lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CCN(CC)CCCC[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](Cc1ccccc1)NC(=O)c1ccc(C(C)(C)C)cc1)C(=O)NCCO
InChIKey: AEXWIZIRHCUOMT-HNJBERQJSA-N
Target: Chromobox protein homolog 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P45973
Assay: Antagonist activity at recombinant human N-terminal His-tagged CBX5 chromodomain (18 to 75 residues) expressed in Escherichia coli Rosetta BL21(DE3)pLysS using ARTKQTARK(Me3)STGGKAPRKQL-K(Biotin)-NH2 measured after 30 mins by AlphaScreen assay
Measurement: IC50 > 60000 nM (pChEMBL 4.2220001220703125)
Descriptors: MW 737, ALogP 3.47, HBA 7, HBD 6, PSA 168.97, QED 0.1
Compound (SMILES): COc1cc(N2CCC(CCS(C)(=O)=O)CC2)c(C)cc1Nc1nccc(-c2c(-c3cccc(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: CCYITMVYHGCYJS-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: Inhibition of IGF1-induced human IGF1R autophosphorylation expressed in mouse NIH-3T3 cells preincubated for 2 hrs followed by IGF-1 induction measured after 15 mins by DELFIA
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 751.86, ALogP 7.7, HBA 10, HBD 2, PSA 130.82, QED 0.14
Compound (SMILES): OC1CCCCCCCNc2ncc3c(-c4ccc(N5CCOCC5)cc4)cn(c3n2)CCCC1
InChIKey: UYSWRVPXWRGZTG-UHFFFAOYSA-N
Target: Tyrosine-protein kinase Mer (SINGLE PROTEIN), Homo sapiens
UniProt: Q12866
Assay: Inhibition of MerTK (unknown origin) by microfluidic capillary electrophoresis assay
Measurement: IC50 = 32 nM (pChEMBL 7.5)
Descriptors: MW 477.65, ALogP 5.23, HBA 7, HBD 2, PSA 75.44, QED 0.53
Compound (SMILES): C[C@@]1(c2cc(Nc3cc(Cl)cc4cc(Cl)cnc34)ccc2F)COCC(N)=N1
InChIKey: LBDVFEXBWOROJV-FQEVSTJZSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition Assay: Inhibition of cytochromes P450 (CYPs) 2C9, 2D6 and 3A4 was assessed using human liver microsomes and CYP-selective substrate metabolism reactions. 50 μl incubations were made up containing (finally) 0.2 mg/ml pooled human liver microsomes, 5 μM substrate (diclofenac for CYP2C9 [4' hydroxylase], dextromethorphan for CYP2D6 [O-demethylase] or midazolam for CYP3A4 [1' hydroxylase]), 0.25 μl, DMSO containing test inhibitor and NADPH regenerating system. Test inhibitor concentrations of 50, 16.7, 5.6, 1.9, 0.6 and 0.2 μM were assessed in singlicate. Incubations were prewarmed to 37° C. for 10 minutes before initiation by addition of NADPH regenerating system. Incubations were quenched after 5 minutes (20 minutes for dextromethorphan) by addition of 50 μl cold acetonitrile containing 20 ng/ml 4-OH-diclofenac-13C6, 20 ng/mL dextrorphan-D3 and 20 ng/mL 1-OH-midazolam-D4. Quenched incubates were stored at -20° C. for at least 1 hour before centrifugation (20,000xg, 20 minutes). Supernatants were removed and diluted 1:1 with water prior to analysis using a RapidFire sample injector system and API4000 mass spectrometer.
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 419.29, ALogP 5.03, HBA 5, HBD 2, PSA 72.53, QED 0.63
Compound (SMILES): COc1cc(OC)cc(N(CCCn2ccnc2C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: WHKAUZLLCXOVEV-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 = 7762.47 nM (pChEMBL 5.110000133514404)
Descriptors: MW 483.58, ALogP 4.78, HBA 9, HBD 0, PSA 83.12, QED 0.3
Compound (SMILES): COc1cccnc1C#CCN(c1ccc2ncc(-c3cnn(C)c3)nc2c1)c1c(Cl)c(OC)cc(OC)c1Cl
InChIKey: PPFQKJGJQXSDJS-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 575.46, ALogP 5.95, HBA 9, HBD 0, PSA 87.42, QED 0.22
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3sc4cccc(F)c4c3Cl)CC2)C1
InChIKey: PONHYSCYLJVGGT-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: In vitro JAK Kinase Assay: The catalytic domains of human JAK1 (a.a. 837-1142), Jak2 (a.a. 828-1132) and Jak3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the 40 microL reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. For the 1 mM IC50 measurements, ATP concentration in the reactions was 1 mM. Reactions were carried out at room temperature for 1 hr and then stopped with 20 μL 45 mM EDTA, 300 nM SA-APC, 6 nM Eu-Py20 in assay buffer (Perkin Elmer, Boston, Mass.). Binding to the Europium labeled antibody took place for 40 minutes and HTRF signal was measured on a Fusion plate reader (Perkin Elmer, Boston, Mass.)
Measurement: IC50 < 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 575.07, ALogP 5.06, HBA 8, HBD 1, PSA 106.73, QED 0.31
Compound (SMILES): COc1ccc(-c2ccc3ncnc(O[C@H]4CCN(C(C)=O)C4)c3c2)cc1OC
InChIKey: XMWNQYUMDITPFO-KRWDZBQOSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P42336
Assay: Inhibition of myristoylated PI3K-alpha (unknown origin) overexpressed in Rat1 cells assessed as inhibition of Akt phosphorylation
Measurement: IC50 = 210 nM (pChEMBL 6.679999828338623)
Descriptors: MW 393.44, ALogP 3.31, HBA 6, HBD 0, PSA 73.78, QED 0.66
Compound (SMILES): CN1CC[C@@H](c2c(O)cc(O)c3c(=O)cc(-c4ccccc4Cl)oc23)[C@@H]1CO
InChIKey: QLUYMIVVAYRECT-OCCSQVGLSA-N
Target: CDK2/Cyclin A2 (PROTEIN COMPLEX), Homo sapiens
UniProt: P20248
Assay: Inhibition of recombinant human N-terminal GST-tagged CDK2/cyclin A expressed in baculovirus expression system using retinoblastoma (792 to 928 residues) as substrate after 30 mins by gamma32P-ATP based scintillation counting analysis
Measurement: IC50 = 224 nM (pChEMBL 6.650000095367432)
Descriptors: MW 401.85, ALogP 3.3, HBA 6, HBD 3, PSA 94.14, QED 0.62
Compound (SMILES): COc1cc(OC)cc(N(CCO)c2ccc3ncc(-c4cnn(C)c4CN(C)C)nc3c2)c1
InChIKey: CPLYQZKEYHJUJZ-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 462.55, ALogP 3.24, HBA 9, HBD 1, PSA 88.77, QED 0.41
Compound (SMILES): CNC(C)C(=O)Nc1ccc(-c2c(-c3ccncc3)nc3cc(C)ccn23)c(C#Cc2ccc(-c3ccon3)cc2)n1
InChIKey: FWYXNWZPJQXBSF-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assays: The final incubation volume contains TRIS buffer (0.1 M), MgCl2 (5 mM), a certain concentration of human liver microsomes dependent on the P450 isoenzyme measured (P450 2C9, P450 3A4: 0.1 mg/ml; P450 2D6: 0.2 mg/ml; P450 2C19: 0.5 mg/ml; P450 2C8: 0.05 mg/ml) and a certain concentration of the individual substrate for each isoenzyme (P450 2C9: Diclofenac 10 μM; P450 3A4: Midazolam 5 μM; P450 2D6: Dextromethorphan 5 μM; P450 2C19: S-Mephenytoin 70 μM; P450 2C8: Amodiaquine 1 μM).
Measurement: IC50 = 2300 nM (pChEMBL 5.639999866485596)
Descriptors: MW 553.63, ALogP 5.37, HBA 8, HBD 2, PSA 110.24, QED 0.27
Compound (SMILES): CCc1ccc(C(=O)NCCCCC(NC(=O)C(Cc2ccc(C(F)(F)P(=O)(O)O)cc2)NC(=O)C(Cc2ccccc2)NC(=O)COC2CC(C)CCC2C(C)C)C(N)=O)cc1
InChIKey: DZZMIHDOJVEPRL-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 11 (SINGLE PROTEIN), Homo sapiens
UniProt: Q06124
Assay: PTP pNPP Assay: PTP activity was assayed using p-nitrophenyl phosphate (pNPP) as a substrate in DMG buffer (50 mM DMG, pH 7.0, 1 mM EDTA, 150 mM NaCl, 2 mM DTT, 0.1 mg/mL BSA) at 25° C. The assays were performed in 96-well plates. Normally, to determine the IC50 values, the reaction was initiated by the addition of enzyme (final concentration of 10 nM) to a reaction mixture (0.2 mL) containing 2 mM (Km for the substrate) pNPP with various concentrations of inhibitors. The reaction rate was measured using a Spectra Max Plus 384 Microplate Spectrophotometer (Molecular Devices). For compound 10, the final TC-PTP concentration was 0.04 nM. The reactions were incubated at room temperature for 30 min and quenched with 5N NaOH. The absorbance at 405 nm was read on the SpectraMax Plus 384 Microplate Spectrophotometer. For the reversibility test, the enzyme was incubated with the inhibitor at room temperature for 30 min before pNPP was added to initiate the reaction. The reaction was then incubated at room temperature.
Measurement: Ki > 1000 nM (pChEMBL 6)
Descriptors: MW 898, ALogP 5.28, HBA 7, HBD 7, PSA 226.25, QED 0.05
Compound (SMILES): COc1cc(OC)cc(N(CCN2CCCC2)c2ccc3ncc(-c4cn[nH]c4)nc3c2)c1.Cl
InChIKey: BJTAMMVWXSCQFA-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 444.54, ALogP 4.27, HBA 7, HBD 1, PSA 79.4, QED 0.43
Compound (SMILES): COc1ccc(Cl)c(N(CCNC(C)C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: QIFORRQQZPOUPH-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 = 1047.13 nM (pChEMBL 5.980000019073486)
Descriptors: MW 450.97, ALogP 4.83, HBA 7, HBD 1, PSA 68.1, QED 0.41
Compound (SMILES): O=C(Nc1nncs1)N1CCC(c2nnn3cnc4[nH]ccc4c23)CC1
InChIKey: LBYCHMOAEQNCHG-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Enzyme Assay: JAK1, JAK2, JAK3 and Tyk2 were purchased from Carna Biosciences, Inc. As the substrate, LANCE Ultra ULight-JAK1 Peptide (manufactured by PerkinElmer Co., Ltd. (PE)) was used. Dilute solutions of compounds and enzymes in assay buffer (50 mM HEPES pH7.5, 1 mM EGTA, 1 mM MgCl2, 2 mM DTT, 0.01% Tween20) were dispensed into wells of a 384-well black plate. After 5 minutes of preincubation, dilute solutions of the substrate and ATP (adenosine triphosphate) were added at a final concentration of 100 μM, and the plate was incubated at room temperature for 2 hours. After addition of a termination reagent containing EDTA (ethylenediamine tetraacetic acid) at a final concentration of 10 mM, LANCE Eu-W1024 Anti-phosphotyrosine (PT66) (manufactured by PE) was added, and after 1 hour of incubation, the fluorescences were measured with ARVO-HTS. From the plot of logarithm of a compound concentration and inhibitory activity, the IC50 was calculated.
Measurement: IC50 = 180 nM (pChEMBL 6.75)
Descriptors: MW 369.41, ALogP 1.87, HBA 8, HBD 2, PSA 116.99, QED 0.56
Compound (SMILES): COc1cc(OC)cc(N(CC(N)=O)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: CRMQCPICYHHFIL-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 418.46, ALogP 2.67, HBA 8, HBD 1, PSA 108.39, QED 0.49
Compound (SMILES): CC(C)(C)Nc1nnc(-c2ccc3[nH]cc(-c4nccc(C5CC5)n4)c3c2)o1
InChIKey: BQKBRLMFCCUJQA-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: Binding affinity to PIM2 (unknown origin) assessed as inhibition constant
Measurement: Ki = 0.28 nM (pChEMBL 9.550000190734863)
Descriptors: MW 374.45, ALogP 4.76, HBA 6, HBD 2, PSA 92.52, QED 0.53
Compound (SMILES): COC(=O)[C@H](CO)NC(=O)[C@H](CCCC[N+](C)(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](Cc1ccccc1)NC(=O)CNC(=O)c1ccccc1
InChIKey: UKJWSRUUPHPDEX-FRJISQSVSA-O
Target: Chromodomain Y-like protein 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8N8U2
Assay: Antagonist activity at recombinant human C-terminal His-tagged CDYL2 chromodomain (1 to 75 residues) expressed in Escherichia coli Rosetta BL21(DE3)pLysS using biotin-labeled H3K9me3 measured after 30 mins by AlphaScreen assay
Measurement: IC50 = 1000 nM (pChEMBL 6)
Descriptors: MW 782.96, ALogP 0.19, HBA 9, HBD 7, PSA 221.13, QED 0.05
Compound (SMILES): COC(=O)[C@@]12C[C@@H]1[C@@H](n1cnc3c(NC(C4CC4)C4CC4)nc(Cl)nc31)[C@H](O)[C@@H]2O
InChIKey: KNEHKBCZXUWEDN-QKZATRHHSA-N
Target: Transmembrane domain-containing protein TMIGD3 (SINGLE PROTEIN), Homo sapiens
UniProt: P0DMS9
Assay: Displacement of [125l]N 6-(4-amino-3-iodobenzyl)adenosine-5'-N-methyluronamide from recombinant human A3AR expressed in CHO cell membranes after 60 mins by gamma counting method
Measurement: Ki = 766 nM (pChEMBL 6.119999885559082)
Descriptors: MW 433.9, ALogP 1.54, HBA 9, HBD 3, PSA 122.39, QED 0.46
Compound (SMILES): S=c1[nH]nc(-c2c(N3CCCCC3)nc3ccc(Cl)cc3c2-c2ccccc2)o1
InChIKey: QNSIEZUINFOQFH-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 = 47000 nM (pChEMBL 4.329999923706055)
Descriptors: MW 422.94, ALogP 6.26, HBA 5, HBD 1, PSA 57.95, QED 0.39
Compound (SMILES): N#CC1CCN(C2CCC(c3nnn4cnc5[nH]ccc5c34)CC2)CC1
InChIKey: YCMBWVCDFHKKAN-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Enzyme Assay: JAK1, JAK2, JAK3 and Tyk2 were purchased from Carna Biosciences, Inc. As the substrate, LANCE Ultra ULight-JAK1 Peptide (manufactured by PerkinElmer Co., Ltd. (PE)) was used. Dilute solutions of compounds and enzymes in assay buffer (50 mM HEPES pH7.5, 1 mM EGTA, 1 mM MgCl2, 2 mM DTT, 0.01% Tween20) were dispensed into wells of a 384-well black plate. After 5 minutes of preincubation, dilute solutions of the substrate and ATP (adenosine triphosphate) were added at a final concentration of 100 μM, and the plate was incubated at room temperature for 2 hours. After addition of a termination reagent containing EDTA (ethylenediamine tetraacetic acid) at a final concentration of 10 mM, LANCE Eu-W1024 Anti-phosphotyrosine (PT66) (manufactured by PE) was added, and after 1 hour of incubation, the fluorescences were measured with ARVO-HTS.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 349.44, ALogP 2.87, HBA 6, HBD 1, PSA 85.9, QED 0.77
Compound (SMILES): COc1cc(N2CCC(N3CCCCC3)CC2)ccc1Nc1nccc(-c2c(-c3cccc(C(=O)Nc4c(F)cccc4F)c3)nc3cc(C)ccn23)n1
InChIKey: VAGKEHAXSSOXOJ-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: Inhibition of IGF1-induced human IGF1R autophosphorylation expressed in mouse NIH-3T3 cells preincubated for 2 hrs followed by IGF-1 induction measured after 15 mins by DELFIA
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 728.85, ALogP 8.5, HBA 9, HBD 2, PSA 99.92, QED 0.15
Compound (SMILES): COc1cc(N2CCN(CCS(C)(=O)=O)CC2)c(C)cc1Nc1nccc(-c2c(-c3ccc(OC)c(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: JYNNMNUKSKPNKE-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: Inhibition of IGF1-induced human IGF1R autophosphorylation expressed in mouse NIH-3T3 cells preincubated for 2 hrs followed by IGF-1 induction measured after 15 mins by DELFIA
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 782.87, ALogP 6.22, HBA 12, HBD 2, PSA 143.29, QED 0.15
Compound (SMILES): CC1(C)CN(C[C@H]2CC[C@H](c3nnn4cnc5[nH]ccc5c34)CC2)C1
InChIKey: JCUSUEBQBXVRKG-HDJSIYSDSA-N
Target: Non-receptor tyrosine-protein kinase TYK2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29597
Assay: Enzyme Assay: JAK1, JAK2, JAK3 and Tyk2 were purchased from Carna Biosciences, Inc. As the substrate, LANCE Ultra ULight-JAK1 Peptide (manufactured by PerkinElmer Co., Ltd. (PE)) was used. Dilute solutions of compounds and enzymes in assay buffer (50 mM HEPES pH7.5, 1 mM EGTA, 1 mM MgCl2, 2 mM DTT, 0.01% Tween20) were dispensed into wells of a 384-well black plate. After 5 minutes of preincubation, dilute solutions of the substrate and ATP (adenosine triphosphate) were added at a final concentration of 100 μM, and the plate was incubated at room temperature for 2 hours. After addition of a termination reagent containing EDTA (ethylenediamine tetraacetic acid) at a final concentration of 10 mM, LANCE Eu-W1024 Anti-phosphotyrosine (PT66) (manufactured by PE) was added, and after 1 hour of incubation, the fluorescences were measured with ARVO-HTS.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 338.46, ALogP 3.22, HBA 5, HBD 1, PSA 62.11, QED 0.8
Compound (SMILES): CC(C)(N)C(=O)N1CC2=NNC(=O)c3cccc4[nH]c(c2c34)C1
InChIKey: MWIUPFYRAAIUMB-UHFFFAOYSA-N
Target: Poly [ADP-ribose] polymerase tankyrase-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9H2K2
Assay: Tankyrase-2 Enzymatic Assay: Tankyrase-2 enzymatic assay was conducted using commercial Tankyrase-2 Chemiluminescent Assay Kit (BPS Biosciences) and the protocol with the kit. GST-fused tankyrase-2 (recombinant protein expressed and purified from Bacluovirus) were coated on a GSH-precoated plate first, and incubated with increasing concentrations of compounds for 0.5 h. Then, biotinylated NAD was added to the wells. The biotinylated auto-PARylation product was measured by adding streptavidin-HRP and HRP substrates which produce chemiluminescence.
Measurement: IC50 = 3800 nM (pChEMBL 5.420000076293945)
Descriptors: MW 311.35, ALogP 0.69, HBA 4, HBD 3, PSA 103.58, QED 0.72
Compound (SMILES): Cl.Clc1ccc2sc(CCCCN3CCc4ccccc4C3)nc2c1
InChIKey: OZTGERNCBCMFEB-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]-ketanserin from human 5-HT2A receptor by liquid scintillation counting method
Measurement: Ki = 702 nM (pChEMBL 6.150000095367432)
Descriptors: MW 356.92, ALogP 5.33, HBA 3, HBD 0, PSA 16.13, QED 0.57
Compound (SMILES): CNC(C)C(=O)Nc1ccc(-c2c(-c3ccncc3)nc3cc(C)ccn23)c(C#Cc2ccccc2)n1
InChIKey: OHIDZTXWEGDQKU-UHFFFAOYSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition Assays: The final incubation volume contains TRIS buffer (0.1 M), MgCl2 (5 mM), a certain concentration of human liver microsomes dependent on the P450 isoenzyme measured (P450 2C9, P450 3A4: 0.1 mg/ml; P450 2D6: 0.2 mg/ml; P450 2C19: 0.5 mg/ml; P450 2C8: 0.05 mg/ml) and a certain concentration of the individual substrate for each isoenzyme (P450 2C9: Diclofenac 10 μM; P450 3A4: Midazolam 5 μM; P450 2D6: Dextromethorphan 5 μM; P450 2C19: S-Mephenytoin 70 μM; P450 2C8: Amodiaquine 1 μM).
Measurement: IC50 = 3000 nM (pChEMBL 5.519999980926514)
Descriptors: MW 486.58, ALogP 4.71, HBA 6, HBD 2, PSA 84.21, QED 0.35
Compound (SMILES): Cn1c(SCCCN2CC[C@]3(C[C@@H]3c3ccc(C(F)(F)F)cc3)C2)nnc1-c1cccc(C(N)=O)c1
InChIKey: XUTJSHVGYIHURB-BWKNWUBXSA-N
Target: Cytochrome P450 1A2 (SINGLE PROTEIN), Homo sapiens
UniProt: P05177
Assay: Inhibition of human CYP1A2 expressed in microsomes using ER as substrate after 10 mins by P450 cypex assay
Measurement: IC50 > 3000 nM (pChEMBL 5.5229997634887695)
Descriptors: MW 515.61, ALogP 4.96, HBA 6, HBD 1, PSA 77.04, QED 0.34
Compound (SMILES): COCCOc1cc2ncnc(Nc3ccc4c(cnn4Cc4ccccc4)c3)c2cc1NC(=O)/C=C/CN1CCN(C)CC1
InChIKey: UCBARNSJTRWXQT-RMKNXTFCSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Irreversible inhibition of human recombinant GST-tagged JAK3 expressed in baculovirus infected Sf9 insect cells assessed as reduction in polyglutamic acid-tyrosine phosphorylation after 30 mins by ELISA
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 606.73, ALogP 4.54, HBA 10, HBD 2, PSA 109.67, QED 0.16
Compound (SMILES): COc1cc(OC)cc(N(CCC2CCN(C(C)C)CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: IWWFPZKWURVISH-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 = 5011.87 nM (pChEMBL 5.300000190734863)
Descriptors: MW 514.67, ALogP 5.7, HBA 8, HBD 0, PSA 68.54, QED 0.28
Compound (SMILES): COc1cc(OC)cc(N(CCCN2CCCC2)c2ccc3ncc(-c4cnn(CCS(C)(=O)=O)c4)nc3c2)c1
InChIKey: RYRVRXVRRSZALT-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 564.71, ALogP 4.18, HBA 10, HBD 0, PSA 102.68, QED 0.25
Compound (SMILES): Cc1cccc(/C=C/c2n[nH]c3cc(-c4ccncc4)ccc23)c1
InChIKey: MMDDRHAWZGATAZ-VMPITWQZSA-N
Target: Cyclin-dependent kinase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P06493
Assay: Inhibition of CDK1 (unknown origin)
Measurement: Ki = 900 nM (pChEMBL 6.050000190734863)
Descriptors: MW 311.39, ALogP 5.1, HBA 2, HBD 1, PSA 41.57, QED 0.57
Compound (SMILES): N#CCC1(n2ccc(-c3ncnc4[nH]ccc34)c2)CN(C2CCN(C(=O)c3c(F)cc(C#N)cc3F)CC2)C1
InChIKey: KEHZDNCDFYPSEL-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of human N-terminal His-tagged JAK1 catalytic domain (837 to 1142 residues) expressed in baculovirus infected insect cells assessed as decrease in phosphorylation of biotinylated peptide substrate after 1 hr in presence of 1 mM ATP by HTRF method
Measurement: IC50 > 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 526.55, ALogP 3.81, HBA 7, HBD 1, PSA 117.63, QED 0.42
Compound (SMILES): Cc1ccc(C(=O)NCCCCCC(=O)Nc2ccccc2N)cc1
InChIKey: VOPDXHFYDJAYNS-UHFFFAOYSA-N
Target: Histone deacetylase 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9BY41
Assay: Inhibition of HDAC8 (unknown origin) preincubated for 2 hrs followed by Fluor-de-Lys substrate addition measured after 30 mins by fluorescence assay
Measurement: IC50 = 10700 nM (pChEMBL 4.96999979019165)
Descriptors: MW 339.44, ALogP 3.51, HBA 3, HBD 3, PSA 84.22, QED 0.51
Compound (SMILES): O=S(=O)(Nc1ccc(-c2nc3cc(NS(=O)(=O)c4cccc(C(F)(F)F)c4)ccc3o2)cc1)c1cccc(C(F)(F)F)c1
InChIKey: CDXUMYOZNLBXMO-UHFFFAOYSA-N
Target: HSP60/HSP10 (PROTEIN COMPLEX), Homo sapiens
UniProt: P61604
Assay: Inhibition of human N-terminal octa-His-tagged HSP60 expressed in Escherichia coli Rosetta(DE3) pLysS/human HSP10 expressed in Escherichia coli Rosetta(DE3) assessed as reduction in HSP60/HSP10-mediated denatured MDH refolding by measuring MDH enzyme activity using sodium mesoxalate as substrate after 40 to 60 mins by spectrometric analysis
Measurement: IC50 = 58000 nM (pChEMBL 4.239999771118164)
Descriptors: MW 641.57, ALogP 7.13, HBA 6, HBD 2, PSA 118.37, QED 0.18
Compound (SMILES): CC(C)Oc1ccc(-c2onc3c2CCc2cc(CN4CC(C(=O)O)C4)ccc2-3)cc1C(F)(F)F
InChIKey: HRHUVEIJQFCGRJ-UHFFFAOYSA-N
Target: Sphingosine 1-phosphate receptor 3 (SINGLE PROTEIN), Homo sapiens
UniProt: Q99500
Assay: Agonist activity at human S1P3 expressed in CHO cell membranes assessed as stimulation of [35S]-GTPgamma-S binding measured after 45 mins by liquid scintillation counting method
Measurement: EC50 = 26000 nM (pChEMBL 4.579999923706055)
Descriptors: MW 486.49, ALogP 5.43, HBA 5, HBD 1, PSA 75.8, QED 0.5
Compound (SMILES): CNS(=O)(=O)N1CC[C@](C)(N2CCc3c(-c4cnc(N)nc4)nc(N4CCOCC4)nc32)C1
InChIKey: ZLADDXGUXPSLGC-FQEVSTJZSA-N
Target: PI3-kinase p110-delta/p85-alpha (PROTEIN COMPLEX), Homo sapiens
UniProt: O00329
Assay: Inhibition of recombinant human PI3K p110delta/p85alpha using phosphatidylinositol 4,5-bisphosphate as substrate preincubated for 15 mins followed by addition of ATP and measured after 30 mins by fluorescence polarisation assay
Measurement: Ki < 0.28 nM (pChEMBL 9.553000450134277)
Descriptors: MW 475.58, ALogP -0.36, HBA 10, HBD 2, PSA 142.7, QED 0.59
Compound (SMILES): COc1ccsc1C(=O)N1CCC(N2CC(CC#N)(n3cc(-c4ncnc5[nH]ccc45)cn3)C2)CC1
InChIKey: SHVUHXZKTMVSJM-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of human N-terminal His-tagged JAK1 catalytic domain (837 to 1142 residues) expressed in baculovirus infected insect cells assessed as decrease in phosphorylation of biotinylated peptide substrate after 1 hr in presence of 1 mM ATP by HTRF method
Measurement: IC50 <= 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 502.6, ALogP 3.12, HBA 9, HBD 1, PSA 115.96, QED 0.43
Compound (SMILES): O=C(c1ccccc1)c1ccc(CN2CCN(c3cc(N4CCCC4)nc(N4CCCC4)n3)CC2)cc1
InChIKey: ZJZZXNFEARKFRC-UHFFFAOYSA-N
Target: Caspase-5 (SINGLE PROTEIN), Homo sapiens
UniProt: P51878
Assay: Inhibition of human recombinant DTT-activated caspase-5 expressed in Escherichia coli using Ac-WEHD-AMC as substrate preincubated for 30 mins followed by substrate addition by fluorescence assay
Measurement: IC50 = 123 nM (pChEMBL 6.909999847412109)
Descriptors: MW 496.66, ALogP 4.23, HBA 7, HBD 0, PSA 55.81, QED 0.45
Compound (SMILES): OCCc1cc(-c2cncc(N3CCCNCC3)c2)on1
InChIKey: VQUBBGRWUMHAJX-UHFFFAOYSA-N
Target: Neuronal acetylcholine receptor; alpha4/beta2 (PROTEIN COMPLEX), Rattus norvegicus
UniProt: P09483
Assay: Displacement of [3H]epibatidine from rat alpha4beta2 nAChR by liquid scintillation counting
Measurement: Ki = 0.8 nM (pChEMBL 9.100000381469727)
Descriptors: MW 288.35, ALogP 1.07, HBA 6, HBD 2, PSA 74.42, QED 0.88
Compound (SMILES): CCN(CC)CCCC[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](Cc1ccccc1)NC(=O)Cc1ccc(C(C)(C)C)cc1)C(=O)N[C@@H](CO)C(=O)OC
InChIKey: WQWSPBKHYFCYOG-OKCLBPDBSA-N
Target: Chromobox protein homolog 5 (SINGLE PROTEIN), Homo sapiens
UniProt: P45973
Assay: Antagonist activity at recombinant human N-terminal His-tagged CBX5 chromodomain (18 to 75 residues) expressed in Escherichia coli Rosetta BL21(DE3)pLysS using ARTKQTARK(Me3)STGGKAPRKQL-K(Biotin)-NH2 measured after 30 mins by AlphaScreen assay
Measurement: IC50 > 60000 nM (pChEMBL 4.2220001220703125)
Descriptors: MW 809.06, ALogP 2.94, HBA 9, HBD 6, PSA 195.27, QED 0.07
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)Nc3cc(F)cc(F)c3F)CC2)C1
InChIKey: PYBFGQAKKRAPGX-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of human N-terminal His-tagged JAK1 catalytic domain (837 to 1142 residues) expressed in baculovirus infected insect cells assessed as decrease in phosphorylation of biotinylated peptide substrate after 1 hr in presence of 1 mM ATP by HTRF method
Measurement: IC50 > 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 535.53, ALogP 3.86, HBA 7, HBD 2, PSA 118.76, QED 0.37
Compound (SMILES): O=C(O)[C@@H]1CCN1c1nc2ccccc2n([C@H]2C[C@H]3CCC[C@@H](C2)N3[C@H]2C[C@@H]3CCC[C@@H](C3)C2)c1=O
InChIKey: FQAQAGMTMTXLRQ-OGXPWPJRSA-N
Target: Opioid growth factor receptor-like protein 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5TC84
Assay: In Vitro ORL-1 Receptor Functional Assay: ORL-1 membrane solution was prepared by sequentially adding final concentrations of 0.066 μg/μL ORL-1 membrane protein, 10 μg/mL saponin, 3 μM GDP and 0.20 nM [35S]GTPγS to binding buffer (100 mM NaCl, 10 mM MgCl2, 20 mM HEPES, pH 7.4) on ice. The prepared membrane solution (190 μL/well) was transferred to 96-shallow well polypropylene plates containing 10 μL of 20× concentrated stock solutions of agonist/nociceptin prepared in DMSO. Plates were incubated for 30 min at about 25 °C. with shaking. Reactions were terminated by rapid filtration onto 96-well Unifilter GF/B filter plates (Packard) using a 96-well tissue harvester (Packard) and followed by three filtration washes with 200 μL ice-cold binding buffer (10 mM NaH2PO4, 10 mM Na2HPO4, pH 7.4). Filter plates were subsequently dried at 50 °C. for 2-3 hours. Fifty μL/well scintillation cocktail (BetaScint; Wallac) was added and plates were counted in Packard Top-Count for 1 min/well.
Measurement: EC50 = 61.3 nM (pChEMBL 7.210000038146973)
Descriptors: MW 490.65, ALogP 4.59, HBA 6, HBD 1, PSA 78.67, QED 0.68
Compound (SMILES): Cc1nc2c(C(=O)O)cc(N3CCOCC3)nn2c1Cc1cccc(C(F)(F)F)c1C
InChIKey: DKTMKUHYROTKCJ-UHFFFAOYSA-N
Target: Serine/threonine-protein kinase mTOR (SINGLE PROTEIN), Homo sapiens
UniProt: P42345
Assay: Binding affinity to human MTOR (1382 to 2549 residues) expressed in mammalian expression system by KINOMEscan assay
Measurement: Kd = 12882 nM (pChEMBL 4.889999866485596)
Descriptors: MW 434.42, ALogP 3.49, HBA 6, HBD 1, PSA 79.96, QED 0.68
Compound (SMILES): CNCCN1CCC(OCc2cccc(-c3ccccc3)c2)CC1
InChIKey: OLFLGFYCUQONAR-UHFFFAOYSA-N
Target: Protein arginine N-methyltransferase 6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96LA8
Assay: Inhibition of human full length PRMT6 (1 to 375 residues) expressed in baculovirus expression system assessed as inhibition of methylation activity preincubated with protein followed by addition of biotin labeled histone H4 (1 to 24) peptide as substrate and [3H]-SAM measured after 3 hrs by scintillation proximity assay
Measurement: IC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 324.47, ALogP 3.55, HBA 3, HBD 1, PSA 24.5, QED 0.84
Compound (SMILES): O=C(c1ccc2cc(Oc3ccc(C(F)(F)F)cn3)ccc2n1)N1CC[C@@H](F)C1
InChIKey: FWLFRXVPNVBXGR-CQSZACIVSA-N
Target: Sodium channel protein type 7 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q01118
Assay: Inhibition of recombinant human Nav 1.7 expressed in HEK293F cells at -65 mV holding potential by Qpatch clamp electrophysiology method
Measurement: IC50 = 3140 nM (pChEMBL 5.5)
Descriptors: MW 405.35, ALogP 4.62, HBA 4, HBD 0, PSA 55.32, QED 0.6
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(S(=O)(=O)c3cccc(C#N)c3)CC2)C1
InChIKey: LHNVUHXNJWADTE-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: In vitro JAK Kinase Assay: The catalytic domains of human JAK1 (a.a. 837-1142), Jak2 (a.a. 828-1132) and Jak3 (a.a. 781-1124) with an N-terminal His tag were expressed using baculovirus in insect cells and purified. The catalytic activity of JAK1, JAK2 or JAK3 was assayed by measuring the phosphorylation of a biotinylated peptide. The phosphorylated peptide was detected by homogenous time resolved fluorescence (HTRF). IC50s of compounds were measured for each kinase in the 40 microL reactions that contain the enzyme, ATP and 500 nM peptide in 50 mM Tris (pH 7.8) buffer with 100 mM NaCl, 5 mM DTT, and 0.1 mg/mL (0.01%) BSA. For the 1 mM IC50 measurements, ATP concentration in the reactions was 1 mM. Reactions were carried out at room temperature for 1 hr and then stopped with 20 μL 45 mM EDTA, 300 nM SA-APC, 6 nM Eu-Py20 in assay buffer (Perkin Elmer, Boston, Mass.). Binding to the Europium labeled antibody took place for 40 minutes and HTRF signal was measured on a Fusion plate reader (Perkin Elmer, Boston, Mass.)
Measurement: IC50 = 25 nM (pChEMBL 7.599999904632568)
Descriptors: MW 527.61, ALogP 2.47, HBA 9, HBD 1, PSA 147.59, QED 0.4
Compound (SMILES): O=C(NO)c1ccc(Cn2cccn2)cc1
InChIKey: DUGDSZFLAKVUEC-UHFFFAOYSA-N
Target: Histone deacetylase 1 (SINGLE PROTEIN), Mus musculus
UniProt: O09106
Assay: Inhibition of HDAC1 in mouse N2A cells
Measurement: IC50 = 6860 nM (pChEMBL 5.159999847412109)
Descriptors: MW 217.23, ALogP 1.05, HBA 4, HBD 2, PSA 67.15, QED 0.6
Compound (SMILES): CCCc1nn(C)c2c(=O)[nH]c(-c3cc(S(=O)(=O)N4CCN(c5ncc(C(=O)NO)cn5)CC4)ccc3OCC)nc12
InChIKey: WNMRXNCXRGFIHO-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of full length recombinant human N-terminal GST tagged HDAC6 expressed in baculovirus infected Sf9 cells using fluorogenic HDAC substrate after 30 mins by fluorescence analysis
Measurement: IC50 = 268 nM (pChEMBL 6.570000171661377)
Descriptors: MW 597.66, ALogP 1.09, HBA 12, HBD 3, PSA 188.53, QED 0.19
Compound (SMILES): C1=C(CCN2CCc3ccccc3C2)CCc2ccccc21
InChIKey: UXAXXXXPTUTANS-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]-ketanserin from human 5-HT2A receptor by liquid scintillation counting method
Measurement: Ki = 975 nM (pChEMBL 6.010000228881836)
Descriptors: MW 289.42, ALogP 4.46, HBA 1, HBD 0, PSA 3.24, QED 0.81
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCC1CN(/C(=N/C#N)N2CCCC2)CCO1
InChIKey: PGISXUXCINKXKL-URGPHPNLSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of recombinant human N-terminal GST-fused KDR (D807 to V1356 residues) expressed in baculovirus infected Escherichia coli or insect Sf9 cells using poly-EY as substrate after 240 mins by luciferase coupled chemiluminescence assay
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 556.45, ALogP 4.7, HBA 8, HBD 1, PSA 108.13, QED 0.26
Compound (SMILES): C[C@@H]1CN(c2sc(Br)nc2-c2nc3ccccc3[nH]2)CCN1C(=O)Cn1cnc2cccnc21
InChIKey: VSHOBSIPZJJYRP-CQSZACIVSA-N
Target: Voltage-gated inwardly rectifying potassium channel KCNH2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12809
Assay: Inhibition of hERG expressed in CHO cells by Q patch-clamp method
Measurement: IC50 = 340 nM (pChEMBL 6.46999979019165)
Descriptors: MW 537.45, ALogP 3.93, HBA 8, HBD 1, PSA 95.83, QED 0.37
Compound (SMILES): CC(C)NC(=O)N(CCN1[C@@H]2CC[C@H]1C[C@@H](c1cccc(C(N)=O)c1)C2)CC1CCCCC1
InChIKey: HQFCOIBMSKWMCF-QEIWAGNOSA-N
Target: Delta-type opioid receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P41143
Assay: Displacement of [3H]-DPN from recombinant human delta opioid receptor expressed in CHO-K1 cell membranes by radioligand binding assay
Measurement: Ki = 1.259 nM (pChEMBL 8.899999618530273)
Descriptors: MW 454.66, ALogP 4.5, HBA 3, HBD 2, PSA 78.67, QED 0.61
Compound (SMILES): COc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(CCF)c4)nc3c2)c1
InChIKey: SEVOZKSFLJRZMK-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 447.51, ALogP 5.03, HBA 7, HBD 0, PSA 65.3, QED 0.36
Compound (SMILES): O=C1NCCCc2c1c1ccccc1n2CCc1ccccc1
InChIKey: MGCVMPGXEBMMCL-UHFFFAOYSA-N
Target: Albumin (SINGLE PROTEIN), Homo sapiens
UniProt: P02768
Assay: Binding affinity to human serum albumin assessed as equilibrium dissociation constant by SPR analysis
Measurement: Kd = 850 nM (pChEMBL 6.070000171661377)
Descriptors: MW 304.39, ALogP 3.56, HBA 2, HBD 1, PSA 34.03, QED 0.79
Compound (SMILES): CC(C)[C@H](NS(=O)(=O)c1ccc(-c2cccc(CNC(=O)c3nc4ccccc4c(=O)[nH]3)c2)cc1)C(=O)O
InChIKey: CUKATAAPVFYVIL-QHCPKHFHSA-N
Target: Macrophage metalloelastase (SINGLE PROTEIN), Homo sapiens
UniProt: P39900
Assay: Inhibition of recombinant human AMPA-activated MMP12 using Cy3-PLGLK(Cy5Q)AR-NH2 as substrate measured after 40 mins by spectrofluorimetric method
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 534.59, ALogP 2.91, HBA 6, HBD 4, PSA 158.32, QED 0.26
Compound (SMILES): C[C@H](c1cc(F)cc(F)c1)N(C(=O)c1ccccc1)[C@@H](C(N)=O)c1ccccc1
InChIKey: NNXPFEMWLZLAHM-QVKFZJNVSA-N
Target: Transient receptor potential cation channel subfamily V member 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q8NER1
Assay: Antagonist activity at human recombinant TRPV1 expressed in HEK293 cells assessed as inhibition of capsaicin-induced calcium increase by Fluo-4 AM based assay
Measurement: IC50 > 30000 nM (pChEMBL 4.5229997634887695)
Descriptors: MW 394.42, ALogP 4.39, HBA 2, HBD 1, PSA 63.4, QED 0.67
Compound (SMILES): O=C(O)c1c(N2CCCCC2)nc2c(Cl)cc(Cl)cc2c1-c1ccccc1
InChIKey: CXDOFNPXCPTGNV-UHFFFAOYSA-N
Target: Cytochrome P450 2D6 (SINGLE PROTEIN), Homo sapiens
UniProt: P10635
Assay: Inhibition of CYP2D6 (unknown origin)
Measurement: IC50 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 401.29, ALogP 5.9, HBA 3, HBD 1, PSA 53.43, QED 0.59
Compound (SMILES): N#Cc1ccc(NC(=O)N2CCCc3ccc(C=O)nc32)nc1
InChIKey: DNJLKERWZGKXBF-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 4 (SINGLE PROTEIN), Mus musculus
UniProt: Q03142
Assay: Inhibition of FGFR4 in mouse BAF3 cells assessed as decrease in FGFR4 phosphorylation incubated for 40 mins
Measurement: IC50 = 108 nM (pChEMBL 6.96999979019165)
Descriptors: MW 307.31, ALogP 2.15, HBA 5, HBD 1, PSA 98.98, QED 0.86
Compound (SMILES): COc1cc(N2CCC(N3CCN(CCS(C)(=O)=O)CC3)CC2)ccc1Nc1nccc(-c2c(-c3ccc(OC)c(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: BUTRIAZZMQWNMT-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: Inhibition of IGF1-induced human IGF1R autophosphorylation expressed in mouse NIH-3T3 cells preincubated for 2 hrs followed by IGF-1 induction measured after 15 mins by DELFIA
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 851.98, ALogP 6.38, HBA 13, HBD 2, PSA 146.53, QED 0.13
Compound (SMILES): COc1cc(OC)cc(N(CCCN2CCC(N3CCCCC3)C2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: YOPGGAOPPHWDEP-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in absence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 = 6025.6 nM (pChEMBL 5.21999979019165)
Descriptors: MW 555.73, ALogP 5.14, HBA 9, HBD 0, PSA 71.78, QED 0.27
Compound (SMILES): Cl.Clc1ccc2sc(CCCCN3CCc4c(Cl)cccc4C3)nc2c1
InChIKey: SWOUGAVDTXEVBX-UHFFFAOYSA-N
Target: 5-hydroxytryptamine receptor 2A (SINGLE PROTEIN), Homo sapiens
UniProt: P28223
Assay: Displacement of [3H]-ketanserin from human 5-HT2A receptor by liquid scintillation counting method
Measurement: Ki = 483 nM (pChEMBL 6.320000171661377)
Descriptors: MW 391.37, ALogP 5.98, HBA 3, HBD 0, PSA 16.13, QED 0.5
Compound (SMILES): O=C(CC(F)(F)F)N1CCCC(c2nnn3cnc4[nH]ccc4c23)C1
InChIKey: SHUVTQRKSSOWEE-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Enzyme Assay: JAK1, JAK2, JAK3 and Tyk2 were purchased from Carna Biosciences, Inc. As the substrate, LANCE Ultra ULight-JAK1 Peptide (manufactured by PerkinElmer Co., Ltd. (PE)) was used. Dilute solutions of compounds and enzymes in assay buffer (50 mM HEPES pH7.5, 1 mM EGTA, 1 mM MgCl2, 2 mM DTT, 0.01% Tween20) were dispensed into wells of a 384-well black plate. After 5 minutes of preincubation, dilute solutions of the substrate and ATP (adenosine triphosphate) were added at a final concentration of 100 μM, and the plate was incubated at room temperature for 2 hours. After addition of a termination reagent containing EDTA (ethylenediamine tetraacetic acid) at a final concentration of 10 mM, LANCE Eu-W1024 Anti-phosphotyrosine (PT66) (manufactured by PE) was added, and after 1 hour of incubation, the fluorescences were measured with ARVO-HTS. From the plot of logarithm of a compound concentration and inhibitory activity, the IC50 was calculated.
Measurement: IC50 = 690 nM (pChEMBL 6.159999847412109)
Descriptors: MW 352.32, ALogP 2.26, HBA 5, HBD 1, PSA 79.18, QED 0.77
Compound (SMILES): Cc1n[nH]c2c1C(c1ccc(F)c(F)c1)c1c([nH]c(=O)[nH]c1=O)O2
InChIKey: QIMOSJIYZCZLKA-UHFFFAOYSA-N
Target: Tryptophan 2,3-dioxygenase (SINGLE PROTEIN), Homo sapiens
UniProt: P48775
Assay: Inhibition of N-terminal 6xHis-tagged human TDO expressed in Escherichia cli Rosetta (DE3) pLysS using L-tryptophan as substrate preincubated for 1 hr measured after 15 mins in presence of bovine liver and methylene blue by spectrophotometric analysis
Measurement: IC50 = 3000 nM (pChEMBL 5.519999980926514)
Descriptors: MW 332.27, ALogP 1.66, HBA 4, HBD 3, PSA 103.63, QED 0.49
Compound (SMILES): Cc1c(C)n(Cc2ccc(C(=O)NO)cc2)c2ccccc12
InChIKey: GQPCGGQDQRAYCE-UHFFFAOYSA-N
Target: Protein deacetylase HDAC6 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9UBN7
Assay: Inhibition of dye-labeled tracer binding to HDAC6 (unknown origin) transfected in human HeLa cells measured after 2 hrs by nano-luciferase reporter gene-based BRET assay
Measurement: IC50 = 31.62 nM (pChEMBL 7.5)
Descriptors: MW 294.35, ALogP 3.43, HBA 3, HBD 2, PSA 54.26, QED 0.57
Compound (SMILES): O=C(COc1ccc2cc(C(O)(C(F)(F)F)C(F)(F)F)c(O)cc2c1)Nc1ccccc1
InChIKey: PGYDWDUBOQNKAR-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 13 (SINGLE PROTEIN), Homo sapiens
UniProt: Q12923
Assay: Inhibition of recombinant FAP1 (unknown origin) using pNPP as substrate by spectrophotometric method
Measurement: IC50 > 20000 nM (pChEMBL 4.698999881744385)
Descriptors: MW 459.34, ALogP 4.88, HBA 4, HBD 3, PSA 78.79, QED 0.48
Compound (SMILES): COc1cc2c(Nc3ccc(Br)c(Cl)c3)ncnc2cc1OC1CCN(C)C1
InChIKey: UJTDMNARLIOVGT-UHFFFAOYSA-N
Target: Vascular endothelial growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P35968
Assay: Inhibition of recombinant human N-terminal GST-fused KDR (D807 to V1356 residues) expressed in baculovirus infected Escherichia coli or insect Sf9 cells using poly-EY as substrate after 240 mins by luciferase coupled chemiluminescence assay
Measurement: IC50 = 50 nM (pChEMBL 7.300000190734863)
Descriptors: MW 463.76, ALogP 4.88, HBA 6, HBD 1, PSA 59.51, QED 0.58
Compound (SMILES): CN1CCN(c2ccc(NC(=O)Nc3ccc(-c4cnco4)cc3)cc2)CC1
InChIKey: JPBBSEUTVZQXIV-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Biochemical JAK and Tyk2 Kinase Assays: A panel of four LanthaScreen JAK biochemical assays (JAK1, 2, 3 and Tyk2) were carried in a common kinase reaction buffer (50 mM HEPES, pH 7.5, 0.01% Brij-35, 10 mM MgCl2, and 1 mM EGTA). Recombinant GST-tagged JAK enzymes and a GFP-tagged STAT1 peptide substrate were obtained from Life Technologies. Serially or discretely diluted compounds were pre-incubated with each of the four JAK enzymes and the substrate in white 384-well microplates (Corning) at ambient temperature for 1 h. ATP was subsequently added to initiate the kinase reactions in 10 μL total volume, with 1% DMSO. The final enzyme concentrations for JAK1, 2, 3 and Tyk2 are 4.2 nM, 0.1 nM, 1 nM, and 0.25 nM respectively; the corresponding Km ATP concentrations used are 25 μM, 3 μM, 1.6 μM, and 10 μM; while the substrate concentration is 200 nM for all four assays. Kinase reactions were allowed to proceed for 1 hour at ambient temperature before a 10 μL preparation of EDTA (10 mM final concentration) and Tb-anti-pSTAT1 (pTyr701) antibody (Life Technologies, 2 nM final concentration) in TR-FRET dilution buffer (Life Technologies) was added. The plates were allowed to incubate at ambient temperature for 1 h before being read on the EnVision reader (Perkin Elmer). Emission ratio signals (520 nm/495 nm) were recorded and utilized to calculate the percent inhibition values based on DMSO and background controls.For dose-response analysis, percent inhibition data were plotted vs. compound concentrations, and IC50 values were determined from a 4-parameter robust fit model with the Prism software (GraphPad Software). Results were expressed as pIC50 (negative logarithm of IC50) and subsequently converted to pKi (negative logarithm of dissociation constant, Ki) using the Cheng-Prusoff equation.
Measurement: Ki = 0.55 nM (pChEMBL 9.260000228881836)
Descriptors: MW 377.45, ALogP 3.74, HBA 5, HBD 2, PSA 73.64, QED 0.72
Compound (SMILES): N#CCC1(n2ccc(-c3ncnc4[nH]ccc34)c2)CN(C2CCN(C(=O)c3nc(C(F)(F)F)cs3)CC2)C1
InChIKey: LLALUBWLLLOTGO-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK1 (SINGLE PROTEIN), Homo sapiens
UniProt: P23458
Assay: Inhibition of human N-terminal His-tagged JAK1 catalytic domain (837 to 1142 residues) expressed in baculovirus infected insect cells assessed as decrease in phosphorylation of biotinylated peptide substrate after 1 hr in presence of 1 mM ATP by HTRF method
Measurement: IC50 <= 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 540.58, ALogP 4.13, HBA 8, HBD 1, PSA 106.73, QED 0.41
Compound (SMILES): COc1cc(N2CCC(N3CCCCC3)CC2)c(Cl)cc1Nc1nccc(-c2c(-c3ccc(OC)c(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: RQSRBQKLFHZWQU-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: Inhibition of IGF1-induced human IGF1R autophosphorylation expressed in mouse NIH-3T3 cells preincubated for 2 hrs followed by IGF-1 induction measured after 15 mins by DELFIA
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 779.29, ALogP 8.86, HBA 10, HBD 2, PSA 109.15, QED 0.14
Compound (SMILES): CCCCCC(O)c1ccc(N2C(=O)CC[C@@H]2CCCc2ccc(C(=O)O)s2)cc1
InChIKey: WXWCSPFQIXPFLD-YMXDCFFPSA-N
Target: Prostaglandin E2 receptor EP4 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P35408
Assay: Agonist activity at human recombinant EP4 receptor expressed in HEK293 cells assessed as effect on calcium accumulation by Fluo-4 AM dye based FLIPR assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 429.58, ALogP 5.58, HBA 4, HBD 2, PSA 77.84, QED 0.46
Compound (SMILES): CCCN1CCC(c2ccc(Nc3nccc(-c4c(-c5ccc(OCC)c(C(=O)Nc6c(F)cccc6F)c5)nc5ccccn45)n3)c(OCC)c2)CC1
InChIKey: WSNNKSMPKZCYGG-UHFFFAOYSA-N
Target: Insulin-like growth factor 1 receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P08069
Assay: Inhibition of IGF1-induced human IGF1R autophosphorylation expressed in mouse NIH-3T3 cells preincubated for 2 hrs followed by IGF-1 induction measured after 15 mins by DELFIA
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 731.85, ALogP 9.12, HBA 9, HBD 2, PSA 105.91, QED 0.12
Compound (SMILES): C=Cc1cc(OC)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: KMJPPWDZUJDQRH-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin) transfected in mouse BA/F3 cells assessed as decrease in cell proliferation in presence of mouse IL3 after 24 hrs by Alamar blue assay
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 411.51, ALogP 5.23, HBA 6, HBD 0, PSA 56.07, QED 0.42
Compound (SMILES): Cc1ccc2c(Nc3ccc(Cl)cc3)nccc2c1NC(=O)c1csc2c(N)ncnc12
InChIKey: FHPTWZJZWOYCKG-UHFFFAOYSA-N
Target: Discoidin domain-containing receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q16832
Assay: Kinase Activity: The compounds prepared in Examples were tested for inhibitory activity against FMS, DDR1 and DDR2 kinases using Kinase Screening and Profiling Service (Invitrogen, U.S.).
Measurement: IC50 = 5 nM (pChEMBL 8.300000190734863)
Descriptors: MW 460.95, ALogP 5.78, HBA 7, HBD 3, PSA 105.82, QED 0.31
Compound (SMILES): CCOc1ccc(-c2nc3ccccn3c2-c2ccnc(Nc3ccc(N4CCN(C(C)C)CC4)cc3OC)n2)cc1C(=O)Nc1c(F)cccc1F
InChIKey: BLMVXEUFSWMMGH-UHFFFAOYSA-N
Target: Insulin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P06213
Assay: Inhibition of insulin-induced human insulin receptor autophosphorylation expressed in mouse NIH-3T3 cells preincubated for 2 hrs followed by insulin induction measured after 15 mins by DELFIA
Measurement: IC50 < 100 nM (pChEMBL 7)
Descriptors: MW 718.81, ALogP 7.67, HBA 10, HBD 2, PSA 109.15, QED 0.14