lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CNCC(O)CN1CCc2c(cccc2OCc2ccc(F)cc2)C1
InChIKey: YALVTUCSYPQWQV-UHFFFAOYSA-N
Target: Histone-arginine methyltransferase CARM1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q86X55
Assay: Inhibition of PRMT4 (unknown origin) using histone H3 (21 to 44 residues) as substrate measured after 60 mins in presence of SAM by AlphaLisa assay
Measurement: IC50 = 228 nM (pChEMBL 6.639999866485596)
Descriptors: MW 344.43, ALogP 2.34, HBA 4, HBD 2, PSA 44.73, QED 0.81
Compound (SMILES): COc1ccc(-c2c(Nc3nncs3)[nH]c3c(-c4ccccc4)c(-c4ccccc4)nn3c2=O)cc1
InChIKey: YAOIFXUDEKZABL-UHFFFAOYSA-N
Target: S-adenosylmethionine synthase isoform type-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P31153
Assay: Inhibition of recombinant His6-tagged MAT2A (unknown origin) expressed in SF9 insect cells using L-Met as substrate preincubated for 60 mins followed by substrate and ATP addition and measured after 60 mins by spectrophotometric analysis
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 492.56, ALogP 5.63, HBA 8, HBD 2, PSA 97.2, QED 0.31
Compound (SMILES): CCCNC1=N[C@@H]2[C@@H](O)[C@H](O)[C@@H](CF)O[C@@H]2S1
InChIKey: XCVBKZPSKQHUMO-JGKVKWKGSA-N
Target: Beta-hexosaminidase subunit beta (SINGLE PROTEIN), Homo sapiens
UniProt: P07686
Assay: Inhibition of human beta hexosaminidase assessed as inhibitory constant using 4-methylumbelliferyl N-acetyl-beta-D-glucosaminide dihydrate as substrate measured every 60 sec for 45 mins by fluorescence spectrophotometry
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 264.32, ALogP -0.13, HBA 6, HBD 3, PSA 74.08, QED 0.66
Compound (SMILES): COc1cc(N2CCC(C)(C(O)Cn3nc(C(F)(F)F)c(Cl)c3C)CC2)ccc1Cl
InChIKey: DWUDTZIVCJBSHJ-UHFFFAOYSA-N
Target: C-C chemokine receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P32246
Assay: Displacement of human [125I]-MIP-1alpha from CCR1 in human THP-1 cells incubated for 30 mins by radioligand binding assay
Measurement: Ki = 1250 nM (pChEMBL 5.900000095367432)
Descriptors: MW 466.33, ALogP 5.19, HBA 5, HBD 1, PSA 50.52, QED 0.66
Compound (SMILES): O=c1[nH]c(-c2cc(S(=O)(=O)N3CCC(C(F)(F)F)CC3)ccn2)nc2c1CCC2
InChIKey: PYWMCZCABVZOAY-UHFFFAOYSA-N
Target: Sepiapterin reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P35270
Assay: Inhibition of terbium-labeled SNAP-tagged human SPR in presence of sulfasalazine-labeled SNAP-tagged EGFP by homogenous TR-FRET assay
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 428.44, ALogP 2.28, HBA 5, HBD 1, PSA 96.02, QED 0.81
Compound (SMILES): O=c1cc(N2CCN(CC3CCCCC3)CC2)sc2c([N+](=O)[O-])cc(C(F)(F)F)cc12
InChIKey: LKTGKSLRRVEZFI-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes after 20 mins by LC-MS/MS analysis
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 455.5, ALogP 4.89, HBA 6, HBD 0, PSA 66.69, QED 0.49
Compound (SMILES): COc1cc(O)c(C(=O)/C=C/c2ccc(N3CCNCC3)cc2)c(OC)c1
InChIKey: RDBYHAGNGNMHQM-VMPITWQZSA-N
Target: ATP-dependent translocase ABCB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08183
Assay: Reversal of P-gp-mediated multidrug resistance in human MCF7/Dox cells assessed as potentiation of doxorubicin-induced cytotoxicity by measuring doxorubicin IC50 at 12.5 uM after 48 hrs by MTT assay (Rvb = 51.19 +/- 0.95 microM)
Measurement: IC50 = 16620 nM (pChEMBL 4.78000020980835)
Descriptors: MW 368.43, ALogP 2.72, HBA 6, HBD 2, PSA 71.03, QED 0.6
Compound (SMILES): Cc1cc(C)n2cc(CSc3nc(-c4ccccc4)cc(C(F)(F)F)n3)nc2n1
InChIKey: NWAVAKJRSREHKD-UHFFFAOYSA-N
Target: cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y233
Assay: Inhibition of human PDE10A2 catalytic domain (446 to 789 residues) expressed in Escherichia coli BL21 cells using [3H]-cGMP as substrate after 15 mins by liquid scintillation analysis
Measurement: IC50 = 39 nM (pChEMBL 7.409999847412109)
Descriptors: MW 415.44, ALogP 5.11, HBA 6, HBD 0, PSA 55.97, QED 0.34
Compound (SMILES): CN1c2ccccc2CCc2ccc(C(N)=S)cc21
InChIKey: UBBHEZHOOIEIAF-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase ASH1L (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR48
Assay: Inhibition of MOCR-fused ASH1L SET-BAH ( 2069 to 2833 amino acids) (unknown origin) expressed as in Escherichia coli BL21 (DE3) T1R cells using SAM and chicken mono/dinucleosomes incubated for 1 hr by scintillation counting assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 268.38, ALogP 3.19, HBA 2, HBD 1, PSA 29.26, QED 0.81
Compound (SMILES): Cc1cc(-c2cnn3c(NCC4CCOCC4)cc(N[C@H]4CCC[C@H]4O)nc23)ccc1C(=O)NC1CC1
InChIKey: ASTZRJYXYNYIHJ-BJKOFHAPSA-N
Target: Dual specificity protein kinase TTK (SINGLE PROTEIN), Homo sapiens
UniProt: P33981
Assay: Inhibition of full length recombinant N-terminal GST-tagged and sumo-tagged human TTK (1 to 275 residues) expressed in Escherichia coli pre-incubated for 5 mins before ATP addition by indirect ELISA
Measurement: IC50 = 2.7 nM (pChEMBL 8.569999694824219)
Descriptors: MW 504.64, ALogP 3.76, HBA 8, HBD 4, PSA 112.81, QED 0.37
Compound (SMILES): O=C(NCc1ccc(O)cc1)c1cccc(C(F)(F)F)c1
InChIKey: UOHDXOURGIDZIR-UHFFFAOYSA-N
Target: cGMP-specific 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Bos taurus
UniProt: Q28156
Assay: Inhibition of bovine aortic smooth muscle PDE5 using cGMP as substrate incubated for 30 mins in presence of EGTA and [3H]cGMP by liquid scintillation counting method
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 295.26, ALogP 3.34, HBA 2, HBD 2, PSA 49.33, QED 0.91
Compound (SMILES): CCc1c(-c2ccccc2C)[nH]c2c(C#N)cnn2c1=O
InChIKey: OXELDRCVUWWSFZ-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P29375
Assay: Inhibition of KDM5A (unknown origin) using ART(Kme3)QTARKSTGGKAPRKQLA-NovaTagPEG-biotin/1 uM 2-OG as substrate/co-factor by TR-FRET assay
Measurement: IC50 = 206 nM (pChEMBL 6.690000057220459)
Descriptors: MW 278.31, ALogP 2.43, HBA 4, HBD 1, PSA 73.95, QED 0.78
Compound (SMILES): CCc1ccc(COc2ccc(C3CN(C(=O)c4cc(OCCN5CCN(C)CC5)ccn4)C3)cc2OC)cc1
InChIKey: IPTAYBOCGZIFMP-UHFFFAOYSA-N
Target: Macrophage colony-stimulating factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P07333
Assay: Inhibition of human CSF1R tyrosine kinase domain (538 to 972 residues) using Poly(Glu, Tyr)-biotinylated peptide as substrate preincubated for 5 mins followed by substrate addition and measured after 10 mins by HTRF assay
Measurement: IC50 = 53 nM (pChEMBL 7.28000020980835)
Descriptors: MW 544.7, ALogP 4.1, HBA 7, HBD 0, PSA 67.37, QED 0.36
Compound (SMILES): NC(=O)c1cc(S(N)(=O)=O)c(Cl)cc1SC1CCCCC1
InChIKey: AUMZYYXDKOTCJB-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Binding affinity to recombinant human carbonic anhydrase 1 expressed in Escherichia coli expression system assessed as observed dissociation constant fluorescent thermal shift assay
Measurement: Kd = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 348.88, ALogP 2.51, HBA 4, HBD 2, PSA 103.25, QED 0.87
Compound (SMILES): CCCn1c(=O)[nH]c2nc(-c3ccc(S(=O)(=O)N4CCN(c5ccccc5)C(C)C4)cc3)[nH]c2c1=O
InChIKey: XKSNOWLSDJNHMP-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Displacement of [3H]PSB-603 from recombinant human A2B adenosine receptor expressed in CHO cell membranes measured after 75 mins in presence of adenosine deaminase by liquid scintillation counting method
Measurement: Ki = 7.15 nM (pChEMBL 8.149999618530273)
Descriptors: MW 508.6, ALogP 2.39, HBA 7, HBD 2, PSA 124.16, QED 0.41
Compound (SMILES): COc1ccc(OC)c(CNC(=O)c2ccc3c(c2)c(C)c(C)n3Cc2cccc(C(F)(F)F)c2)c1
InChIKey: MOQQEUVUJIAQSD-UHFFFAOYSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Displacement of fluormone PPAR green tracer ligand from recombinant GST-tagged PPARgamma ligand binding domain (unknown origin) incubated for 4 hrs by competitive fluorescence polarization binding assay
Measurement: IC50 = 48 nM (pChEMBL 7.320000171661377)
Descriptors: MW 496.53, ALogP 6.27, HBA 4, HBD 1, PSA 52.49, QED 0.33
Compound (SMILES): COc1cccc(C(=O)Nc2cc(C#N)ccc2N2CCC(Oc3ccc(F)cc3F)CC2)n1
InChIKey: PIYMXOFICQHOSH-UHFFFAOYSA-N
Target: G-protein coupled receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P46095
Assay: Modulator activity at GPR6 receptor (unknown origin) expressed in CHO-K1 cells assessed as inhibition of constitutive cAMP activity incubated for 45 mins by Eu-cAMP tracer based HTRF Ultra cAMP assay
Measurement: EC50 = 100 nM (pChEMBL 7)
Descriptors: MW 464.47, ALogP 4.54, HBA 6, HBD 1, PSA 87.48, QED 0.58
Compound (SMILES): OCCOc1ccc(CN2CCN(Cc3ccc(F)c(F)c3)[C@@H](CCO)C2)cc1
InChIKey: HMJJTMNNPGHSFP-IBGZPJMESA-N
Target: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: Q15118
Assay: Inhibition of PDK1 (unknown origin) using PDC E1 as substrate measured after 30 mins by kinase-glo assay
Measurement: IC50 = 410 nM (pChEMBL 6.389999866485596)
Descriptors: MW 406.47, ALogP 2.4, HBA 5, HBD 2, PSA 56.17, QED 0.67
Compound (SMILES): CC1=NN(c2cc(F)c(O)c(F)c2)C(=O)/C1=C\c1ccc(-c2ccccc2OC(F)(F)F)o1
InChIKey: AFRQRFQUCYWYQT-GDNBJRDFSA-N
Target: Histone acetyltransferase p300 (SINGLE PROTEIN), Homo sapiens
UniProt: Q09472
Assay: Inhibition of p300 (unknown origin) using biotinylated histone H3 (1 to 21 residues) as substrate measured after 90 mins in presence of Acetyl CoA by AlphaLISA assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 464.35, ALogP 5.64, HBA 5, HBD 1, PSA 75.27, QED 0.4
Compound (SMILES): COc1ccc(S(=O)(=O)c2ccc(CN)s2)cc1
InChIKey: WIIILIVKQKEPAB-UHFFFAOYSA-N
Target: Protein-lysine 6-oxidase (SINGLE PROTEIN), Homo sapiens
UniProt: P28300
Assay: LOX Enzyme Activity Assay: The following reagents were prepared:Reagents500 mM CHES, pH 9 (with NaOH), filtered (MW=207.29)20.7 g in 200 ml in dH2O10% Pluronic F-127 (store at 4° C.)1 g in 10 ml in dH2O10 % BSA (store at 4° C.)−2.5 g in 25 ml dH2O1 M MgCl2.6H2O (MW=203)5.1 g in 25 ml dH2O5 M Urea (MW=60.06)60 g in 200 ml dH2O5 M NaCl (MW=58.44)14.6 g in 50 ml dH2O8.5 M Cadaverine Dihydrochloride (MW=175.10): Sigma, Cat No: C85611.49 g in 1 ml dH2O10 mM Na3VO4, pH 10 (with HCl), boil to activate (MW=183.91): Sigma, Cat No: S65080.1839 g in 10 ml dH2O20 mM Amplex Red (MW=257.25): Invitrogen, Cat No: A12222.5 mg in 1 ml DMSO (aliquot into 40 μl and store at −20° C.)1000 U/ml HRP in dH2O (store at 4° C.): Sigma, Cat No: P2088H2O2 (store at 4° C.): Sigma, Cat No: H1009DMSOLOX Assay Buffer: Volume (μl) Reagent 1 × plate Final Concn 500 mM CHES, pH 9 5000 100 mM 10% Pluronic F-127 125 0.05% 10% BSA 1250 0.5% 1M MgCl2 25  1 mM 5M Urea 5000 1M 5M NaCl 500 100 mM dH2O 13100 — Total Volume 25 000 —Inhibitors (Test Compounds):10 mM stock diluted to 10, 3, 1, 0.3, 0.1, 0.03, 0.01, 0.003, 0.001, and 0.0003 mM in drug plate, resulting in a concentration of 100, 30, 10, 3, 1, 0.3, 0.1, 0.03, 0.01, and 0.003 uM in the assay.LOX enzyme:LOX enzyme was obtained from pig skin by the method of Shackleton et al 1990.Assay Plates:Black, flat bottom 96 well platesProcedure:1. Dilute LOX enzyme in Assay Buffer (˜4 ml for one plate, 8 ml for two plates) (dilution dependent on batch activity)2. Add 0.5 μl test compound serial dilutions, in duplicate3. Add 0.5 μl serial dilutions of positive control, BAPN, down column 11 (no duplication)4. Add following controls: 0.5 μl DMSO (100% activity control)5. Cover plate and incubate for 20 min at room temperature on a plate shaker6. Prepare Start Mix: Volume Reagent 1 × plate 2 × plate Final Concn Assay Buffer 2 ml 3 ml — 8.5M Cadaverine 23 μl 34.5 μl 97.8 mM 20 mM Amplex Red 10 μl 15 μl 100 μM 1000 U/ml HRP 10 μl 15 μl 5 U/ml7. Add 10 μl Start Mix to No HRP control wells8. Add HRP to the Start Mix. Add 10 ul to all wells EXCEPT No HRP control wells9. Incubate for 45 min at room temp on a plate shaker, protected from light10. Measure fluorescence using a plate reader: Excitation wavelength: 545 nm Emission wavelength: 585 nm HRP Counter Assay Protocol1. Dilute 5 μl H2O2 in 640 μl dH2O. Add 1 μl diluted H2O2 to 10 ml Assay Buffer. Vortex2. Add 40 μl H2O2+Assay Buffer into every well on the counter assay plate EXCEPT no H2O2 control wells (add 40 μl Assay Buffer only)3. Add 0.5 μl test compound serial dilutions, in duplicate4. Add 0.5 μl serial dilutions of positive control, Na3VO4, down column 11 (no duplication)5. Add following controls: 0.5 μl DMSO (100% activity control) 1 μl diluted H2O2 (blow out control)6. Incubate for 20 min at room temp on a plate shaker.
Measurement: IC50 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 283.37, ALogP 2.05, HBA 5, HBD 1, PSA 69.39, QED 0.93
Compound (SMILES): NCc1ncc(S(=O)(=O)c2ccccc2)s1
InChIKey: MOUTWMBJLUKFLK-UHFFFAOYSA-N
Target: Lysyl oxidase homolog 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y4K0
Assay: LOXL2 Enzyme Activity Assay (a): LOXL2 batch is obtained from R&D systems/Bio-techne. Incubate for 20 min at room temp on a plate shaker.
Measurement: IC50 = 2200 nM (pChEMBL 5.659999847412109)
Descriptors: MW 254.34, ALogP 1.43, HBA 5, HBD 1, PSA 73.05, QED 0.9
Compound (SMILES): Cl.Clc1ccc(OCc2cc(OC[C@@H]3CCCN3)no2)cc1
InChIKey: WLBORAVQYRQHJB-YDALLXLXSA-N
Target: Sigma non-opioid intracellular receptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9R0C9
Assay: Displacement of [3H]-pentazocine from rat brain sigma1 receptor by PDSP assay
Measurement: Ki = 13 nM (pChEMBL 7.889999866485596)
Descriptors: MW 308.76, ALogP 3.04, HBA 5, HBD 1, PSA 56.52, QED 0.89
Compound (SMILES): O=c1oc2ccccc2c2nn(S(=O)(=O)c3ccc(Br)cc3)cc12
InChIKey: CZSPIYVWAWTZOS-UHFFFAOYSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of PI3Kalpha (unknown origin) using diC8-PI(4,5)P2 as substrate incubated for 3 hrs by fluorescence polarization assay
Measurement: IC50 = 27670 nM (pChEMBL 4.559999942779541)
Descriptors: MW 405.23, ALogP 3.14, HBA 6, HBD 0, PSA 82.17, QED 0.48
Compound (SMILES): CS(=O)(=O)Nc1ccc(-c2nc3ccccc3o2)cc1
InChIKey: OYZNNGHQVAYFKR-UHFFFAOYSA-N
Target: Phosphotyrosine protein phosphatase (SINGLE PROTEIN), Mycobacterium tuberculosis
UniProt: A0A045ISB3
Assay: Inhibition of Mycobacterium tuberculosis His-tagged PtpB expressed in Escherichia coli Rosetta 2 (DE3) using pNPP as substrate after 30 mins by spectrophotometric method
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 288.33, ALogP 2.87, HBA 4, HBD 1, PSA 72.2, QED 0.8
Compound (SMILES): OCc1ccc(-c2cnc3ccc(-c4ccc(F)cc4)nn23)cc1
InChIKey: LKNBDJNQZLBIRO-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Fyn (SINGLE PROTEIN), Homo sapiens
UniProt: P06241
Assay: ADP-Glo Kinase Assay: The assay procedure determines the IC50 of each potential FYN kinase inhibitor by measuring the enzyme catalyzed ATP-dependent phosphorylation of the FYN substrate peptide. The ADP-Glo Kinase Assay is specifically designed to quantify kinase activity by measuring the ADP produced in the reaction The reaction buffer comprises 40 mM Tris.HCl (pH 7.5), 20 mM MgCl2, 0.1 mg/ml BSA and 5 microM DTT. Individual compounds within the chemical library were dissolved in DMSO at known concentrations. Briefly, 2.5 microliters of reaction buffer containing 3 picograms of FYN kinase and serial dilutions of each potential FYN kinase inhibitor (9 3-fold dilutions of a 10 micromolar top sample) are placed into each well of a 384 well microtiter plate and incubated at room temperature for 30 minutes. An additional 2.5 microliters of reaction buffer containing 100 picograms of the FYN substrate and 12.5 picomoles of ATP are then added to each well and the reaction carried out for 90 minutes at room temperature.
Measurement: IC50 = 2944 nM (pChEMBL 5.53000020980835)
Descriptors: MW 319.34, ALogP 3.69, HBA 4, HBD 1, PSA 50.42, QED 0.63
Compound (SMILES): CCOCCOc1ccc2ccc(N)nc2c1
InChIKey: SHNCKVFTKGUDER-UHFFFAOYSA-N
Target: Neutrophil cytosol factor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14598
Assay: Covalent inhibition of recombinant human His-tagged p47phox SH3A-B domain (151 to 285 residues) expressed in Escherichia coli BL21 (DE3) cells interaction with Cy5-p22phox149-162 incubated for 10 mins by fluorescence polarization competition assay
Measurement: Ki = 254000 nM (pChEMBL 3.5999999046325684)
Descriptors: MW 232.28, ALogP 2.23, HBA 4, HBD 1, PSA 57.37, QED 0.8
Compound (SMILES): C#CCNc1ccc2c(C)cc(=O)oc2c1
InChIKey: UWUMXXUKMBZAIY-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of recombinant human carbonic anhydrase 1 incubated for 6 hrs prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 213.24, ALogP 2.15, HBA 3, HBD 1, PSA 42.24, QED 0.61
Compound (SMILES): CC(C)NC(=O)c1ccc(C(=O)NC(C(=O)NO)c2ccc(-c3cc(F)c(F)c(F)c3)cc2)cc1
InChIKey: FCQNHMMJMTXOFZ-UHFFFAOYSA-N
Target: Aminopeptidase N (SINGLE PROTEIN), Homo sapiens
UniProt: P15144
Assay: Inhibition of soluble human APN ectodomain stably expressed in HEK293 GnTI(-) cells using H-Leu-NHMec as substrate preincubated for 10 mins followed by substrate addition and measured for 1 hr by spectrofluorimetric method
Measurement: Ki = 631 nM (pChEMBL 6.199999809265137)
Descriptors: MW 485.46, ALogP 3.89, HBA 4, HBD 4, PSA 107.53, QED 0.23
Compound (SMILES): CN1C(=O)S/C(=C\c2cc3c(-c4ccc(N)cc4)c[nH]c3cc2Br)C1=O
InChIKey: YRCKFQLGCKZBPI-IDUWFGFVSA-N
Target: Cyclic GMP-AMP synthase (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N884
Assay: Inhibition of recombinant His6-SUMO tagged human CGAS expressed in Escherichia coli BL21/pLys cells incubated for 20 mins by Kinase Glo chemiluminescence assay
Measurement: IC50 = 500 nM (pChEMBL 6.300000190734863)
Descriptors: MW 428.31, ALogP 4.85, HBA 4, HBD 2, PSA 79.19, QED 0.45
Compound (SMILES): O=C(O)C(=O)O.c1ccc(-c2ccc(OCCCCCN3CCCCCC3)cc2)cc1
InChIKey: OBGUKBYLZRTUDN-UHFFFAOYSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG expressed in CHO cells at holding potential of -90 mV by patch clamp method
Measurement: IC50 = 2030 nM (pChEMBL 5.690000057220459)
Descriptors: MW 337.51, ALogP 5.78, HBA 2, HBD 0, PSA 12.47, QED 0.57
Compound (SMILES): NC(=S)c1cccc(-c2cn(CC(CF)CF)c3cc(NC(=O)c4cnc[nH]4)ccc23)c1
InChIKey: ZBBHNGPLXLPHGM-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase ASH1L (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR48
Assay: Inhibition of MOCR-fused ASH1L SET-BAH ( 2069 to 2833 amino acids) (unknown origin) expressed as in Escherichia coli BL21 (DE3) T1R cells using SAM and chicken mono/dinucleosomes incubated for 1 hr by scintillation counting assay
Measurement: IC50 < 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 453.52, ALogP 4.47, HBA 4, HBD 3, PSA 88.73, QED 0.34
Compound (SMILES): O=C(Nc1ccccc1)Nc1ccc(OCc2nc3ccccc3s2)cc1
InChIKey: MJWMXSIZIUBKTH-UHFFFAOYSA-N
Target: Polyunsaturated fatty acid 5-lipoxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P09917
Assay: Inhibition of 5-LO in human neutrophils preincubated for 10 mins followed by Ca2+ ionophore A23187 addition and measured after 10 mins by RP-HPLC analysis
Measurement: IC50 = 420 nM (pChEMBL 6.380000114440918)
Descriptors: MW 375.45, ALogP 5.52, HBA 4, HBD 2, PSA 63.25, QED 0.48
Compound (SMILES): O=C(N[C@H](C(=O)N1CCC[C@H]1c1ncc(-c2ccc(-c3ccc(-c4cnc([C@@H]5CCCN5C(=O)[C@H](NC(=O)c5cccs5)c5ccccc5)s4)cc3)cc2)s1)c1ccccc1)c1cccs1
InChIKey: AGRYTHOOPDGAEC-PILDEOJGSA-N
Target: Nonstructural protein 5A (SINGLE PROTEIN), Hepatitis C virus
UniProt: Q5L478
Assay: Inhibition of NS5A in HCV genotype 1b infected in human HuH7 replicon cells assessed as reduction in subgenomic viral RNA replication treated for 2 days followed by compound washout and subsequent compound dosing measured after 1 day by SEAP reporter gene assay
Measurement: EC50 = 109.8 nM (pChEMBL 6.960000038146973)
Descriptors: MW 945.23, ALogP 11.39, HBA 10, HBD 2, PSA 124.6, QED 0.12
Compound (SMILES): CN(C)C/C=C/C(=O)Nc1ccc(C(=O)N2CCC[C@@H](NC(=O)c3n[nH]cc3NC(=O)c3c(Cl)cccc3Cl)C2)cc1.O=C(O)C(F)(F)F
InChIKey: PXSBWEUAFKSFKU-ACQWBDGOSA-N
Target: Cyclin-dependent kinase 14/Cyclin-Y (PROTEIN COMPLEX), Homo sapiens
UniProt: Q8ND76
Assay: Inhibition of recombinant GST-tagged human full length CDK14/cyclin Y (2 to end residues) preincubated for 30 mins by Lantha screen eu binding assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 612.52, ALogP 4.06, HBA 6, HBD 4, PSA 139.53, QED 0.27
Compound (SMILES): COc1ccc(C(=O)Nc2ccc(O)c3ncccc23)cc1OC1CCCC1.Cl
InChIKey: XNAZLLONQWVKTH-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4D (SINGLE PROTEIN), Homo sapiens
UniProt: Q08499
Assay: Inhibition of human PDE4D2 (86 to 413 residues) catalytic domain using [3H]-cAMP as substrate after 15 mins by liquid scintillation counting method
Measurement: IC50 = 492 nM (pChEMBL 6.309999942779541)
Descriptors: MW 378.43, ALogP 4.52, HBA 5, HBD 2, PSA 80.68, QED 0.64
Compound (SMILES): O=C(CCN1C[C@H]2CN[C@H]2C1)Nc1sc2c(c1-c1nc3cnccc3s1)CCNC2
InChIKey: FMKUMAFCMMUIBV-DOMZBBRYSA-N
Target: Myc proto-oncogene protein (SINGLE PROTEIN), Homo sapiens
UniProt: P01106
Assay: Inhibition of human c-Myc assessed as reduction in c-Myc/Max/Ebox DNA complex formation using pre-formed complex of c-Myc and biotinylated DNA containing single Ebox-sequence followed by compound addition and further addition of his6-tagged c-Max and incubated for 2 hrs by AlphaScreen assay
Measurement: IC50 < 500 nM (pChEMBL 6.301000118255615)
Descriptors: MW 440.6, ALogP 2.3, HBA 8, HBD 3, PSA 82.18, QED 0.56
Compound (SMILES): COc1ccc2nc3c(c(NCCCCCCCNC(=O)[C@@H](N)Cc4c[nH]c5ccccc45)c2c1)CCCC3.Cl.Cl
InChIKey: FRTXZUBNXVERCX-LPCSYZHESA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human recombinant AChE using acetylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition and measured over 2 mins by UV-Vis spectrophotometric analysis based Ellman's method
Measurement: IC50 = 980 nM (pChEMBL 6.010000228881836)
Descriptors: MW 527.71, ALogP 5.65, HBA 5, HBD 4, PSA 105.06, QED 0.17
Compound (SMILES): O=C(c1ccccc1)N1CCc2c([nH]c3ccccc23)C1c1ccccc1F
InChIKey: OQNGHEVWUBCJMX-UHFFFAOYSA-N
Target: Broad substrate specificity ATP-binding cassette transporter ABCG2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UNQ0
Assay: Inhibition of human ABCG2 expressed in MDCK2 cells assessed as reduction in Hoechst 33342 efflux pre-incubated for 30 mins before Hoechst 33342 addition and measured for 120 mins by microplate reader analysis
Measurement: IC50 = 4490 nM (pChEMBL 5.349999904632568)
Descriptors: MW 370.43, ALogP 5.09, HBA 1, HBD 1, PSA 36.1, QED 0.52
Compound (SMILES): CC(=O)N[C@@H](CC(C)C)CN(CC(=O)N[C@@H](Cc1ccccc1)CN(CC(=O)N[C@@H](CCC(=O)O)CN(CC(=O)N[C@@H](Cc1c[nH]c2ccccc12)CN(CC(=O)N[C@@H](CCCCN)CN(CC(=O)N[C@@H](CC(C)C)CN(CC(N)=O)S(=O)(=O)CC(C)C)S(C)(=O)=O)S(C)(=O)=O)S(C)(=O)=O)S(C)(=O)=O)S(C)(=O)=O
InChIKey: SJSCVONYWXSWQT-VICXIOLRSA-N
Target: E3 ubiquitin-protein ligase Mdm2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00987
Assay: Binding affinity to human MDM2 expressed in Escherichia coli expression system by using (FITC)-labeled p53 peptide based fluorescence polarization competitive assay
Measurement: Kd = 109 nM (pChEMBL 6.960000038146973)
Descriptors: MW 1645.12
Compound (SMILES): Cn1c(=O)[nH]c2nc(SC/C(=N/O)c3ccc(Br)cc3)[nH]c2c1=O
InChIKey: BUCODYDUXJTFDB-OCKHKDLRSA-N
Target: Epidermal growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P00533
Assay: Inhibition of human EGFR measured after 3 hrs by ELISA
Measurement: IC50 = 2880 nM (pChEMBL 5.539999961853027)
Descriptors: MW 410.25, ALogP 1.68, HBA 7, HBD 3, PSA 116.13, QED 0.26
Compound (SMILES): C[C@@H]1C[C@H]2C(=O)OC[C@H](NC(=O)[C@H](Cc3ccccc3)NC(=O)Nc3ccc(N(C)C)cc3)C(=O)N3CCC[C@H]3C(=O)N3CCCC[C@H]3C(=O)N[C@@H](C)C(=O)N2C1
InChIKey: ZGZCACXWBULWLD-KRCFFJRGSA-N
Target: ATP-dependent Clp protease proteolytic subunit (SINGLE PROTEIN), Staphylococcus aureus (strain NCTC 8325)
UniProt: Q2G036
Assay: Activation of Staphylococcus aureus ClpP expressed in Escherichia coli BL21 (DE3) using BODIPY-FL-casein as substrate by fluorescence based assay
Measurement: EC50 = 1300 nM (pChEMBL 5.889999866485596)
Descriptors: MW 786.93, ALogP 1.64, HBA 9, HBD 4, PSA 189.8, QED 0.3
Compound (SMILES): CCC(CC)CN(C[C@@H](O)[C@H](Cc1ccccc1)NC(=O)O[C@H]1CO[C@H]2OCC[C@H]21)S(=O)(=O)c1ccc([C@@H](C)O)cc1
InChIKey: QJTBJHOQMPDSSA-NORYVHHUSA-N
Target: Protease (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q9YQ12
Assay: Inhibition of HIV1 NL4-3 protease I84V mutant expressed in Escherichia coli TAP-106 cells using EDANS/DABCYL-labelled 10-amino acid containing natural MA/CA cleavage site as substrate preincubated for 1 hr followed by substrate addition and measured for 60 mins by FRET assay
Measurement: Ki = 0.028 nM (pChEMBL 10.550000190734863)
Descriptors: MW 604.77, ALogP 3.63, HBA 8, HBD 3, PSA 134.63, QED 0.3
Compound (SMILES): O=C(COc1cccc(C(F)(F)F)c1)N1CCN(c2ccc([N+](=O)[O-])cc2)CC1
InChIKey: VRPCXLICHHDRTG-UHFFFAOYSA-N
Target: Autotaxin (SINGLE PROTEIN), Homo sapiens
UniProt: Q13822
Assay: Inhibition of C-terminal FLAG tagged human recombinant ATX expressed in insect sf9 cells using FS-3 as substrate measured every 2 mins for 60 mins by FRET assay
Measurement: IC50 = 4900 nM (pChEMBL 5.309999942779541)
Descriptors: MW 409.36, ALogP 3.34, HBA 5, HBD 0, PSA 75.92, QED 0.56
Compound (SMILES): COc1ccc2c3c1O[C@H]1/C(=N\OCC(=O)NCCCCCCN)CC[C@@]4(O)[C@@H](C2)N(C)CC[C@]314
InChIKey: XQNZPKPPVZDHBE-JYMHZSFDSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Rattus norvegicus
UniProt: P33535
Assay: Displacement of [3H]DAMGO from MOR in Wistar rat brain membranes after 60 mins by liquid scintillation analysis
Measurement: Ki = 41 nM (pChEMBL 7.389999866485596)
Descriptors: MW 486.61, ALogP 1.49, HBA 8, HBD 3, PSA 118.64, QED 0.34
Compound (SMILES): C=CCCn1cc(-c2cc(OC(F)F)cc(C(=O)N3CCOCC3)c2)c2cc[nH]c2c1=O
InChIKey: HVFFRODVHZGRAZ-UHFFFAOYSA-N
Target: Chromatin remodeling regulator CECR2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BXF3
Assay: IC50 Measurements for Inhibitors Using TAF1-BD2 TR-FRET Binding Assay: His/Flag epitope tagged TAF1-BD21504-1635 was cloned, expressed, and purified to homogeneity. TAF1-BD2 binding and inhibition was assessed by monitoring the engagement of a biotinylated small molecule compound 1000 (Example 124) with the target using the TR-FRET assay technology (Perkin-Elmer). Specifically, in a 384 well ProxiPlate TAF1-BD2 (6 nM final) was combined with biotin-ligand (50 nM final) in 50 mM HEPES (pH 7.5), 50 mM NaCl, 1 mM TCEP, 0.01% (w/v) BSA, and 0.008% (w/v) Brij-35 either in the presence of DMSO (final 0.2% DMSO) or compound dilution series in DMSO. After 10 minutes incubation at room temperature, a mixture Eu-W1024 Anti-6×His antibody (Perkin Elmer AD0110) and SureLight¿ Allophycocyanin-Streptavidin (APC-SA, Perkin Elmer CR130-100) were added to a final concentrations of 0.2 nMolar antibody and 25 nMolar APC-SA, respectively. After twenty minutes of equilibration, the plates were read on an Envision instrument and IC50s calculated using a four parameter non-linear curve fit. Novel compound 1000 and the TAF1-BD2 TR-FRET Binding Assay described above represent additional embodiments of the invention.
Measurement: IC50 = 10 nM (pChEMBL 8)
Descriptors: MW 443.45, ALogP 3.65, HBA 5, HBD 1, PSA 76.56, QED 0.57
Compound (SMILES): Cc1ccc(CNC(=O)c2csc(CCNCCc3nc4ccccc4[nH]3)n2)nn1.Cl.Cl.Cl
InChIKey: WAJAGRCDXJXVQN-UHFFFAOYSA-N
Target: Ferroportin (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NP59
Assay: Inhibition of GFP-tagged human ferroportin expressed in HEK293 #354 cells assessed as induction of ferroportin internalization and degradation incubated overnight by FACS assay
Measurement: EC50 = 3960 nM (pChEMBL 5.400000095367432)
Descriptors: MW 421.53, ALogP 2.42, HBA 7, HBD 3, PSA 108.48, QED 0.36
Compound (SMILES): CC(=O)Nc1ccc(-c2ccc3nc(-c4cccnc4N)n(-c4ccc(CN)cc4)c3n2)cc1.Cl
InChIKey: ALRZVZVURPJCDW-UHFFFAOYSA-N
Target: RAC-alpha serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P31749
Assay: Inhibition of full length unphosphorylated AKT1 (1 to 480 residues) (unknown origin) expressed in baculovirus infected Sf9 insect cells using biotin-GRPRTSSFAEG as substrate preincubated for 20 mins followed by substrate addition measured after 30 mins by Alphascreen assay
Measurement: IC50 = 72 nM (pChEMBL 7.139999866485596)
Descriptors: MW 449.52, ALogP 4.15, HBA 7, HBD 3, PSA 124.74, QED 0.37
Compound (SMILES): COc1ccccc1/N=N/c1ccc(F)c(C(=O)Nc2cnc3[nH]nc(OC)c3c2)c1F
InChIKey: UVHOEUNRULJPLG-CYYJNZCTSA-N
Target: Serine/threonine-protein kinase B-raf (SINGLE PROTEIN), Homo sapiens
UniProt: P15056
Assay: Inhibition of human recombinant N-terminal GST/His6-tagged BRAF V600E mutant (Q417 to H766 residues) expressed in Sf9 insect cells using MEK1 as substrate measured after 1 hr using preheated compound at 60 degC for 30 mins by Western blot analysis
Measurement: IC50 = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 438.39, ALogP 4.92, HBA 7, HBD 2, PSA 113.85, QED 0.41
Compound (SMILES): CN1CCN(S(=O)(=O)c2ccc(CNC(=O)c3cccc4c3cnn4-c3ccc(F)cc3)cc2)CC1
InChIKey: HRRUHZIKMAGKFB-UHFFFAOYSA-N
Target: C-C chemokine receptor type 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P32246
Assay: Antagonist activity at recombinant CCR1 (unknown origin) expressed in non-adherent cells co-expressing Galpha16 assessed as inhibition of MIP-1 alpha-induced calcium flux by Fluo-4 NW or Calcium 4 dye based FLIPR TETRA assay
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 507.59, ALogP 3.03, HBA 6, HBD 1, PSA 87.54, QED 0.43
Compound (SMILES): CCCCC[C@@H](C(=O)NCNC(=O)c1ccc(-c2ccc(C(=O)N[C@@H](CC(=O)O)C(=O)O)c(OCC(=O)O)c2)o1)[C@@H](CC)N(C=O)OC(=O)c1cccc(C(=O)O)c1
InChIKey: UWNUKDUPXOWRDD-FXVJXKIMSA-N
Target: Bone morphogenetic protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P13497
Assay: Inhibition of C-terminal FLAG-6x-His epitope tagged and N-terminal human RAGE signal sequence tagged human BMP1 (121 to 721 amino acids) expressed in CHO-E1a cells pre-incubated for 10 mins before promyostatin peptide substrate addition and measured after 60 mins using 0.5 nM BMP1 by FRET based assay
Measurement: IC50 < 125.89 nM (pChEMBL 6.900000095367432)
Descriptors: MW 810.77, ALogP 2.77, HBA 12, HBD 7, PSA 305.48, QED 0.03
Compound (SMILES): Nc1ncnc2c1c(SCCO)nn2[C@@H]1O[C@H](COS(N)(=O)=O)[C@@H](O)[C@@H]1F
InChIKey: DDLKQSFEKUYLFN-ADVRJHOBSA-N
Target: Ubiquitin-like modifier-activating enzyme ATG7 (SINGLE PROTEIN), Homo sapiens
UniProt: O95352
Assay: Inhibition of recombinant His-tagged human ATG7 incubated for 105 mins in presence of GST-tagged ATG3 and Flag-tagged Gabarap and measured after 2 hrs by FRET assay
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 424.44, ALogP -1.69, HBA 12, HBD 4, PSA 188.7, QED 0.37
Compound (SMILES): Cc1ccccc1S(=O)(=O)Nc1ccc2oc(-c3ccccc3)nc2c1
InChIKey: LMBJRPUERDYYNX-UHFFFAOYSA-N
Target: Phosphotyrosine protein phosphatase (SINGLE PROTEIN), Mycobacterium tuberculosis
UniProt: A0A045ISB3
Assay: Inhibition of Mycobacterium tuberculosis His-tagged PtpB expressed in Escherichia coli Rosetta 2 (DE3) using pNPP as substrate after 30 mins by spectrophotometric method
Measurement: IC50 = 59000 nM (pChEMBL 4.230000019073486)
Descriptors: MW 364.43, ALogP 4.6, HBA 4, HBD 1, PSA 72.2, QED 0.57
Compound (SMILES): NC(=O)c1cc(-c2ccc(F)cc2)n2nc(CCc3ccncc3)cc2n1
InChIKey: BIZBSFIOAMBGEL-UHFFFAOYSA-N
Target: Metabotropic glutamate receptor 2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P31421
Assay: Negative allosteric modulation of rat mGlu2R expressed in HEK293 cells co-expressing Galpha15 assessed as decrease in glutamate-induced calcium mobilization preincubated for 2.3 mins followed by glutamate addition and measured after 1.7 mins by Fluo-4-AM dye based fluorescence assay
Measurement: IC50 = 1047 nM (pChEMBL 5.980000019073486)
Descriptors: MW 361.38, ALogP 2.81, HBA 5, HBD 1, PSA 86.17, QED 0.59
Compound (SMILES): Cc1c(-c2cccc(S(=O)(=O)N(C)C)c2)c2cc(C(=O)O)ccc2n1C/C=C/CN.Cl
InChIKey: BTMSFFVTGUSLDQ-FXRZFVDSSA-N
Target: Lysyl oxidase homolog 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y4K0
Assay: Inhibition of recombinant human C-terminal His-tagged LOLX2 (1-774 residues) expressed in mouse myeloma cells using putrescine as substrate preincubated with enzyme for 30 mins followed by substrate addition and measured every 2.5 mins for 30 mins by Amplex-Red oxidation assay
Measurement: IC50 = 794.33 nM (pChEMBL 6.099999904632568)
Descriptors: MW 427.53, ALogP 3.08, HBA 5, HBD 2, PSA 105.63, QED 0.56
Compound (SMILES): O=C1C(O)=C(N2CCN(c3cccc(Cl)c3Cl)CC2)C(=O)c2ccccc21
InChIKey: NZGZDODHKDOVOY-UHFFFAOYSA-N
Target: Dihydroorotate dehydrogenase (quinone), mitochondrial (SINGLE PROTEIN), Schistosoma mansoni
UniProt: G4VFD7
Assay: Inhibition of Schistosoma mansoni DHODH using DHO as substrate measured at 4 secs interval for 60 secs by DCIP reduction based indirect assay
Measurement: IC50 = 436 nM (pChEMBL 6.360000133514404)
Descriptors: MW 403.27, ALogP 3.96, HBA 5, HBD 1, PSA 60.85, QED 0.82
Compound (SMILES): c1ccc(-n2nccc2-c2ccc3nnn(-c4ccc5cn[nH]c5c4)c3c2)cc1
InChIKey: OBMPSNTXKCWXHE-UHFFFAOYSA-N
Target: 5'-nucleotidase (SINGLE PROTEIN), Homo sapiens
UniProt: P21589
Assay: Inhibition of recombinant human CD73 expressed in CHO cells using AMP as substrate preincubated for 60 mins followed by substrate addition and measured after 60 mins by colorimetric assay
Measurement: IC50 = 9000 nM (pChEMBL 5.050000190734863)
Descriptors: MW 377.41, ALogP 4.15, HBA 6, HBD 1, PSA 77.21, QED 0.5
Compound (SMILES): O=C(Nc1ccc(OS(=O)(=O)c2ccccc2)cc1)C1CCCC1
InChIKey: YPGLAIJFSZRSFJ-UHFFFAOYSA-N
Target: Ectonucleotide pyrophosphatase/phosphodiesterase family member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P22413
Assay: Inhibition of human NPP1 expressed in African green monkey COS7 cell membranes pre-incubated for 10 mins before pNP-TMP substrate addition and further incubated for 15 mins by colorimetric method
Measurement: IC50 = 46670 nM (pChEMBL 4.329999923706055)
Descriptors: MW 345.42, ALogP 3.58, HBA 4, HBD 1, PSA 72.47, QED 0.84
Compound (SMILES): CCN(CC)CCCNc1nc(/C=C/c2cccs2)nc2ccccc12
InChIKey: HFCRPHDXRGIYMT-OUKQBFOZSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 ITD mutant (unknown origin) using TAMRA-Src-tide as substrate measured after 1 hr in presence of ATP at its Km concentration by IMAP-FP assay
Measurement: IC50 = 10190 nM (pChEMBL 4.989999771118164)
Descriptors: MW 366.53, ALogP 5.01, HBA 5, HBD 1, PSA 41.05, QED 0.54
Compound (SMILES): C[C@H]1CO[C@H](c2ccc(N)nc2)CN1
InChIKey: UXRVFSIWSWPXSI-CBAPKCEASA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Displacement of [3H]-(R)-(+)-7-OH-DPAT from recombinant human D2L receptor expressed in HEK293 cell membranes measured after 90 mins by microbeta scintillation counting analysis
Measurement: Ki = 7100 nM (pChEMBL 5.150000095367432)
Descriptors: MW 193.25, ALogP 0.71, HBA 4, HBD 2, PSA 60.17, QED 0.69
Compound (SMILES): CN(C(=O)c1ccccc1)c1cc(N(C)c2ccc3c(c2)CCc2ccc(C(=O)NCCN4CCOCC4)cc2C3=O)ccc1F
InChIKey: RHXKLUBQGQKHCH-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase 14 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16539
Assay: NanoBRET (MAPK14)
Measurement: IC50 = 11300 nM (pChEMBL 4.949999809265137)
Descriptors: MW 620.73, ALogP 5.26, HBA 6, HBD 1, PSA 82.19, QED 0.29
Compound (SMILES): COc1cc(OC)c(-c2cn3ccc(C4=CCN(C(C)=O)CC4)cc3n2)cc1Cl
InChIKey: OLECGJHAKZOTMN-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase SUV39H2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H5I1
Assay: Inhibition of SUV39H2 (unknown origin) using H3 histone peptide substrate and [3H]-SAM incubated for 3 hrs by microbeta counting based assay
Measurement: IC50 = 36.4 nM (pChEMBL 7.440000057220459)
Descriptors: MW 411.89, ALogP 4.31, HBA 5, HBD 0, PSA 56.07, QED 0.64
Compound (SMILES): Cc1ccccc1OCC(=O)Nc1ccn(C)n1
InChIKey: DJFXMHAELCWWOV-UHFFFAOYSA-N
Target: Palmitoleoyl-protein carboxylesterase NOTUM (SINGLE PROTEIN), Homo sapiens
UniProt: Q6P988
Assay: Inhibition of His6-tagged NOTUM purified from human HEK293S cells using OPTS as substrate incubated for 1 hr by fluorescence based assay
Measurement: IC50 = 72000 nM (pChEMBL 4.139999866485596)
Descriptors: MW 245.28, ALogP 1.75, HBA 4, HBD 1, PSA 56.15, QED 0.89
Compound (SMILES): COC[C@H]1C[C@@](CC(C)C)(C(=O)O)N(C(=O)c2ccc(C(C)(C)C)c(OC)c2)[C@H]1CN=[N+]=[N-]
InChIKey: PFZRZBAQSPVPBZ-VUMVONDWSA-N
Target: RNA-directed RNA polymerase (SINGLE PROTEIN), Hepacivirus hominis
UniProt: O39930
Assay: Inhibition of NS5B RNA dependent RNA polymerase in HCV 1b Con1 infected in human Huh5-2 cells assessed as reduction in viral RNA replication measured after 3 days by luciferase reporter gene assay
Measurement: EC50 = 100000 nM (pChEMBL 4)
Descriptors: MW 460.58, ALogP 4.65, HBA 5, HBD 1, PSA 124.83, QED 0.33
Compound (SMILES): COc1ccc(NC(=O)N[C@@H](Cc2ccccc2)C(=O)N[C@H]2COC(=O)[C@@H]3C[C@@H](C)CN3C(=O)[C@H](C)NC(=O)[C@@H]3CCCCN3C(=O)[C@@H]3CCCN3C2=O)cc1
InChIKey: YHLOGNVIFQWMHS-IPEXGAJJSA-N
Target: ATP-dependent Clp protease proteolytic subunit (SINGLE PROTEIN), Staphylococcus aureus (strain NCTC 8325)
UniProt: Q2G036
Assay: Activation of Staphylococcus aureus ClpP expressed in Escherichia coli BL21 (DE3) using BODIPY-FL-casein as substrate by fluorescence based assay
Measurement: EC50 = 2000 nM (pChEMBL 5.699999809265137)
Descriptors: MW 773.89, ALogP 1.58, HBA 9, HBD 4, PSA 195.79, QED 0.3
Compound (SMILES): COc1cc(OC)cc(C(=O)Nc2nc(-c3ccccc3)c(CCCN(C)C)s2)c1.Cl.Cl
InChIKey: MNCFPFSTGMPZBF-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9HBA0
Assay: Inhibition of human TRPV4 expressed in HEK293 cells assessed as reduction in Ca2+ influx incubated for 30 mins by Fluo4-AM dye based
Measurement: IC50 = 86 nM (pChEMBL 7.070000171661377)
Descriptors: MW 425.55, ALogP 4.57, HBA 6, HBD 1, PSA 63.69, QED 0.54
Compound (SMILES): CCCCC[C@H](CN(O)C=O)C(=O)NCNC(=O)c1ccc(-c2cc(OC)cc(C(=O)O)c2)o1
InChIKey: GMHJUNNICSWWRZ-OAHLLOKOSA-N
Target: Bone morphogenetic protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P13497
Assay: Inhibition of C-terminal FLAG-6x-His epitope tagged and N-terminal human RAGE signal sequence tagged human BMP1 (23 to 721 amino acids) expressed in CHO-E1 cells pre-incubated for 10 mins before promyostatin peptide substrate addition and measured after 60 mins using 0.5 nM BMP1 by FRET based assay
Measurement: IC50 < 125.89 nM (pChEMBL 6.900000095367432)
Descriptors: MW 475.5, ALogP 2.5, HBA 7, HBD 4, PSA 158.41, QED 0.11
Compound (SMILES): CN(c1cccc(CNc2nc(Nc3ccc(OCCOCCOCCC(=O)NCCOc4cccc5c4C(=O)N(C4CCC(=O)NC4=O)C5=O)cc3)ncc2C(F)(F)F)c1)S(C)(=O)=O
InChIKey: RKQPBRYWQQLESB-UHFFFAOYSA-N
Target: Focal adhesion kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q05397
Assay: Inhibition of human recombinant FAK using poly[Glu:Tyr] (4:1) substrate in presence of 10 mM ATP and [gamma33P]-ATP
Measurement: IC50 = 4.7 nM (pChEMBL 8.329999923706055)
Descriptors: MW 926.93, ALogP 3.65, HBA 15, HBD 4, PSA 236.79, QED 0.07
Compound (SMILES): Cl.Nc1nc(N)c(-c2ccccc2)c(CCCOc2cccc(OCCCC(=O)O)c2)n1
InChIKey: MGULVEZYIYOSEV-UHFFFAOYSA-N
Target: Dihydrofolate reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P00374
Assay: Inhibition of human dihydrofolate reductase using dihydrofolate as substrate in presence of NADPH by UV-vis spectrophotometry analysis
Measurement: Ki = 29.05 nM (pChEMBL 7.539999961853027)
Descriptors: MW 422.49, ALogP 3.56, HBA 7, HBD 3, PSA 133.58, QED 0.4
Compound (SMILES): CCCCN(Cc1ccc(-c2ccccc2-c2nnn[nH]2)cc1)c1nc2cc(Cl)cc(C)c2o1
InChIKey: CFNYGJPKAJCXRK-UHFFFAOYSA-N
Target: Chemerin-like receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99788
Assay: Inhibition of chemR23 in human CAL1 cells assessed as reduction in chemerin-induced intracellular calcium ion concentration preincubated for 45 mins followed by chemerin addition
Measurement: IC50 = 2500 nM (pChEMBL 5.599999904632568)
Descriptors: MW 472.98, ALogP 6.44, HBA 6, HBD 1, PSA 83.73, QED 0.28
Compound (SMILES): O=C1Nc2ccc(Cl)cc2S(=O)(=O)N1
InChIKey: SDCJBUKXFVQVKG-UHFFFAOYSA-N
Target: Carbonic anhydrase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P00915
Assay: Inhibition of recombinant human carbonic anhydrase 1 incubated for 1 hr prior to testing measured for 10 to 100 secs by phenol red-based stopped-flow CO2 hydration assay
Measurement: Ki = 1864 nM (pChEMBL 5.730000019073486)
Descriptors: MW 232.65, ALogP 1.16, HBA 3, HBD 2, PSA 75.27, QED 0.7
Compound (SMILES): CC(C)(CS(C)(=O)=O)Nc1nc(-c2ccncc2)nc2cnccc12
InChIKey: POQZSRVIOIFGKW-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase LATS1 (SINGLE PROTEIN), Homo sapiens
UniProt: O95835
Assay: Inhibition of human LATS1 kinase domain (589 to 1130 amino acids) incubated for 30 mins by HTRF assay
Measurement: IC50 = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 357.44, ALogP 2.32, HBA 7, HBD 1, PSA 97.73, QED 0.75
Compound (SMILES): COc1cc(OC)c(-c2cn3ccc(N4CCN(c5ccnc(NCCO)n5)CC4)cc3n2)cc1Cl
InChIKey: UEKQUHSQPTZSGN-UHFFFAOYSA-N
Target: Histone-lysine N-methyltransferase SUV39H2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H5I1
Assay: Inhibition of SUV39H2 (unknown origin) using H3 histone peptide substrate and [3H]-SAM incubated for 3 hrs by microbeta counting based assay
Measurement: IC50 = 21.3 nM (pChEMBL 7.670000076293945)
Descriptors: MW 510, ALogP 3.19, HBA 10, HBD 2, PSA 100.28, QED 0.37
Compound (SMILES): CSCC[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)C(C)(C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1cccnc1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)Cc1cnc[nH]1)[C@@H](C)O)[C@@H](C)O)C(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)O)[C@@H](C)O
InChIKey: ZVVRDTXBGOSEFB-ILZSVGFRSA-N
Target: Glucagon receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P47871
Assay: Activation of glucagon receptor (unknown origin) transfected in HEK293 cells coinfected with luciferase reporter gene linked CRE element assessed as cAMP accumulation after 5 hrs in presence of luclite substrate by liquid scintillation counting
Measurement: EC50 = 0.0379 nM (pChEMBL 10.420000076293945)
Descriptors: MW 3465.82
Compound (SMILES): COc1cc([C@](O)(CCN(C)C)[C@@H](c2cc3cc(C#N)ccc3nc2OC)c2cccc3c2CCC3)cc(OC)n1
InChIKey: OUSVFSOUSSBDJX-ZQWAWDFXSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 = 4500 nM (pChEMBL 5.349999904632568)
Descriptors: MW 552.68, ALogP 4.99, HBA 8, HBD 1, PSA 100.73, QED 0.29
Compound (SMILES): CC(C)[C@H](NC(=O)c1ccc(Br)cc1)C(=O)N1CCOC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)CF
InChIKey: VPYYOKXRDQXRPD-BJLQDIEVSA-N
Target: Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UDY8
Assay: Biological Assay: For exemplary compounds of the disclosure, Ki for inhibition of MALT1 was measured (Table E11). A concentration of 100 nM MALT1 was used for the assay.
Measurement: Ki = 70 nM (pChEMBL 7.159999847412109)
Descriptors: MW 585.48, ALogP 0.72, HBA 6, HBD 5, PSA 166.71, QED 0.14
Compound (SMILES): CN1CCN(c2ccc3c(c2)N(S(=O)(=O)c2ccccc2)CC3)CC1
InChIKey: LLNWCPKEPUSMNT-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 6 (SINGLE PROTEIN), Homo sapiens
UniProt: P50406
Assay: Displacement of [3H]LSD from human recombinant 5-HT6 receptor expressed in CHO-K1 cells incubated for 3 hrs by scintillation counting analysis
Measurement: Ki = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 357.48, ALogP 2.19, HBA 4, HBD 0, PSA 43.86, QED 0.84
Compound (SMILES): CC(C(=O)NCc1ccc(C(F)(F)F)cc1N1CCC(Cc2ccccc2)(N(C)C)CC1)c1ccc(NS(C)(=O)=O)c(F)c1
InChIKey: PDAXSLZUMLDCAK-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NER1
Assay: Antagonist activity at recombinant human TRPV1 expressed in CHO cells assessed as as inhibition of capsaicin-induced calcium uptake incubated for 5 mins in presence of 45Ca2+ by liquid scintillation counter
Measurement: EC50 = 8.2 nM (pChEMBL 8.09000015258789)
Descriptors: MW 634.74, ALogP 5.78, HBA 5, HBD 2, PSA 81.75, QED 0.28
Compound (SMILES): O=C(c1cc2ccncc2[nH]1)N1CCC(c2ccccc2C(F)(F)F)CC1
InChIKey: CPTVUPCVDOXJKD-UHFFFAOYSA-N
Target: Retinol-binding protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P02753
Assay: Competitive displacement of 3[H]retinol from biotinylated RBP4 (unknown origin) by surface plasmon resonance analysis
Measurement: IC50 = 84.2 nM (pChEMBL 7.079999923706055)
Descriptors: MW 373.38, ALogP 4.6, HBA 2, HBD 1, PSA 48.99, QED 0.71
Compound (SMILES): Cc1c(C(=O)N2CCC[C@H](C(F)(F)F)C2)cnn1-c1nc2c(c(=O)[nH]1)CCC2
InChIKey: RMTFKVQQWWDVDP-NSHDSACASA-N
Target: Sepiapterin reductase (SINGLE PROTEIN), Homo sapiens
UniProt: P35270
Assay: Inhibition of terbium-labeled SNAP-tagged human SPR in presence of sulfasalazine-labeled SNAP-tagged EGFP by homogenous TR-FRET assay
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 395.39, ALogP 2.17, HBA 5, HBD 1, PSA 83.88, QED 0.84
Compound (SMILES): CS(=O)(=O)c1ccc2nc(NC(=O)CCCOc3ccc(Cl)cc3)sc2c1
InChIKey: KWWWKTVOBKBUFS-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase TAO2 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9JLS3
Assay: Inhibition of rat TAOK2 (1 to 320 residues) expressed in Baculovirus/insect cell expression system assessed as remaining activity using MBP as substrate and [32P]ATP measured after 10 mins by Kinase-Glo assay
Measurement: IC50 = 5000 nM (pChEMBL 5.300000190734863)
Descriptors: MW 424.93, ALogP 4.15, HBA 6, HBD 1, PSA 85.36, QED 0.58
Compound (SMILES): N#CN1CCOC(C(=O)Nc2ccc(-c3ccccc3)cn2)C1
InChIKey: UYOMRDDVMMLAIJ-UHFFFAOYSA-N
Target: Ubiquitin carboxyl-terminal hydrolase 30 (SINGLE PROTEIN), Homo sapiens
UniProt: Q70CQ3
Assay: USP30 Biochemical IC50 Assay: Dilution plates were prepared at 21 times the final concentration (2100 μM for a final concentration of 100 μM) in 50% DMSO in a 96-well polypropylene V-bottom plate (Greiner #651201). A typical 8-point dilution series would be 100, 30, 10, 3, 1, 0.3, 0.1, 0.03 μM final. Reactions were performed in duplicate in black 384 well plates (small volume, Greiner 784076) in a final reaction volume of 21 μl. Either 1 μl of 50% DMSO or diluted compound was added to the plate. USP30 was diluted in reaction buffer (40 mM Tris, pH 7.5, 0.005% Tween 20, 0.5 mg/ml BSA, 5 mM beta-mercaptoethanol) to the equivalent of 0.05 μl/well and 10 μl of diluted USP30 was added to the compound. Enzyme and compound were incubated for 30 min at room temp. Reactions were initiated by the addition of 50 nM of TAMRA labelled peptide linked to ubiquitin via an iso-peptide bond as fluorescence polarisation substrate. Reactions were read immediately after addition of substrate and following a 2 h incubation at room temperature. Readings were performed on a Pherastar Plus (BMG Labtech). λ Excitation 540 nm; λ Emission 590 nm.
Measurement: IC50 = 2750 nM (pChEMBL 5.559999942779541)
Descriptors: MW 308.34, ALogP 1.87, HBA 5, HBD 1, PSA 78.25, QED 0.88
Compound (SMILES): CCc1ccc(NC(=O)N[C@@H](Cc2cc(F)cc(F)c2)C(=O)N[C@@H]2C(=O)N3CCC[C@H]3C(=O)N(C)[C@@H]([C@H](C)O)C(=O)N[C@@H](C)C(=O)N3C[C@@H](C)C[C@H]3C(=O)O[C@H]2C)cc1
InChIKey: DEBVNRXWDWZPCH-LUYSPTTLSA-N
Target: ATP-dependent Clp protease proteolytic subunit (SINGLE PROTEIN), Staphylococcus aureus (strain NCTC 8325)
UniProt: Q2G036
Assay: Displacement of ADEP2591 from Staphylococcus aureus ClpP expressed in Escherichia coli BL21 (DE3) incubated for 120 mins by fluorescence polarization assay
Measurement: IC50 = 7000 nM (pChEMBL 5.159999847412109)
Descriptors: MW 825.91, ALogP 1.63, HBA 9, HBD 5, PSA 206.79, QED 0.25
Compound (SMILES): Cc1cc(C(=O)N(C)C)c(O)c2c1C[C@@H](C)OC2=O
InChIKey: POBWASUDBIRBOA-MRVPVSSYSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of human recombinant MAOA using kynuramine as substrate incubated for 10 mins by UPLC-ESI-MS/MS analysis
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 263.29, ALogP 1.5, HBA 4, HBD 1, PSA 66.84, QED 0.78