lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CCN(C)C(=O)Oc1ccc(-c2cc(=O)c3c(OC(=O)N(C)CC)cc(OC(=O)N(C)CC)cc3o2)cc1
InChIKey: MBGXXUPMENAELF-UHFFFAOYSA-N
Target: Butyrylcholinesterase (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q9JKC1
Assay: Inhibition of rat serum Butyrylcholine esterase using butyrylthiocholine as substrate incubated for 15 mins by DTNB reagent based Ellman's method
Measurement: IC50 = 14300 nM (pChEMBL 4.840000152587891)
Descriptors: MW 525.56, ALogP 4.81, HBA 8, HBD 0, PSA 118.83, QED 0.43
Compound (SMILES): C=CC(=O)Nc1cccc(-c2c[nH]c3ncnc(Nc4ccc(OCc5ccccn5)c(Cl)c4)c23)c1
InChIKey: GOAJIFLFYKGQGD-UHFFFAOYSA-N
Target: Receptor tyrosine-protein kinase erbB-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P04626
Assay: Inhibition of C-terminal His6-tagged HER2 (703 to 1029 residues) (unknown origin) expressed in Sf9 insect cells using TK as substrate preincubated for 30 mins followed by substrate addition and measured after 60 mins in presence of XL665-labeled streptavidin by HTRF assay
Measurement: IC50 = 11 nM (pChEMBL 7.960000038146973)
Descriptors: MW 496.96, ALogP 6.12, HBA 6, HBD 3, PSA 104.82, QED 0.22
Compound (SMILES): CC#C[C@@H](CC(=O)O)c1ccc(OCc2ccc(CN3CCC4(CCc5ccccc54)CC3)s2)cc1
InChIKey: LGIUHWQDGPFXSG-VWLOTQADSA-N
Target: Free fatty acid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O14842
Assay: Agonist activity at human recombinant full length GPR40 overexpressed in human HEK293 cells assessed as increase in inositol phosphate accumulation in presence of terbium cryptate-labeled anti IP1/d2-labelled IP1 measured after 120 mins by HTRF assay
Measurement: EC50 = 6.1 nM (pChEMBL 8.210000038146973)
Descriptors: MW 499.68, ALogP 6.39, HBA 4, HBD 1, PSA 49.77, QED 0.37
Compound (SMILES): Cc1ccc(NC(=O)c2cccc(C(F)(F)F)c2)cc1C#Cc1nn(C2CCN(C)CC2)c2ncnc(N)c12
InChIKey: LQSGDXCDNZWTJN-UHFFFAOYSA-N
Target: RAF proto-oncogene serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P04049
Assay: Kinase Inhibition Assays: The aim of this experiment is to detect the inhibitory activity of the compounds of the present invention against in vitro protein kinases using isotope labeling (labeled gamma phosphate groups on ATP). Kinase inhibition profiles were determined using KinaseProfiler services provided by Euro fins, and ATP concentrations used are the Km of corresponding kinases. In this study, we examined Abl (T315I) (h), ALK (h), ARK5 (h), Axl (h), Blk (h), Bmx (h), BTK (h), B-Raf (H), ckit (h), cSRC (h), CDK7, CHK1 (h), c-RAF (h), DDR2 (h), EGFR (h), EphA1 (h), EphA2 (h), EphA8 (h (H), FGF (h), Ft (h), Ft (h), F (h), F (h), Ft (h), Hb (h), ErbB2 (h), FAK (h) (H), JK3 (h), IKKalpha (h), IKKbeta (h), Itk (h), JAK3 (h), JNK11 (h), KDR (h), Lyn (h), MAPK1 (h), MEK1 (h (H), PKA (h), PKB [alpha](h), PKB [beta] (h), PKC [alpha] (h), Ret (H), RIPK2 (h), Src (1-530) (h), TAK1 (h), TBK1 (h), Tec (h) activated, Tie2 (h), TrkA (h), ULK3 (h) Yes (h), PI3 Kinase a (h) and other kinase in vitro inhibitory activity. The kinase inhibitory activity of the test compound is expressed as IC50 (half inhibitory concentration) or the inhibitory rate of the test compound at a concentration of 10 ??M for kinase activity. IC50 values can be obtained by calculating the inhibition rate of the kinase activity by the test compound at a series of different concentrations. The assay was as follows: In a reaction tube, the buffer (8 mM MOPS, pH 7.0, 0.2 mM EDTA, 10 mM MnCl2), the kinase to be tested (5-10 mU), the substrate to be tested kinase, 10 mM acetic acid Magnesium and gamma 33P-ATP solutions, as well as different concentrations of the test compound. MgATP was then added to the reaction to initiate the enzymatic reaction and incubated at room temperature for 40 minutes. The reaction was finally quenched with 5 ul of 3% phosphate buffer and 10 uL of the reaction solution was titrated onto a filtermat A membrane, washed three times with 75 mM phosphate solution for 5 minutes each, and washed again with methanol. Finally, the filtermat A film is dried and scintigraphized, and the size of the scintillation count reflects the degree to which the substrate is phosphorylated, thereby demonstrating that the kinase activity is inhibited. Among them, the percentage of the remaining active protein=the active protein of the experimental group the active protein of the control group 100%.
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 533.56, ALogP 4.65, HBA 7, HBD 2, PSA 101.96, QED 0.37
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](Cc1ccccc1)NC(=O)CNC(=O)CNC(=O)[C@@H](C)Cc1c(C)cc(O)cc1C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(=O)O
InChIKey: KIXBLNINVHGOFN-NJFSYGJFSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Displacement of [3H]deltorphin-II from human DOR expressed in CHO cell membranes incubated for 2 hrs by liquid scintillation counting based radioligand competition assay
Measurement: IC50 = 1122.02 nM (pChEMBL 5.949999809265137)
Descriptors: MW 1233.53
Compound (SMILES): CN(C)C/C=C/C(=O)Nc1ccc(C(=O)N2CCC[C@@H](Nc3ncc(Cl)c(-c4c[nH]c5ccccc45)n3)C2)nc1
InChIKey: HJNYNZZNOGDODX-CLOLKSBNSA-N
Target: Cyclin-dependent kinase 13/Cyclin-K (PROTEIN COMPLEX), Homo sapiens
UniProt: O75909
Assay: Inhibition of human recombinant CDK13/CyclinK assessed as reduction in substrate phosphorylation using His-c-Myc as substrate preincubated with enzyme for 5 mins followed by substrate addition for 15 mins in presence of [gamma 32P-ATP] by radioactive kinase assay
Measurement: IC50 = 1636 nM (pChEMBL 5.789999961853027)
Descriptors: MW 559.07, ALogP 4.45, HBA 7, HBD 3, PSA 119.14, QED 0.27
Compound (SMILES): COCc1ccnc2c1CC[C@@H]1CNCCN21
InChIKey: JZNPRZRCDYEBIG-LLVKDONJSA-N
Target: 5-hydroxytryptamine receptor 2B (SINGLE PROTEIN), Homo sapiens
UniProt: P41595
Assay: Displacement of [3H]-LSB from recombinant human 5HT2BR transfected in human HEK293 cells incubated for 45 mins by radioligand binding assay
Measurement: Ki = 125.89 nM (pChEMBL 6.900000095367432)
Descriptors: MW 233.31, ALogP 0.95, HBA 4, HBD 1, PSA 37.39, QED 0.83
Compound (SMILES): CN1CCC[C@H]1[C@@H]1COc2ccc(N)cc2O1
InChIKey: NZWMSQXPQAEDAS-GWCFXTLKSA-N
Target: Neuronal acetylcholine receptor; alpha4/beta2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P43681
Assay: Partial agonist activity at high sensitivity isoform human (alpha4)2(beta2)3 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response at holding potential of -50 mV by two-electrode voltage clamp technique
Measurement: EC50 = 799 nM (pChEMBL 6.099999904632568)
Descriptors: MW 234.3, ALogP 1.5, HBA 4, HBD 1, PSA 47.72, QED 0.75
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3cc4ccccc4cn3)C2)cc1
InChIKey: CKXQPVNWDKKSSJ-HXUWFJFHSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51948
Assay: Protein Kinase Assay Condition A (Thiol Containing Conditions): A radiometric protein kinase assay (33PanQinase® Activity Assay) was used for measuring the kinase activity of the three protein kinases. All kinase assays were performed in 96-well FlashPlates™ from PerkinElmer (Boston, Mass., USA) in a 50 μl reaction volume. The reaction cocktail was pipetted in four steps in the following order:20 μl of assay buffer (standard buffer)5 μl of ATP solution (in H2O)5 μl of test compound (in 10% DMSO)20 μl enzyme/substrate mixThe assay for all protein kinases contained 70 mM HEPES-NaOH pH 7.5, 3 mM MgCl2, 3 mM MnCl2, 3 μM Na-orthovanadate, 1.2 mM DTT, 50 μg/ml PEG20000, ATP (variable concentrations, corresponding to the apparent ATP-Km of the respective kinase), [γ-33P]-ATP (approx. 9×1005 cpm per well), protein kinase (variable amounts), and substrate (variable amounts).
Measurement: IC50 = 550 nM (pChEMBL 6.260000228881836)
Descriptors: MW 386.45, ALogP 3.69, HBA 4, HBD 2, PSA 74.33, QED 0.66
Compound (SMILES): CCOC(=O)c1ccc(C(=O)Nc2ccc(-c3cn4c(=O)n(-c5ccccc5)nc4c(N)n3)cc2)cc1
InChIKey: ACRJLRFSMBLFGK-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human CA12 incubated for 15 mins by stopped- flow CO2 hydrase assay method
Measurement: Ki > 100000 nM (pChEMBL 4)
Descriptors: MW 494.51, ALogP 3.56, HBA 9, HBD 2, PSA 133.61, QED 0.34
Compound (SMILES): CNC(=O)c1csc2c(C(F)(F)F)cc(N3CCC(OC(=O)N[C@@H](C)COC(F)(F)F)CC3)nc12
InChIKey: UQQUABVWYAPTIQ-JTQLQIEISA-N
Target: UDP-glucuronosyltransferase 2B15 (SINGLE PROTEIN), Homo sapiens
UniProt: P54855
Assay: Inhibition of UGT2B15 (unknown origin)
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 528.48, ALogP 4.29, HBA 7, HBD 2, PSA 92.79, QED 0.54
Compound (SMILES): Cc1nc(-c2cccc(C#N)c2)n(OCc2ccc(C#N)cc2)c1C(=O)O
InChIKey: JLOKENLSGFWDSP-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes using phenacetin as substrate preincubated for 5 mins followed by NADPH generating system addition and measured after 120 mins by LC-MS/MS
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 358.36, ALogP 2.93, HBA 6, HBD 1, PSA 111.93, QED 0.75
Compound (SMILES): COc1cccc(OCCNCC2(F)CCN(C(=O)c3ccc(F)c(Cl)c3)CC2)c1
InChIKey: QLLXKLMQMYRBID-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Biased agonist activity at Gal4-VP16 transcription factor linked human 5-HT1A receptor expressed in human U2OS cells assessed as induction of beta-arrestin2 recruitment measured after 5 hrs by Tango assay
Measurement: EC50 = 2.291 nM (pChEMBL 8.640000343322754)
Descriptors: MW 438.9, ALogP 4.1, HBA 4, HBD 1, PSA 50.8, QED 0.63
Compound (SMILES): Nc1nc(-c2ccc(OCCNC(=O)c3ccc(S(N)(=O)=O)cc3)cc2)cn2c(=O)n(-c3ccccc3)nc12
InChIKey: MNEFMHDHCVMLFV-UHFFFAOYSA-N
Target: Carbonic anhydrase 12 (SINGLE PROTEIN), Homo sapiens
UniProt: O43570
Assay: Inhibition of human CA12 incubated for 15 mins by stopped- flow CO2 hydrase assay method
Measurement: Ki = 528.3 nM (pChEMBL 6.28000020980835)
Descriptors: MW 545.58, ALogP 1.59, HBA 10, HBD 3, PSA 176.7, QED 0.25
Compound (SMILES): CCOCCC[C@H]1CCc2cc([C@H]3CC[C@](N)(COP(=O)(O)O)C3)ccc2C1
InChIKey: VHKORLDZIRFKDI-ORYQWCPZSA-N
Target: Sphingosine 1-phosphate receptor 5 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H228
Assay: Agonist activity at recombinant human S1P5 expressed in CHO cell membranes assessed as stimulation of [35S]-GTPgammaS binding measured after 45 mins by liquid scintillation counting method
Measurement: EC50 = 4.9 nM (pChEMBL 8.3100004196167)
Descriptors: MW 411.48, ALogP 3.68, HBA 4, HBD 3, PSA 102.01, QED 0.42
Compound (SMILES): FC(F)(F)c1cnc(N[C@H]2CCCNC2)nc1-c1c[nH]c2ccccc12
InChIKey: QVBVFLKFEISMLZ-NSHDSACASA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/cyclin T1 (unknown origin) using 5-FAM-labeled peptide as substrate in presence of ATP by mobility shift assay
Measurement: IC50 = 21 nM (pChEMBL 7.679999828338623)
Descriptors: MW 361.37, ALogP 3.81, HBA 4, HBD 3, PSA 65.63, QED 0.66
Compound (SMILES): CCOC(=O)CCNc1cc(N2CCc3ccccc3CC2)nc(-c2cccnc2)n1
InChIKey: LQPGVGSKBNXQDU-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5A (SINGLE PROTEIN), Homo sapiens
UniProt: P29375
Assay: Inhibition of KDM5A (1 to 1090 residues)(unknown origin) by Alphalisa assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 417.51, ALogP 3.51, HBA 7, HBD 1, PSA 80.24, QED 0.59
Compound (SMILES): Cc1nc2c(=O)n(C3CC3)c3c(Cl)c(N4CC[C@@H]([C@H](C)N)C4)c(F)cc3c2o1
InChIKey: LOCSNCVSEDLFDP-GXSJLCMTSA-N
Target: Sodium channel protein type 5 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q14524
Assay: Inhibition of Nav1.5 (unknown origin) by patch clamp assay
Measurement: IC50 = 21500 nM (pChEMBL 4.670000076293945)
Descriptors: MW 404.87, ALogP 3.75, HBA 6, HBD 1, PSA 77.29, QED 0.72
Compound (SMILES): Cc1cc(-c2cnc3cc(-c4ccc(N5CCNCC5)cc4)ccn23)c2cc(F)cc(F)c2n1
InChIKey: RUBWYYYEDDAWLB-UHFFFAOYSA-N
Target: Bone morphogenetic protein receptor type-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13873
Assay: Inhibition of human BMPR2 using MBP as substrate by [gamma-33P]-ATP assay
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 455.51, ALogP 5.21, HBA 5, HBD 1, PSA 45.46, QED 0.41
Compound (SMILES): O=C(c1ccc(F)c(Cl)c1)N1CCC(F)(CNCCCc2ccccn2)CC1
InChIKey: WPKJQVXIPXZKJQ-UHFFFAOYSA-N
Target: Alpha-1A adrenergic receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P35348
Assay: Radioligand Binding Assay: Alpha1-adrenergic Receptor: Radioligand binding was performed using tissue (rat cortex). All assays were carried out in duplicates. 50 μL working solution of the tested compounds, 50 μL [3H]-prazosin (final concentration 0.2 nM, Kd 0.2 nM) and 150 μL tissue suspension prepared in assay buffer (50 mM Tris-HCl, pH 7.6) were transferred to polypropylene 96well microplate using 96wells pipetting station Rainin Liquidator (MettlerToledo). Phentolamine (10 μM) was used to define nonspecific binding. Microplate was covered with a sealing tape, mixed and incubated for 30 minutes at 30° C. The reaction was terminated by rapid filtration through GF/B filter mate. Ten rapid washes with 200 μL 50 mM Tris-HCl buffer (4° C., pH 7.6) were performed using automated harvester system Harvester-96 MACH III FM (Tomtec). The filter mates were dried at 37° C. in forced air fan incubator and soaked in 10 mL of liquid scintillation cocktail Ultima Gold MV (PerkinElmer, USA). After even distribution of scintillation cocktail filter bag was sealed. Radioactivity was counted in MicroBeta2 scintillation counter (PerkinElmer) at approximately 30% efficiency. Data were fitted to a one-site curve-fitting equation with Prism 6 (Graph Pad Software) and Ki values were estimated from the Cheng-Prusoff equation.
Measurement: Ki = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 407.89, ALogP 4.04, HBA 3, HBD 1, PSA 45.23, QED 0.7
Compound (SMILES): CC1(C)CNC[C@@H](Nc2ncc(C(F)(F)F)c(-c3c[nH]c4ccccc34)n2)C1
InChIKey: BFEWHEFVBQRIIR-LBPRGKRZSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/cyclin T1 (unknown origin) using 5-FAM-labeled peptide as substrate in presence of ATP by mobility shift assay
Measurement: IC50 = 41 nM (pChEMBL 7.389999866485596)
Descriptors: MW 389.43, ALogP 4.44, HBA 4, HBD 3, PSA 65.63, QED 0.62
Compound (SMILES): COC[C@H](C)N[C@H]1CC[C@H](Nc2cc(-c3cccc(NCC4(C#N)CCOCC4)n3)c(Cl)cn2)CC1
InChIKey: XWQVQSXLXAXOPJ-ACRUOGEOSA-N
Target: Cyclin-dependent kinase 6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q00534
Assay: Inhibition of CDK6 (unknown origin)
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 513.09, ALogP 4.88, HBA 8, HBD 3, PSA 104.12, QED 0.41
Compound (SMILES): CP(C)(=O)c1cccc2c(-c3nc(N[C@H]4CCCNC4)ncc3C(F)(F)F)c[nH]c12
InChIKey: DIIRGFRZMVBYSW-LBPRGKRZSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/cyclin T1 (unknown origin) using 5-FAM-labeled peptide as substrate in presence of ATP by mobility shift assay
Measurement: IC50 = 286 nM (pChEMBL 6.539999961853027)
Descriptors: MW 437.41, ALogP 4.06, HBA 5, HBD 3, PSA 82.7, QED 0.54
Compound (SMILES): C[C@@H](NC(=O)c1ccc(Cl)cc1)[C@H]1CC[C@@H](c2ccnc3ccc(F)cc32)CC1
InChIKey: AOJCHFNHRLPISK-ZACQAIPSSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in IFNgamma/LPS-stimulated human whole blood preincubated for 4 hrs followed by IFNgamma/LPS stimulation and incubated for 18 hrs by Rapid-fire mass spectrometry analysis
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 410.92, ALogP 6.12, HBA 2, HBD 1, PSA 41.99, QED 0.56
Compound (SMILES): CC(=O)c1nnn(-c2ccc(S(N)(=O)=O)cc2)c1C
InChIKey: QJBPFELDRXSCTJ-UHFFFAOYSA-N
Target: Prostaglandin G/H synthase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35354
Assay: Inhibition of COX-2 (unknown origin)
Measurement: IC50 = 2610 nM (pChEMBL 5.579999923706055)
Descriptors: MW 280.31, ALogP 0.43, HBA 6, HBD 1, PSA 107.94, QED 0.82
Compound (SMILES): C#Cc1nc(Nc2cccc(CC(N)=O)c2)nc2[nH]cnc12
InChIKey: CJQGLUJHMXCLQY-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16584
Assay: Inhibition of human MLK3 by kinase-profiling analysis
Measurement: IC50 = 320 nM (pChEMBL 6.5)
Descriptors: MW 292.3, ALogP 1.11, HBA 5, HBD 3, PSA 109.58, QED 0.62
Compound (SMILES): CC1(C)CC[C@H](Nc2ncc(C(F)(F)F)c(-c3c[nH]c4ccccc34)n2)CN1
InChIKey: YDHKLKQGRRFWHD-LBPRGKRZSA-N
Target: CDK9/cyclin T1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P50750
Assay: Inhibition of CDK9/cyclin T1 (unknown origin) using 5-FAM-labeled peptide as substrate in presence of ATP by mobility shift assay
Measurement: IC50 = 71 nM (pChEMBL 7.150000095367432)
Descriptors: MW 389.43, ALogP 4.59, HBA 4, HBD 3, PSA 65.63, QED 0.61
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCCN)NC(=O)[C@@H]1CCCN1C(=O)Cc1ccc(O)cc1)C(N)=O
InChIKey: UVDZRYDWESJRQX-TZPCGENMSA-N
Target: N-terminal Xaa-Pro-Lys N-methyltransferase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BV86
Assay: Inhibition of recombinant human full-length His6-tagged NTMT1 (1 to 222 residues) expressed in Escherichia coli BL21-CodonPlus(DE3)-RIL competent cells assessed as Me2RCC1 level at 10 uM pre-incubated for 0 mins before RCC1 substrate addition and measured after 15 mins by Western blot analysis relative to control
Measurement: IC50 = 900 nM (pChEMBL 6.050000190734863)
Descriptors: MW 1313.59
Compound (SMILES): CCCCCn1c(-c2ccco2)nc2c(N(C)CCCO)nccc21
InChIKey: FXTXXZMNWIDRNU-UHFFFAOYSA-N
Target: 3',5'-cyclic-AMP phosphodiesterase 4D (SINGLE PROTEIN), Homo sapiens
UniProt: Q08499
Assay: Inhibition of human recombinant PDE4D using cAMP as substrate incubated for 20 mins measured by Kinase Glo reagent based microplate reader assay
Measurement: IC50 = 25760 nM (pChEMBL 4.590000152587891)
Descriptors: MW 342.44, ALogP 3.7, HBA 6, HBD 1, PSA 67.32, QED 0.6
Compound (SMILES): Nc1ncc(-c2nc(N3CCOCC3)c3ncn(CCCCCCC(=O)NO)c3n2)cn1
InChIKey: SHWBIBURMMWDKZ-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Inhibition of human mTOR
Measurement: IC50 = 288 nM (pChEMBL 6.539999961853027)
Descriptors: MW 441.5, ALogP 1.16, HBA 11, HBD 3, PSA 157.2, QED 0.25
Compound (SMILES): CCN(C)C(=O)Oc1ccc(-c2cc(=O)c3c(OC(=O)N(C)CC)cc(OC(=O)N(C)CC)cc3o2)cc1
InChIKey: MBGXXUPMENAELF-UHFFFAOYSA-N
Target: Acetylcholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P22303
Assay: Inhibition of human erythrocyte AChE using acetylthiocholine as substrate incubated for 15 mins by DTNB reagent based Ellman's method
Measurement: IC50 = 12300 nM (pChEMBL 4.909999847412109)
Descriptors: MW 525.56, ALogP 4.81, HBA 8, HBD 0, PSA 118.83, QED 0.43
Compound (SMILES): CC#C[C@@H](CC(=O)O)c1ccc(OCc2ccc(CN3CCC4(CCc5ccccc54)CC3)s2)cc1
InChIKey: LGIUHWQDGPFXSG-VWLOTQADSA-N
Target: Free fatty acid receptor 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O14842
Assay: Displacement of [3H]-(S)-2-(6-((2',6'-dimethyl-4'-(3-(methylsulfonyl)propoxy)biphenyl-3-yl)methoxy)-2,3-dihydrobenzofuran-3-yl)acetic acid from human recombinant full-length GPR40 expressed in human HEK293 cell membrane assessed as dissociation constant measured after 2 hrs by radioligand competitive assay
Measurement: Kd = 3.5 nM (pChEMBL 8.460000038146973)
Descriptors: MW 499.68, ALogP 6.39, HBA 4, HBD 1, PSA 49.77, QED 0.37
Compound (SMILES): Cc1ccc(NC(=O)c2cccc(C(F)(F)F)c2)cc1C#Cc1nn(C2CCN(C)CC2)c2ncnc(N)c12
InChIKey: LQSGDXCDNZWTJN-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Yes (SINGLE PROTEIN), Homo sapiens
UniProt: P07947
Assay: Kinase Inhibition Assays: The aim of this experiment is to detect the inhibitory activity of the compounds of the present invention against in vitro protein kinases using isotope labeling (labeled gamma phosphate groups on ATP). Kinase inhibition profiles were determined using KinaseProfiler services provided by Euro fins, and ATP concentrations used are the Km of corresponding kinases. In this study, we examined Abl (T315I) (h), ALK (h), ARK5 (h), Axl (h), Blk (h), Bmx (h), BTK (h), B-Raf (H), ckit (h), cSRC (h), CDK7, CHK1 (h), c-RAF (h), DDR2 (h), EGFR (h), EphA1 (h), EphA2 (h), EphA8 (h (H), FGF (h), Ft (h), Ft (h), F (h), F (h), Ft (h), Hb (h), ErbB2 (h), FAK (h) (H), JK3 (h), IKKalpha (h), IKKbeta (h), Itk (h), JAK3 (h), JNK11 (h), KDR (h), Lyn (h), MAPK1 (h), MEK1 (h (H), PKA (h), PKB [alpha](h), PKB [beta] (h), PKC [alpha] (h), Ret (H), RIPK2 (h), Src (1-530) (h), TAK1 (h), TBK1 (h), Tec (h) activated, Tie2 (h), TrkA (h), ULK3 (h) Yes (h), PI3 Kinase a (h) and other kinase in vitro inhibitory activity. The kinase inhibitory activity of the test compound is expressed as IC50 (half inhibitory concentration) or the inhibitory rate of the test compound at a concentration of 10 ??M for kinase activity. IC50 values can be obtained by calculating the inhibition rate of the kinase activity by the test compound at a series of different concentrations. The assay was as follows: In a reaction tube, the buffer (8 mM MOPS, pH 7.0, 0.2 mM EDTA, 10 mM MnCl2), the kinase to be tested (5-10 mU), the substrate to be tested kinase, 10 mM acetic acid Magnesium and gamma 33P-ATP solutions, as well as different concentrations of the test compound. MgATP was then added to the reaction to initiate the enzymatic reaction and incubated at room temperature for 40 minutes. The reaction was finally quenched with 5 ul of 3% phosphate buffer and 10 uL of the reaction solution was titrated onto a filtermat A membrane, washed three times with 75 mM phosphate solution for 5 minutes each, and washed again with methanol. Finally, the filtermat A film is dried and scintigraphized, and the size of the scintillation count reflects the degree to which the substrate is phosphorylated, thereby demonstrating that the kinase activity is inhibited. Among them, the percentage of the remaining active protein=the active protein of the experimental group the active protein of the control group 100%.
Measurement: IC50 < 1 nM (pChEMBL 9)
Descriptors: MW 533.56, ALogP 4.65, HBA 7, HBD 2, PSA 101.96, QED 0.37
Compound (SMILES): COCc1ccnc2c1CC[C@@H]1CNCCN21
InChIKey: JZNPRZRCDYEBIG-LLVKDONJSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]-DOI from recombinant human 5HT2AR transfected in human HEK293 cells incubated for 45 mins by radioligand binding assay
Measurement: Ki = 100 nM (pChEMBL 7)
Descriptors: MW 233.31, ALogP 0.95, HBA 4, HBD 1, PSA 37.39, QED 0.83
Compound (SMILES): CN1CCC[C@H]1[C@@H]1COc2ccc(N)cc2O1
InChIKey: NZWMSQXPQAEDAS-GWCFXTLKSA-N
Target: Neuronal acetylcholine receptor; alpha4/beta2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P43681
Assay: Partial agonist activity at low sensitivity isoform human (alpha4)3(beta2)2 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current response at holding potential of -50 mV by two-electrode voltage clamp technique
Measurement: EC50 = 4800 nM (pChEMBL 5.320000171661377)
Descriptors: MW 234.3, ALogP 1.5, HBA 4, HBD 1, PSA 47.72, QED 0.75
Compound (SMILES): C=CC(=O)Nc1ccc(C(=O)N2CC[C@@H](Nc3cc4ccccc4cn3)C2)cc1
InChIKey: CKXQPVNWDKKSSJ-HXUWFJFHSA-N
Target: CDK7/Cyclin H/MNAT1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P51948
Assay: Protein Kinase Assay Condition B (Thiol-Free Conditions): A radiometric protein kinase assay (33PanQinase® Activity Assay) was used for measuring the kinase activity of the protein kinase. All kinase assays were performed in 96-well FlashPlates from PerkinElmer (Boston, Mass., USA) in a 50 microliter reaction volume. The reaction cocktail was pipetted in four steps in the following order: 20 microliter of assay buffer (standard buffer)5 microliter of ATP solution (in H2O)5 microliter of test compound (in 10% DMSO)20 microliter enzyme/substrate mix. Each assay for the protein kinase contained 70 mM HEPES-NaOH pH 7.5, 3 mM MgCl2, 3 mM MnCl2, 3 microM Na-orthovanadate, 1 mM TCEP, 50 μg/ml PEG20000, ATP (corresponding to the apparent ATP-Km of the kinase, see Table A), [gamma-33P]-ATP (approx. 6×10×E5 cpm per well), with the protein kinase and relevant substrate being used in pre-determined amounts, depending on the kinase in question. For all experiments labeled as Thiol-free, all glutathione was exchanged from protein preparations so as to be removed from the assay and final buffer conditions contained no thiol-containing reagents. In addition, the DTT in the thiol-containing assays is replaced by TCEP in the thiol-free assays and all enzymes and substrates are produced under thiol-free conditions for the thiol-free assays.
Measurement: IC50 = 5500 nM (pChEMBL 5.260000228881836)
Descriptors: MW 386.45, ALogP 3.69, HBA 4, HBD 2, PSA 74.33, QED 0.66
Compound (SMILES): CCOC(=O)c1ccc(C(=O)Nc2ccc(-c3cn4c(=O)n(-c5ccccc5)nc4c(N)n3)cc2)cc1
InChIKey: ACRJLRFSMBLFGK-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Antagonist activity at human A2B receptor expressed in CHO cell membrane assessed as reduction in NECA-stimulated AMP level by GloSensor CAMP assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 494.51, ALogP 3.56, HBA 9, HBD 2, PSA 133.61, QED 0.34
Compound (SMILES): CNC(=O)c1csc2c(C(F)(F)F)cc(N3CCC(OC(=O)N[C@@H](C)COC(F)(F)F)CC3)nc12
InChIKey: UQQUABVWYAPTIQ-JTQLQIEISA-N
Target: 2-hydroxyacylsphingosine 1-beta-galactosyltransferase (SINGLE PROTEIN), Mus musculus
UniProt: Q64676
Assay: Inhibition of mouse UGT8 assessed as redcution in SFT accumulation
Measurement: IC50 = 0.3 nM (pChEMBL 9.520000457763672)
Descriptors: MW 528.48, ALogP 4.29, HBA 7, HBD 2, PSA 92.79, QED 0.54
Compound (SMILES): Cc1nc(-c2cccc(C#N)c2)n(OCc2ccc(C#N)cc2)c1C(=O)O
InChIKey: JLOKENLSGFWDSP-UHFFFAOYSA-N
Target: P2Y purinoceptor 1 (SINGLE PROTEIN), Rattus norvegicus
UniProt: P49651
Assay: Antagonist activity at P2Y1 receptor in platelet-rich plasma of rat assessed as inhibition of ADP-induced cytosolic Ca2+ level pretreated for 5 mins followed by ADP addition by FLUO-4 AM dye based analysis
Measurement: IC50 = 2950 nM (pChEMBL 5.53000020980835)
Descriptors: MW 358.36, ALogP 2.93, HBA 6, HBD 1, PSA 111.93, QED 0.75
Compound (SMILES): COc1cccc(OCCNCC2(F)CCN(C(=O)c3ccc(F)c(Cl)c3)CC2)c1
InChIKey: QLLXKLMQMYRBID-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: Biased agonist activity at human 5-HT1A receptor stably expressed in CHO-K1 cells co-expressing Galpha16/GPCR assessed as increase in calcium mobilization measured for 30 secs in presence of coelenterazine by aequorin-reporter gene based luminescence assay
Measurement: EC50 = 70.79 nM (pChEMBL 7.150000095367432)
Descriptors: MW 438.9, ALogP 4.1, HBA 4, HBD 1, PSA 50.8, QED 0.63
Compound (SMILES): Nc1nc(-c2ccc(OCCNC(=O)c3ccc(S(N)(=O)=O)cc3)cc2)cn2c(=O)n(-c3ccccc3)nc12
InChIKey: MNEFMHDHCVMLFV-UHFFFAOYSA-N
Target: Adenosine receptor A2b (SINGLE PROTEIN), Homo sapiens
UniProt: P29275
Assay: Antagonist activity at human A2B receptor expressed in CHO cell membrane assessed as reduction in NECA-stimulated AMP level by GloSensor CAMP assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 545.58, ALogP 1.59, HBA 10, HBD 3, PSA 176.7, QED 0.25
Compound (SMILES): FC(F)(F)c1cnc(N[C@H]2CCCNC2)nc1-c1c[nH]c2ccccc12
InChIKey: QVBVFLKFEISMLZ-NSHDSACASA-N
Target: CDK12/Cyclin K (PROTEIN COMPLEX), Homo sapiens
UniProt: O75909
Assay: Inhibition of CDK12/cyclin K (unknown origin) using 5-FAM-labeled peptide as substrate in presence of ATP by mobility shift assay
Measurement: IC50 = 24 nM (pChEMBL 7.619999885559082)
Descriptors: MW 361.37, ALogP 3.81, HBA 4, HBD 3, PSA 65.63, QED 0.66
Compound (SMILES): CCOC(=O)CCNc1cc(N2CCc3ccccc3CC2)nc(-c2cccnc2)n1
InChIKey: LQPGVGSKBNXQDU-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UGL1
Assay: Inhibition of KDM5B (1 to 809 residues)(unknown origin) by Alphalisa assay
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 417.51, ALogP 3.51, HBA 7, HBD 1, PSA 80.24, QED 0.59
Compound (SMILES): Cc1nc2c(=O)n(C3CC3)c3c(Cl)c(N4CC[C@@H]([C@H](C)N)C4)c(F)cc3c2o1
InChIKey: LOCSNCVSEDLFDP-GXSJLCMTSA-N
Target: Voltage-dependent L-type calcium channel subunit alpha-1C (SINGLE PROTEIN), Homo sapiens
UniProt: Q13936
Assay: Inhibition of Cav1.2 (unknown origin) by patch clamp assay
Measurement: IC50 = 93600 nM (pChEMBL 4.03000020980835)
Descriptors: MW 404.87, ALogP 3.75, HBA 6, HBD 1, PSA 77.29, QED 0.72
Compound (SMILES): Cc1cc(-c2cnc3cc(-c4ccc(N5CCNCC5)cc4)ccn23)c2cc(F)cc(F)c2n1
InChIKey: RUBWYYYEDDAWLB-UHFFFAOYSA-N
Target: TGF-beta receptor type-2 (SINGLE PROTEIN), Homo sapiens
UniProt: P37173
Assay: Inhibition of human TGFBR2 using MBP as substrate by [gamma-33P]-ATP assay
Measurement: IC50 = 170.7 nM (pChEMBL 6.769999980926514)
Descriptors: MW 455.51, ALogP 5.21, HBA 5, HBD 1, PSA 45.46, QED 0.41
Compound (SMILES): CC1(C)CNC[C@@H](Nc2ncc(C(F)(F)F)c(-c3c[nH]c4ccccc34)n2)C1
InChIKey: BFEWHEFVBQRIIR-LBPRGKRZSA-N
Target: CDK12/Cyclin K (PROTEIN COMPLEX), Homo sapiens
UniProt: O75909
Assay: Inhibition of CDK12/cyclin K (unknown origin) using 5-FAM-labeled peptide as substrate in presence of ATP by mobility shift assay
Measurement: IC50 = 36 nM (pChEMBL 7.440000057220459)
Descriptors: MW 389.43, ALogP 4.44, HBA 4, HBD 3, PSA 65.63, QED 0.62
Compound (SMILES): COC[C@H](C)N[C@H]1CC[C@H](Nc2cc(-c3cccc(NCC4(C#N)CCOCC4)n3)c(Cl)cn2)CC1
InChIKey: XWQVQSXLXAXOPJ-ACRUOGEOSA-N
Target: Cyclin-dependent kinase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: P50613
Assay: Inhibition of CDK7 (unknown origin)
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 513.09, ALogP 4.88, HBA 8, HBD 3, PSA 104.12, QED 0.41
Compound (SMILES): CP(C)(=O)c1cccc2c(-c3nc(N[C@H]4CCCNC4)ncc3C(F)(F)F)c[nH]c12
InChIKey: DIIRGFRZMVBYSW-LBPRGKRZSA-N
Target: CDK12/Cyclin K (PROTEIN COMPLEX), Homo sapiens
UniProt: O75909
Assay: Inhibition of CDK12/cyclin K (unknown origin) using 5-FAM-labeled peptide as substrate in presence of ATP by mobility shift assay
Measurement: IC50 = 102 nM (pChEMBL 6.989999771118164)
Descriptors: MW 437.41, ALogP 4.06, HBA 5, HBD 3, PSA 82.7, QED 0.54
Compound (SMILES): C[C@@H](NC(=O)c1ccc(Cl)cc1)[C@H]1CC[C@@H](c2ccnc3ccc(F)cc32)CC1
InChIKey: AOJCHFNHRLPISK-ZACQAIPSSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Mus musculus
UniProt: P28776
Assay: Inhibition of IDO1 in IFNgamma-stimulated mouse M109 cells preincubated for 2 hrs followed by IFNgamma stimulation and measured after 18 hrs by
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 410.92, ALogP 6.12, HBA 2, HBD 1, PSA 41.99, QED 0.56
Compound (SMILES): C#Cc1nc(Nc2cccc(CC(N)=O)c2)nc2[nH]cnc12
InChIKey: CJQGLUJHMXCLQY-UHFFFAOYSA-N
Target: NUAK family SNF1-like kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O60285
Assay: Inhibition of human NAUK1 by kinase-profiling analysis
Measurement: IC50 = 120 nM (pChEMBL 6.920000076293945)
Descriptors: MW 292.3, ALogP 1.11, HBA 5, HBD 3, PSA 109.58, QED 0.62
Compound (SMILES): CC1(C)CC[C@H](Nc2ncc(C(F)(F)F)c(-c3c[nH]c4ccccc34)n2)CN1
InChIKey: YDHKLKQGRRFWHD-LBPRGKRZSA-N
Target: CDK12/Cyclin K (PROTEIN COMPLEX), Homo sapiens
UniProt: O75909
Assay: Inhibition of CDK12/cyclin K (unknown origin) using 5-FAM-labeled peptide as substrate in presence of ATP by mobility shift assay
Measurement: IC50 = 95 nM (pChEMBL 7.019999980926514)
Descriptors: MW 389.43, ALogP 4.59, HBA 4, HBD 3, PSA 65.63, QED 0.61
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCCN)NC(=O)[C@@H]1CCCN1C(=O)Cc1ccc(O)cc1)C(N)=O
InChIKey: UVDZRYDWESJRQX-TZPCGENMSA-N
Target: N-terminal Xaa-Pro-Lys N-methyltransferase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BV86
Assay: Binding affinity to recombinant human full-length His6-tagged NTMT1 (1 to 222 residues) by ITC assay
Measurement: Kd = 300 nM (pChEMBL 6.519999980926514)
Descriptors: MW 1313.59
Compound (SMILES): CCCCCn1c(-c2ccco2)nc2c(N(C)CCCO)nccc21
InChIKey: FXTXXZMNWIDRNU-UHFFFAOYSA-N
Target: cGMP-specific 3',5'-cyclic phosphodiesterase (SINGLE PROTEIN), Homo sapiens
UniProt: O76074
Assay: Inhibition of human recombinant PDE5A using cGMP as substrate incubated for 20 mins measured by Kinase Glo reagent based microplate reader assay
Measurement: IC50 = 2910 nM (pChEMBL 5.539999961853027)
Descriptors: MW 342.44, ALogP 3.7, HBA 6, HBD 1, PSA 67.32, QED 0.6
Compound (SMILES): Nc1ncc(-c2nc(N3CCOCC3)c3ncn(CCCCCCC(=O)NO)c3n2)cn1
InChIKey: SHWBIBURMMWDKZ-UHFFFAOYSA-N
Target: Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: O00443
Assay: Inhibition of human PI3K2alpha incubated for 1 hr by ADP-Glo kinase assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 441.5, ALogP 1.16, HBA 11, HBD 3, PSA 157.2, QED 0.25
Compound (SMILES): CCN(C)C(=O)Oc1ccc(-c2cc(=O)c3c(OC(=O)N(C)CC)cc(OC(=O)N(C)CC)cc3o2)cc1
InChIKey: MBGXXUPMENAELF-UHFFFAOYSA-N
Target: Cholinesterase (SINGLE PROTEIN), Homo sapiens
UniProt: P06276
Assay: Inhibition of human serum BuChE using butyrylthiocholine as substrate incubated for 15 mins by DTNB reagent based Ellman's method
Measurement: IC50 = 20600 nM (pChEMBL 4.690000057220459)
Descriptors: MW 525.56, ALogP 4.81, HBA 8, HBD 0, PSA 118.83, QED 0.43
Compound (SMILES): CC#C[C@@H](CC(=O)O)c1ccc(OCc2ccc(CN3CCC4(CCc5ccccc54)CC3)s2)cc1
InChIKey: LGIUHWQDGPFXSG-VWLOTQADSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of human ERG
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 499.68, ALogP 6.39, HBA 4, HBD 1, PSA 49.77, QED 0.37
Compound (SMILES): Cc1ccc(NC(=O)c2cccc(C(F)(F)F)c2)cc1C#Cc1nn(C2CCN(C)CC2)c2ncnc(N)c12
InChIKey: LQSGDXCDNZWTJN-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Fyn (SINGLE PROTEIN), Homo sapiens
UniProt: P06241
Assay: Kinase Inhibition Assays: The aim of this experiment is to detect the inhibitory activity of the compounds of the present invention against in vitro protein kinases using isotope labeling (labeled gamma phosphate groups on ATP). Kinase inhibition profiles were determined using KinaseProfiler services provided by Euro fins, and ATP concentrations used are the Km of corresponding kinases. In this study, we examined Abl (T315I) (h), ALK (h), ARK5 (h), Axl (h), Blk (h), Bmx (h), BTK (h), B-Raf (H), ckit (h), cSRC (h), CDK7, CHK1 (h), c-RAF (h), DDR2 (h), EGFR (h), EphA1 (h), EphA2 (h), EphA8 (h (H), FGF (h), Ft (h), Ft (h), F (h), F (h), Ft (h), Hb (h), ErbB2 (h), FAK (h) (H), JK3 (h), IKKalpha (h), IKKbeta (h), Itk (h), JAK3 (h), JNK11 (h), KDR (h), Lyn (h), MAPK1 (h), MEK1 (h (H), PKA (h), PKB [alpha](h), PKB [beta] (h), PKC [alpha] (h), Ret (H), RIPK2 (h), Src (1-530) (h), TAK1 (h), TBK1 (h), Tec (h) activated, Tie2 (h), TrkA (h), ULK3 (h) Yes (h), PI3 Kinase a (h) and other kinase in vitro inhibitory activity. The kinase inhibitory activity of the test compound is expressed as IC50 (half inhibitory concentration) or the inhibitory rate of the test compound at a concentration of 10 ??M for kinase activity. IC50 values can be obtained by calculating the inhibition rate of the kinase activity by the test compound at a series of different concentrations. The assay was as follows: In a reaction tube, the buffer (8 mM MOPS, pH 7.0, 0.2 mM EDTA, 10 mM MnCl2), the kinase to be tested (5-10 mU), the substrate to be tested kinase, 10 mM acetic acid Magnesium and gamma 33P-ATP solutions, as well as different concentrations of the test compound. MgATP was then added to the reaction to initiate the enzymatic reaction and incubated at room temperature for 40 minutes. The reaction was finally quenched with 5 ul of 3% phosphate buffer and 10 uL of the reaction solution was titrated onto a filtermat A membrane, washed three times with 75 mM phosphate solution for 5 minutes each, and washed again with methanol. Finally, the filtermat A film is dried and scintigraphized, and the size of the scintillation count reflects the degree to which the substrate is phosphorylated, thereby demonstrating that the kinase activity is inhibited. Among them, the percentage of the remaining active protein=the active protein of the experimental group the active protein of the control group 100%.
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 533.56, ALogP 4.65, HBA 7, HBD 2, PSA 101.96, QED 0.37
Compound (SMILES): CNC(=O)c1csc2c(C(F)(F)F)cc(N3CCC(OC(=O)N[C@@H](C)COC(F)(F)F)CC3)nc12
InChIKey: UQQUABVWYAPTIQ-JTQLQIEISA-N
Target: 2-hydroxyacylsphingosine 1-beta-galactosyltransferase (SINGLE PROTEIN), Mus musculus
UniProt: Q64676
Assay: Inhibition of mouse UGT8 assessed as redcution in GalCer accumulation
Measurement: IC50 = 0.2 nM (pChEMBL 9.699999809265137)
Descriptors: MW 528.48, ALogP 4.29, HBA 7, HBD 2, PSA 92.79, QED 0.54
Compound (SMILES): CCOC(=O)CCNc1cc(N2CCc3ccccc3CC2)nc(-c2cccnc2)n1
InChIKey: LQPGVGSKBNXQDU-UHFFFAOYSA-N
Target: Lysine-specific demethylase 5C (SINGLE PROTEIN), Homo sapiens
UniProt: P41229
Assay: Inhibition of KDM5C (2 to 1560 residues)(unknown origin) by Alphalisa assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 417.51, ALogP 3.51, HBA 7, HBD 1, PSA 80.24, QED 0.59
Compound (SMILES): Cc1nc2c(=O)n(C3CC3)c3c(Cl)c(N4CC[C@@H]([C@H](C)N)C4)c(F)cc3c2o1
InChIKey: LOCSNCVSEDLFDP-GXSJLCMTSA-N
Target: DNA gyrase (PROTEIN COMPLEX), Staphylococcus aureus
UniProt: P0A0K8
Assay: Inhibition of Staphylococcus aureus DNA gyrase using relaxed pBR322 as substrate incubated for 30 mins by ethidium bromide staining based gel electrophoresis analysis
Measurement: IC50 = 1820 nM (pChEMBL 5.739999771118164)
Descriptors: MW 404.87, ALogP 3.75, HBA 6, HBD 1, PSA 77.29, QED 0.72
Compound (SMILES): Cc1cc(-c2cnc3cc(-c4ccc(N5CCNCC5)cc4)ccn23)c2cc(F)cc(F)c2n1
InChIKey: RUBWYYYEDDAWLB-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of human KDR using poly[Glu:Tyr] (4:1) as substrate by [gamma-33P]-ATP assay
Measurement: IC50 = 20560 nM (pChEMBL 4.690000057220459)
Descriptors: MW 455.51, ALogP 5.21, HBA 5, HBD 1, PSA 45.46, QED 0.41
Compound (SMILES): C[C@@H](NC(=O)c1ccc(Cl)cc1)[C@H]1CC[C@@H](c2ccnc3ccc(F)cc32)CC1
InChIKey: AOJCHFNHRLPISK-ZACQAIPSSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 in IFNgamma-stimulated human HeLa cells preincubated for 2 hrs followed by IFNgamma stimulation and measured after 18 hrs by
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 410.92, ALogP 6.12, HBA 2, HBD 1, PSA 41.99, QED 0.56
Compound (SMILES): C#Cc1nc(Nc2cccc(CC(N)=O)c2)nc2[nH]cnc12
InChIKey: CJQGLUJHMXCLQY-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase TBK1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UHD2
Assay: Inhibition of human TBK1 by kinase-profiling analysis
Measurement: IC50 = 740 nM (pChEMBL 6.130000114440918)
Descriptors: MW 292.3, ALogP 1.11, HBA 5, HBD 3, PSA 109.58, QED 0.62
Compound (SMILES): N=C(N)NCCC[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCCN)NC(=O)[C@@H]1CCCN1C(=O)Cc1ccc(O)cc1)C(N)=O
InChIKey: UVDZRYDWESJRQX-TZPCGENMSA-N
Target: N-terminal Xaa-Pro-Lys N-methyltransferase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5VVY1
Assay: Binding affinity to recombinant human full-length His6-tagged NTMT2 by ITC assay
Measurement: Kd = 1000 nM (pChEMBL 6)
Descriptors: MW 1313.59
Compound (SMILES): Nc1ncc(-c2nc(N3CCOCC3)c3ncn(CCCCCCC(=O)NO)c3n2)cn1
InChIKey: SHWBIBURMMWDKZ-UHFFFAOYSA-N
Target: Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit beta (SINGLE PROTEIN), Homo sapiens
UniProt: O00750
Assay: Inhibition of PI3K2beta (unknown origin) incubated for 1 hr by ADP-Glo kinase assay
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 441.5, ALogP 1.16, HBA 11, HBD 3, PSA 157.2, QED 0.25
Compound (SMILES): CC#C[C@@H](CC(=O)O)c1ccc(OCc2ccc(CN3CCC4(CCc5ccccc54)CC3)s2)cc1
InChIKey: LGIUHWQDGPFXSG-VWLOTQADSA-N
Target: Peroxisome proliferator-activated receptor alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q07869
Assay: Agonist activity at human Gal4-fused PPARalpha LBD expressed in African green monkey CV1 cells cotransfected with pRL-SV40 plasmid measured after 24 hrs by luciferase reporter gene assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 499.68, ALogP 6.39, HBA 4, HBD 1, PSA 49.77, QED 0.37
Compound (SMILES): Cc1ccc(NC(=O)c2cccc(C(F)(F)F)c2)cc1C#Cc1nn(C2CCN(C)CC2)c2ncnc(N)c12
InChIKey: LQSGDXCDNZWTJN-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Blk (SINGLE PROTEIN), Homo sapiens
UniProt: P51451
Assay: Kinase Inhibition Assays: The aim of this experiment is to detect the inhibitory activity of the compounds of the present invention against in vitro protein kinases using isotope labeling (labeled gamma phosphate groups on ATP). Kinase inhibition profiles were determined using KinaseProfiler services provided by Euro fins, and ATP concentrations used are the Km of corresponding kinases. In this study, we examined Abl (T315I) (h), ALK (h), ARK5 (h), Axl (h), Blk (h), Bmx (h), BTK (h), B-Raf (H), ckit (h), cSRC (h), CDK7, CHK1 (h), c-RAF (h), DDR2 (h), EGFR (h), EphA1 (h), EphA2 (h), EphA8 (h (H), FGF (h), Ft (h), Ft (h), F (h), F (h), Ft (h), Hb (h), ErbB2 (h), FAK (h) (H), JK3 (h), IKKalpha (h), IKKbeta (h), Itk (h), JAK3 (h), JNK11 (h), KDR (h), Lyn (h), MAPK1 (h), MEK1 (h (H), PKA (h), PKB [alpha](h), PKB [beta] (h), PKC [alpha] (h), Ret (H), RIPK2 (h), Src (1-530) (h), TAK1 (h), TBK1 (h), Tec (h) activated, Tie2 (h), TrkA (h), ULK3 (h) Yes (h), PI3 Kinase a (h) and other kinase in vitro inhibitory activity. The kinase inhibitory activity of the test compound is expressed as IC50 (half inhibitory concentration) or the inhibitory rate of the test compound at a concentration of 10 ??M for kinase activity. IC50 values can be obtained by calculating the inhibition rate of the kinase activity by the test compound at a series of different concentrations. The assay was as follows: In a reaction tube, the buffer (8 mM MOPS, pH 7.0, 0.2 mM EDTA, 10 mM MnCl2), the kinase to be tested (5-10 mU), the substrate to be tested kinase, 10 mM acetic acid Magnesium and gamma 33P-ATP solutions, as well as different concentrations of the test compound. MgATP was then added to the reaction to initiate the enzymatic reaction and incubated at room temperature for 40 minutes. The reaction was finally quenched with 5 ul of 3% phosphate buffer and 10 uL of the reaction solution was titrated onto a filtermat A membrane, washed three times with 75 mM phosphate solution for 5 minutes each, and washed again with methanol. Finally, the filtermat A film is dried and scintigraphized, and the size of the scintillation count reflects the degree to which the substrate is phosphorylated, thereby demonstrating that the kinase activity is inhibited. Among them, the percentage of the remaining active protein=the active protein of the experimental group the active protein of the control group 100%.
Measurement: IC50 = 12 nM (pChEMBL 7.920000076293945)
Descriptors: MW 533.56, ALogP 4.65, HBA 7, HBD 2, PSA 101.96, QED 0.37
Compound (SMILES): CCOC(=O)CCNc1cc(N2CCc3ccccc3CC2)nc(-c2cccnc2)n1
InChIKey: LQPGVGSKBNXQDU-UHFFFAOYSA-N
Target: Lysine-specific demethylase 6A (SINGLE PROTEIN), Homo sapiens
UniProt: O15550
Assay: Inhibition of KDM6A (919 to 1401 residues)(unknown origin) by Alphalisa assay
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 417.51, ALogP 3.51, HBA 7, HBD 1, PSA 80.24, QED 0.59
Compound (SMILES): Cc1nc2c(=O)n(C3CC3)c3c(Cl)c(N4CC[C@@H]([C@H](C)N)C4)c(F)cc3c2o1
InChIKey: LOCSNCVSEDLFDP-GXSJLCMTSA-N
Target: Topoisomerase IV (PROTEIN COMPLEX), Staphylococcus aureus
UniProt: P0C1S7
Assay: Inhibition of Staphylococcus aureus topoisomerase IV using kDNA as substrate incubated for 30 mins by ethidium bromide staining based gel electrophoresis analysis
Measurement: IC50 = 6100 nM (pChEMBL 5.210000038146973)
Descriptors: MW 404.87, ALogP 3.75, HBA 6, HBD 1, PSA 77.29, QED 0.72
Compound (SMILES): Cc1cc(-c2cnc3cc(-c4ccc(N5CCNCC5)cc4)ccn23)c2cc(F)cc(F)c2n1
InChIKey: RUBWYYYEDDAWLB-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: Inhibition of human PDGFRbeta using poly[Glu:Tyr] (4:1) as substrate by [gamma-33P]-ATP assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 455.51, ALogP 5.21, HBA 5, HBD 1, PSA 45.46, QED 0.41
Compound (SMILES): C[C@@H](NC(=O)c1ccc(Cl)cc1)[C@H]1CC[C@@H](c2ccnc3ccc(F)cc32)CC1
InChIKey: AOJCHFNHRLPISK-ZACQAIPSSA-N
Target: Indoleamine 2,3-dioxygenase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P14902
Assay: Inhibition of IDO1 (unknown origin)
Measurement: IC50 < 50 nM (pChEMBL 7.301000118255615)
Descriptors: MW 410.92, ALogP 6.12, HBA 2, HBD 1, PSA 41.99, QED 0.56
Compound (SMILES): C#Cc1nc(Nc2cccc(CC(N)=O)c2)nc2[nH]cnc12
InChIKey: CJQGLUJHMXCLQY-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase 7 (SINGLE PROTEIN), Homo sapiens
UniProt: O43318
Assay: Inhibition of human TAK1 by kinase-profiling analysis
Measurement: IC50 = 240 nM (pChEMBL 6.619999885559082)
Descriptors: MW 292.3, ALogP 1.11, HBA 5, HBD 3, PSA 109.58, QED 0.62
Compound (SMILES): Nc1ncc(-c2nc(N3CCOCC3)c3ncn(CCCCCCC(=O)NO)c3n2)cn1
InChIKey: SHWBIBURMMWDKZ-UHFFFAOYSA-N
Target: DNA-dependent protein kinase catalytic subunit (SINGLE PROTEIN), Homo sapiens
UniProt: P78527
Assay: Inhibition of human DNA-PK
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 441.5, ALogP 1.16, HBA 11, HBD 3, PSA 157.2, QED 0.25
Compound (SMILES): CC#C[C@@H](CC(=O)O)c1ccc(OCc2ccc(CN3CCC4(CCc5ccccc54)CC3)s2)cc1
InChIKey: LGIUHWQDGPFXSG-VWLOTQADSA-N
Target: Peroxisome proliferator-activated receptor delta (SINGLE PROTEIN), Homo sapiens
UniProt: Q03181
Assay: Agonist activity at human Gal4-fused PPARdelta LBD expressed in African green monkey CV1 cells cotransfected with pRL-SV40 plasmid measured after 24 hrs by luciferase reporter gene assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 499.68, ALogP 6.39, HBA 4, HBD 1, PSA 49.77, QED 0.37