKGGAKRHRKVGGK-Biotin and 3H-SAM as substrates preincubated for 5 mins followed by substrate addition incubated for 60 mins by TopCount scintillation counting method
Measurement: IC50 < 10 nM (pChEMBL 8)
Descriptors: MW 495.58, ALogP 4.06, HBA 8, HBD 3, PSA 119.31, QED 0.31
Compound (SMILES): N/C(=N/C(=N/S(=O)(=O)N1CCCCC1)N1CC(c2ccccc2)C(c2ccc(Cl)cc2)=N1)c1ccc(F)cc1
InChIKey: VVSCELSGVFIXSR-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]- CP55940 from human CB2R expressed in CHO-K1 cells membrane by Cheng-Prusoff equation analysis
Measurement: Ki = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 567.09, ALogP 4.77, HBA 3, HBD 1, PSA 103.72, QED 0.35
Compound (SMILES): Cn1ccc(-c2cn(-c3cncc(C[S+]([O-])c4ccc5ccc(N6CCC6)nc5c4)c3)c3ncnc(N)c23)n1
InChIKey: JNWITMIYHJYMLM-UHFFFAOYSA-N
Target: N6-adenosine-methyltransferase catalytic subunit (SINGLE PROTEIN), Homo sapiens
UniProt: Q86U44
Assay: Inhibition of METTL3 (unknown origin) using UCUGGACUAAA-biotin and 3H-SAM as substrates preincubated for 5 mins followed by substrate addition incubated for 30 mins by TopCount scintillation counting method
Measurement: IC50 >= 1000 nM (pChEMBL 6)
Descriptors: MW 535.64, ALogP 3.86, HBA 10, HBD 1, PSA 126.63, QED 0.32
Compound (SMILES): NC(=O)[C@@H]1[C@H](Nc2nc(Nc3ccc(N4CCOCC4)nc3)ncc2-c2cccc(F)c2)[C@H]2C=C[C@@H]1C2
InChIKey: ZJOCDAGVCZOCSS-HJOCRKTISA-N
Target: Mitogen-activated protein kinase kinase kinase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: O43318
Assay: Inhibition of TAK1 (unknown origin) in presence of MBP as substrate by ADP-Glo assay
Measurement: IC50 = 450 nM (pChEMBL 6.349999904632568)
Descriptors: MW 501.57, ALogP 3.35, HBA 8, HBD 3, PSA 118.29, QED 0.42
Compound (SMILES): Cc1nc2ccc(-c3cc(N)nc(N)c3)nc2n1C1CCCC1
InChIKey: DGTHPUFVPBPNPD-UHFFFAOYSA-N
Target: Cyclin-dependent kinase 9 (SINGLE PROTEIN), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9 (unknown origin) using Ulight-MBP as substrate and ATP as co-substrate incubated for 40 mins and measured after 1 hr by TR-FRET assay
Measurement: IC50 = 314 nM (pChEMBL 6.5)
Descriptors: MW 308.39, ALogP 3.08, HBA 6, HBD 2, PSA 95.64, QED 0.76
Compound (SMILES): CS/C(N)=N/C(=N/S(=O)(=O)N1CCOCC1)N1CC(c2ccccc2)C(c2ccc(Cl)cc2)=N1
InChIKey: RUBIFOSYRVSJLF-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]- CP55940 from human CB2R expressed in CHO-K1 cells membrane by Cheng-Prusoff equation analysis
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 521.07, ALogP 2.75, HBA 5, HBD 1, PSA 112.95, QED 0.49
Compound (SMILES): C[C@@H](C(=O)O)c1nn(Cc2cn3cc(OCC4CC4)c(Cl)cc3n2)c2ccccc2c1=O
InChIKey: SYONIANMTRUMEL-CYBMUJFWSA-N
Target: Sphingosine 1-phosphate receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O95136
Assay: Antagonist activity at human S1P2 receptor expressed in CHO cells assessed as inhibition of [35S]GTPgammaS binding
Measurement: IC50 = 253 nM (pChEMBL 6.599999904632568)
Descriptors: MW 452.9, ALogP 3.72, HBA 7, HBD 1, PSA 98.72, QED 0.46
Compound (SMILES): CC(C)n1cc(-c2ccc3c(=O)[nH]nc(CN)c3c2)cn1
InChIKey: FIRHAFQRKGTUSH-UHFFFAOYSA-N
Target: Protein arginine N-methyltransferase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: O14744
Assay: Inhibition of MTA-bound human PRMT5 co-complexed with MEP50 using biotin labelled histone H4 peptide (1 to 15) as substrate assessed as inhibition of tritiated methyl group transfer from SAM to histone H4 preincubated for 20 mins followed by SAM addition and measured after 20 mins by scintillation counting analysis
Measurement: IC50 = 670 nM (pChEMBL 6.170000076293945)
Descriptors: MW 283.34, ALogP 1.83, HBA 5, HBD 2, PSA 89.59, QED 0.77
Compound (SMILES): C=C1[C@@H]2CCC[C@@]1(COC(=O)c1ccccc1-c1ccc(NC(C)=O)cn1)CN(CC)C2
InChIKey: DHOOKRIBJXOPKQ-IBVKSMDESA-N
Target: Neuronal acetylcholine receptor; alpha4/beta2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P43681
Assay: Inhibition of human (alpha4)2(beta2)3 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response in presence of 3 uM acetylcholine by two-electrode voltage-clamp method
Measurement: IC50 = 29100 nM (pChEMBL 4.539999961853027)
Descriptors: MW 433.55, ALogP 4.54, HBA 5, HBD 1, PSA 71.53, QED 0.53
Compound (SMILES): CNc1nc2cc(OC[C@H]3O[C@@H](n4cc(-c5ccn(C)n5)c5c(N)ncnc54)[C@@H](F)[C@@H]3O)ccc2o1
InChIKey: PIKVCCPJNPODBC-ITBLURSFSA-N
Target: Protein arginine N-methyltransferase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: O14744
Assay: Inhibition of PRMT5 (unknown origin) using Ac-SGRGKGGKGLGKGGAKRHRKVGGK-Biotin and 3H-SAM as substrates preincubated for 5 mins followed by substrate addition incubated for 60 mins by TopCount scintillation counting method
Measurement: IC50 >= 1000 nM (pChEMBL 6)
Descriptors: MW 494.49, ALogP 2.27, HBA 12, HBD 3, PSA 151.3, QED 0.32
Compound (SMILES): CNC(=O)c1c(-c2ccc(O)cc2F)oc2ccc(O)c(CN3CCC4(COC4)C3)c12
InChIKey: BTOAYMJQHLHUNC-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG ion channel by Q patch-clamp method
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 426.44, ALogP 3.23, HBA 6, HBD 3, PSA 95.17, QED 0.59
Compound (SMILES): O=C(NCc1ccccc1C(F)(F)F)c1ccc2c(c1)[nH]c(=O)n2Cc1ccccc1
InChIKey: VAEOQKKZUWWMTJ-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Partial agonist activity at GAL4-tagged human PPARgamma LBD expressed in HEK293T cells incubated for 12 to 14 hrs by dual-Glo luciferase assay
Measurement: EC50 = 540 nM (pChEMBL 6.269999980926514)
Descriptors: MW 425.41, ALogP 4.33, HBA 3, HBD 2, PSA 66.89, QED 0.5
Compound (SMILES): Cc1ccc2c(c1)Oc1cc(C)ccc1C2NC(=O)c1cc(C2CCOCC2)c(C(F)(F)F)[nH]c1=O
InChIKey: YIACAYYOSCIGLN-UHFFFAOYSA-N
Target: 17-beta-hydroxysteroid dehydrogenase type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P37059
Assay: Inhibition of HSD17B2 (unknown origin) using estradiol as substrate incubated for 45 mins and measured after 1 hr by NADH Glo luminescence assay
Measurement: IC50 = 45400 nM (pChEMBL 4.340000152587891)
Descriptors: MW 498.5, ALogP 5.53, HBA 4, HBD 2, PSA 80.42, QED 0.5
Compound (SMILES): CC(CC(=O)N1CCC(O)(Cn2cnc(-c3ccccc3F)cc2=O)C(C)(C)C1)C1CCCCC1
InChIKey: PBFLCYRZFKIERV-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 19 (SINGLE PROTEIN), Homo sapiens
UniProt: O94966
Assay: USP19 Activity Assay: USP19 activity was monitored in a fluorescence polarisation (FP) homogeneous assay using the isopeptide Ubiquitin-Lys-TAMRA substrate (either AUB-101, Almac Sciences Scotland Limited, or U-558, Boston Biochem, both of which gave identical results). Full-length USP19 was purchased from Boston Biochem (E-576). Unless otherwise stated, all other reagents were purchased from Sigma. Enzymatic reactions were conducted in black flat bottom polystyrene 384-well plates (Nunc) and 30 μL total volume. USP19 (2.5 nM, 10 μL) was incubated in assay buffer (50 mM HEPES (pH 7.4), 150 mM NaCl, 5 mM DTT, 0.05% BSA (w/v), 0.05% CHAPS) in the presence or absence of inhibitor (10 μL). Inhibitors were stored as 10 mM DMSO stocks in an inert environment (low humidity, dark, low oxygen, room temperature) using the Storage Pod System and serial dilutions were prepared in buffer just prior to the assay (from 200 μM to 2 pM, 8-18 data point curve). Following incubation at RT for 30 min, the enzymatic reactions were initiated by dispensing the Ub substrate (500 nM, 10 μL). FP was measured every 15 min over a period of 90 min (within the linear range of the assay) using a Synergy 4 plate reader (BioTek) exciting at 530 nm and measuring the amount of parallel and perpendicular light at 575 nm. The FP signal was subsequently normalised to the no compound control. Data were plotted and fitted, and the concentrations resulting in 50% inhibition (IC50) were calculated using the non-linear regression curve fitting model using GraphPad (Prism).
Measurement: IC50 = 2750 nM (pChEMBL 5.559999942779541)
Descriptors: MW 483.63, ALogP 4.65, HBA 5, HBD 1, PSA 75.43, QED 0.65
Compound (SMILES): CCc1ccc(-n2[se]c3ccccc3c2=O)cc1
InChIKey: MCSRHGLYNCIRNI-UHFFFAOYSA-N
Target: Replicase polyprotein 1ab (SINGLE PROTEIN), Severe acute respiratory syndrome coronavirus 2
UniProt: P0DTD1
Assay: Inhibition of recombinant SARS CoV-2 main protease by FRET assay
Measurement: IC50 = 6180.16 nM (pChEMBL 5.210000038146973)
Descriptors: MW 302.24
Compound (SMILES): Cl.O=C(N[C@H]1CC[C@@]2(O)[C@H]3Cc4ccc(O)c5c4[C@@]2(CCN3CC2CC2)[C@H]1O5)c1cccs1
InChIKey: JUFOSYKDKSXYHX-LYYAMDBGSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Mus musculus
UniProt: P33534
Assay: Displacement of [3H]-diprenorphine from mouse kappa opioid receptor expressed in CHO cell membranes assessed as inhibition constant incubated for 1.5 hrs by competitive binding assay
Measurement: Ki = 1.59 nM (pChEMBL 8.800000190734863)
Descriptors: MW 452.58, ALogP 2.82, HBA 6, HBD 3, PSA 82.03, QED 0.66
Compound (SMILES): CCc1cc(O)c(F)cc1-c1cc(NC2CCN(C(C)=O)CC2)c2nc(N)ncc2c1
InChIKey: GFPMHEFIOGIAGK-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of GST-fused human JAK1 (854 to 1154 residues) expressed in insect cells using ULight-JAK-1 Tyr1023 peptide as substrate preincubated for 30 mins followed by substrate addition and further incubated for 20 mins in presence of ATP by FRET assay
Measurement: IC50 = 0.7943 nM (pChEMBL 9.100000381469727)
Descriptors: MW 423.49, ALogP 3.71, HBA 6, HBD 3, PSA 104.37, QED 0.59
Compound (SMILES): C[C@H](Sc1nncn1C)c1cccc(NC(=O)c2cc(C(F)(F)F)cc(Cl)n2)c1
InChIKey: SRGBEUFIOCCTDD-JTQLQIEISA-N
Target: E3 ubiquitin-protein ligase CBL-B (SINGLE PROTEIN), Homo sapiens
UniProt: Q13191
Assay: Binding affinity towards N-terminal biotinylated Avi-tagged human CBL-B (36 to 427 residues) measured by surface plasmon resonance assay
Measurement: Kd = 3001 nM (pChEMBL 5.519999980926514)
Descriptors: MW 441.87, ALogP 4.99, HBA 6, HBD 1, PSA 72.7, QED 0.45
Compound (SMILES): C=CC(=O)N1CCN(CCCCCn2nc(-c3cc(OC)cc(OC)c3)c3c(N)ncnc32)CC1
InChIKey: QIXCNXNXARCJIU-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 (458 to 768 residues) expressed in Escherichia coli BL21 (DE3) by HTRF assay
Measurement: IC50 = 1.42 nM (pChEMBL 8.850000381469727)
Descriptors: MW 479.59, ALogP 2.59, HBA 9, HBD 1, PSA 111.63, QED 0.35
Compound (SMILES): CNCC(C(=O)N1Cc2cn(S(=O)(=O)c3ccc4c(c3)OCCO4)cc2C1)c1cc(C)c(F)cc1OC
InChIKey: FFWULPMTFHNSCP-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 9X (SINGLE PROTEIN), Homo sapiens
UniProt: Q93008
Assay: Inhibition of USP9X (unknown origin) using Ubiquitin-Rhoadmine 110 as substrate preincubated for 30 mins followed by substrate addition and measured after 11 mins by fluorescence assay
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 529.59, ALogP 2.8, HBA 8, HBD 1, PSA 99.1, QED 0.5
Compound (SMILES): COc1ccc(-c2cc(NC(=O)COCC(=O)N3CCN(CC(=O)NC(C)(C)C)CC3)nc(-c3ccc(OC)cc3)n2)cc1
InChIKey: UTFQQPREKIXIFF-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of CELT-228 from human adenosine A3 receptor expressed in human HeLa cells incubated for 30 mins by fluorescence polarization binding assay
Measurement: Ki = 4000 nM (pChEMBL 5.400000095367432)
Descriptors: MW 604.71, ALogP 2.84, HBA 9, HBD 2, PSA 135.22, QED 0.34
Compound (SMILES): COc1ccc2oc(NC3=NC(c4ccccc4Cl)C(C(=O)Nc4cc(C(=O)O)ccn4)=C(C)N3)nc2c1
InChIKey: RDLILPUSNCEQGL-UHFFFAOYSA-N
Target: Galactokinase (SINGLE PROTEIN), Homo sapiens
UniProt: P51570
Assay: Inhibition of recombinant human GALK1 using galactose as substrate incubated for 1 hrs in the presence of ATP by Kinase-Glo reagent based luminescence assay
Measurement: IC50 = 6606.93 nM (pChEMBL 5.179999828338623)
Descriptors: MW 532.94, ALogP 4.61, HBA 9, HBD 4, PSA 150.97, QED 0.28
Compound (SMILES): Cc1cc(N)c2ccc(OC[C@H]3O[C@@H](n4cc(Br)c5c(N)ncnc54)[C@@H](F)[C@@H]3O)cc2n1
InChIKey: OPTWLYCKKBTKGQ-LNNXQNCSSA-N
Target: Protein arginine N-methyltransferase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: O14744
Assay: Inhibition of PRMT5 (unknown origin) using Ac-SGRGKGGKGLGKGGAKRHRKVGGK-Biotin and 3H-SAM as substrates preincubated for 5 mins followed by substrate addition incubated for 60 mins by TopCount scintillation counting method
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 503.33, ALogP 2.89, HBA 9, HBD 3, PSA 134.33, QED 0.39
Compound (SMILES): Cc1cc(NS(=O)(=O)c2ccc(/N=N/N3CCN(c4cc5c(cc4F)c(=O)c(C(=O)O)cn5C4CC4)CC3)cc2)no1
InChIKey: OPYFYWGZFLECPY-UUDCSCGESA-N
Target: DNA gyrase (PROTEIN COMPLEX), Escherichia coli
UniProt: P0AES4
Assay: Inhibition of Escherichia coli DNA gyrase supercoiling activity using pBR322 as substrate incubated for 30 mins by fluorimetric assay
Measurement: IC50 = 1950 nM (pChEMBL 5.710000038146973)
Descriptors: MW 595.61, ALogP 4.09, HBA 10, HBD 2, PSA 162.7, QED 0.29
Compound (SMILES): COc1cc2nc(C)nc(N[C@H](C)c3cccc(C(F)(F)F)c3)c2cc1OC
InChIKey: UWEJNKMEGIGAGY-LLVKDONJSA-N
Target: Son of sevenless homolog 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q07889
Assay: Binding affinity to SOS1 (unknown origin) assessed as dissociation constant by SPR analysis
Measurement: Kd = 104 nM (pChEMBL 6.980000019073486)
Descriptors: MW 391.39, ALogP 5.15, HBA 5, HBD 1, PSA 56.27, QED 0.65
Compound (SMILES): Cc1cc(Oc2cccc(-c3c(C)nnn3C3CCNCC3)n2)cc(C(C)C)c1
InChIKey: WVYHJSWCINMSJN-UHFFFAOYSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to BRD4 BD2 (unknown origin) by fluorescence anisotropy method
Measurement: IC50 = 12500 nM (pChEMBL 4.900000095367432)
Descriptors: MW 391.52, ALogP 4.8, HBA 6, HBD 1, PSA 64.86, QED 0.68
Compound (SMILES): O=c1c2cccnc2ncn1Cc1nc([C@H]2[C@@H]3CN(c4cc(Cl)ccn4)C[C@@H]32)no1
InChIKey: XATNITDFSRCWBI-HALDLXJZSA-N
Target: Transient receptor potential cation channel subfamily A member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O75762
Assay: FLIPR Assay (90 minutes): The IC50 (effective concentration) of compounds on the human TRPA1 channel was determined using a FLIPR Tetra instrument. CHO cells expressing TRPA1 were plated into 384-well plates, incubated overnight at 37° C., and loaded with BD calcium indicator dye for 1 hr at 37° C. followed by 90 minutes at room temperature. The assay buffer was Hank's Balanced Salt Solution (HBSS) containing 20 mM HEPES (pH readjusted to 7.4) along with 0.02% BSA.Following dye load and plate cool down, compounds were added to the cells using FLIPR Tetra. Plates were then incubated with compounds for 10 minutes or 90 minutes at room temperature prior to adding agonist. Following this incubation, about an EC50 concentration of cinnamaldehyde (75) was added to active the channels and block of cinnamaldehyde induced calcium influx was measured.The IC50 results were fit with a standard Hill function, keeping the Hill coefficient (n) fixed to 1.5. Fixing the Hill coefficient will generally reduce variability of the IC50 determination. The IC50 results were individually examined to make sure the MIN and MAX points were set correctly prior to validation of the results.
Measurement: IC50 = 52 nM (pChEMBL 7.28000020980835)
Descriptors: MW 421.85, ALogP 2.12, HBA 9, HBD 0, PSA 102.83, QED 0.49
Compound (SMILES): COc1cccc(NC(=O)[C@H]2CC[C@@H](n3cnc4c(N)nc(N5CCN(C)CC5)nc43)CC2)c1
InChIKey: DRDFWPRJOTTXGN-MAEOIBBWSA-N
Target: Choline/ethanolamine kinase (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y259
Assay: Inhibition of ChoKbeta (unknown origin) by HTS assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 464.57, ALogP 2.54, HBA 9, HBD 2, PSA 114.43, QED 0.59
Compound (SMILES): [2H]C1([2H])Oc2cc(S(=O)(=O)N3CC4=C(CN(C(=O)C(O)c5cccc6oc(C)nc56)C4)C3)cnc2OC1([2H])[2H]
InChIKey: SCFWBZTVFCUBIZ-NZLXMSDQSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 9X (SINGLE PROTEIN), Homo sapiens
UniProt: Q93008
Assay: Inhibition of USP9X (unknown origin) using Ubiquitin-Rhoadmine 110 as substrate preincubated for 30 mins followed by substrate addition and measured after 11 mins by fluorescence assay
Measurement: IC50 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 498.52, ALogP 1.18, HBA 9, HBD 1, PSA 135.3, QED 0.53
Compound (SMILES): CC(C)C[C@H](NC(=O)[C@H]1Cn2nncc2CCCC(=O)NCC(=O)N2CCC[C@H]2C(=O)N[C@@H](Cc2cccc3ccccc23)C(=O)N1)C(N)=O
InChIKey: LSXQVMZOPNHOBG-FKWFRFQNSA-N
Target: GTPase KRas (SINGLE PROTEIN), Homo sapiens
UniProt: P01116
Assay: Inhibition of alexa fluor 647-labeled kinase tracer 314 binding to biotinylated-KRAS G12V mutant (unknown origin) measured after 60 mins by HTRF competition binding assay
Measurement: IC50 = 31622.78 nM (pChEMBL 4.5)
Descriptors: MW 687.8, ALogP 0.1, HBA 9, HBD 5, PSA 210.51, QED 0.23
Compound (SMILES): CC(C)Nc1cc([C@H](C)Cc2nncn2C)cc(N2Cc3c(cccc3C(F)(F)F)C2=O)n1
InChIKey: JCEJFAGAEHSOAC-CQSZACIVSA-N
Target: E3 ubiquitin-protein ligase CBL-B (SINGLE PROTEIN), Homo sapiens
UniProt: Q13191
Assay: Binding affinity towards N-terminal biotinylated Avi-tagged human CBL-B (36 to 427 residues) measured by surface plasmon resonance assay
Measurement: Kd < 100 nM (pChEMBL 7)
Descriptors: MW 458.49, ALogP 4.56, HBA 6, HBD 1, PSA 75.94, QED 0.59
Compound (SMILES): C[C@@H]1Cc2c([nH]c3ccccc23)[C@@H](c2c(F)cc(-n3ccc(C(=O)O)n3)cc2F)N1CC(C)(C)F
InChIKey: KDDITTKNXMSLDP-JBEBIEQOSA-N
Target: Estrogen receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P03372
Assay: Induction of degradation of ERalpha in human MCF7 cells incubated for 4 hrs in presence of anti-ERalpha rabbit monoclonal antibodies measured after 4 hrs by immunofluorescent staining based assay
Measurement: EC50 = 0.26 nM (pChEMBL 9.59000015258789)
Descriptors: MW 482.51, ALogP 5.41, HBA 4, HBD 2, PSA 74.15, QED 0.4
Compound (SMILES): O=[N+]([O-])CC(c1ccccc1)c1c(-c2cccs2)[nH]c2ccccc12
InChIKey: QNQUTJGZWCWWQV-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Positive allosteric modulation of human CB1 receptor expressed in CHO-K1 cells assessed as beta-arrestin 2 recruitment incubated for 90 mins by PathHunter chemiluminescence based assay
Measurement: EC50 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 348.43, ALogP 5.31, HBA 3, HBD 1, PSA 58.93, QED 0.39
Compound (SMILES): CNc1ccc2ccc(OCc3cncc(-n4cc(-c5ccnn5C)c5c(N)ncnc54)c3)cc2n1
InChIKey: VAZCIDBCHRWUPK-UHFFFAOYSA-N
Target: Protein arginine N-methyltransferase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: O14744
Assay: Inhibition of PRMT5 (unknown origin) using Ac-SGRGKGGKGLGKGGAKRHRKVGGK-Biotin and 3H-SAM as substrates preincubated for 5 mins followed by substrate addition incubated for 60 mins by TopCount scintillation counting method
Measurement: IC50 >= 1000 nM (pChEMBL 6)
Descriptors: MW 477.53, ALogP 3.97, HBA 10, HBD 2, PSA 121.59, QED 0.37
Compound (SMILES): Cc1cc2[nH]c(-c3n[nH]c4c3C[C@@H]3C[C@]3(C)C4)nc2cc1N(C)C(=O)[C@H](C)N1CCOCC1
InChIKey: DVXKDRBZBOJVGG-JAUXOLPYSA-N
Target: Interleukin-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P60568
Assay: Inhibition of IL-2 in CD3/CD28 activated human CD4+ve Th cells preincubated for 15 mins followed by addition of immuno-cult and measured after 24 hrs by HTRF assay
Measurement: IC50 = 39 nM (pChEMBL 7.409999847412109)
Descriptors: MW 448.57, ALogP 3.07, HBA 5, HBD 2, PSA 90.14, QED 0.64
Compound (SMILES): Cc1ccc(CCNC(=O)Nc2ccc(Cl)cc2)cc1
InChIKey: CQBUCSOBEYHPPY-UHFFFAOYSA-N
Target: Cannabinoid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P21554
Assay: Allosteric antagonist activity against human CB1 receptor expressed in HEK293 cells membrane measured after 60 mins by [35S]GTPgammaS binding assay
Measurement: IC50 = 13803.84 nM (pChEMBL 4.860000133514404)
Descriptors: MW 288.78, ALogP 4.01, HBA 1, HBD 2, PSA 41.13, QED 0.88
Compound (SMILES): O=C1CCC(N2Cc3cc(C4CCN(Cc5ccc(-n6cccn6)cc5)CC4)ccc3C2=O)C(=O)N1
InChIKey: FYHGDCNVRQYJDO-UHFFFAOYSA-N
Target: Eukaryotic peptide chain release factor GTP-binding subunit ERF3A (SINGLE PROTEIN), Homo sapiens
UniProt: P15170
Assay: Induction of GSPT1 degradation in human GripTite 293 MSR cells assessed as reduction in GSPT1 level measured by PathHunter assay
Measurement: EC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 483.57, ALogP 3.01, HBA 6, HBD 1, PSA 87.54, QED 0.56
Compound (SMILES): CCCO[C@@H]1O[C@H](CNC(=O)c2ccc(S(N)(=O)=O)cc2)[C@H](O)[C@H](O)[C@H]1O
InChIKey: YOJAMANFZBEUHY-WZYWGQKZSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of recombinant human CA2 using 4-nitrophenylacetate as substrate by esterase assay
Measurement: IC50 = 110 nM (pChEMBL 6.960000038146973)
Descriptors: MW 404.44, ALogP -1.7, HBA 8, HBD 5, PSA 168.41, QED 0.36
Compound (SMILES): NS(=O)(=O)c1ccc(C(=O)N2CCN(Cc3ccccc3)C(CCO)C2)cc1
InChIKey: URRVQZIATPXFAS-UHFFFAOYSA-N
Target: Carbonic anhydrase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P00918
Assay: Inhibition of human CA2 incubated for 15 mins prior to testing by phenol red dye based stopped flow CO2 hydration assay
Measurement: Ki = 11.6 nM (pChEMBL 7.940000057220459)
Descriptors: MW 403.5, ALogP 1.04, HBA 5, HBD 2, PSA 103.94, QED 0.75
Compound (SMILES): CNC(=O)c1c(-c2ccc(O)cn2)oc2ccc(O)c(CN3CCCC3)c12
InChIKey: YSFBPXVQYPPRBW-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG ion channel by Q patch-clamp method
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 367.41, ALogP 2.86, HBA 6, HBD 3, PSA 98.83, QED 0.66
Compound (SMILES): O=C1CCC(N2Cc3cc(C4CCN(Cc5ccc6ccc(F)cc6n5)CC4)ccc3C2=O)C(=O)N1
InChIKey: LJBBUSNWLWQUMC-UHFFFAOYSA-N
Target: Eukaryotic peptide chain release factor GTP-binding subunit ERF3A (SINGLE PROTEIN), Homo sapiens
UniProt: P15170
Assay: Induction of GSPT1 degradation in human GripTite 293 MSR cells assessed as reduction in GSPT1 level measured by PathHunter assay
Measurement: EC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 486.55, ALogP 3.51, HBA 5, HBD 1, PSA 82.61, QED 0.57
Compound (SMILES): Cc1cc(-n2ncn(-c3ccc(C(F)(F)F)cc3)c2=O)cc(C)c1OC(C)(C)C(=O)O
InChIKey: AZAUWYRRCDGTFI-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor delta (SINGLE PROTEIN), Homo sapiens
UniProt: Q03181
Assay: Agonist activity at PPARdelta (unknown origin)
Measurement: EC50 > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 435.4, ALogP 3.9, HBA 6, HBD 1, PSA 86.35, QED 0.66
Compound (SMILES): Cc1nnn(C)c1-c1ccc2c3ncc(C(C)(C)O)cc3n([C@H](c3ccccc3)C3CCOCC3)c2c1F
InChIKey: XYVCWEWEPXYPNF-MUUNZHRXSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Inhibition of BRD4 (unknown origin)
Measurement: IC50 = 4 nM (pChEMBL 8.399999618530273)
Descriptors: MW 513.62, ALogP 5.68, HBA 7, HBD 1, PSA 77.99, QED 0.33
Compound (SMILES): O=C(O)c1cnc(SCCc2ccccc2)[nH]c1=O
InChIKey: XJDNGNGXQUTGPB-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2K7
Assay: Inhibition of human N-terminal His6-tagged KDM2A (M1 to P517 residues) expressed in insect cells using H3K36(Me2) as substrate preincubated for 15 mins followed by substrate addition and measured after 30 mins by Alphascreen assay
Measurement: IC50 = 52700 nM (pChEMBL 4.28000020980835)
Descriptors: MW 276.32, ALogP 1.8, HBA 4, HBD 2, PSA 83.05, QED 0.64
Compound (SMILES): N/C(=N\C(=N\S(=O)(=O)N1CCCC1)N1CC(c2ccccc2)C(c2ccc(Cl)cc2)=N1)c1ccc(F)cc1
InChIKey: OPECFVRNMDHMNE-UHFFFAOYSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]- CP55940 from human CB2R expressed in CHO-K1 cells membrane by Cheng-Prusoff equation analysis
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 553.06, ALogP 4.38, HBA 3, HBD 1, PSA 103.72, QED 0.37
Compound (SMILES): CCOc1cc([C@H](C)Cc2nncn2C)cc(N2Cc3c(cccc3C(F)(F)F)C2=O)n1
InChIKey: ZLAOKVPTSVSNRB-CYBMUJFWSA-N
Target: E3 ubiquitin-protein ligase CBL-B (SINGLE PROTEIN), Homo sapiens
UniProt: Q13191
Assay: Binding affinity towards N-terminal biotinylated Avi-tagged human CBL-B (36 to 427 residues) measured by surface plasmon resonance assay
Measurement: Kd < 100 nM (pChEMBL 7)
Descriptors: MW 445.45, ALogP 4.13, HBA 6, HBD 0, PSA 73.14, QED 0.57
Compound (SMILES): Cc1cc(C(=O)Nc2cccc([C@H](C)Cc3nncn3C)c2)nc(C2CC2)n1
InChIKey: KZXKWROQQPFRET-CYBMUJFWSA-N
Target: E3 ubiquitin-protein ligase CBL-B (SINGLE PROTEIN), Homo sapiens
UniProt: Q13191
Assay: Binding affinity towards N-terminal biotinylated Avi-tagged human CBL-B (36 to 427 residues) measured by surface plasmon resonance assay
Measurement: Kd < 100 nM (pChEMBL 7)
Descriptors: MW 376.46, ALogP 3.39, HBA 6, HBD 1, PSA 85.59, QED 0.71
Compound (SMILES): COc1cc(/C=C/C(=O)NCCCCNC(=O)Oc2ccc3c(c2)CN2CCc4ccccc4C2N3C)ccc1O
InChIKey: SKFATRLUVYBNSY-GXDHUFHOSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human BChE using butyrylthiocholine iodide as substrate incubated for 20 mins followed by substrate addition by Ellman's method
Measurement: IC50 = 114.82 nM (pChEMBL 6.940000057220459)
Descriptors: MW 556.66, ALogP 4.61, HBA 7, HBD 3, PSA 103.37, QED 0.26
Compound (SMILES): CCCCNc1nc(N)nc2ccc(Cc3ccccc3C(=O)OC)nc12
InChIKey: BWXYWOGDGUWDQR-UHFFFAOYSA-N
Target: Toll-like receptor 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR97
Assay: Agonist activity at human TLR8 expressed in HEK293 cells incubated for 6 to 16 hrs by SEAP reporter gene assay
Measurement: EC50 = 2280 nM (pChEMBL 5.639999866485596)
Descriptors: MW 365.44, ALogP 3.2, HBA 7, HBD 2, PSA 103.02, QED 0.49
Compound (SMILES): CNc1ccc2ccc(OC[C@H]3O[C@@H](n4cc(-c5cc(F)cc(F)c5)c5c(N)ncnc54)[C@@H](F)[C@@H]3O)cc2n1
InChIKey: YJICMHRPAOFCRY-WJKQRCEYSA-N
Target: Protein arginine N-methyltransferase 5 (SINGLE PROTEIN), Homo sapiens
UniProt: O14744
Assay: Inhibition of PRMT5 (unknown origin) using Ac-SGRGKGGKGLGKGGAKRHRKVGGK-Biotin and 3H-SAM as substrates preincubated for 5 mins followed by substrate addition incubated for 60 mins by TopCount scintillation counting method
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 536.51, ALogP 4.22, HBA 9, HBD 3, PSA 120.34, QED 0.3
Compound (SMILES): NC(=O)[C@@H]1CC(O)CN1C(=O)c1ccc(NC(=O)Nc2ccc(-c3nc(N4CCOCC4)nc(N4CCOCC4)n3)cc2)cc1
InChIKey: LILBAKYEAUUWIF-CGAIIQECSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Inhibition of mTOR (unknown origin) using U-Light-4E-BP1 peptide as a substrate in presence of ATP incubated for 45 mins by Lance ultra assay
Measurement: IC50 = 2.2 nM (pChEMBL 8.65999984741211)
Descriptors: MW 617.67, ALogP 0.92, HBA 11, HBD 4, PSA 188.37, QED 0.3
Compound (SMILES): CNC(=O)c1c(-c2cccc(O)c2)oc2ccc(O)c(CN3CCC4(COC4)C3)c12
InChIKey: HFIAZGUOIGBSNX-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG ion channel by Q patch-clamp method
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 408.45, ALogP 3.09, HBA 6, HBD 3, PSA 95.17, QED 0.61
Compound (SMILES): CC(C)O[C@H]1CC[C@H](C(=O)N2Cc3cc(F)cnc3Nc3ccc(N4CC5CCC4CO5)cc32)CC1
InChIKey: CNUHIEXZNDMQEL-ABKYZYHSSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: R132H IDH1 Enzymatic Assay: Each test compound (10 mM stock in DMSO) is diluted in DMSO to make a 10-point, 3-fold dilution series. 125 nL of each dilution or DMSO alone is dispensed to a 384-well Greiner Lumitrac 200 assay plate using an Echo® Liquid Handler. To each well of the plate is added 20 uL of enzyme in assay buffer or assay buffer alone. Assay buffer consists of 50 mM sodium phosphate, pH 7.0, 50 mM magnesium chloride, 50 mM sodium chloride, and 0.01% (w/v) bovine serum albumin. When present, the R132H mutant IDH1 enzyme is at a working concentration of 1.875 nM (final concentration in assay of 1.5 nM). The assay plate is allowed to incubate for 30 minutes at room temperature and 5 uL of 5× substrate mixture (2.5 uM nicotinamide adenine dinucleotide phosphate, 100 uM adenosine diphosphate, 7.5 mM glyceraldehyde-3-phosphate, 7.5 ug/mL of spinach glyceraldehyde-3-phosphate dehydrogenase, 25 nM phosphoglycerate kinase, and 5 mM alpha-ketoglutarate in assay buffer) is added to all wells. The reaction plate is incubated for 60 minutes followed by addition of 25 uL of Promega Kinase-GLO reagent to all wells and 10-minute incubation.Luminescence is measured using a PerkinElmer Envision plate reader. The percent activity of each dilution is determined as the ratio of background corrected signal to the background corrected signal of wells receiving only DMSO. IC50 values are determined by fitting percent activity data to a four-parameter logistic dose response equation.
Measurement: IC50 = 35.5 nM (pChEMBL 7.449999809265137)
Descriptors: MW 494.61, ALogP 5.16, HBA 6, HBD 1, PSA 66.93, QED 0.63
Compound (SMILES): COC(=O)CCC(=O)N1CCc2ccccc21
InChIKey: AYMVNVWATJUROX-UHFFFAOYSA-N
Target: Palmitoleoyl-protein carboxylesterase NOTUM (SINGLE PROTEIN), Homo sapiens
UniProt: Q6P988
Assay: Inhibition of Notum 1 (unknown origin) expressed in HEK293 cells harbouring TCF/LEF luciferase reporter gene assessed as modulation of Wnt/beta-catenin signalling pathway preincubated with recombinant Wnt-3A for 1 hr followed by addition to reporter cell plate incubated overnight by luminescence based microplate reader analysis
Measurement: EC50 = 530 nM (pChEMBL 6.28000020980835)
Descriptors: MW 233.27, ALogP 1.53, HBA 3, HBD 0, PSA 46.61, QED 0.74
Compound (SMILES): COc1cc(N2CCC(N3CCN(C(=O)CNc4cccc5c4C(=O)N(C4CCC(=O)NC4=O)C5=O)CC3)CC2)ccc1Nc1ncc(Cl)c(Nc2ccccc2P(C)(C)=O)n1
InChIKey: AQGLXXCBEXDRNS-UHFFFAOYSA-N
Target: ALK tyrosine kinase receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UM73
Assay: Binding affinity to ALK G1202R mutant (unknown origin)
Measurement: IC50 = 6.6 nM (pChEMBL 8.180000305175781)
Descriptors: MW 883.35, ALogP 4.5, HBA 14, HBD 4, PSA 198.51, QED 0.11
Compound (SMILES): CN1CCC(NC(=O)c2cc(-c3ccc(NS(=O)(=O)c4cccc(Cl)c4Cl)cc3)nc3[nH]ncc23)C1
InChIKey: LGILVONNASJJBC-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase Sgk1 (SINGLE PROTEIN), Homo sapiens
UniProt: O00141
Assay: Inhibition of recombinant human SGK1 expressed in baculovirus expression system using 5-carboxyfluorescein -RPRAATF-NH2 as substrate preincubated for 30 mins followed by substrate addition in presence of 500 uM ATP and measured after 60 mins by microfluidics assay
Measurement: IC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 545.45, ALogP 4.17, HBA 6, HBD 3, PSA 120.08, QED 0.33
Compound (SMILES): CCC(=O)N(CC(C)(C)N1CCN(Cc2ccccc2)CC1)c1ccccc1
InChIKey: AORIOLLAPPJVNF-UHFFFAOYSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35372
Assay: Displacement of [3H]-DAMGO from human MOR expressed in CHO-K1 cell membranes incubated for 60 mins measured by MicroBeta scintillation counter method
Measurement: Ki = 95 nM (pChEMBL 7.019999980926514)
Descriptors: MW 379.55, ALogP 4.03, HBA 3, HBD 0, PSA 26.79, QED 0.73
Compound (SMILES): CNc1nc(-c2ccccc2)c(C#N)c(-c2cc(OC)c(OC)c(OC)c2)n1
InChIKey: WPAJIVUBONCJIM-UHFFFAOYSA-N
Target: Adenosine receptor A2a (SINGLE PROTEIN), Homo sapiens
UniProt: P29274
Assay: Displacement of [3H]HZ241385 from human A2AAR expressed in HeLa cell membrane incubated for 30 mins by microbeta trilux scintillation counter analysis
Measurement: Ki = 3.63 nM (pChEMBL 8.4399995803833)
Descriptors: MW 376.42, ALogP 3.75, HBA 7, HBD 1, PSA 89.29, QED 0.7
Compound (SMILES): Cc1c(CN2CCN(C(=O)C3CCCC3)CC2)cccc1NC(=O)Nc1ccccc1
InChIKey: FXDHHICKEURBRU-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (quinone), mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q02127
Assay: Inhibition of human recombinant DHODH expressed in Escherichia coli BL21 (DE3) using dihydroorotate as substrate and CoQ6 as co-substrate incubated for 10 mins by DCIP based multimode microplate reader analysis
Measurement: IC50 = 11300 nM (pChEMBL 4.949999809265137)
Descriptors: MW 420.56, ALogP 4.47, HBA 3, HBD 2, PSA 64.68, QED 0.75
Compound (SMILES): COc1cc(/C=C/c2n[nH]c(=O)o2)cc(OC)c1OC
InChIKey: WHCQYBLJAMXFBL-SNAWJCMRSA-N
Target: Amine oxidase [flavin-containing] B (SINGLE PROTEIN), Homo sapiens
UniProt: P27338
Assay: Inhibition of human recombinant MAO-B using tyramine as substrate by fluorescence assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 278.26, ALogP 1.56, HBA 6, HBD 1, PSA 86.58, QED 0.89
Compound (SMILES): O=C(Nc1ccc(NS(=O)(=O)c2ccc(F)cc2)cc1)c1ccc([N+](=O)[O-])o1
InChIKey: IXRKSCXINNDKBQ-UHFFFAOYSA-N
Target: Urea transporter 1 (SINGLE PROTEIN), Mus musculus
UniProt: Q8VHL0
Assay: Inhibition of mouse UT-B expressed in MDCK cells
Measurement: IC50 = 1310 nM (pChEMBL 5.880000114440918)
Descriptors: MW 405.36, ALogP 3.38, HBA 6, HBD 2, PSA 131.55, QED 0.48
Compound (SMILES): C=C1C(=O)O[C@@H]2/C=C(\C)[C@@H](O)C/C=C(\C)C[C@@H](OC(=O)/C(=C\C)COC(C)=O)[C@@H]12
InChIKey: OTQFWNFLOYRPGC-QUNVVSSUSA-N
Target: Tyrosine-protein phosphatase non-receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P17706
Assay: Inhibition of human recombinant TCPTP using pNPP as substrate assessed as reduction in p-nitrophenol release incubated for 30 mins by absorbance based analysis
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 404.46, ALogP 2.55, HBA 7, HBD 1, PSA 99.13, QED 0.33
Compound (SMILES): C#CCN1CCC(CCC(=O)c2ccc(N3CCN(CCCCc4c[nH]c5ccc(C#N)cc45)CC3)cc2)CC1
InChIKey: UJOYNUWZWLPODQ-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Agonist activity at human 5-HT1A receptor expressed in HEK293 cells incubated for 60 mins by Eu-cAMP tracer based LANCE ultra cAMP assay
Measurement: EC50 = 29 nM (pChEMBL 7.539999961853027)
Descriptors: MW 535.74, ALogP 5.49, HBA 5, HBD 1, PSA 66.37, QED 0.2
Compound (SMILES): O=C(NC12CC3CC(Cl)(CC(C1)c1ccccc13)C2)N[C@H]1CC[C@H](Oc2ccc(C(=O)O)cc2)CC1
InChIKey: RMDYCVFIANAQPV-ZDQKIBCQSA-N
Target: Bifunctional epoxide hydrolase 2 (SINGLE PROTEIN), Mus musculus
UniProt: P34914
Assay: Inhibition of mouse recombinant sEH using CMNPC as substrate incubated for 5 mins by fluorescent based assay
Measurement: IC50 = 0.4 nM (pChEMBL 9.399999618530273)
Descriptors: MW 509.05, ALogP 5.95, HBA 3, HBD 3, PSA 87.66, QED 0.44
Compound (SMILES): COc1cc(NC(=O)c2cc(=O)c3ccccc3o2)c(-c2nnn(-c3ccc(CCN4CCn5cncc5C4)cc3)n2)cc1OC
InChIKey: JUDGYJOURFAWRX-UHFFFAOYSA-N
Target: ATP-dependent translocase ABCB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08183
Assay: Inhibition of wild type human P-gp in human MES-SA/Dx5 cells incubated for 3 days by MTT assay
Measurement: IC50 > 1280 nM (pChEMBL 5.89300012588501)
Descriptors: MW 618.65, ALogP 3.96, HBA 12, HBD 1, PSA 142.43, QED 0.25
Compound (SMILES): Cc1nn(CC(F)(F)F)cc1Nc1ncc(C2CC2)c(NCc2ccc(S(N)(=O)=O)cc2)n1
InChIKey: MKXAPJAJZRQNMB-UHFFFAOYSA-N
Target: MAP/microtubule affinity-regulating kinase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P27448
Assay: Displacement of tracer K9 from NLuc fused MARK3 (unknown origin) expressed in HEK293 cells by NanoBRET assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 481.5, ALogP 3.42, HBA 8, HBD 3, PSA 127.82, QED 0.45
Compound (SMILES): Cc1cc(Nc2ncc(Cl)c(Nc3ccccc3P(C)(C)=O)n2)ccc1N1CCC(N2CCN(C)CC2)CC1
InChIKey: AFIJTZLVCCKWKO-UHFFFAOYSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of EGFR L858R/T790M/C797S triple mutant (unknown origin) measured by ELISA
Measurement: IC50 = 0.7 nM (pChEMBL 9.149999618530273)
Descriptors: MW 568.11, ALogP 5.39, HBA 8, HBD 2, PSA 76.63, QED 0.37
Compound (SMILES): CC(C)(Oc1ccc(Cn2ncn(-c3ccc(OC(F)(F)F)cc3)c2=O)cc1C(F)(F)F)C(=O)O
InChIKey: PFRJTIMCBPCWPY-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor delta (SINGLE PROTEIN), Homo sapiens
UniProt: Q03181
Assay: Agonist activity at PPARdelta (unknown origin)
Measurement: EC50 = 90.7 nM (pChEMBL 7.039999961853027)
Descriptors: MW 505.37, ALogP 4.24, HBA 7, HBD 1, PSA 95.58, QED 0.48
Compound (SMILES): CC(C)c1ccccc1-c1nc(NCc2ccccn2)c2ncccc2n1
InChIKey: JQFZVOONUHIJMR-UHFFFAOYSA-N
Target: Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P48426
Assay: Inhibition of PI5P4Kalpha (unknown origin) by ADP-Glo assay
Measurement: IC50 > 50118.72 nM (pChEMBL 4.300000190734863)
Descriptors: MW 355.45, ALogP 4.82, HBA 5, HBD 1, PSA 63.59, QED 0.56
Compound (SMILES): CC(C)(C)c1cn(CCNc2nonc2/C(=N/O)Nc2ccc(F)c(Br)c2)nn1
InChIKey: STBXVMPQYWHXKI-UHFFFAOYSA-N
Target: Indoleamine 2,3-dioxygenase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6ZQW0
Assay: Inhibition of IDO2 (unknown origin) assessed as reduction in kynurenine formation using L-tryptophan as substrate by methylene blue reagent based assay
Measurement: IC50 = 1874 nM (pChEMBL 5.730000019073486)
Descriptors: MW 467.3, ALogP 3.22, HBA 9, HBD 3, PSA 126.28, QED 0.22
Compound (SMILES): Cc1nnc2c(N)cc(C(=O)N3[C@H]4Cc5ccccc5[C@@H]3CNC4=O)nn12
InChIKey: RNMUWJXNHYJGEP-GJZGRUSLSA-N
Target: ATPase family AAA domain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6PL18
Assay: Inhibition of GST-ATAD2 BD (951 to 1132 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) and biotinylated tetra-acetylated histone H4 peptides as substrate incubated for 30 mins by TR-FRET assay
Measurement: IC50 = 280 nM (pChEMBL 6.550000190734863)
Descriptors: MW 363.38, ALogP 0.25, HBA 7, HBD 2, PSA 118.51, QED 0.64
Compound (SMILES): Fc1cc(-c2ccc3c(c2)[nH]c2ccncc23)ccn1
InChIKey: BPSQAPCJHLZFPT-UHFFFAOYSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Mus musculus
UniProt: Q64133
Assay: Displacement of [18F]-FEH from MAO-A in mouse brain homogenate incubated for 60 mins by imaging analysis
Measurement: IC50 = 51 nM (pChEMBL 7.289999961853027)
Descriptors: MW 263.27, ALogP 3.92, HBA 2, HBD 1, PSA 41.57, QED 0.53