lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CC(C)(C)c1ccc(-n2cnc3c(NC(=O)Cc4ccc(C(=O)O)cc4)cccc32)cc1
InChIKey: VEHCUCLQBZOABJ-UHFFFAOYSA-N
Target: Bile acid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RI1
Assay: Agonist activity at FXR (unknown origin)
Measurement: EC50 = 780 nM (pChEMBL 6.110000133514404)
Descriptors: MW 427.5, ALogP 5.2, HBA 4, HBD 2, PSA 84.22, QED 0.46
Compound (SMILES): C/C=C1\CN2CC[C@@]34c5ccccc5N(CCc5ccccc5)[C@]35OC[C@@]4(C(=O)OC)[C@H]1C[C@H]25
InChIKey: MDHIFDZZMWLNKL-WZOWOQAZSA-N
Target: Mu-type opioid receptor (SINGLE PROTEIN), Mus musculus
UniProt: P42866
Assay: Agonist activity at HA-tagged mouse mu opioid receptor expressed in human HEK293 cells assessed as inhibition of forskolin-induced cAMP accumulation by Glo Sensor assay
Measurement: EC50 = 79.43 nM (pChEMBL 7.099999904632568)
Descriptors: MW 456.59, ALogP 3.93, HBA 5, HBD 0, PSA 42.01, QED 0.52
Compound (SMILES): C[N+]1=C(/C=C/C=C/C=C2\N(CCCCCC(=O)NCCCCCCn3cc(CCCCN4CCC5(CC4)OCc4ccccc45)c4ccccc43)c3ccccc3C2(C)C)C(C)(C)c2ccccc21.[I-]
InChIKey: PYGSKQVDDNNOJX-UHFFFAOYSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: Binding affinity to sigma 2 receptor in human MCF7 cells assessed as displacement of compound by measuring inhibition constant of 2-(3-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)propyl)-5-methoxy-3,4-dihydroisoquinolin-1(2H)-one incubated for 120 mins by saturation binding assay
Measurement: Ki = 4.07 nM (pChEMBL 8.390000343322754)
Descriptors: MW 925.34, ALogP 13.22, HBA 5, HBD 1, PSA 52.75, QED 0.05
Compound (SMILES): Cc1c(Oc2ccc(CN)cc2F)ccc2c1B(O)OC2
InChIKey: ZCITXZXBLWIHHP-UHFFFAOYSA-N
Target: Ribosomal protein S6 kinase alpha-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15418
Assay: Competition Binding Assay: Phosphorylation of activity of ROCK1 and ROCK2 and those of other kinases, AKT1, GRK2, PKA, PKCa and RSK1 were performed by Reaction Biology (Malvern, Pa.) (Ma et al., 2008) The ROCK1 enzyme tested was GST[1-535] ROCK1 (Genbank, NP 005397), ROCK2 was GST[5-554] (Genbank, 3327051). For the kinase assay buffers contained 20 mM Hepes, 10 mM MgCl2, 2 mM DTT, 0.02 mg/mL BSA, 0.1% DMSO, 1 mM EGTA, 0.02% Brij-35, 10 uM ATP, [γP33]-ATP and for ROCK enzymes, 20 uM long S6-peptide (32 amino acids length). Appropriate substrates and activation was applied for the other kinases tested. Each enzyme was preincubated with test compound for 15 min., and the reaction started by addition of ATP. Samples were incubated at room temperature for 120 min, and applied to P81 ion exchange paper and washed extensively; the radioactive content of the filters were determined.
Measurement: IC50 = 5.01 nM (pChEMBL 8.300000190734863)
Descriptors: MW 287.1
Compound (SMILES): Cc1ccccc1/N=N/c1cc(S(=O)(=O)O)c2ccccc2c1N
InChIKey: PIWJSAOBFMHEAW-FMQUCBEESA-N
Target: Sentrin-specific protease 2/Small ubiquitin-related modifier 1 (PROTEIN COMPLEX), Homo sapiens
UniProt: P63165
Assay: Enzyme Kinetic Assay: The inhibitors confer the non-competitive inhibitory mechanism, as shown by nuclear magnetic resonance (NMR) and quantitative enzyme kinetic analysis.
Measurement: IC50 = 3620 nM (pChEMBL 5.440000057220459)
Descriptors: MW 341.39, ALogP 4.39, HBA 5, HBD 2, PSA 105.11, QED 0.42
Compound (SMILES): Cc1cccc(-c2[nH]c(NCc3cccc(F)c3)nc2-c2ccc3c(cnn3C(F)F)c2)n1
InChIKey: FRYSBKWOXOBQNB-UHFFFAOYSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 (unknown origin)
Measurement: IC50 = 8500 nM (pChEMBL 5.070000171661377)
Descriptors: MW 448.45, ALogP 5.94, HBA 5, HBD 2, PSA 71.42, QED 0.34
Compound (SMILES): C=CC(=O)N1CCC(Oc2cc3c(Nc4cccc(Cl)c4F)ncnc3cc2O[C@H]2CCOC2)CC1
InChIKey: WAYSVGLDKMEZLH-KRWDZBQOSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Binding affinity to human ERG
Measurement: IC50 > 15000 nM (pChEMBL 4.823999881744385)
Descriptors: MW 512.97, ALogP 4.89, HBA 7, HBD 1, PSA 85.81, QED 0.45
Compound (SMILES): Cc1ncc(-c2nc3c(OC4(C)CC4)nc(Nc4cnn(C5CCN(C)CC5)c4)nc3cc2F)cn1
InChIKey: SZURKEABSBIIMJ-UHFFFAOYSA-N
Target: High affinity nerve growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P04629
Assay: Inhibition of TRKA (unknown origin) in presence of 400 uM ATP
Measurement: IC50 = 270 nM (pChEMBL 6.570000171661377)
Descriptors: MW 489.56, ALogP 4.07, HBA 10, HBD 1, PSA 106.77, QED 0.43
Compound (SMILES): CC(C)=CCN1CC[C@@]2(C)c3cc(O)ccc3C[C@H]1[C@H]2C
InChIKey: VOKSWYLNZZRQPF-MDASCCDHSA-N
Target: Sigma intracellular receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5BJF2
Assay: Displacement of [3H]DTG from sigma 2 receptor (unknown origin) assessed as inhibition constant in presence of haloperidol measured for 120 mins by scintillation counting analysis
Measurement: Ki = 83.1 nM (pChEMBL 7.079999923706055)
Descriptors: MW 285.43, ALogP 3.88, HBA 2, HBD 1, PSA 23.47, QED 0.83
Compound (SMILES): CNCc1cc(F)c(-c2cc3c(-c4cnn(C)c4)n[nH]c3cn2)c(C(F)(F)F)c1
InChIKey: WECCALUSSAUMLJ-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92918
Assay: Inhibition of human HPK1 in human Jurkat cells assessed as reduction in SLP76 phosphorylation incubated for 1 hr by HTRF assay
Measurement: IC50 = 128 nM (pChEMBL 6.889999866485596)
Descriptors: MW 404.37, ALogP 3.9, HBA 5, HBD 2, PSA 71.42, QED 0.51
Compound (SMILES): CC(=O)Nc1cc(Oc2ccc(NC(=O)Cc3ccccc3C(F)(F)F)cc2)ncn1
InChIKey: PFGNOYJAWUKCEW-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 ITD mutant (unknown origin) preincubated for 60 mins followed by ATP addition and measured after 1 hr by ADP-Glo assay
Measurement: IC50 = 23.9 nM (pChEMBL 7.619999885559082)
Descriptors: MW 430.39, ALogP 4.43, HBA 5, HBD 2, PSA 93.21, QED 0.6
Compound (SMILES): CC(C)CN1CCC(C(=O)Nc2cc3cc(-c4cnn(C)c4)ccc3cn2)CC1
InChIKey: OGPJOAYIAOEJAM-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of recombinant human DYRK1A expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 = 6 nM (pChEMBL 8.220000267028809)
Descriptors: MW 391.52, ALogP 3.94, HBA 5, HBD 1, PSA 63.05, QED 0.72
Compound (SMILES): CC(C)c1cnc(-c2cc(Cl)ccc2F)cc1Nc1ccncc1C(=O)NC[C@H](C)O
InChIKey: JZVPITOQWJPGIA-AWEZNQCLSA-N
Target: Bone morphogenetic protein receptor type-1B (SINGLE PROTEIN), Homo sapiens
UniProt: O00238
Assay: In Vitro Kinase Assay: Compound of the invention were screened in an in vitro kinase assay against several members of the TGFβ family of Ser/Thr kinases. The kinases tested were ALK1 (ACVRL1), ALK2 (ACVR1), ALK3 (BMPR1A), ALK4 (ACVR1B), ALK5 (TGFBR1), and ALK6 (BMPR1B). Standard kinase testing conditions and techniques were employed. For each case, specific kinase/substrate pairs along with required cofactors were prepared in reaction buffer. Compound of the invention were delivered into the reaction, followed 15-20 min later by addition of a mixture of ATP and 33P ATP to a final concentration of 10 μM. Reactions were carried out at RT for 120 min, followed by spotting of the reactions onto P81 ion exchange filter paper. Unbound phosphate was removed by extensive washing of filters in 0.75% phosphoric acid. Kinase activity data was expressed as the percent of remaining kinase activity in test samples compared to vehicle.
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 442.92, ALogP 4.91, HBA 5, HBD 3, PSA 87.14, QED 0.48
Compound (SMILES): Cc1cc(CN2CCC2)cc(F)c1-c1cc2c(-c3cnn(C)c3)n[nH]c2cn1
InChIKey: DWZVSFJBZRFDFR-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes using diclofenac as substrate by LC-MS analysis
Measurement: IC50 > 15000 nM (pChEMBL 4.823999881744385)
Descriptors: MW 376.44, ALogP 3.68, HBA 5, HBD 1, PSA 62.63, QED 0.59
Compound (SMILES): C/C=C/Cn1cc(-c2cc(OC)c(C(C)(C)O)cc2OC)c2cc(C)[nH]c2c1=O
InChIKey: QVMOJFHRHLLSOT-BQYQJAHWSA-N
Target: ATPase family AAA domain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q6PL18
Assay: Binding affinity to human partial length ATAD2A (Q981 to R1108 residues) expressed in bacterial expression system by BROMOscan assay
Measurement: Kd = 9300 nM (pChEMBL 5.03000020980835)
Descriptors: MW 396.49, ALogP 4.13, HBA 5, HBD 2, PSA 76.48, QED 0.61
Compound (SMILES): Fc1ccc(CN2CCCC3(CCN(Cc4cc5ccc(Cl)cc5[nH]4)C3)C2)cc1F
InChIKey: JGUJMJSODMVSHV-UHFFFAOYSA-N
Target: D(1A) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P21728
Assay: Displacement of [3H]SCH23390 from D1 receptor in HEK293 cell membrane assessed as inhibition constant
Measurement: Ki = 1527 nM (pChEMBL 5.820000171661377)
Descriptors: MW 429.94, ALogP 5.59, HBA 2, HBD 1, PSA 22.27, QED 0.58
Compound (SMILES): CC[C@@H](Nc1c(C#N)c(-c2ccc(-c3cccc(Cl)c3F)cc2)nc2cnccc12)C(N)=O
InChIKey: LACMSNCHWBQXEK-HXUWFJFHSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of CYP1A2 in human liver microsomes using phenacetin as substrate by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 459.91, ALogP 5.3, HBA 5, HBD 2, PSA 104.69, QED 0.41
Compound (SMILES): Nc1ncncc1-c1ccnc2c1cnn2-c1ccc(F)cc1
InChIKey: OEVSKJAZBGCGII-UHFFFAOYSA-N
Target: Steroid 17-alpha-hydroxylase/17,20 lyase (SINGLE PROTEIN), Macaca fascicularis
UniProt: Q2XVA1
Assay: Inhibition of cynomolgus monkey CYP17A1 hydroxylase activity
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 306.3, ALogP 2.6, HBA 6, HBD 1, PSA 82.51, QED 0.62
Compound (SMILES): CN1CC2CCC(C1=O)C2c1ncc2[nH]nc(-c3cnn(C)c3)c2n1
InChIKey: NRBSFHSUWBAYCI-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 3 (SINGLE PROTEIN), Mus musculus
UniProt: Q61851
Assay: Inhibition of FGFR3 phosphorylation in mouse BaF3 cells incubated for 2 hrs
Measurement: IC50 = 70 nM (pChEMBL 7.159999847412109)
Descriptors: MW 337.39, ALogP 1.34, HBA 6, HBD 1, PSA 92.59, QED 0.76
Compound (SMILES): C/C=C1\CN2CC[C@@]34c5ccccc5N(CCc5ccccc5)[C@]35OC[C@@]4(C(=O)OC)[C@H]1C[C@H]25
InChIKey: MDHIFDZZMWLNKL-WZOWOQAZSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Agonist activity at delta opioid receptor (unknown origin) expressed in human HEK293 cells assessed as inhibition of forskolin-induced cAMP accumulation by Glo Sensor assay
Measurement: EC50 = 610 nM (pChEMBL 6.210000038146973)
Descriptors: MW 456.59, ALogP 3.93, HBA 5, HBD 0, PSA 42.01, QED 0.52
Compound (SMILES): Cc1ccccc1/N=N/c1cc(S(=O)(=O)O)c2ccccc2c1N
InChIKey: PIWJSAOBFMHEAW-FMQUCBEESA-N
Target: Sentrin-specific protease 2/Small ubiquitin-related modifier 2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P61956
Assay: Enzyme Kinetic Assay: The inhibitors confer the non-competitive inhibitory mechanism, as shown by nuclear magnetic resonance (NMR) and quantitative enzyme kinetic analysis.
Measurement: IC50 = 10700 nM (pChEMBL 4.96999979019165)
Descriptors: MW 341.39, ALogP 4.39, HBA 5, HBD 2, PSA 105.11, QED 0.42
Compound (SMILES): Cc1cccc(-c2[nH]c(NCc3cccc(F)c3)nc2-c2ccc3c(cnn3C(F)F)c2)n1
InChIKey: FRYSBKWOXOBQNB-UHFFFAOYSA-N
Target: Activin receptor type-1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q04771
Assay: Inhibition of human ALK2 by NanoBERT assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 448.45, ALogP 5.94, HBA 5, HBD 2, PSA 71.42, QED 0.34
Compound (SMILES): Cc1ncc(-c2nc3c(OC4(C)CC4)nc(Nc4cnn(C5CCN(C)CC5)c4)nc3cc2F)cn1
InChIKey: SZURKEABSBIIMJ-UHFFFAOYSA-N
Target: BDNF/NT-3 growth factors receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16620
Assay: Inhibition of TRKB (unknown origin) in presence of 25 uM ATP
Measurement: IC50 = 760 nM (pChEMBL 6.119999885559082)
Descriptors: MW 489.56, ALogP 4.07, HBA 10, HBD 1, PSA 106.77, QED 0.43
Compound (SMILES): CNCc1cc(F)c(-c2cc3c(-c4cnn(C)c4)n[nH]c3cn2)c(C(F)(F)F)c1
InChIKey: WECCALUSSAUMLJ-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate by LC-MS analysis
Measurement: IC50 > 25000 nM (pChEMBL 4.6020002365112305)
Descriptors: MW 404.37, ALogP 3.9, HBA 5, HBD 2, PSA 71.42, QED 0.51
Compound (SMILES): CC(C)CN1CCC(C(=O)Nc2cc3cc(-c4cnn(C)c4)ccc3cn2)CC1
InChIKey: OGPJOAYIAOEJAM-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y463
Assay: Inhibition of recombinant human DYRK1B expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 = 15.2 nM (pChEMBL 7.820000171661377)
Descriptors: MW 391.52, ALogP 3.94, HBA 5, HBD 1, PSA 63.05, QED 0.72
Compound (SMILES): Cc1cc(CN2CCC2)cc(F)c1-c1cc2c(-c3cnn(C)c3)n[nH]c2cn1
InChIKey: DWZVSFJBZRFDFR-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using bufuralol as substrate by LC-MS analysis
Measurement: IC50 > 15000 nM (pChEMBL 4.823999881744385)
Descriptors: MW 376.44, ALogP 3.68, HBA 5, HBD 1, PSA 62.63, QED 0.59
Compound (SMILES): C/C=C/Cn1cc(-c2cc(OC)c(C(C)(C)O)cc2OC)c2cc(C)[nH]c2c1=O
InChIKey: QVMOJFHRHLLSOT-BQYQJAHWSA-N
Target: ATPase family AAA domain-containing protein 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9ULI0
Assay: Binding affinity to human partial length ATAD2B (Q955 to R1082 residues) expressed in bacterial expression system by BROMOscan assay
Measurement: Kd > 10000 nM (pChEMBL 5)
Descriptors: MW 396.49, ALogP 4.13, HBA 5, HBD 2, PSA 76.48, QED 0.61
Compound (SMILES): CC[C@@H](Nc1c(C#N)c(-c2ccc(-c3cccc(Cl)c3F)cc2)nc2cnccc12)C(N)=O
InChIKey: LACMSNCHWBQXEK-HXUWFJFHSA-N
Target: Cytochrome P450 2C8 (SINGLE PROTEIN), Homo sapiens
UniProt: P10632
Assay: Inhibition of CYP2C8 in human liver microsomes using amodiaquine as substrate by LC-MS/MS analysis
Measurement: IC50 = 2300 nM (pChEMBL 5.639999866485596)
Descriptors: MW 459.91, ALogP 5.3, HBA 5, HBD 2, PSA 104.69, QED 0.41
Compound (SMILES): Nc1ncncc1-c1ccnc2c1cnn2-c1ccc(F)cc1
InChIKey: OEVSKJAZBGCGII-UHFFFAOYSA-N
Target: Steroid 17-alpha-hydroxylase/17,20 lyase (SINGLE PROTEIN), Homo sapiens
UniProt: P05093
Assay: Inhibition of human adrenal gland CYP17A1
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 306.3, ALogP 2.6, HBA 6, HBD 1, PSA 82.51, QED 0.62
Compound (SMILES): C/C=C1\CN2CC[C@@]34c5ccccc5N(CCc5ccccc5)[C@]35OC[C@@]4(C(=O)OC)[C@H]1C[C@H]25
InChIKey: MDHIFDZZMWLNKL-WZOWOQAZSA-N
Target: Kappa-type opioid receptor (SINGLE PROTEIN), Mus musculus
UniProt: P33534
Assay: Agonist activity at FLAG-tagged mouse kappa opioid receptor expressed in human HEK293 cells assessed as inhibition of forskolin-induced cAMP accumulation by Glo Sensor assay
Measurement: EC50 = 740 nM (pChEMBL 6.130000114440918)
Descriptors: MW 456.59, ALogP 3.93, HBA 5, HBD 0, PSA 42.01, QED 0.52
Compound (SMILES): Cc1ncc(-c2nc3c(OC4(C)CC4)nc(Nc4cnn(C5CCN(C)CC5)c4)nc3cc2F)cn1
InChIKey: SZURKEABSBIIMJ-UHFFFAOYSA-N
Target: NT-3 growth factor receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q16288
Assay: Inhibition of TRKC (unknown origin) in presence of 50 uM ATP
Measurement: IC50 = 270 nM (pChEMBL 6.570000171661377)
Descriptors: MW 489.56, ALogP 4.07, HBA 10, HBD 1, PSA 106.77, QED 0.43
Compound (SMILES): CC(C)CN1CCC(C(=O)Nc2cc3cc(-c4cnn(C)c4)ccc3cn2)CC1
InChIKey: OGPJOAYIAOEJAM-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92630
Assay: Inhibition of recombinant human DYRK2 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 = 215 nM (pChEMBL 6.670000076293945)
Descriptors: MW 391.52, ALogP 3.94, HBA 5, HBD 1, PSA 63.05, QED 0.72
Compound (SMILES): Cc1cc(CN2CCC2)cc(F)c1-c1cc2c(-c3cnn(C)c3)n[nH]c2cn1
InChIKey: DWZVSFJBZRFDFR-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using testosterone as substrate by LC-MS analysis
Measurement: IC50 > 15000 nM (pChEMBL 4.823999881744385)
Descriptors: MW 376.44, ALogP 3.68, HBA 5, HBD 1, PSA 62.63, QED 0.59
Compound (SMILES): C/C=C/Cn1cc(-c2cc(OC)c(C(C)(C)O)cc2OC)c2cc(C)[nH]c2c1=O
InChIKey: QVMOJFHRHLLSOT-BQYQJAHWSA-N
Target: Bromodomain adjacent to zinc finger domain protein 2A (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UIF9
Assay: Binding affinity to human partial length BAZ2A (M1792 to L1905 residues) expressed in bacterial expression system by BROMOscan assay
Measurement: Kd > 10000 nM (pChEMBL 5)
Descriptors: MW 396.49, ALogP 4.13, HBA 5, HBD 2, PSA 76.48, QED 0.61
Compound (SMILES): CC[C@@H](Nc1c(C#N)c(-c2ccc(-c3cccc(Cl)c3F)cc2)nc2cnccc12)C(N)=O
InChIKey: LACMSNCHWBQXEK-HXUWFJFHSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 in human liver microsomes using diclofenac as substrate by LC-MS/MS analysis
Measurement: IC50 = 3400 nM (pChEMBL 5.46999979019165)
Descriptors: MW 459.91, ALogP 5.3, HBA 5, HBD 2, PSA 104.69, QED 0.41
Compound (SMILES): Nc1ncncc1-c1ccnc2c1cnn2-c1ccc(F)cc1
InChIKey: OEVSKJAZBGCGII-UHFFFAOYSA-N
Target: Steroid 17-alpha-hydroxylase/17,20 lyase (SINGLE PROTEIN), Macaca fascicularis
UniProt: Q2XVA1
Assay: Inhibition of cynomolgus monkey adrenal gland CYP17A1
Measurement: IC50 = 2 nM (pChEMBL 8.699999809265137)
Descriptors: MW 306.3, ALogP 2.6, HBA 6, HBD 1, PSA 82.51, QED 0.62
Compound (SMILES): CC(C)CN1CCC(C(=O)Nc2cc3cc(-c4cnn(C)c4)ccc3cn2)CC1
InChIKey: OGPJOAYIAOEJAM-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O43781
Assay: Inhibition of recombinant human DYRK3 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 = 682.8 nM (pChEMBL 6.170000076293945)
Descriptors: MW 391.52, ALogP 3.94, HBA 5, HBD 1, PSA 63.05, QED 0.72
Compound (SMILES): Cc1cc(CN2CCC2)cc(F)c1-c1cc2c(-c3cnn(C)c3)n[nH]c2cn1
InChIKey: DWZVSFJBZRFDFR-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 in human liver microsomes using S mephenytoin as substrate by LC-MS analysis
Measurement: IC50 > 15000 nM (pChEMBL 4.823999881744385)
Descriptors: MW 376.44, ALogP 3.68, HBA 5, HBD 1, PSA 62.63, QED 0.59
Compound (SMILES): C/C=C/Cn1cc(-c2cc(OC)c(C(C)(C)O)cc2OC)c2cc(C)[nH]c2c1=O
InChIKey: QVMOJFHRHLLSOT-BQYQJAHWSA-N
Target: Bromodomain adjacent to zinc finger domain protein 2B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UIF8
Assay: Binding affinity to human partial length BAZ2B (S2054 to S2168 residues) expressed in bacterial expression system by BROMOscan assay
Measurement: Kd > 10000 nM (pChEMBL 5)
Descriptors: MW 396.49, ALogP 4.13, HBA 5, HBD 2, PSA 76.48, QED 0.61
Compound (SMILES): CC[C@@H](Nc1c(C#N)c(-c2ccc(-c3cccc(Cl)c3F)cc2)nc2cnccc12)C(N)=O
InChIKey: LACMSNCHWBQXEK-HXUWFJFHSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 in human liver microsomes using dextromethorphan as substrate by LC-MS/MS analysis
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 459.91, ALogP 5.3, HBA 5, HBD 2, PSA 104.69, QED 0.41
Compound (SMILES): Nc1ncncc1-c1ccnc2c1cnn2-c1ccc(F)cc1
InChIKey: OEVSKJAZBGCGII-UHFFFAOYSA-N
Target: Steroid 21-hydroxylase (SINGLE PROTEIN), Homo sapiens
UniProt: P08686
Assay: Inhibition of human CYP21A2
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 306.3, ALogP 2.6, HBA 6, HBD 1, PSA 82.51, QED 0.62
Compound (SMILES): CC(C)CN1CCC(C(=O)Nc2cc3cc(-c4cnn(C)c4)ccc3cn2)CC1
InChIKey: OGPJOAYIAOEJAM-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NR20
Assay: Inhibition of recombinant human DYRK4 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 = 2475 nM (pChEMBL 5.610000133514404)
Descriptors: MW 391.52, ALogP 3.94, HBA 5, HBD 1, PSA 63.05, QED 0.72
Compound (SMILES): Cc1cc(CN2CCC2)cc(F)c1-c1cc2c(-c3cnn(C)c3)n[nH]c2cn1
InChIKey: DWZVSFJBZRFDFR-UHFFFAOYSA-N
Target: Mitogen-activated protein kinase kinase kinase kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92918
Assay: HPK1 Kinase Binding Assay: A stock solution of 1 mM test compound was prepared in DMSO. The compound plate was prepared by 3-fold and 11-point serial dilutions. 0.1 μL of the compound in DMSO was transferred from the compound plate to the white 384 well polystyrene plates. The assay buffer contained 50 mM HEPES, pH 7.5, 0.01% Tween-20, 5 mM MgCl2, 0.01% BSA, and 5 mM DTT. 5 μl of 4 nM active HPK1 (SignalChem M23-11G) prepared in the buffer was added to the plate. The enzyme concentration given was based on the given stock concentration reported by the vender. 5 μl of 18 nM tracer 222 (ThermoFisher PV6121) and 4 nM LanthaScreen Eu-Anti GST antibody (ThermoFisher PV5595) were added. After one hour incubation at 25° C., the plates were read on a PHERAstar FS plate reader (BMG Labtech).
Measurement: Ki < 100 nM (pChEMBL 7)
Descriptors: MW 376.44, ALogP 3.68, HBA 5, HBD 1, PSA 62.63, QED 0.59
Compound (SMILES): C/C=C/Cn1cc(-c2cc(OC)c(C(C)(C)O)cc2OC)c2cc(C)[nH]c2c1=O
InChIKey: QVMOJFHRHLLSOT-BQYQJAHWSA-N
Target: Bromodomain-containing protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: O95696
Assay: Binding affinity to human partial length BRD1 (E556 to A688 residues) expressed in bacterial expression system by BROMOscan assay
Measurement: Kd > 10000 nM (pChEMBL 5)
Descriptors: MW 396.49, ALogP 4.13, HBA 5, HBD 2, PSA 76.48, QED 0.61
Compound (SMILES): CC[C@@H](Nc1c(C#N)c(-c2ccc(-c3cccc(Cl)c3F)cc2)nc2cnccc12)C(N)=O
InChIKey: LACMSNCHWBQXEK-HXUWFJFHSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes using dextromethorphan as substrate by LC-MS/MS analysis
Measurement: IC50 = 10000 nM (pChEMBL 5)
Descriptors: MW 459.91, ALogP 5.3, HBA 5, HBD 2, PSA 104.69, QED 0.41
Compound (SMILES): Nc1ncncc1-c1ccnc2c1cnn2-c1ccc(F)cc1
InChIKey: OEVSKJAZBGCGII-UHFFFAOYSA-N
Target: Cytochrome P450 11B1, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P15538
Assay: Inhibition of human CYP11B1
Measurement: IC50 = 2611 nM (pChEMBL 5.579999923706055)
Descriptors: MW 306.3, ALogP 2.6, HBA 6, HBD 1, PSA 82.51, QED 0.62
Compound (SMILES): CC(C)CN1CCC(C(=O)Nc2cc3cc(-c4cnn(C)c4)ccc3cn2)CC1
InChIKey: OGPJOAYIAOEJAM-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Inhibition of recombinant human GSK-3beta expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis
Measurement: IC50 = 45.6 nM (pChEMBL 7.340000152587891)
Descriptors: MW 391.52, ALogP 3.94, HBA 5, HBD 1, PSA 63.05, QED 0.72
Compound (SMILES): C/C=C/Cn1cc(-c2cc(OC)c(C(C)(C)O)cc2OC)c2cc(C)[nH]c2c1=O
InChIKey: QVMOJFHRHLLSOT-BQYQJAHWSA-N
Target: Bromodomain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25440
Assay: Binding affinity to human partial length BRD2 bromodomain 1 long isoform (K71 to N194 residues) expressed in bacterial expression system by BROMOscan assay
Measurement: Kd > 10000 nM (pChEMBL 5)
Descriptors: MW 396.49, ALogP 4.13, HBA 5, HBD 2, PSA 76.48, QED 0.61
Compound (SMILES): CC[C@@H](Nc1c(C#N)c(-c2ccc(-c3cccc(Cl)c3F)cc2)nc2cnccc12)C(N)=O
InChIKey: LACMSNCHWBQXEK-HXUWFJFHSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of CYP3A4 in human liver microsomes preincubated with compound followed by substrate addition using dextromethorphan as substrate by LC-MS/MS analysis
Measurement: IC50 = 8350 nM (pChEMBL 5.079999923706055)
Descriptors: MW 459.91, ALogP 5.3, HBA 5, HBD 2, PSA 104.69, QED 0.41
Compound (SMILES): Nc1ncncc1-c1ccnc2c1cnn2-c1ccc(F)cc1
InChIKey: OEVSKJAZBGCGII-UHFFFAOYSA-N
Target: Nuclear receptor subfamily 1 group I member 2 (SINGLE PROTEIN), Homo sapiens
UniProt: O75469
Assay: Inhibition of PXR (unknown origin)
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 306.3, ALogP 2.6, HBA 6, HBD 1, PSA 82.51, QED 0.62
Compound (SMILES): CC(C)CN1CCC(C(=O)Nc2cc3cc(-c4cnn(C)c4)ccc3cn2)CC1
InChIKey: OGPJOAYIAOEJAM-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P49759
Assay: Inhibition of recombinant human CLK1 expressed in Sf9 insect cells using myelin basic protein as substrate incubated for 110 mins in presence of ATP by non-radioactive ADP-Glo luminescence microplate reader assay
Measurement: IC50 = 15 nM (pChEMBL 7.820000171661377)
Descriptors: MW 391.52, ALogP 3.94, HBA 5, HBD 1, PSA 63.05, QED 0.72
Compound (SMILES): C/C=C/Cn1cc(-c2cc(OC)c(C(C)(C)O)cc2OC)c2cc(C)[nH]c2c1=O
InChIKey: QVMOJFHRHLLSOT-BQYQJAHWSA-N
Target: Bromodomain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25440
Assay: Binding affinity to human partial length BRD2 bromodomain 1/2 isoform 1 (K71 to D455 residues) by BROMOscan assay
Measurement: Kd = 1700 nM (pChEMBL 5.769999980926514)
Descriptors: MW 396.49, ALogP 4.13, HBA 5, HBD 2, PSA 76.48, QED 0.61
Compound (SMILES): CC[C@@H](Nc1c(C#N)c(-c2ccc(-c3cccc(Cl)c3F)cc2)nc2cnccc12)C(N)=O
InChIKey: LACMSNCHWBQXEK-HXUWFJFHSA-N
Target: Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P48426
Assay: Binding affinity to human PIP4K2A in human THP-1 cell lysate assessed as thermal stability by measuring shift in temperature incubated for 30 mins at 60 degreeC by CETSA assay
Measurement: EC50 = 2100 nM (pChEMBL 5.679999828338623)
Descriptors: MW 459.91, ALogP 5.3, HBA 5, HBD 2, PSA 104.69, QED 0.41
Compound (SMILES): Nc1ncncc1-c1ccnc2c1cnn2-c1ccc(F)cc1
InChIKey: OEVSKJAZBGCGII-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of recombinant human CYP3A4
Measurement: IC50 = 36000 nM (pChEMBL 4.440000057220459)
Descriptors: MW 306.3, ALogP 2.6, HBA 6, HBD 1, PSA 82.51, QED 0.62
Compound (SMILES): CC(C)CN1CCC(C(=O)Nc2cc3cc(-c4cnn(C)c4)ccc3cn2)CC1
InChIKey: OGPJOAYIAOEJAM-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Inhibition of recombinant human DYRK1A expressed in Escherichia coli using DYRKtide peptide as substrate incubated for 110 mins in presence of ATP by non-radioactive ADP-Glo luminescence microplate reader assay
Measurement: IC50 = 8 nM (pChEMBL 8.100000381469727)
Descriptors: MW 391.52, ALogP 3.94, HBA 5, HBD 1, PSA 63.05, QED 0.72
Compound (SMILES): C/C=C/Cn1cc(-c2cc(OC)c(C(C)(C)O)cc2OC)c2cc(C)[nH]c2c1=O
InChIKey: QVMOJFHRHLLSOT-BQYQJAHWSA-N
Target: Bromodomain-containing protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P25440
Assay: Binding affinity to human partial length BRD2 bromodomain 2 isoform 1 (E348 to D455 residues) expressed in bacterial expression system by BROMOscan assay
Measurement: Kd > 10000 nM (pChEMBL 5)
Descriptors: MW 396.49, ALogP 4.13, HBA 5, HBD 2, PSA 76.48, QED 0.61
Compound (SMILES): CC[C@@H](Nc1c(C#N)c(-c2ccc(-c3cccc(Cl)c3F)cc2)nc2cnccc12)C(N)=O
InChIKey: LACMSNCHWBQXEK-HXUWFJFHSA-N
Target: Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P48426
Assay: Binding affinity to human PIP4K2A in human THP-1 intact cells sessed as thermal stability by measuring shift in temperature incubated for 30 mins at 56 degreeC by CETSA assay
Measurement: EC50 = 1600 nM (pChEMBL 5.800000190734863)
Descriptors: MW 459.91, ALogP 5.3, HBA 5, HBD 2, PSA 104.69, QED 0.41
Compound (SMILES): CC(C)CN1CCC(C(=O)Nc2cc3cc(-c4cnn(C)c4)ccc3cn2)CC1
InChIKey: OGPJOAYIAOEJAM-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1B (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y463
Assay: Inhibition of recombinant human DYRK1B expressed in Sf9 insect cells using DYRKtide peptide as substrate incubated for 110 mins in presence of ATP by non-radioactive ADP-Glo luminescence microplate reader assay
Measurement: IC50 = 9.7 nM (pChEMBL 8.010000228881836)
Descriptors: MW 391.52, ALogP 3.94, HBA 5, HBD 1, PSA 63.05, QED 0.72
Compound (SMILES): C/C=C/Cn1cc(-c2cc(OC)c(C(C)(C)O)cc2OC)c2cc(C)[nH]c2c1=O
InChIKey: QVMOJFHRHLLSOT-BQYQJAHWSA-N
Target: Bromodomain-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15059
Assay: Binding affinity to human partial length BRD3 bromodomain 1 (P24 to E144 residues) expressed in bacterial expression system by BROMOscan assay
Measurement: Kd = 9200 nM (pChEMBL 5.039999961853027)
Descriptors: MW 396.49, ALogP 4.13, HBA 5, HBD 2, PSA 76.48, QED 0.61
Compound (SMILES): CC[C@@H](Nc1c(C#N)c(-c2ccc(-c3cccc(Cl)c3F)cc2)nc2cnccc12)C(N)=O
InChIKey: LACMSNCHWBQXEK-HXUWFJFHSA-N
Target: Phosphatidylinositol 5-phosphate 4-kinase type-2 alpha (SINGLE PROTEIN), Homo sapiens
UniProt: P48426
Assay: Inhibition of human PIP4K2A in human THP-1 cells assessed as increase in mitochondrial ROS level incubated for 1 hrs by MitoSOX Red based flow cytometry
Measurement: EC50 = 18100 nM (pChEMBL 4.739999771118164)
Descriptors: MW 459.91, ALogP 5.3, HBA 5, HBD 2, PSA 104.69, QED 0.41
Compound (SMILES): CC(C)CN1CCC(C(=O)Nc2cc3cc(-c4cnn(C)c4)ccc3cn2)CC1
InChIKey: OGPJOAYIAOEJAM-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: Binding affinity to human DYRK1A assessed as equilibrium dissociation constant measured upto 240 min by TR-FRET assay
Measurement: Kd = 0.283 nM (pChEMBL 9.550000190734863)
Descriptors: MW 391.52, ALogP 3.94, HBA 5, HBD 1, PSA 63.05, QED 0.72
Compound (SMILES): C/C=C/Cn1cc(-c2cc(OC)c(C(C)(C)O)cc2OC)c2cc(C)[nH]c2c1=O
InChIKey: QVMOJFHRHLLSOT-BQYQJAHWSA-N
Target: Bromodomain-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15059
Assay: Binding affinity to BRD3 bromodomain 1/2 (unknown origin) by BROMOscan assay
Measurement: Kd > 10000 nM (pChEMBL 5)
Descriptors: MW 396.49, ALogP 4.13, HBA 5, HBD 2, PSA 76.48, QED 0.61
Compound (SMILES): CC(C)CN1CCC(C(=O)Nc2cc3cc(-c4cnn(C)c4)ccc3cn2)CC1
InChIKey: OGPJOAYIAOEJAM-UHFFFAOYSA-N
Target: Dual specificity protein kinase CLK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P49759
Assay: Binding affinity to human CLK1 assessed as equilibrium dissociation constant measured upto 240 min by TR-FRET assay
Measurement: Kd = 0.968 nM (pChEMBL 9.010000228881836)
Descriptors: MW 391.52, ALogP 3.94, HBA 5, HBD 1, PSA 63.05, QED 0.72
Compound (SMILES): C/C=C/Cn1cc(-c2cc(OC)c(C(C)(C)O)cc2OC)c2cc(C)[nH]c2c1=O
InChIKey: QVMOJFHRHLLSOT-BQYQJAHWSA-N
Target: Bromodomain-containing protein 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q15059
Assay: Binding affinity to human partial length BRD3 bromodomain 2 (G306 to P416 residues) expressed in bacterial expression system by BROMOscan assay
Measurement: Kd > 10000 nM (pChEMBL 5)
Descriptors: MW 396.49, ALogP 4.13, HBA 5, HBD 2, PSA 76.48, QED 0.61
Compound (SMILES): CC(C)CN1CCC(C(=O)Nc2cc3cc(-c4cnn(C)c4)ccc3cn2)CC1
InChIKey: OGPJOAYIAOEJAM-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Binding affinity to human GSK-3beta assessed as equilibrium dissociation constant measured upto 240 min by TR-FRET assay
Measurement: Kd = 6.214 nM (pChEMBL 8.210000038146973)
Descriptors: MW 391.52, ALogP 3.94, HBA 5, HBD 1, PSA 63.05, QED 0.72
Compound (SMILES): C/C=C/Cn1cc(-c2cc(OC)c(C(C)(C)O)cc2OC)c2cc(C)[nH]c2c1=O
InChIKey: QVMOJFHRHLLSOT-BQYQJAHWSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to human partial length BRD4 bromodomain 1 long isoform (N44 to E168 residues) expressed in bacterial expression system by BROMOscan assay
Measurement: Kd = 9400 nM (pChEMBL 5.03000020980835)
Descriptors: MW 396.49, ALogP 4.13, HBA 5, HBD 2, PSA 76.48, QED 0.61
Compound (SMILES): CC(C)CN1CCC(C(=O)Nc2cc3cc(-c4cnn(C)c4)ccc3cn2)CC1
InChIKey: OGPJOAYIAOEJAM-UHFFFAOYSA-N
Target: Proto-oncogene Wnt-1 (SINGLE PROTEIN), Homo sapiens
UniProt: P04628
Assay: The screening assay for Wnt activity: The screening assay for Wnt activity is described as follows. Reporter cell lines can be generated by stably transducing cancer cell lines (e.g., colon cancer) or primary cells (e.g., IEC-6 intestinal cells) with a lentiviral construct that includes a Wnt-responsive promoter driving expression of the firefly luciferase gene.SW480 colon carcinoma cells were transduced with a lentiviral vector expressing luciferase with a human Sp5 promoter consisting of a sequence of eight TCF/LEF binding sites. SW480 cells stably expressing the Sp5-Luc reporter gene and a hygromycin resistance gene were selected by treatment with 150 μg/mL of hygromycin for 7 days. These stably transduced SW480 cells were expanded in cell culture and used for all further screening activities. Each compound was dissolved in DMSO as a 10 mM stock and used to prepare compound source plates. Serial dilution (1:3, 10-point dose-response curves starting from 10 μM) and compound transfer was performed using the ECHO 550 (Labcyte, Sunnyvale, Calif.) into 384-well white solid bottom assay plates (Greiner Bio-One) with appropriate DMSO backfill for a final DMSO concentration of 0.1%. For Sp5-Luc reporter gene assays, the cells were plated at 4,000 cells/well in 384-well plates with a DMEM medium containing 1% fetal bovine serum, and 1% Penicillin-Streptomycin and incubated for 36 to 48 hours at 37° C. and 5% CO2. Following incubation, 15 μl of BriteLite Plus luminescence reagent (Perkin Elmer) was added to each well of the 384-well assay plates. The plates were placed on an orbital shaker for 2 min and then luminescence was quantified using the Envision (Perkin Elmer) plate reader. Readings were normalized to DMSO only treated cells, and normalized activities were utilized for EC50 calculations using the dose-response log (inhibitor) vs. response variable slope (four parameters) nonlinear regression feature available in GraphPad Prism 5.0 (or Dotmatics).
Measurement: EC50 = 514 nM (pChEMBL 6.289999961853027)
Descriptors: MW 391.52, ALogP 3.94, HBA 5, HBD 1, PSA 63.05, QED 0.72
Compound (SMILES): C/C=C/Cn1cc(-c2cc(OC)c(C(C)(C)O)cc2OC)c2cc(C)[nH]c2c1=O
InChIKey: QVMOJFHRHLLSOT-BQYQJAHWSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to BRD4 bromodomain 1/2 long isoform (unknown origin) by BROMOscan assay
Measurement: Kd > 10000 nM (pChEMBL 5)
Descriptors: MW 396.49, ALogP 4.13, HBA 5, HBD 2, PSA 76.48, QED 0.61
Compound (SMILES): CC(C)CN1CCC(C(=O)Nc2cc3cc(-c4cnn(C)c4)ccc3cn2)CC1
InChIKey: OGPJOAYIAOEJAM-UHFFFAOYSA-N
Target: Dual specificity tyrosine-phosphorylation-regulated kinase 1A (SINGLE PROTEIN), Homo sapiens
UniProt: Q13627
Assay: The screening assay for DYRK1A kinase activity : Each compound was dissolved in DMSO as a 10 mM stock and used to prepare compound source plates. Serial dilution (1:3, 11-point dose-response curves from 10 μM to 0.00016 μM) and compound transfer was performed using the ECHO 550 (Labcyte, Sunnyvale, Calif.) into 1536-well black-walled round bottom plates (Corning).The DYRK1A kinase assay was run using the Ser/Thr 18 peptide Z-lyte assay kit according to manufacturer's instructions (Life Technologiesa Division of Thermo-Fisher). This is a non-radioactive assay using fluorescence resonance energy transfer (FRET) between coumarin and fluorescein to detect kinase activity which is represented as a ratio of coumarin emission/fluorescein emission.Briefly, recombinant DYRK1A kinase, ATP and Ser/Thr peptide 18 were prepared in 1× Kinase buffer to final concentrations of 0.19 μg/mL, 30 μM, and 4 μM respectively. The mixture was allowed to incubate with the representative compounds for one hour at room temperature. All reactions were performed in duplicate. Unphosphorylated (0% Control) and phosphorylated (100% control) forms of Ser/Thr 18 served as control reactions. Additionally, an 11-point dose-response curve of Staurosporine (1 uM top) was run to serve as a positive compound control.After incubation, Development Reagent A was diluted in Development Buffer then added to the reaction and allowed to further incubate for one hour at room temperature. The plate was read at Ex 400 Em 455 to detect the coumarin signal and Ex 400 Em 520 to measure the signal (EnVision Multilabel Plate Reader, PerkinElmer).The Emission ratio (Em) was calculated as a ratio of the coumarin (C) emission signal (at 445 nm)/Fluorescein (F) emission signal (at 520 nm). The percent phosphorylation was then calculated using the following formula: [1−((Em ratio×F100%)−C100%)/((C0%−C100%)+(Em ratio×(F100%−F0%)))]. Dose-response curves were generated and inhibitory concentration (IC50) values were calculated using non-linear regression curve fit in the Dotmatics' Studies Software (Bishops Stortford, UK).
Measurement: EC50 = 3.5 nM (pChEMBL 8.460000038146973)
Descriptors: MW 391.52, ALogP 3.94, HBA 5, HBD 1, PSA 63.05, QED 0.72
Compound (SMILES): C/C=C/Cn1cc(-c2cc(OC)c(C(C)(C)O)cc2OC)c2cc(C)[nH]c2c1=O
InChIKey: QVMOJFHRHLLSOT-BQYQJAHWSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to human partial length BRD4 bromodomain 2 long isoform (K333 to E460 residues) expressed in bacterial expression system by BROMOscan assay
Measurement: Kd > 10000 nM (pChEMBL 5)
Descriptors: MW 396.49, ALogP 4.13, HBA 5, HBD 2, PSA 76.48, QED 0.61
Compound (SMILES): CC(C)CN1CCC(C(=O)Nc2cc3cc(-c4cnn(C)c4)ccc3cn2)CC1
InChIKey: OGPJOAYIAOEJAM-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: The screening for GSK3beta kinase activity: Each compound is dissolved in DMSO as a 10 mM stock and used to prepare compound source plates. Serial dilution (1:3, 11-point dose-response curves from 10 μM to 0.0003 μM) and compound transfer was performed using the ECHO 550 (Labcyte, Sunnyvale, Calif.) into 1536-well black-walled round bottom plates (Corning). The GSK3β kinase assay is run using the Ser/Thr 09 peptide Z-lyte assay kit according to manufacturer's instructions (Life Technologiesa Division of Thermo-Fisher). This is a non-radioactive assay using fluorescence resonance energy transfer (FRET) between coumarin and fluorescein to detect kinase activity which is represented as ratio of coumarin emission/fluorescein emission. Briefly, recombinant GSK3β kinase, ATP and Ser/Thr peptide 09 are prepared in 1× Kinase buffer to final concentrations of 0.04 μg/mL, 46 μM, and 4 μM respectively. The mixture is allowed to incubate with the representative compounds for one hour at room temperature. All reactions were performed in duplicate. Unphosphorylated (0% Control) and phosphorylated (100% control) forms of Ser/Thr 18 serve as control reactions. After incubation, diluted Development Buffer is added to the reaction and allowed to further incubate for one hour at room temperature. The plate is read at Ex 400 Em 455 to detect the coumarin signal and Ex 400 Em 520 to measure the signal (EnVision Multilabel Plate Reader, PerkinElmer). The Emission ratio (Em) is calculated as a ratio of the coumarin (C) emission signal (at 445 nm)/Fluorescein (F) emission signal (at 520 nm). The percent phosphorylation is then calculated using the following formula: [1−((Em ratio×F100%)−C100%)/((C0%−C100%)+(Em ratio×(F100%−F0%)))]. Dose-response curves are generated and inhibitory concentration (IC50) values are calculated using non-linear regression curve fit in the Dotmatics' Studies Software (Bishops Stortford, UK).
Measurement: EC50 = 64 nM (pChEMBL 7.190000057220459)
Descriptors: MW 391.52, ALogP 3.94, HBA 5, HBD 1, PSA 63.05, QED 0.72
Compound (SMILES): C/C=C/Cn1cc(-c2cc(OC)c(C(C)(C)O)cc2OC)c2cc(C)[nH]c2c1=O
InChIKey: QVMOJFHRHLLSOT-BQYQJAHWSA-N
Target: Bromodomain-containing protein 4 (SINGLE PROTEIN), Homo sapiens
UniProt: O60885
Assay: Binding affinity to full length BRD4 short isoform (unknown origin) by BROMOscan assay
Measurement: Kd > 10000 nM (pChEMBL 5)
Descriptors: MW 396.49, ALogP 4.13, HBA 5, HBD 2, PSA 76.48, QED 0.61
Compound (SMILES): CC(C)CN1CCC(C(=O)Nc2cc3cc(-c4cnn(C)c4)ccc3cn2)CC1
InChIKey: OGPJOAYIAOEJAM-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: The screening for GSK3beta kinase activity: Each compound is dissolved in DMSO as a 10 mM stock and used to prepare compound source plates. Serial dilution (1:3, 11-point dose-response curves from 10 μM to 0.0003 μM) and compound transfer was performed using the ECHO 550 (Labcyte, Sunnyvale, Calif.) into 1536-well black-walled round bottom plates (Corning). The GSK3β kinase assay is run using the Ser/Thr 09 peptide Z-lyte assay kit according to manufacturer's instructions (Life Technologiesa Division of Thermo-Fisher). This is a non-radioactive assay using fluorescence resonance energy transfer (FRET) between coumarin and fluorescein to detect kinase activity which is represented as ratio of coumarin emission/fluorescein emission. Briefly, recombinant GSK3β kinase, ATP and Ser/Thr peptide 09 are prepared in 1× Kinase buffer to final concentrations of 0.04 μg/mL, 46 μM, and 4 μM respectively. The mixture is allowed to incubate with the representative compounds for one hour at room temperature. All reactions were performed in duplicate. Unphosphorylated (0% Control) and phosphorylated (100% control) forms of Ser/Thr 18 serve as control reactions. After incubation, diluted Development Buffer is added to the reaction and allowed to further incubate for one hour at room temperature. The plate is read at Ex 400 Em 455 to detect the coumarin signal and Ex 400 Em 520 to measure the signal (EnVision Multilabel Plate Reader, PerkinElmer). The Emission ratio (Em) is calculated as a ratio of the coumarin (C) emission signal (at 445 nm)/Fluorescein (F) emission signal (at 520 nm). The percent phosphorylation is then calculated using the following formula: [1−((Em ratio×F100%)−C100%)/((C0%−C100%)+(Em ratio×(F100%−F0%)))]. Dose-response curves are generated and inhibitory concentration (IC50) values are calculated using non-linear regression curve fit in the Dotmatics' Studies Software (Bishops Stortford, UK).
Measurement: EC50 = 28 nM (pChEMBL 7.550000190734863)
Descriptors: MW 391.52, ALogP 3.94, HBA 5, HBD 1, PSA 63.05, QED 0.72
Compound (SMILES): C/C=C/Cn1cc(-c2cc(OC)c(C(C)(C)O)cc2OC)c2cc(C)[nH]c2c1=O
InChIKey: QVMOJFHRHLLSOT-BQYQJAHWSA-N
Target: Bromodomain-containing protein 7 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NPI1
Assay: Binding affinity to human partial length BRD7 (L125 to R254 residues) expressed in mammalian expression system by BROMOscan assay
Measurement: Kd = 520 nM (pChEMBL 6.28000020980835)
Descriptors: MW 396.49, ALogP 4.13, HBA 5, HBD 2, PSA 76.48, QED 0.61
Compound (SMILES): CC(C)CN1CCC(C(=O)Nc2cc3cc(-c4cnn(C)c4)ccc3cn2)CC1
InChIKey: OGPJOAYIAOEJAM-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: The screening for GSK3beta kinase activity: Each compound is dissolved in DMSO as a 10 mM stock and used to prepare compound source plates. Serial dilution (1:3, 11-point dose-response curves from 10 μM to 0.0003 μM) and compound transfer was performed using the ECHO 550 (Labcyte, Sunnyvale, Calif.) into 1536-well black-walled round bottom plates (Corning). The GSK3β kinase assay is run using the Ser/Thr 09 peptide Z-lyte assay kit according to manufacturer's instructions (Life Technologiesa Division of Thermo-Fisher). This is a non-radioactive assay using fluorescence resonance energy transfer (FRET) between coumarin and fluorescein to detect kinase activity which is represented as ratio of coumarin emission/fluorescein emission. Briefly, recombinant GSK3β kinase, ATP and Ser/Thr peptide 09 are prepared in 1× Kinase buffer to final concentrations of 0.04 μg/mL, 46 μM, and 4 μM respectively. The mixture is allowed to incubate with the representative compounds for one hour at room temperature. All reactions were performed in duplicate. Unphosphorylated (0% Control) and phosphorylated (100% control) forms of Ser/Thr 18 serve as control reactions. After incubation, diluted Development Buffer is added to the reaction and allowed to further incubate for one hour at room temperature. The plate is read at Ex 400 Em 455 to detect the coumarin signal and Ex 400 Em 520 to measure the signal (EnVision Multilabel Plate Reader, PerkinElmer). The Emission ratio (Em) is calculated as a ratio of the coumarin (C) emission signal (at 445 nm)/Fluorescein (F) emission signal (at 520 nm). The percent phosphorylation is then calculated using the following formula: [1−((Em ratio×F100%)−C100%)/((C0%−C100%)+(Em ratio×(F100%−F0%)))]. Dose-response curves are generated and inhibitory concentration (IC50) values are calculated using non-linear regression curve fit in the Dotmatics' Studies Software (Bishops Stortford, UK).
Measurement: EC50 = 37 nM (pChEMBL 7.429999828338623)
Descriptors: MW 391.52, ALogP 3.94, HBA 5, HBD 1, PSA 63.05, QED 0.72
Compound (SMILES): C/C=C/Cn1cc(-c2cc(OC)c(C(C)(C)O)cc2OC)c2cc(C)[nH]c2c1=O
InChIKey: QVMOJFHRHLLSOT-BQYQJAHWSA-N
Target: Bromodomain-containing protein 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H0E9
Assay: Binding affinity to BRD8 bromodomain 1 (unknown origin) by BROMOscan assay
Measurement: Kd > 10000 nM (pChEMBL 5)
Descriptors: MW 396.49, ALogP 4.13, HBA 5, HBD 2, PSA 76.48, QED 0.61
Compound (SMILES): CC(C)CN1CCC(C(=O)Nc2cc3cc(-c4cnn(C)c4)ccc3cn2)CC1
InChIKey: OGPJOAYIAOEJAM-UHFFFAOYSA-N
Target: Glycogen synthase kinase-3 beta (SINGLE PROTEIN), Homo sapiens
UniProt: P49841
Assay: Fluorescence Resonance Energy Transfer (FRET) Assay: Briefly, recombinant GSK3β kinase, ATP and Ser/Thr peptide 09 are prepared in 1Ã Kinase buffer to final concentrations of 0.04 μg/mL, 46 μM, and 4 μM respectively. The mixture is allowed to incubate with the representative compounds for one hour at room temperature. All reactions were performed in duplicate. Unphosphorylated and phosphorylated forms of Ser/Thr 18 serve as control reactions.After incubation, diluted Development Buffer is added to the reaction and allowed to further incubate for one hour at room temperature. The plate is read at Ex 400 Em 455 to detect the coumarin signal and Ex 400 Em 520 to measure the signal (EnVision Multilabel Plate Reader, PerkinElmer).
Measurement: EC50 = 51 nM (pChEMBL 7.289999961853027)
Descriptors: MW 391.52, ALogP 3.94, HBA 5, HBD 1, PSA 63.05, QED 0.72
Compound (SMILES): C/C=C/Cn1cc(-c2cc(OC)c(C(C)(C)O)cc2OC)c2cc(C)[nH]c2c1=O
InChIKey: QVMOJFHRHLLSOT-BQYQJAHWSA-N
Target: Bromodomain-containing protein 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H0E9
Assay: Binding affinity to BRD8 bromodomain 2 (unknown origin) by BROMOscan assay
Measurement: Kd > 10000 nM (pChEMBL 5)
Descriptors: MW 396.49, ALogP 4.13, HBA 5, HBD 2, PSA 76.48, QED 0.61