lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): COc1ccc(-n2c(C(=O)c3sc(Nc4ccccc4)nc3C)cnc2N)cc1
InChIKey: XIJBZUAPZQCRSL-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Antagonist activity at recombinant human A2B receptor expressed in CHO cell membranes assessed as inhibition of NECA-stimulated adenylyl cyclase activity
Measurement: Ki > 10000 nM (pChEMBL 5)
Descriptors: MW 405.48, ALogP 4.2, HBA 8, HBD 2, PSA 95.06, QED 0.47
Compound (SMILES): C=C1C[C@H]2c3c(cc(CCCCC)cc3OS(=O)(=O)c3ccc(C)cc3)OC(C)(C)[C@@H]2CC1OO
InChIKey: SSTGRNSQXXIYRX-YOQGVNIDSA-N
Target: Cannabinoid receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P34972
Assay: Displacement of [3H]CP-55,940 from recombinant human full length CB2 receptor expressed in HEK293 cell membranes after 90 mins by topcount method
Measurement: Ki = 1030 nM (pChEMBL 5.989999771118164)
Descriptors: MW 500.66, ALogP 6.57, HBA 6, HBD 1, PSA 82.06, QED 0.15
Compound (SMILES): CN[C@@H](C)C(=O)N[C@@H](Cc1ccc(S(=O)(=O)O)cc1)C(=O)N1CCC[C@@H]1c1cncc(Cc2ccccc2)n1
InChIKey: BSKILDRWLGURMA-VFHOHQAYSA-N
Target: E3 ubiquitin-protein ligase XIAP (SINGLE PROTEIN), Homo sapiens
UniProt: P98170
Assay: Displacement of AVPIAQKSEK-biotin from N-terminal His-tagged human recombinant XIAP BIR3 (253 to 347 residues) expressed in Escherichia coli BL21(DE3) Gold after 1 hr by DELFIA
Measurement: IC50 = 190.7 nM (pChEMBL 6.71999979019165)
Descriptors: MW 551.67, ALogP 2.31, HBA 7, HBD 3, PSA 141.59, QED 0.33
Compound (SMILES): CCCCOc1cc(F)ccc1-c1c(-c2cc(-c3nn[nH]n3)ccn2)ncn1C
InChIKey: HWLLTDBRLRZLGC-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NHM5
Assay: FBXL10 Assay: The ability of test compounds to inhibit the activity of FBXL10 was determined in 384-well plate format under the following reaction conditions: 0.3 nM FBXL10, 30 nM H3K36me2-biotin labeled peptide (Anaspec cat #64442), 0.2 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, and 5 μM ammonium iron(II) sulfate. Reaction product was determined quantitatively by AlphaScreen detection after the addition of detection reagents anti-H3K36me1 antibody, AlphaScreen® Streptavidin-coated Donor beads, and AlphaScreen® Protein A Acceptor beads in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA to final 10 μg/ml beads.The assay reaction was initiated by the following: 3 μl of the mixture of 90 nM H3K36me2-biotin labeled peptide and 0.6 μM alpha-ketoglutaric acid with 3 μl of 11-point serial diluted inhibitor in 3% DMSO were added to each well of 384 well Proxiplate (Perkin Elmer), followed by the addition of 3 μl of 0.9 nM FBXL10 to initiate the reaction. The reaction mixture was incubated at room temperature for 30 minutes, and terminated by the addition of 3 μl of 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA containing appropriate dilution of anti H3K36me1 antibody. Plates were incubated at room temperature for 40 minutes, followed by addition of 3 μl of 50 μg/ml AlphaScreen® Streptavidin-coated Donor beads and AlphaScreen® Protein A Acceptor beads in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA. Plates were read by EnVisionMultilabel Reader in AlphaScreen mode after a minimum of 2 hour or up to overnight incubation at room temperature. The AlphaScreen signal for each well was used to determine inhibition constant (IC50).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 393.43, ALogP 3.65, HBA 7, HBD 1, PSA 94.4, QED 0.48
Compound (SMILES): COc1ccc(CCNC(=O)c2cnc(SC)nc2N2CCOCC2)cc1OC
InChIKey: NULJNWINBNQZPW-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4B (SINGLE PROTEIN), Homo sapiens
UniProt: Q07343
Assay: Inhibition of recombinant human full length N-terminal GST-tagged PDE4B1 expressed in baculovirus infected Sf9 cells using cAMP as substrate after 1 hr by LANCE TR-FRET assay
Measurement: IC50 = 61 nM (pChEMBL 7.210000038146973)
Descriptors: MW 418.52, ALogP 2.02, HBA 8, HBD 1, PSA 85.81, QED 0.51
Compound (SMILES): O=c1cc(-c2ccccc2)oc2cc(OCCN(Cc3ccccc3)Cc3cn(CCOCCOCCOc4ccc(-c5oc6ccccc6c(=O)c5OCc5ccccc5)cc4)nn3)ccc12
InChIKey: SWCDVWZUGYTBHV-UHFFFAOYSA-N
Target: ATP-dependent translocase ABCB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08183
Assay: Inhibition of P-gp (unknown origin) expressed in human LCC6MDR cells assessed as reversal of paclitaxel resistance after 5 days by MTS/PMS assay
Measurement: EC50 = 983.3 nM (pChEMBL 6.010000228881836)
Descriptors: MW 911.02, ALogP 9.6, HBA 13, HBD 0, PSA 140.52, QED 0.06
Compound (SMILES): CSc1cccc(NC(=O)Nc2cc(S(N)(=O)=O)ccc2O)c1
InChIKey: ATZDENJYNKEIBX-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human CA12 assessed as enzyme inhibitor complex formation preincubated for 15 mins and measured for 10 to 100 secs by phenol red dye based stopped-flow CO2 hydrase assay
Measurement: Ki = 35.9 nM (pChEMBL 7.449999809265137)
Descriptors: MW 353.43, ALogP 2.41, HBA 5, HBD 4, PSA 121.52, QED 0.5
Compound (SMILES): CC(c1ccc(-c2cnc3c(-c4ccc(S(N)(=O)=O)c5ccccc45)cnn3c2)cc1)N1CCCC1
InChIKey: IPESYYFOXATSFJ-UHFFFAOYSA-N
Target: Activin receptor type-1B (SINGLE PROTEIN), Homo sapiens
UniProt: P36896
Assay: Inhibition of ALK4 (unknown origin) using Ulight topo IIa (Thr 1342) peptide as substrate preincubated for 10 mins followed by substrate addition and measured after 1 hr by TR-FRET analysis
Measurement: IC50 = 18330 nM (pChEMBL 4.739999771118164)
Descriptors: MW 497.62, ALogP 5.02, HBA 6, HBD 1, PSA 93.59, QED 0.37
Compound (SMILES): Cn1cc(-c2ccc(S(=O)(=O)n3ccc(/C=C/C(=O)Nc4ccccc4N)c3)cc2)cn1
InChIKey: PRXXYMVLYKJITB-IZZDOVSWSA-N
Target: Lysine-specific histone demethylase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: O60341
Assay: Inhibition of LSD-1 (unknown origin)
Measurement: IC50 = 1200 nM (pChEMBL 5.920000076293945)
Descriptors: MW 447.52, ALogP 3.36, HBA 7, HBD 2, PSA 112.01, QED 0.35
Compound (SMILES): CCNC1=NC(C(F)(F)F)C(S(=O)(=O)c2ccc(C(C)(O)C(F)(F)F)cc2)S1
InChIKey: DBUACKSDVHYFNR-UHFFFAOYSA-N
Target: Glycine receptor alpha-3/beta (PROTEIN COMPLEX), Homo sapiens
UniProt: P48167
Assay: Positive allosteric modulation of human GlyRalpha3beta expressed in HEK293T cells assessed as increase in glycine-induced chloride ion flux measured for 4 mins in presence of GlyRs inhibitor strychnine by FLIPR assay
Measurement: EC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 450.43, ALogP 3.2, HBA 6, HBD 2, PSA 78.76, QED 0.69
Compound (SMILES): COc1cccc(Cn2cnc(-c3cc(-c4c[nH]nn4)ccn3)c2)c1F
InChIKey: TXLXRFMNSKJPLV-UHFFFAOYSA-N
Target: Histone lysine demethylase PHF8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UPP1
Assay: PHF8 Assay: The ability of test compounds to inhibit the activity of PHF8 was determined in 384-well plate format under the following reaction conditions: 3 nM PHF8, 200 nM H3K9me1-biotin labeled peptide (Anaspec cat #64358), 0.5 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, and 5 μM ammonium iron(II) sulfate. Reaction product was determined quantitatively by TR-FRET after the addition of detection reagent Phycolink Streptavidin-allophycocyanin (Prozyme) and Europium-anti-unmodified-histone H3 lysine 9/lysine27 (H3K9/K27) antibody (PerkinElmer) in the presence of 5 mM EDTA in LANCE detection buffer (PerkinElmer) at a final concentration of 25 nM and 0.5 nM, respectively.The assay reaction was initiated by the following: 2 μl of the mixture of 600 nM H3K9me1-biotin labeled peptide and 1.5 μM alpha-ketoglutaric acid with 2 μl of 11-point serial diluted inhibitor in 3% DMSO were added to each well of the plate, followed by the addition of 2 μl of 9 nM PHF8 to initiate the reaction. The reaction mixture was incubated at rt for 15 min, and terminated by the addition of 6 μl of 5 mM EDTA in LANCE detection buffer containing 50 nM Phycolink Streptavidin-allophycocyanin and 1 nM Europium-anti-unmodified H3K9/K27 antibody. Plates were read by EnVision Multilabel Reader in TR-FRET mode (excitation at 320 nm, emission at 615 nm and 665 nm) after 1 hr incubation at rt. A ratio was calculated (665/615) for each well and fitted to determine inhibition constant (IC50).
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 350.36, ALogP 2.93, HBA 6, HBD 1, PSA 81.51, QED 0.6
Compound (SMILES): NS(=O)(=O)c1cc(NC(=O)Nc2ccc3c(c2)OCO3)c(O)c([N+](=O)[O-])c1
InChIKey: ORVNHJJKEJHGBW-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of carbonic anhydrase 12 (unknown origin) preincubated for 15 mins by stopped flow CO2 hydration assay
Measurement: Ki = 250 nM (pChEMBL 6.599999904632568)
Descriptors: MW 396.34, ALogP 1.32, HBA 8, HBD 4, PSA 183.12, QED 0.34
Compound (SMILES): Clc1ccc2c(n1)OC13CCC1NCC23
InChIKey: CRXFCGUGNWJSEY-UHFFFAOYSA-N
Target: Neuronal acetylcholine receptor; alpha4/beta2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P43681
Assay: Displacement of [3H]epibatidine from alpha4beta2 nAChR (unknown origin) expressed in HEK cell membranes after 4 hrs by liquid scintillation counting method
Measurement: Ki = 0.35 nM (pChEMBL 9.460000038146973)
Descriptors: MW 222.67, ALogP 1.72, HBA 3, HBD 1, PSA 34.15, QED 0.68
Compound (SMILES): CC[C@H](C)[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)CC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)O)[C@@H](C)O)C(C)C
InChIKey: AVQSWYGMSSNQGT-QVJUSLJMSA-N
Target: Neuropeptide Y receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15761
Assay: Displacement of [125I]-PYY(1 to 36 residues) from human Y5R expressed in HEK293 cell membranes after 2 hrs by scintillation proximity assay
Measurement: Ki = 400 nM (pChEMBL 6.400000095367432)
Descriptors: MW 4064.54
Compound (SMILES): FC(F)(F)c1ccccc1CCn1cnc(-c2cc(-c3c[nH]nn3)ccn2)c1
InChIKey: DVSWCXBLPJUQDT-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NHM5
Assay: FBXL10 Assay: The ability of test compounds to inhibit the activity of FBXL10 was determined in 384-well plate format under the following reaction conditions: 0.3 nM FBXL10, 30 nM H3K36me2-biotin labeled peptide (Anaspec cat #64442), 0.2 uM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 uM sodium L-ascorbate, 5 uM ammonium iron(II) sulfate. Reaction product is determined quantitatively by AlphaScreen detection after the addition of detection reagents anti-H3K36me1 antibody, AlphaScreen Streptavidin-coated Donor beads, and AlphaScreen Protein A Acceptor beads in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA to final 10 ug/ml beads.
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 384.37, ALogP 3.99, HBA 5, HBD 1, PSA 72.28, QED 0.56
Compound (SMILES): CC1(C)O[C@H]2O[C@H](CNCCCCCCCCNc3c4c(nc5ccccc35)CCCC4)[C@H](O)[C@H]2O1
InChIKey: VODYWRFVVQVYTG-KCPYNUOSSA-N
Target: Cholinesterase (SINGLE PROTEIN), Mus musculus
UniProt: Q03311
Assay: Inhibition of mouse serum BuChE
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 497.68, ALogP 4.69, HBA 7, HBD 3, PSA 84.87, QED 0.37
Compound (SMILES): NC(=O)c1cnc2c(NC3CC3)cc(NC3CCCCC3)nn12
InChIKey: LWGWNDZZYKEIAA-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of JAK2 JH2 domain (unknown origin)
Measurement: IC50 > 2000 nM (pChEMBL 5.698999881744385)
Descriptors: MW 314.39, ALogP 2.15, HBA 6, HBD 3, PSA 97.34, QED 0.79
Compound (SMILES): O=C(c1cscn1)N1CCN(Cc2c(-c3ccc(Cl)cc3Cl)nc3cnc(C4CC4)cn23)CC1
InChIKey: HSLRZRADDCJIKN-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P14672
Assay: Inhibition of human GluT4 expressed in HEK293 cells assessed as reduction in 3H]-deoxy-D-glucose uptake incubated for 30 mins by scintillation counting method
Measurement: IC50 <= 1000 nM (pChEMBL 6)
Descriptors: MW 513.45, ALogP 5, HBA 7, HBD 0, PSA 66.63, QED 0.38
Compound (SMILES): Cc1nn(C(=O)c2ccncc2)c(C)c1Cl
InChIKey: YCKMMEWZFSKOHG-UHFFFAOYSA-N
Target: Alkaline phosphatase, tissue-nonspecific isozyme (SINGLE PROTEIN), Homo sapiens
UniProt: P05186
Assay: Inhibition of human TNAP expressed in COS7 cells using CDP-star as substrate preincubated for 5 to 10 mins followed by substrate addition measured after 20 mins by luminescence-based assay
Measurement: IC50 = 42000 nM (pChEMBL 4.380000114440918)
Descriptors: MW 235.67, ALogP 2.24, HBA 4, HBD 0, PSA 47.78, QED 0.76
Compound (SMILES): Cc1ccc2oc(-c3ccc(OCCCCc4cn(CCOCCOCCOc5ccc(-c6oc7ccccc7c(=O)c6OCc6ccccc6)cc5)nn4)cc3)cc(=O)c2c1
InChIKey: GGTRLVCBBDICME-UHFFFAOYSA-N
Target: ATP-dependent translocase ABCB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08183
Assay: Inhibition of P-gp (unknown origin) expressed in human LCC6MDR cells assessed as reversal of paclitaxel resistance after 5 days by MTS/PMS assay
Measurement: EC50 = 421.7 nM (pChEMBL 6.380000114440918)
Descriptors: MW 833.94, ALogP 9.23, HBA 12, HBD 0, PSA 137.28, QED 0.06
Compound (SMILES): CCN(CCOc1ccc(/C=C2\COc3ccccc3C2=O)cc1)Cc1ccccc1
InChIKey: ZDBZMDPOTIZOER-PTGBLXJZSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human erythrocytes AChE using acetylthiocholine iodide as substrate preincubated for 5 mins followed by substrate addition measured at 1 to 3 mins time interval by Ellman's method
Measurement: IC50 = 22300 nM (pChEMBL 4.650000095367432)
Descriptors: MW 413.52, ALogP 5.25, HBA 4, HBD 0, PSA 38.77, QED 0.47
Compound (SMILES): Cn1cc(-c2cnc(OCC3CC3)c(Cl)c2)c2ccc(C(=O)NS(=O)(=O)C3CC3)cc21
InChIKey: KYKNUVNUVQMZFY-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q15858
Assay: Inhibition of human Nav1.7 expressed in HEK293 cells after 600 secs at -60 mV holding potential by ion works barracuda population patch clamp method
Measurement: IC50 = 82 nM (pChEMBL 7.090000152587891)
Descriptors: MW 459.96, ALogP 3.9, HBA 6, HBD 1, PSA 90.29, QED 0.58
Compound (SMILES): N=C1NC(=O)/C(=C/c2ccc3c(c2)CCO3)S1
InChIKey: GRHRWVRWLAIBGN-POHAHGRESA-N
Target: Dual specificity protein kinase CLK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49761
Assay: Inhibition of human CLK3
Measurement: IC50 = 116 nM (pChEMBL 6.940000057220459)
Descriptors: MW 246.29, ALogP 1.76, HBA 4, HBD 2, PSA 62.18, QED 0.74
Compound (SMILES): O=c1cc(-c2ccccc2)oc2cc(OCCOCc3cn(CCOCCOc4ccc(-c5oc6ccccc6c(=O)c5OCc5ccccc5)cc4)nn3)ccc12
InChIKey: YDKSMTZVBRGHKI-UHFFFAOYSA-N
Target: ATP-dependent translocase ABCB1 (SINGLE PROTEIN), Homo sapiens
UniProt: P08183
Assay: Inhibition of P-gp (unknown origin) expressed in human LCC6MDR cells assessed as reversal of paclitaxel resistance after 5 days by MTS/PMS assay
Measurement: EC50 = 345 nM (pChEMBL 6.460000038146973)
Descriptors: MW 777.83, ALogP 8.1, HBA 12, HBD 0, PSA 137.28, QED 0.08
Compound (SMILES): O=C(O)[C@H]1[C@H](c2ccccc2)[C@H](C(=O)Oc2ccccc2I)[C@H]1c1ccccc1
InChIKey: ABZLPONEGJOVGF-CMOCDZPBSA-N
Target: Fatty acid-binding protein, heart (SINGLE PROTEIN), Homo sapiens
UniProt: P05413
Assay: High Throughput Fluorescence Displacement Assay : FABP5 was purified and delipidated as described previously (Kaczocha, M. et al. 2012). FABP5 (30 μg), NBD-stearate (1 μM), and a competitor test compound were incubated in 30 mM Tris-HCl, 100 mM NaCl buffer (pH 7.6). Competitors included arachidonic acid, BMS309403, 48 test compounds from ChemDiv library, Compound 26 and Compound 49. The initial assay was run with buffer (30 mM Tris-HCl buffer), negative controls (buffer and NBD-stearate), positive controls (buffer, NBD-stearate, FABP5), and experimental wells with a variable test compound added (arachidonic acid or one of the 48 test compounds) at 10 μM. Test compounds that produced high inhibition and proved statistically significant were then added to the fluorescent assay at 10 μM and tested in triplicate to verify their success. The most effective test compound and BMS309403 were measured in increasing concentrations (0.01-50 μM), as were the Compound 26 and γ-truxillic acid 1-naphthyl ester, which were discovered following the test. The fluorescent assays were tested in the wells of Microtest 96-well Assay Plates, Optilux (BD Biosciences, Franklin Lakes, N.J.) and loss of fluorescence intensity was measured with a FLUOstar OPTIMA spectrofluorometer set to excitation and emission wavelengths of 460 nm and 544 nm, respectively. For the most effective test compounds, IC50 values were calculated with GraphPad Prism. GraphPad Prism was also used to determine the Ki of these select competitors from the equation Ki=IC50/(1+([NBD-stearate]/Kd)).
Measurement: Ki = 100 nM (pChEMBL 7)
Descriptors: MW 498.32, ALogP 5.09, HBA 3, HBD 1, PSA 63.6, QED 0.3
Compound (SMILES): CC[C@H](Nc1nc(N[C@@H](CC)C(F)(F)F)nc(-c2ccnc(C(F)(F)F)n2)n1)C(F)(F)F
InChIKey: BAHJVQDALFYMEG-IUCAKERBSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of DH1 R132H mutant in human TS603 cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 477.33, ALogP 4.85, HBA 7, HBD 2, PSA 88.51, QED 0.55
Compound (SMILES): CN(C)CCOc1ccc(/C=C2\COc3ccccc3C2=O)cc1
InChIKey: PEOGEDONFNSDPX-DTQAZKPQSA-N
Target: Amine oxidase [flavin-containing] A (SINGLE PROTEIN), Homo sapiens
UniProt: P21397
Assay: Inhibition of recombinant human MAO-A assessed as reduction in H2O2 production using p-tyramine as substrate preincubated for 15 mins followed by substrate addition by Amplex red reagent based fluorescence assay
Measurement: IC50 = 38100 nM (pChEMBL 4.420000076293945)
Descriptors: MW 323.39, ALogP 3.29, HBA 4, HBD 0, PSA 38.77, QED 0.79
Compound (SMILES): CC(=O)N1CCN(Cc2c(-c3ccc(Cl)cc3)nc3cnc(C4CC4)cn23)CC1
InChIKey: UOMWSKSFOUHOSR-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P14672
Assay: Inhibition of human GluT4 expressed in HEK293 cells assessed as reduction in 3H]-deoxy-D-glucose uptake incubated for 30 mins by scintillation counting method
Measurement: IC50 <= 1000 nM (pChEMBL 6)
Descriptors: MW 409.92, ALogP 3.59, HBA 5, HBD 0, PSA 53.74, QED 0.66
Compound (SMILES): CC(Nc1nc(NC(C)C(F)(F)F)nc(-c2cccc(Cl)n2)n1)C(F)(F)F
InChIKey: QCZAWDGAVJMPTA-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP], mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P48735
Assay: Inhibition of IDH2 R140Q mutant homodimer (unknown origin) expressed in Sf9 cells pre-incubated for 1 hr before addition of alpha-KG followed by 16 hrs incubation in presence of NADPH, NADP, diaphorase and resazurin by fluorescence spectrometry based cofactor depletion assay
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 414.74, ALogP 4.31, HBA 6, HBD 2, PSA 75.62, QED 0.56
Compound (SMILES): Cc1ccc(Oc2c(C)nn(C(=O)c3ccc(N)cc3)c2C)cc1
InChIKey: LYKACYGNLIPXJZ-UHFFFAOYSA-N
Target: Alkaline phosphatase, tissue-nonspecific isozyme (SINGLE PROTEIN), Homo sapiens
UniProt: P05186
Assay: Inhibition of human TNAP expressed in COS7 cells using CDP-star as substrate preincubated for 5 to 10 mins followed by substrate addition measured after 20 mins by luminescence-based assay
Measurement: IC50 = 4910 nM (pChEMBL 5.309999942779541)
Descriptors: MW 321.38, ALogP 3.87, HBA 5, HBD 1, PSA 70.14, QED 0.74
Compound (SMILES): N#C/C=C/c1ccc(Nc2nc(Nc3ccc(C#N)cc3)ncc2C(=O)NCCCN2CCCC2)cc1
InChIKey: AJZLXLLTXVDOHY-HWKANZROSA-N
Target: Human immunodeficiency virus type 1 reverse transcriptase (SINGLE PROTEIN), Human immunodeficiency virus 1
UniProt: Q72547
Assay: Inhibition of HIV1 reverse transcriptase Y181C mutant infected in human MT4 cells harboring GFP by scanning microscopic analysis
Measurement: EC50 = 19.95 nM (pChEMBL 7.699999809265137)
Descriptors: MW 492.59, ALogP 4.59, HBA 8, HBD 3, PSA 129.76, QED 0.28
Compound (SMILES): CNc1ncc(C(=O)NCc2ccc(OC)cc2)c2nc(-c3ccco3)nn12
InChIKey: ZYXGKENMDDPQIE-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of [3H]HEMADO from human adenosine A3 receptor expressed in CHO cell membranes after 3 hrs by micro beta scintillation counting method
Measurement: Ki = 12.5 nM (pChEMBL 7.900000095367432)
Descriptors: MW 378.39, ALogP 2.36, HBA 8, HBD 2, PSA 106.58, QED 0.53
Compound (SMILES): CC(F)(F)c1csc(-c2nc(NC3CCC(F)(F)CC3)nc(NC3CCC(F)(F)CC3)n2)n1
InChIKey: SPXMCXYDNWDRAD-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of DH1 R132H mutant in human TS603 cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 494.51, ALogP 6.09, HBA 7, HBD 2, PSA 75.62, QED 0.47
Compound (SMILES): Cc1nn(C(=O)C2CCC2)c(N)c1-c1ccc(Cl)c(Cl)c1
InChIKey: IVRWFRCEURYSHX-UHFFFAOYSA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: O15111
Assay: Inhibition of recombinant full length human His-tagged IKKalpha expressed in baculovirus expression system using ERLLDDRHDSGLDSMKDEE peptide as substrate measured after 60 mins by ADP-Glo kinase assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 324.21, ALogP 4.19, HBA 4, HBD 1, PSA 60.91, QED 0.9
Compound (SMILES): CC[C@H](C)[C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](CO)Cc1ccc(O)cc1)[C@@H](C)O)C(C)C
InChIKey: WUZMWLFGANYAOT-VGAMMVJNSA-N
Target: Neuropeptide Y receptor type 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15761
Assay: Displacement of [125I]-PYY(1 to 36 residues) from human Y5R expressed in HEK293 cell membranes after 2 hrs by scintillation proximity assay
Measurement: Ki = 160 nM (pChEMBL 6.800000190734863)
Descriptors: MW 4036.53
Compound (SMILES): O=C(O)c1ccnc(-n2nc(Cc3c(F)cccc3F)cc2O)c1
InChIKey: FNUATYZIINTYTJ-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NHM5
Assay: FBXL10 Assay: The ability of test compounds to inhibit the activity of FBXL10 was determined in 384-well plate format under the following reaction conditions: 0.3 nM FBXL10, 30 nM H3K36me2-biotin labeled peptide (Anaspec cat #64442), 0.2 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, and 5 μM ammonium iron(II) sulfate. Reaction product was determined quantitatively by AlphaScreen detection after the addition of detection reagents anti-H3K36me1 antibody, AlphaScreen® Streptavidin-coated Donor beads, and AlphaScreen® Protein A Acceptor beads in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA to final 10 μg/ml beads. The assay reaction was initiated by the following: 3 μl of the mixture of 90 nM H3K36me2-biotin labeled peptide and 0.6 μM alpha-ketoglutaric acid with 3 μl of 11-point serial diluted inhibitor in 3% DMSO were added to each well of 384 well Proxiplate (Perkin Elmer), followed by the addition of 3 μl of 0.9 nM FBXL10 to initiate the reaction. The reaction mixture was incubated at room temperature for 30 minutes, and terminated by the addition of 3 μl of 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA containing appropriate dilution of anti H3K36me1 antibody. Plates were incubated at room temperature for 40 minutes, followed by addition of 3 μl of 50 m/ml AlphaScreen® Streptavidin-coated Donor beads and AlphaScreen® Protein A Acceptor beads in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA. Plates were read by EnVisionMultilabel Reader in AlphaScreen mode after a minimum of 2 hour or up to overnight incubation at room temperature. The AlphaScreen signal for each well was used to determine inhibition constant (IC50).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 331.28, ALogP 2.54, HBA 5, HBD 2, PSA 88.24, QED 0.77
Compound (SMILES): COCCCOc1cc2c(cc1OC)-c1cc(=O)c(C(=O)O)cn1[C@H](C(C)C)C2
InChIKey: KBXLMOYQNDMHQT-KRWDZBQOSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Reversible inhibition of CYP2C19 in human liver microsomes using S-mephenytoin as substrate pre-incubated for 30 mins followed by NADPH addition and measured after 10 mins by LC-MS/MS analysis
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 401.46, ALogP 3.39, HBA 6, HBD 1, PSA 86.99, QED 0.68
Compound (SMILES): Cn1cnc(-c2cc(C(=O)O)ccn2)c1-c1ccc(C(C)(C)C)cc1
InChIKey: MDRIPRQWTFFXTF-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P29375
Assay: Jarid1A Assay: The enzymatic assay of Jarid1A activity is based upon Time Resolved-Fluorescence Resonance Energy Transfer (TR-FRET) detection. The ability of test compounds to inhibit the activity of Jarid1A was determined in 384-well plate format under the following reaction conditions: 1 nM Jarid1A, 300 nM H3K4me3-biotin labeled peptide (Anaspec cat #64357), 2 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, and 2 μM ammonium iron(II) sulfate. Reaction product was determined quantitatively by TR-FRET after the addition of detection reagent Phycolink Streptavidin-allophycocyanin (Prozyme) and Europium-anti-mono- or di-methylated histone H3 lysine 4 (H3K4me1-2) antibody (PerkinElmer) in the presence of 5 mM EDTA in LANCE detection buffer (PerkinElmer) at a final concentration of 25 nM and 1 nM, respectively.The assay reaction was initiated by the following: 2 μl of the mixture of 900 nM H3K4me3-biotin labeled peptide and 6 μM alpha-ketoglutaric acid with 2 μl of 11-point serial diluted inhibitor in 3% DMSO was added to each well of plate, followed by the addition of 2 μl of 3 nM Jarid1A to initiate the reaction. The reaction mixture was incubated at room temperature for 30 minutes, and terminated by the addition of 6 μl of 5 mM EDTA in LANCE detection buffer containing 50 nM Phycolink Streptavidin-allophycocyanin and 2 nM Europium-anti-H3K4me1-2 antibody. Plates were read by EnVisionMultilabel Reader in TR-FRET mode (excitation at 320 nm, emission at 615 nm and 665 nm) after 1 hour incubation at room temperature. A ratio was calculated (665/615) for each well and fitted to determine inhibition constant (IC50).
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 335.41, ALogP 4.14, HBA 4, HBD 1, PSA 68.01, QED 0.78
Compound (SMILES): N#Cc1cccc(C(=O)Nc2ccc3[nH]cc(C4CCN(C(=O)C5CCCC5)CC4)c3c2)c1
InChIKey: HDYDGYGIQGBWPQ-UHFFFAOYSA-N
Target: Nuclear receptor ROR-gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P51449
Assay: Inverse agonist activity at GAL4-fused RORC2 LBD (unknown origin) expressed in mouse neuro2A cells assessed as inhibition of transcriptional activity after 20 to 24 hrs by luciferase reporter gene assay
Measurement: IC50 = 2700 nM (pChEMBL 5.570000171661377)
Descriptors: MW 440.55, ALogP 5.19, HBA 3, HBD 2, PSA 88.99, QED 0.59
Compound (SMILES): CC(c1ccccc1)n1cnc(-c2cc(-c3c[nH]nn3)ccn2)c1
InChIKey: TYWLTGPEEXPZAQ-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y2K7
Assay: FBXL11 Assay: The ability of test compounds to inhibit the activity of FBXL11 was determined in 384-well plate format under the following reaction conditions: 0.15 nM FBXL11, 30 nM H3K36me2-biotin labeled peptide (Anaspec cat #64442), 0.2 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, 5 μM ammonium iron(II) sulfate. Reaction product is determined quantitatively by AlphaScreen detection after the addition of detection reagents anti-H3K36me1 antibody, AlphaScreen® Streptavidin-coated Donor beads, and AlphaScreen® Protein A Acceptor beads in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA to final 10 μg/ml beads.The assay reaction was initiated by the following: 3 μl of the mixture of 90 nM H3K36me2-biotin labeled peptide and 0.6 μM alpha-ketoglutaric acid with 3 μl of 11-point serial diluted inhibitor in 3% DMSO are added to each well of 384 well Proxiplate (Perkin Elmer), followed by the addition of 3 μl of 0.45 nM FBXL11 to initiate the reaction. The reaction mixture is incubated at room temperature for 1 hour, and terminated by the addition of 3 μl of appropriate dilution of anti H3K36me1 antibody in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA. Plates will then incubated at rt for 40 min, followed by addition of 3 μl of 50 μg/ml ALPHASCREEN® Streptavidin-coated Donor beads and ALPHASCREEN® Protein A Acceptor beads in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA. Plates will then be read by EnVision Multilabel Reader in AlphaScreen mode after minimum 2 hr incubation at rt. The AlphaScreen signal for each well is used to determine inhibition constant (IC50).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 316.37, ALogP 3.34, HBA 5, HBD 1, PSA 72.28, QED 0.63
Compound (SMILES): Cc1cc(Cn2c(=O)c3cc(S(=O)(=O)NC4(C)CC4)ccc3n(CC3COC3)c2=O)on1
InChIKey: MTOVWWKAXXWCCM-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin)
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 460.51, ALogP 0.99, HBA 9, HBD 1, PSA 125.43, QED 0.56
Compound (SMILES): Cc1[nH]nc(N)c1-c1ccc(Cl)c(Cl)c1
InChIKey: ZMBGAELSODJIRD-UHFFFAOYSA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: O15111
Assay: Inhibition of recombinant full length human His-tagged IKKalpha expressed in baculovirus expression system using ERLLDDRHDSGLDSMKDEE peptide as substrate measured after 60 mins by ADP-Glo kinase assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 242.11, ALogP 3.27, HBA 2, HBD 2, PSA 54.7, QED 0.81
Compound (SMILES): CN(CCn1cnc(-c2cc(C(=O)O)ccn2)c1)Cc1ccc(C(F)(F)F)cc1
InChIKey: VLKUKBMREASUQY-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: O75164
Assay: Inhibition of recombinant human N-terminal His-tagged JMJD2A (1 to 350 residues) expressed in Escherichia coli using H3K9me3-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by LANCE TR-FRET assay
Measurement: IC50 <= 100 nM (pChEMBL 7)
Descriptors: MW 404.39, ALogP 3.79, HBA 5, HBD 1, PSA 71.25, QED 0.65
Compound (SMILES): Cc1ccc(COc2ccnn2-c2cc(C(=O)O)ccn2)c(Cl)c1
InChIKey: BNEDYWDXODJLAY-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: O75164
Assay: Inhibition of recombinant human N-terminal His-tagged JMJD2A (1 to 350 residues) expressed in Escherichia coli using H3K9me3-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by LANCE TR-FRET assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 343.77, ALogP 3.51, HBA 5, HBD 1, PSA 77.24, QED 0.77
Compound (SMILES): c1ccc2c(c1)CCC(Cn1cnc(-c3cc(-c4nn[nH]n4)ccn3)c1)C2
InChIKey: BPQJRTYHBQULJV-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NHM5
Assay: FBXL10 Assay: The ability of test compounds to inhibit the activity of FBXL10 was determined in 384-well plate format under the following reaction conditions: 0.3 nM FBXL10, 30 nM H3K36me2-biotin labeled peptide (Anaspec cat #64442), 0.2 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, and 5 μM ammonium iron(II) sulfate. Reaction product was determined quantitatively by AlphaScreen detection after the addition of detection reagents anti-H3K36me1 antibody, AlphaScreen® Streptavidin-coated Donor beads, and AlphaScreen® Protein A Acceptor beads in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA to final 10 μg/ml beads.The assay reaction was initiated by the following: 3 μl of the mixture of 90 nM H3K36me2-biotin labeled peptide and 0.6 μM alpha-ketoglutaric acid with 3 μl of 11-point serial diluted inhibitor in 3% DMSO were added to each well of 384 well Proxiplate (Perkin Elmer), followed by the addition of 3 μl of 0.9 nM FBXL10 to initiate the reaction. The reaction mixture was incubated at room temperature for 30 minutes, and terminated by the addition of 3 μl of 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA containing appropriate dilution of anti H3K36me1 antibody. Plates were incubated at room temperature for 40 minutes, followed by addition of 3 μl of 50 μg/ml AlphaScreen® Streptavidin-coated Donor beads and AlphaScreen® Protein A Acceptor beads in 50 mM HEPES, pH7.3, 10 mM NaCl, 0.005% Brij35, 5 mM EDTA, 2 mg/ml BSA. Plates were read by EnVisionMultilabel Reader in AlphaScreen mode after a minimum of 2 hour or up to overnight incubation at room temperature. The AlphaScreen signal for each well was used to determine inhibition constant (IC50).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 357.42, ALogP 2.93, HBA 6, HBD 1, PSA 85.17, QED 0.61
Compound (SMILES): COc1cc2c(cc1O)CN(CCCCNC(=O)c1ccc(Cl)cc1)CC2
InChIKey: WOEVFFPIBHQXIQ-UHFFFAOYSA-N
Target: D(4) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21917
Assay: Displacement of [3H]N-Methylspiperone from human dopamine D4 receptor expressed in HEK cell membranes
Measurement: Ki = 140 nM (pChEMBL 6.849999904632568)
Descriptors: MW 388.89, ALogP 3.62, HBA 4, HBD 2, PSA 61.8, QED 0.71
Compound (SMILES): O=C(c1ccccc1)N1CCC(Nc2nc(NC3CCC(F)(F)C3)nc(-c3cccc(C(F)(F)F)n3)n2)C1
InChIKey: IGICKZPCOKPPMZ-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP], mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P48735
Assay: Inhibition of IDH2 R140Q mutant homodimer (unknown origin) expressed in Sf9 cells pre-incubated for 6 hrs before addition of alpha-KG followed by 60 mins incubation in presence of NADPH, NADP, diaphorase and resazurin by fluorescence spectrometry based cofactor depletion assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 533.51, ALogP 4.88, HBA 7, HBD 2, PSA 95.93, QED 0.44
Compound (SMILES): CN(CCn1cnc(-c2cc(C(=O)O)ccn2)c1)Cc1ccccc1
InChIKey: CODSMUFGDSEQOV-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NHM5
Assay: Inhibition of recombinant human C-terminal FLAG-tagged FBXL10 (1 to 650 residues) expressed in baculovirus infected sf9 cells using H3K36me2-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by AlphaScreen assay
Measurement: IC50 <= 100 nM (pChEMBL 7)
Descriptors: MW 336.4, ALogP 2.78, HBA 5, HBD 1, PSA 71.25, QED 0.72
Compound (SMILES): CC(F)(F)c1cc(Nc2nc(N[C@H]3CCC(F)(F)C3)nc(-c3cccc(C(F)(F)F)n3)n2)ccn1
InChIKey: RJZGABPOSOZJRY-LBPRGKRZSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of DH1 R132H mutant in human TS603 cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 501.41, ALogP 5.8, HBA 7, HBD 2, PSA 88.51, QED 0.41
Compound (SMILES): CC(C)(C)NC(=O)C(c1c(C(=O)O)[nH]c2cc(Cl)ccc12)N1C(=O)CC1c1ccc(OCc2ccccc2)cc1
InChIKey: LWYHFSNUGRPVLE-UHFFFAOYSA-N
Target: Protein Mdm4 (SINGLE PROTEIN), Homo sapiens
UniProt: O15151
Assay: Inhibition of 5'-FAM-LTFEHYWAQLTS binding to N-terminal domain of recombinant human MDMX after 15 mins by fluorescence polarization assay
Measurement: Ki = 2100 nM (pChEMBL 5.679999828338623)
Descriptors: MW 560.05, ALogP 6.03, HBA 4, HBD 3, PSA 111.73, QED 0.23
Compound (SMILES): Cn1cnc(-c2cc(C(=O)O)ccn2)c1-c1ccc(F)cc1
InChIKey: ONKWECDQZPASOC-UHFFFAOYSA-N
Target: Lysine-specific demethylase 4A (SINGLE PROTEIN), Homo sapiens
UniProt: O75164
Assay: Inhibition of recombinant human N-terminal His-tagged JMJD2A (1 to 350 residues) expressed in Escherichia coli using H3K9me3-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by LANCE TR-FRET assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 297.29, ALogP 2.99, HBA 4, HBD 1, PSA 68.01, QED 0.81
Compound (SMILES): Cc1cc(C#N)ccc1COc1ccnn1-c1cc(C(=O)O)ccn1
InChIKey: HWBFUMCZKFJIFB-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P29375
Assay: Jarid1A Assay: The enzymatic assay of Jarid1A activity is based upon Time Resolved-Fluorescence Resonance Energy Transfer (TR-FRET) detection. The ability of test compounds to inhibit the activity of Jarid1A was determined in 384-well plate format under the following reaction conditions: 1 nM Jarid1A, 300 nM H3K4me3-biotin labeled peptide (Anaspec cat #64357), 2 μM alpha-ketoglutaric acid in assay buffer of 50 mM HEPES, pH7.3, 0.005% Brij35, 0.5 mM TCEP, 0.2 mg/ml BSA, 50 μM sodium L-ascorbate, and 2 μM ammonium iron(II) sulfate. Reaction product was determined quantitatively by TR-FRET after the addition of detection reagent Phycolink Streptavidin-allophycocyanin (Prozyme) and Europium-anti-mono- or di-methylated histone H3 lysine 4 (H3K4me1-2) antibody (PerkinElmer) in the presence of 5 mM EDTA in LANCE detection buffer (PerkinElmer) at a final concentration of 25 nM and 1 nM, respectively. The assay reaction was initiated by the following: 2 μl of the mixture of 900 nM H3K4me3-biotin labeled peptide and 6 μM alpha-ketoglutaric acid with 2 μl of 11-point serial diluted inhibitor in 3% DMSO was added to each well of plate, followed by the addition of 2 μl of 3 nM Jarid1A to initiate the reaction. The reaction mixture was incubated at room temperature for 30 minutes, and terminated by the addition of 6 μl of 5 mM EDTA in LANCE detection buffer containing 50 nM Phycolink Streptavidin-allophycocyanin and 2 nM Europium-anti-H3K4me1-2 antibody. Plates were read by EnVisionMultilabel Reader in TR-FRET mode (excitation at 320 nm, emission at 615 nm and 665 nm) after 1 hour incubation at room temperature. A ratio was calculated (665/615) for each well and fitted to determine inhibition constant (IC50).
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 334.34, ALogP 2.72, HBA 6, HBD 1, PSA 101.03, QED 0.77
Compound (SMILES): CN(c1ncnc2[nH]ccc12)C1CN(C(=O)CC#N)CC12CC2
InChIKey: VCBQNQKWRAHHIR-UHFFFAOYSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: In Vitro JAK Kinase Inhibition Test: Kinases used were human-derived JAK1, JAK2, JAK3, and TYK2 (Millipore, Germany). Each of these kinases was diluted with a suitable buffer solution as described below, and then mixed with reagents. Kinase-activity inhibitory effects of some of the compounds of Examples 1 to 73 (for example, Examples 5, 55, and 66) for JAK1, JAK2, JAK3, and TYK2 were measured at various concentrations by the above-described method, and IC50 values were determined. The IC50 values of the test compounds were calculated from % inhibition values of the compounds, by the Cheng-Prusoff method (Biochem. Pharmacol. (1973) 22, 3099-3108).
Measurement: IC50 = 40.4 nM (pChEMBL 7.389999866485596)
Descriptors: MW 310.36, ALogP 1.3, HBA 5, HBD 1, PSA 88.91, QED 0.92
Compound (SMILES): Fc1cc(F)cc(Nc2nc(NC3CCC(F)(F)C3)nc(-c3cncc(Cl)n3)n2)c1
InChIKey: FQSFRGSJYCFQDI-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP] cytoplasmic (SINGLE PROTEIN), Homo sapiens
UniProt: O75874
Assay: Inhibition of DH1 R132H mutant in human TS603 cells assessed as reduction in 2-HG formation incubated for 48 hrs by LC-MS method
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 439.8, ALogP 4.6, HBA 7, HBD 2, PSA 88.51, QED 0.56
Compound (SMILES): CS(=O)(=O)N1CCC(Nc2nc(NC3CCC(F)(F)CC3)nc(-c3cccc(C(F)(F)F)n3)n2)CC1
InChIKey: XMCNRFYMKPJZQG-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP], mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P48735
Assay: Inhibition of IDH2 R140Q mutant homodimer (unknown origin) expressed in Sf9 cells pre-incubated for 6 hrs before addition of alpha-KG followed by 60 mins incubation in presence of NADPH, NADP, diaphorase and resazurin by fluorescence spectrometry based cofactor depletion assay
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 535.54, ALogP 3.78, HBA 8, HBD 2, PSA 113, QED 0.54
Compound (SMILES): C=CC(=O)Nc1ccccc1C(=O)Nc1cc(CCc2cc(OC)cc(OC)c2)[nH]n1
InChIKey: VJRPDSCCZRPRJC-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P22607
Assay: Inhibition of phosphorylated FGFR3 (411 to 806 residues) (unknown origin) using 5-Fluo-Ahx-EEPLYWSFPAKKKCONH2 as substrate after 60 mins by microfluidic mobility shift assay
Measurement: IC50 = 1.7 nM (pChEMBL 8.770000457763672)
Descriptors: MW 420.47, ALogP 3.59, HBA 5, HBD 3, PSA 105.34, QED 0.46
Compound (SMILES): COCC(=O)N1CCN(Cc2c(-c3ccc(Cl)cc3Cl)nc3ccc(NS(C)(=O)=O)cn23)CC1
InChIKey: SLGVOHUXGCFNAX-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P14672
Assay: Inhibition of human GluT4 expressed in HEK293 cells assessed as reduction in 3H]-deoxy-D-glucose uptake incubated for 30 mins by scintillation counting method
Measurement: IC50 <= 1000 nM (pChEMBL 6)
Descriptors: MW 526.45, ALogP 2.97, HBA 7, HBD 1, PSA 96.25, QED 0.51
Compound (SMILES): CCCCCCCCCCC/C(=N\O)c1cc(-c2ccc(O)c(F)c2)ccc1O
InChIKey: OOBRWNCJQGNMST-XTCLZLMSSA-N
Target: Monoacylglycerol lipase ABHD6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BV23
Assay: Inhibition of recombinant human ABHD6 expressed in HEK293 cells using 2-OG as substrate pretreated for 30 mins followed by substrate addition and measured after 5 mins by liquid scintillation spectroscopy analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 401.52, ALogP 7, HBA 4, HBD 3, PSA 73.05, QED 0.16
Compound (SMILES): C#Cc1ccc(-c2c(-c3cc(C(=O)O)ccn3)ncn2C)cc1
InChIKey: JHTVAONQTGIKOP-UHFFFAOYSA-N
Target: Lysine-specific demethylase 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NHM5
Assay: Inhibition of recombinant human C-terminal FLAG-tagged FBXL10 (1 to 650 residues) expressed in baculovirus infected sf9 cells using H3K36me2-biotin peptide as substrate after 30 mins in presence of alpha-ketoglutaric acid by AlphaScreen assay
Measurement: IC50 <= 100 nM (pChEMBL 7)
Descriptors: MW 303.32, ALogP 2.83, HBA 4, HBD 1, PSA 68.01, QED 0.76
Compound (SMILES): CC(=O)n1nc(C)c(-c2cccc(Cl)c2)c1N
InChIKey: YPXQKEQSEMZXEP-UHFFFAOYSA-N
Target: Inhibitor of nuclear factor kappa-B kinase subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: O15111
Assay: Inhibition of recombinant full length human His-tagged IKKalpha expressed in baculovirus expression system using ERLLDDRHDSGLDSMKDEE peptide as substrate measured after 60 mins by ADP-Glo kinase assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 249.7, ALogP 2.75, HBA 4, HBD 1, PSA 60.91, QED 0.85
Compound (SMILES): CNc1ncc(C(=O)OCc2ccc(F)cc2)c2nc(-c3ccco3)nn12
InChIKey: OJWAGAHNGMBHHI-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of [3H]HEMADO from human adenosine A3 receptor expressed in CHO cell membranes after 3 hrs by micro beta scintillation counting method
Measurement: Ki = 5.21 nM (pChEMBL 8.279999732971191)
Descriptors: MW 367.34, ALogP 2.92, HBA 8, HBD 1, PSA 94.55, QED 0.54
Compound (SMILES): O=C(NCCCC1CCN(Cc2ccccc2)CC1)c1cc(=O)c2cc(O)ccc2o1
InChIKey: OZAWXAOXPMUIGP-UHFFFAOYSA-N
Target: Polyunsaturated fatty acid 5-lipoxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P09917
Assay: Inhibition of human 5-lipoxygenase using arachidonic acid as substrate pretreated for 10 mins followed by substrate and ATP addition and measured after 20 mins by H2DCFDA probe based fluorescence assay
Measurement: IC50 = 15100 nM (pChEMBL 4.820000171661377)
Descriptors: MW 420.51, ALogP 3.92, HBA 5, HBD 2, PSA 82.78, QED 0.57
Compound (SMILES): CC(=O)Nc1cc(-c2[nH]c3cccnc3c2-c2cccc(C(F)F)n2)ccn1
InChIKey: VWSFKHLXKXHRDY-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 (unknown origin)
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 379.37, ALogP 4.58, HBA 4, HBD 2, PSA 83.56, QED 0.54
Compound (SMILES): CCC[C@@H](Nc1ncc2c(-c3ccc(CN4CCN(C)CC4)cc3)cn([C@H]3CC[C@H](O)CC3)c2n1)C(F)(F)F
InChIKey: REBYLZSNXNCLMK-JQYIIUTOSA-N
Target: Tyrosine-protein kinase Mer (SINGLE PROTEIN), Homo sapiens
UniProt: Q12866
Assay: Inhibition of MERTK (unknown origin) using 5'-FAM-EFPIYDFLPAKKK-CONH2 as substrate after 180 mins by MCE assay
Measurement: IC50 = 20 nM (pChEMBL 7.699999809265137)
Descriptors: MW 544.67, ALogP 5.46, HBA 7, HBD 2, PSA 69.45, QED 0.39
Compound (SMILES): CC(C)Nc1nc(Nc2ccnc(C(C)(F)F)c2)nc(-c2nccc(C(F)(F)F)n2)n1
InChIKey: MNWAUMZTPYXVGO-UHFFFAOYSA-N
Target: Isocitrate dehydrogenase [NADP], mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P48735
Assay: Inhibition of IDH2 R140Q mutant homodimer (unknown origin) expressed in Sf9 cells pre-incubated for 1 hr before addition of alpha-KG followed by 16 hrs incubation in presence of NADPH, NADP, diaphorase and resazurin by fluorescence spectrometry based cofactor depletion assay
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 440.38, ALogP 4.42, HBA 8, HBD 2, PSA 101.4, QED 0.54
Compound (SMILES): CC(C)c1cnn2c(NCc3ccc(-c4ccccn4)cc3)nc(N[C@H]3CC[C@H](N)CC3)nc12
InChIKey: PRJNNPMIUGYOST-MEMLXQNLSA-N
Target: Dual specificity protein kinase CLK1 (SINGLE PROTEIN), Mus musculus
UniProt: P22518
Assay: Inhibition of recombinant GST-tagged mouse CLK1 expressed in Escherichia coli using RS peptide as substrate after 30 mins in presence of [gamma-33P] by scintillation counting method
Measurement: IC50 = 100 nM (pChEMBL 7)
Descriptors: MW 456.6, ALogP 4.6, HBA 8, HBD 3, PSA 106.05, QED 0.37
Compound (SMILES): CCCCn1c(=O)c2c(nc3n2CCCN3CCc2ccc(OCC(=O)NCc3cccc(OC)c3)cc2)n(CCCC)c1=O
InChIKey: TXGKLRCXBKGTOQ-UHFFFAOYSA-N
Target: Adenosine receptor A3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS8
Assay: Displacement of [3H]PSB-11 from human adenosine A3 receptor expressed in CHO cell membranes
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 616.76, ALogP 4.12, HBA 10, HBD 1, PSA 112.62, QED 0.21
Compound (SMILES): Clc1ccc(-c2nc3cnc(C4CC4)cn3c2CN2CCOCC2)cc1
InChIKey: ACBPNASACKZFEB-UHFFFAOYSA-N
Target: Solute carrier family 2, facilitated glucose transporter member 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P14672
Assay: Inhibition of human GluT4 expressed in HEK293 cells assessed as reduction in 3H]-deoxy-D-glucose uptake incubated for 30 mins by scintillation counting method
Measurement: IC50 <= 1000 nM (pChEMBL 6)
Descriptors: MW 368.87, ALogP 3.76, HBA 5, HBD 0, PSA 42.66, QED 0.7
Compound (SMILES): CCCNC(=S)NCC1(C)CCc2ccc3ccc(OC)cc3c21
InChIKey: VXVVYBFJBHSBRI-UHFFFAOYSA-N
Target: Melatonin receptor type 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P48039
Assay: Agonist activity at human MT1 receptor expressed in CHO cell membranes after 1 hr by [35S]GTPgammaS binding assay
Measurement: EC50 = 100 nM (pChEMBL 7)
Descriptors: MW 342.51, ALogP 3.93, HBA 2, HBD 2, PSA 33.29, QED 0.81