lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): CO[C@H]1C[C@H](Oc2cc(F)c(F)c(-c3ccc4c(c3)CC[C@H](CCC(=O)O)O4)n2)C1
InChIKey: PGPQNVUVHSSUSY-BZUAXINKSA-N
Target: Free fatty acid receptor 4 (SINGLE PROTEIN), Mus musculus
UniProt: Q7TMA4
Assay: Agonist activity at mouse GPR120 expressed in human U2OS cells assessed as beta-arrestin recruitment after 90 mins by luminescence assay
Measurement: EC50 = 6.8 nM (pChEMBL 8.170000076293945)
Descriptors: MW 419.42, ALogP 4.14, HBA 5, HBD 1, PSA 77.88, QED 0.73
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)c1ccccc1
InChIKey: KWZNJTOCNMNMAZ-LJEIBCANSA-O
Target: E3 SUMO-protein ligase CBX4 (SINGLE PROTEIN), Homo sapiens
UniProt: O00257
Assay: Antagonist activity at recombinant human N-terminal His-tagged CBX4 chromodomain (8 to 65 residues) expressed in Escherichia coli Rosetta BL21(DE3)pLysS using biotin-labeled H3K9me3 measured after 30 mins by AlphaScreen assay
Measurement: IC50 = 6900 nM (pChEMBL 5.159999847412109)
Descriptors: MW 725.91, ALogP 1.07, HBA 8, HBD 6, PSA 192.03, QED 0.06
Compound (SMILES): Cn1c(=O)c2c(CC(=O)Nc3nc(-c4cc(F)c(CCC(F)(F)F)c(F)c4)cs3)coc2n(C)c1=O
InChIKey: SBACLEGKEWSXLI-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily M member 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z2W7
Assay: Radiometric Calcium Assay: The inhibition of TRPA1 receptor activation was measured as inhibition of allylisothiocyanate (AITC) induced cellular uptake of radioactive calcium. Test compounds were dissolved in DMSO to prepare 10 mM stock solution and then diluted using plain medium with 0.1% BSA and 1.8 mM CaCl2 to get desired concentration. Final concentration of DMSO in the reaction was 0.5% (v/v). Human TRPA1 expressing CHO cells were grown in F-12 DMEM medium with 10% FBS, 1% penicillin-streptomycin solution, and 400 ug/ml of G-418. Cells were seeded 24 h prior to the assay in 96 well plates so as to get 50,000 cells per well on the day of experiment. Cells were treated with test compounds for 10 min followed by addition of AITC at a final concentration of 30 micromolar and 5 uCi/ml 45Ca+2 for 3 min at 25° C. Cells were washed and lysed using buffer containing 1% Triton X-100, 0.1% deoxycholate and 0.1% SDS. Radioactivity in the lysate was measured in Packard Top count.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 528.46, ALogP 3.91, HBA 8, HBD 1, PSA 99.13, QED 0.38
Compound (SMILES): CN[C@@H](C)C(=O)Nc1ccc(-c2c(-c3cnn(C)c3)nc3cc(C)ccn23)c(C#Cc2ccc3c(C)nccc3c2)n1
InChIKey: GKUKREOTCLQGRX-QFIPXVFZSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
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 > 50000 nM (pChEMBL 4.301000118255615)
Descriptors: MW 554.66, ALogP 4.91, HBA 8, HBD 2, PSA 102.03, QED 0.29
Compound (SMILES): COc1cc(OC)cc(N(CCN2CCN(C(C)=O)CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: ZMWVHMVSBKMRAW-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 515.62, ALogP 3.35, HBA 9, HBD 0, PSA 88.85, QED 0.35
Compound (SMILES): COc1cc(F)cc(N(CCO)c2ccc3ncc(-c4cn[nH]c4)nc3c2)c1
InChIKey: JLQHGFULSVHTBJ-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 379.4, ALogP 3.3, HBA 6, HBD 2, PSA 87.16, QED 0.53
Compound (SMILES): N#CCC1(n2cc(-c3ccnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3cncc(C(F)(F)F)n3)CC2)C1
InChIKey: XXKCOXXPYUNIQL-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of human N-terminal His-tagged JAK2 catalytic domain (828 to 1132 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 > 100 nM (pChEMBL 7)
Descriptors: MW 535.53, ALogP 3.46, HBA 8, HBD 1, PSA 119.62, QED 0.42
Compound (SMILES): C#CCN(c1ccc2ncc(-c3cnn(C)c3)nc2c1)c1c(Cl)c(OC)cc(OC)c1Cl
InChIKey: PQLSSHDPNXYVAQ-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 468.34, ALogP 5.13, HBA 7, HBD 0, PSA 65.3, QED 0.37
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)Nc3ccc(F)cc3F)CC2)C1
InChIKey: NCRFGVSZWAOANP-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of human N-terminal His-tagged JAK2 catalytic domain (828 to 1132 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 > 10 nM (pChEMBL 8)
Descriptors: MW 517.54, ALogP 3.72, HBA 7, HBD 2, PSA 118.76, QED 0.42
Compound (SMILES): O=C(c1c(F)ccc(NS(=O)(=O)c2cccc(F)c2)c1F)c1c[nH]c2nccc(Cl)c12
InChIKey: JZVJCDLWFRCCRA-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin) using CEC as substrate after 30 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 465.84, ALogP 4.67, HBA 4, HBD 2, PSA 91.92, QED 0.42
Compound (SMILES): COC[C@]1(OC)CC[C@@]2(CC1)NC(=O)C(c1cc(-c3ccc(Cl)c(F)c3)ccc1C)=C2O
InChIKey: OAWROPVLCGVWIS-SOAUALDESA-N
Target: Acetyl-CoA carboxylase 1 (SINGLE PROTEIN), Homo sapiens
UniProt: Q13085
Assay: Human ACC1 Enzyme Assay: For the assay, 50 nl of a 100-times concentrated solution of the test substance in DMSO were pipetted into a white low-volume 384-well microtitre plate (Greiner Bio-One, Frickenhausen, Germany), 2.5 μl of a solution of hACC1 in assay buffer [50 mM HEPES/NaOH pH 7.5, 2 mM MgCl2, 2 mM potassium citrate, 12 mM NaHCO3, 2 mM dithiothreitol (DTT), 0.005% (w/v) bovine serum albumin (BSA)] were added and the mixture was incubated for 15 min to allow prebinding of the substances to the enzyme prior to the enzyme reaction. The enzyme reaction was then started by addition of 2.5 μl of a solution of adenosine triphosphate (ATP, 100 μM=>final concentration in 5 μl of assay volume: 50 μM) and acetyl-CoA (20 μM=>final concentration in 5 μl assay volume: 10 μM) in assay buffer, and the resulting mixture was incubated at 22 °C. for the reaction time of 45 min. The concentration of the hACC1 was adjusted to the respective activity of the enzyme and set such that the assay was carried out in the linear range. Typical concentrations were in the range of 1.75 μl. The reaction was stopped by addition of 2.5 μl of the "ADP-GLO reagent" (1:1.5-times diluted), and the resulting mixture was incubated at 22 °C. for 1 h to convert the unreacted ATP completely into cAMP. 2.5 μl of the "kinase detection reagent" were then added (1.2-times more concentrated than recommended by the manufacturer), the resulting mixture was incubated at 22 °C. for 1 h and the luminescence was then measured using a suitable measuring instrument (Viewlux or Topcount from Perkin-Elmer or Pherastar from BMG Labtechnologies).
Measurement: IC50 = 84 nM (pChEMBL 7.079999923706055)
Descriptors: MW 459.95, ALogP 5.2, HBA 4, HBD 2, PSA 67.79, QED 0.64
Compound (SMILES): Cn1nc2c(c1CC(=O)Nc1nc(-c3ccc(C(F)(F)F)c(F)c3)cs1)c(=O)n(C)c(=O)n2C
InChIKey: URFBKMSDRKBRGT-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily M member 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z2W7
Assay: Radiometric Calcium Assay: The inhibition of TRPA1 receptor activation was measured as inhibition of allylisothiocyanate (AITC) induced cellular uptake of radioactive calcium. Test compounds were dissolved in DMSO to prepare 10 mM stock solution and then diluted using plain medium with 0.1% BSA and 1.8 mM CaCl2 to get desired concentration. Final concentration of DMSO in the reaction was 0.5% (v/v). Human TRPA1 expressing CHO cells were grown in F-12 DMEM medium with 10% FBS, 1% penicillin-streptomycin solution, and 400 ug/ml of G-418. Cells were seeded 24 h prior to the assay in 96 well plates so as to get 50,000 cells per well on the day of experiment. Cells were treated with test compounds for 10 min followed by addition of AITC at a final concentration of 30 micromolar and 5 uCi/ml 45Ca+2 for 3 min at 25° C. Cells were washed and lysed using buffer containing 1% Triton X-100, 0.1% deoxycholate and 0.1% SDS. Radioactivity in the lysate was measured in Packard Top count.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 496.45, ALogP 2.43, HBA 9, HBD 1, PSA 103.81, QED 0.44
Compound (SMILES): Cc1c(CC(=O)O)c2cccnc2n1Cc1ccc(S(C)(=O)=O)cc1Cl
InChIKey: KJGIZBAFYZZEKQ-UHFFFAOYSA-N
Target: Prostaglandin D2 receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9Y5Y4
Assay: Antagonist activity against human CRTh2 expressed in CHO-K1 cells assessed as inhibition of PGD2-mediated attenuation of forskolin-induced cAMP accumulation incubated for 60 mins by scintillation counting method
Measurement: IC50 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 392.86, ALogP 3.08, HBA 5, HBD 1, PSA 89.26, QED 0.72
Compound (SMILES): Cl.[2H]C([2H])([2H])Oc1cc(OC)cc(N(CCNC(C)C)c2ccc3ncc(-c4cn[nH]c4)nc3c2)c1
InChIKey: LROUZHGAXKBMPL-FJCVKDQNSA-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 432.53, ALogP 4.17, HBA 7, HBD 2, PSA 88.19, QED 0.41
Compound (SMILES): CCCS(=O)(=O)Nc1ccc(F)c(C(=O)c2c[nH]c3ncc(-c4ccc(S(C)(=O)=O)cc4)cc23)c1F
InChIKey: IOYCMCLTXHCZLI-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin) using MFC as substrate after 45 mins
Measurement: IC50 = 5000 nM (pChEMBL 5.300000190734863)
Descriptors: MW 533.58, ALogP 4.29, HBA 6, HBD 2, PSA 126.06, QED 0.33
Compound (SMILES): COc1cc2c(Nc3ccc(Br)c(Cl)c3Cl)ncnc2cc1OCC1CN(C)C(C)(C)CO1
InChIKey: MGIPMVSOOMJZHR-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 556.29, ALogP 5.94, HBA 7, HBD 1, PSA 68.74, QED 0.38
Compound (SMILES): CCCNC(=O)COc1ccc2cc(C(O)(C(F)(F)F)C(F)(F)F)c(O)cc2c1
InChIKey: OSWWTMZGHKYJTP-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 425.32, ALogP 3.76, HBA 4, HBD 3, PSA 78.79, QED 0.62
Compound (SMILES): O=C(O)COC[C@H]1CC[C@H](COC(=O)N(c2ccccc2)c2ccc(F)c(F)c2)CC1
InChIKey: KDHKZSVRIRHRKL-QAQDUYKDSA-N
Target: Prostacyclin receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P43119
Assay: Agonist activity at IP receptor in human primary platelets assessed as inhibition of ADP-induced platelet aggregation
Measurement: IC50 = 19 nM (pChEMBL 7.71999979019165)
Descriptors: MW 433.45, ALogP 5.15, HBA 4, HBD 1, PSA 76.07, QED 0.62
Compound (SMILES): CCOc1cc(N2CCC(N3CCN(CCS(C)(=O)=O)CC3)CC2)ccc1Nc1nccc(-c2c(-c3cccc(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: MJERNARJUQAGLR-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 835.98, ALogP 6.76, HBA 12, HBD 2, PSA 137.3, QED 0.13
Compound (SMILES): CN(C)C/C=C/C(=O)Nc1cc2c(Nc3ccc(OCc4cccc(F)c4)c(Cl)c3)ncnc2cn1
InChIKey: AUMBQDJVOLYTCC-QPJJXVBHSA-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 = 1220 nM (pChEMBL 5.909999847412109)
Descriptors: MW 506.97, ALogP 5.2, HBA 7, HBD 2, PSA 92.27, QED 0.3
Compound (SMILES): O=C(O)c1ccc(CC[C@H]2C(=O)CC[C@@H]2/C=C/C(O)Cc2cccc(F)c2F)cc1
InChIKey: ZHIYYJVFRSDGIT-SATSMNEMSA-N
Target: Prostaglandin E2 receptor EP4 subtype (SINGLE PROTEIN), Homo sapiens
UniProt: P35408
Assay: cAMP Assay: A 384-well drug plate was prepared to contain test compounds, PGE2 and cAMP in 16 serial dilutions in triplicate, using a Biomek station. HEK-EBNA cells expressing a target PG receptor subtype (EP2 or EP4) were suspended in a stimulation buffer (HBSS, 0.1% BSA, 0.5 mM IBMX and 5 mM HEPES, pH 7.4) in a density of 104 cells/5 μl. The reaction was initiated by mixing 5 μL drug dilutions with 5 μl of HEK-EBNA cells in a well, carried out for 30 min at room temperature, and followed by the addition of 5 μl anti-cAMP acceptor beads in the control buffer with Tween-20 (25 mM NaCl, 0.03% Tween-20, 5 mM HEPES, pH7.4). After 30 min in the dark at room temperature, the mixtures were incubated with 15 μl biotinylated-cAMP/strpavidin donor beads in Lysis/Detection buffer (0.1% BSA, 0.3% Tween-20 and 5 mM HEPES, pH7.4) for 45 min at the room temperature. Fluorescence changes were read using a Fusion-alpha HT microplate reader.
Measurement: EC50 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 414.45, ALogP 4.35, HBA 3, HBD 2, PSA 74.6, QED 0.63
Compound (SMILES): COc1cc2c(Oc3ccc(NC(=O)C4(C(=O)Nc5ccc(F)cc5)CC4)cc3F)ccnc2cc1OCCCC(=O)NO
InChIKey: LYXOBSREVZDKST-UHFFFAOYSA-N
Target: Mast/stem cell growth factor receptor Kit (SINGLE PROTEIN), Homo sapiens
UniProt: P10721
Assay: Kinase Inhibition Assay: This example shows that the inhibitory activity of the compound, N1'-[3-fluoro-4-[[7-[4-(hydroxyamino)-4-oxobutoxy]-6-methoxy-4-quinolyl]oxy]phenyl]-N1-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide prepared in Example 9 in cells against kinases including ALK, AXL, FLT3, VEGFR2, c-KIT, c-MET, PDGFR-beta, RET and SRC (tested by Advanced Cellular Dynamics, 3550 General Atomics Court, Building 2, Room 639, San Diego, CA 92121. www.advancedcelldynamics.com and Carna Biosciences, Inc.(www.carnabio.com)) measured according to the method described in the literature (Reference: Daley, G. Q.; Baltimore, D. Proc. Natl. Acd. Sci. USA 1988, 85(23), 9312). Specific steps were as follows: The compound of the present invention was dissolved in dimethyl sulfoxide (DMSO) to make a stock solution of 2 mM, then the stock solution was diluted with DMSO following a 7 half-log series to concentrations ranging from 2 uM to 600 pM.
Measurement: IC50 = 115 nM (pChEMBL 6.940000057220459)
Descriptors: MW 606.58, ALogP 5.34, HBA 8, HBD 4, PSA 148.11, QED 0.07
Compound (SMILES): CC[C@H](C)[C@H](NC(=O)OC)C(=O)N1CCC[C@H]1c1ncc(-c2ccc3cc(-c4ccc5[nH]c([C@@H]6CCCN6C(=O)[C@@H](NC(=O)OC)C(C)C)nc5c4)ccc3c2)[nH]1
InChIKey: GDBODYVKBMWJEG-IVLWUQRZSA-N
Target: Nonstructural protein 5A (SINGLE PROTEIN), Hepatitis C virus
UniProt: Q5L478
Assay: Transient Transfection Assay: In a transient set-up, a Huh-7 lunet hepatoma cell line was transiently transfected with an autonomously replicating RNA encoding a bi-cistronic expression construct. This construct comprises a firefly luciferase reporter gene preceding the NS3-NS5B subgenomic region of HCV (genotype 1a H77 or 1b Con1). Translation of the HCV subgenomic region is mediated by an internal ribosome entry site of encephalomyocarditis virus. The construct is furthermore flanked by 5' and 3' untranslated regions of HCV (genotype 1a H77 or 1b Con 1, respectively), which allow for replication of the RNA. In addition to the wild-type constructs, site-directed mutations were introduced into the transient HCV genotype 1b replicon in the gene encoding for the non-structural protein 5A (NS5A). More precisely, amino acid residues 28, 30, 31 and 93 in NS5A were independently altered. Cells were plated in 384 well plates in the presence of test and control compounds, which were added in various concentrations. Following an incubation of two days, replication of the HCV subgenomic replicon RNA was measured by assaying luciferase activity (using standard luciferase assay substrates and reagents and a Perkin Elmer ViewLux™ ultraHTS microplate imager).
Measurement: EC50 = 0.411 nM (pChEMBL 9.390000343322754)
Descriptors: MW 776.94, ALogP 7.25, HBA 8, HBD 4, PSA 174.64, QED 0.11
Compound (SMILES): CC(C)COc1ccc(-c2csc(NC(=O)Cc3cccc4c3c(=O)n(C)c(=O)n4C)n2)cc1
InChIKey: VHUHAUBXPXCHGU-UHFFFAOYSA-N
Target: Transient receptor potential cation channel subfamily M member 8 (SINGLE PROTEIN), Homo sapiens
UniProt: Q7Z2W7
Assay: Radiometric Calcium Assay: The inhibition of TRPA1 receptor activation was measured as inhibition of allylisothiocyanate (AITC) induced cellular uptake of radioactive calcium. Test compounds were dissolved in DMSO to prepare 10 mM stock solution and then diluted using plain medium with 0.1% BSA and 1.8 mM CaCl2 to get desired concentration. Final concentration of DMSO in the reaction was 0.5% (v/v). Human TRPA1 expressing CHO cells were grown in F-12 DMEM medium with 10% FBS, 1% penicillin-streptomycin solution, and 400 ug/ml of G-418. Cells were seeded 24 h prior to the assay in 96 well plates so as to get 50,000 cells per well on the day of experiment. Cells were treated with test compounds for 10 min followed by addition of AITC at a final concentration of 30 micromolar and 5 uCi/ml 45Ca+2 for 3 min at 25° C. Cells were washed and lysed using buffer containing 1% Triton X-100, 0.1% deoxycholate and 0.1% SDS. Radioactivity in the lysate was measured in Packard Top count.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 478.57, ALogP 3.58, HBA 8, HBD 1, PSA 95.22, QED 0.44
Compound (SMILES): CN(Cc1ccccc1OCCC[C@@H]1C[C@@H]1C(=O)O)C(=O)c1ccc(-c2ccco2)cc1
InChIKey: SCHIHSWLJKKKDG-IRLDBZIGSA-N
Target: Peroxisome proliferator-activated receptor gamma (SINGLE PROTEIN), Homo sapiens
UniProt: P37231
Assay: Activation of human PPARgamma LBD expressed in CHO-K1 cells by beta galactosidase enzyme fragment complement based fluorescence assay
Measurement: EC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 433.5, ALogP 5.1, HBA 4, HBD 1, PSA 79.98, QED 0.45
Compound (SMILES): O=C(O)Cn1nc(Cn2nc(-c3ccc(Cl)cc3)n(C[C@H](O)C(F)(F)F)c2=O)nc1-c1ccccc1Cl
InChIKey: BWMSBDDWGDIHBZ-INIZCTEOSA-N
Target: Vasopressin V1a receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P37288
Assay: Cellular In Vitro Assay for Determining Vasopressin V1a Receptor Activity: The identification of agonists and antagonists of the V1a and V2 vasopressin receptors from humans, rats and dogs as well as the quantification of the activity of the compounds of the invention is carried out using recombinant cell lines. These cell lines originally derive from a hamster's ovary epithelial cell (Chinese Hamster Ovary, CHO K1, ATCC: American Type Culture Collection, Manassas, Va. 20108, USA). The test cell lines constitutively express the human, rat or dog V1a or V2 receptors. In case of the Gαq-coupled V1a receptors, cells are also stably transfected with a modified form of the calcium-sensitive photoproteins aequorin (human and rat V1a) or obelin (dog V1a), which, after reconstitution with the cofactor coelenterazine, emit light when there are increases in free calcium concentrations [Rizzuto R, Simpson A W, Brini M, Pozzan T, Nature 358, 325-327 (1992); Illarionov B A, Bondar V S, Illarionova V A, Vysotski E S, Gene 153 (2), 273-274 (1995)]. The resulting vasopressin receptor cells react to stimulation of the recombinantly expressed V1a receptors by intracellular release of calcium ions, which can be quantified by the resulting photoprotein luminescence. The Gs-coupled V2 receptors are stably transfected into cell lines expressing the gene for firefly luciferase under control of a CRE-responsible promoter. Activation of V2 receptors induces the activation of the CRE-responsive promoter via cAMP increase, thereby inducing the expression of firefly luciferase. The light emitted by photoproteins of V1a cell lines as well as the light emitted by firefly luciferase of V2 cell lines corresponds to the activation or inhibition of the respective vasopressin receptor. The bioluminescence of the cell lines is detected using a suitable luminometer [Milligan G, Marshall F, Rees S, Trends in Pharmacological Sciences 17, 235-237 (1996)].Vasopressin V2 Receptor Cell Lines:On the day before the assay, the cells are plated out in culture medium (DMEM/F12, 2% FCS, 2 mM glutamine, 10 mM HEPES) in 384-well microtiter plates and kept in a cell incubator (96% humidity, 5% v/v CO2, 37° C.). On the day of the assay, test compounds in various concentrations and the agonist [Arg8]-vasopressin at EC50 concentration are added together to the wells, and plates are incubated for 3 hours in a cell incubator. Upon addition of the cell lysis reagent Triton and the substrate luciferin, luminescence of firefly luciferase is measured in a luminometer.
Measurement: IC50 = 54.2 nM (pChEMBL 7.269999980926514)
Descriptors: MW 557.32, ALogP 3.33, HBA 9, HBD 2, PSA 128.06, QED 0.34
Compound (SMILES): COc1cc(OC)cc(N(CCNC2CC(C)(C)NC(C)(C)C2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: GLFQAWRMXLTAFH-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 543.72, ALogP 5.08, HBA 9, HBD 2, PSA 89.36, QED 0.3
Compound (SMILES): CC(C)Oc1cc(N2CCC(N3CCCCC3)CC2)ccc1Nc1nccc(-c2c(-c3cccc(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: QSNLBMCGRQUEPH-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 742.87, ALogP 8.97, HBA 9, HBD 2, PSA 99.92, QED 0.14
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CC3CCC(C2)N3C(=O)c2ccc(C#N)c(F)c2)C1
InChIKey: SBMMUIKKJSOVJT-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 535.59, ALogP 3.59, HBA 8, HBD 1, PSA 130.52, QED 0.41
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3cc(Cl)sc3Cl)CC2)C1
InChIKey: RJVFCWDKCFHFCU-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 541.47, ALogP 4.42, HBA 8, HBD 1, PSA 106.73, QED 0.4
Compound (SMILES): CCC#CC(=O)Nc1cc(-c2cnc3[nH]ccc3c2)ccc1F
InChIKey: AQMRYTCSVWYPPS-UHFFFAOYSA-N
Target: Tyrosine-protein kinase ITK/TSK (SINGLE PROTEIN), Homo sapiens
UniProt: Q08881
Assay: In Vitro Inhibition Assay: ITK and JAK3 Kinase assay procedures:Enzyme was incubated with substrate peptide in reaction buffer in the presence and absence of test compounds or Staurosporine. All additions were done on ice, followed by the addition of ATP mix. Wells were uniformly mixed using an Eppendorff plate shaker and incubated at 30° C. for 20 min, and stopped by the addition of 5 μL of 3% phosphoric acid. Volume was increased to 100 μL by adding 0.8% phosphoric acid which was then transferred to PC filter mats (Millipore), pre-equilibrated with 70% ethanol and water. Plates were washed thrice with 100 μL 0.8% phosphoric acid and dried for an hour at 60° C. 100 μL scintillation fluid was added into each well and reading taken in Perkin Elmer TOPCOUNT beta counter. The data analysis was performed by averaging the duplicate top count readings for each standard, negative, positive control (enzyme control) and samples and subtracting the average negative control from each reading which results in corrected values.
Measurement: IC50 > 1000 nM (pChEMBL 6)
Descriptors: MW 307.33, ALogP 3.72, HBA 2, HBD 2, PSA 57.78, QED 0.71
Compound (SMILES): CCCS(=O)(=O)Nc1ccc(F)c(C(=O)c2c[nH]c3ncc(-c4ccc(S(=O)(=O)N5CCOCC5)cc4)cc23)c1F
InChIKey: OTPBIQXOUJIYKY-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin) using CEC as substrate after 30 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 604.66, ALogP 3.91, HBA 7, HBD 2, PSA 138.53, QED 0.28
Compound (SMILES): COc1cc(OCCO)cc(N(CCO)c2ccc3ncc(-c4cnn(CCO)c4)nc3c2)c1
InChIKey: ZNCQPSDLZARYKS-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 465.51, ALogP 2, HBA 10, HBD 3, PSA 125.99, QED 0.3
Compound (SMILES): COc1cc(OC)c(Cl)c(N(CCNC(C)C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1Cl
InChIKey: JQUMBFRGCVDDBS-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 = 7244.36 nM (pChEMBL 5.139999866485596)
Descriptors: MW 515.45, ALogP 5.49, HBA 8, HBD 1, PSA 77.33, QED 0.32
Compound (SMILES): C=CC(=O)N1CCN(S(=O)(=O)c2cccc(Nc3ncc4c(n3)N(C)c3ccc(C)cc3C(=O)N4C)c2)CC1
InChIKey: ZOKVMFNJBPBZCE-UHFFFAOYSA-N
Target: Aurora kinase B (SINGLE PROTEIN), Homo sapiens
UniProt: Q96GD4
Assay: In Vitro Kinase Assay: The enzymatic activities against PI3K-α, PI3K-β, PI3K-γ and PI3K-δ were tested in ADAPTA assays. Activity against AURKB and AURKB were tested in Z′-Lyte assays. All assays were performed with ATP concentrations of Km for each kinase. BRD4_1 binding was tested using an AlphaScreen assay. All protocols are available from Life Technologies.
Measurement: IC50 = 16 nM (pChEMBL 7.800000190734863)
Descriptors: MW 547.64, ALogP 2.91, HBA 8, HBD 1, PSA 119.05, QED 0.48
Compound (SMILES): CC(C)c1cccc(-c2c(C(=O)O)c(N(C)C)nc3ccc(Cl)cc23)c1
InChIKey: CKMUEMURCFDTSJ-UHFFFAOYSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of CYP2C9 (unknown origin)
Measurement: IC50 = 9700 nM (pChEMBL 5.010000228881836)
Descriptors: MW 368.86, ALogP 5.44, HBA 3, HBD 1, PSA 53.43, QED 0.67
Compound (SMILES): CCCS(=O)(=O)Nc1ccc(F)c(C(=O)c2c[nH]c3ncc(-c4ccc(NS(C)(=O)=O)cc4)cc23)c1F
InChIKey: NEZSZZWQZCSHAP-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin) using CEC as substrate after 30 mins
Measurement: IC50 = 5000 nM (pChEMBL 5.300000190734863)
Descriptors: MW 548.59, ALogP 4.26, HBA 6, HBD 3, PSA 138.09, QED 0.27
Compound (SMILES): COC1CN(CC(=O)Nc2ccc(-n3ccccc3=O)cc2F)CC1NC(=O)c1ccc(Cl)s1
InChIKey: BOCLXHFYRGMFSC-UHFFFAOYSA-N
Target: Coagulation factor X (SINGLE PROTEIN), Homo sapiens
UniProt: P00742
Assay: Biochemical assay using fluorogenic peptide substrate.Step 1: Compound transfer to plate (50 nl).Step 2: Dilute FXa in Assay Buffer.Step 3: Dilute substrate in Assay Buffer.Step 4: Add equal volumes to Assay plate (total assay volume 10 uL).Step 5: Centrifuge plate, 1 min, 1000 rpm.Step 6: Detect fluorescence signal: ex: 320 nm; Em. 405 nm (EnVision), every 10 min. 30 min pre-incubation of enzyme with compound and 30 min reaction time after substrate addition.
Measurement: IC50 = 1.03 nM (pChEMBL 8.989999771118164)
Descriptors: MW 504.97, ALogP 2.76, HBA 7, HBD 2, PSA 92.67, QED 0.52
Compound (SMILES): CCC#CC(=O)Nc1cccc(-c2cnc3[nH]cc(-c4cccc(S(=O)(=O)N(C)C(C)(C)C)c4)c3c2)c1
InChIKey: OVTPHNAWDBWUFE-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: Biochemical Inhibition Assay: 1H-pyrrolo[2,3-b]pyridine, 1H-pyrazolo[3,4-b]pyridine and 5H-pyrrolo[2,3-b]pyrazine series of compounds exhibited over >100 fold selective against Janus and TEC family of kinases except for the BMX and TXK it had activity of 30 and 45 nM respectively.
Measurement: IC50 < 5 nM (pChEMBL 8.300999641418457)
Descriptors: MW 514.65, ALogP 5.67, HBA 4, HBD 2, PSA 95.16, QED 0.34
Compound (SMILES): COc1cc(OC)cc(N(Cc2cc(C)on2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: QVLVKBIGNUAHQR-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 456.51, ALogP 4.68, HBA 9, HBD 0, PSA 91.33, QED 0.35
Compound (SMILES): COc1cc(-c2cccc(C(F)(F)F)c2)ccc1-n1c(=O)ccc2cc(S(=O)(=O)Nc3ncccn3)ccc21
InChIKey: HSOCYPPAQYZHMJ-UHFFFAOYSA-N
Target: Sodium channel protein type 3 subunit alpha (SINGLE PROTEIN), Homo sapiens
UniProt: Q9NY46
Assay: Inhibition of human Nav1.3 expressed in CHO cells assessed as use-dependent block at pulse 26 after 3 to 8 mins by ionworks quattro electrophysiology assay
Measurement: IC50 > 42500 nM (pChEMBL 4.372000217437744)
Descriptors: MW 552.53, ALogP 5.28, HBA 7, HBD 1, PSA 103.18, QED 0.31
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3ccc(O)c(F)c3)CC2)C1
InChIKey: FEHGTLOEQXJQIQ-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
Assay: Inhibition of human N-terminal His-tagged JAK2 catalytic domain (828 to 1132 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 > 10 nM (pChEMBL 8)
Descriptors: MW 500.54, ALogP 2.9, HBA 8, HBD 2, PSA 126.96, QED 0.43
Compound (SMILES): N#Cc1ccnc2[nH]cc(C(=O)c3c(F)ccc(NS(=O)(=O)c4cccc(F)c4)c3F)c12
InChIKey: RKVXTXWZZKPUHS-UHFFFAOYSA-N
Target: Cytochrome P450 2C19 (SINGLE PROTEIN), Homo sapiens
UniProt: P33261
Assay: Inhibition of CYP2C19 (unknown origin) using CEC as substrate after 30 mins
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 456.4, ALogP 3.88, HBA 5, HBD 2, PSA 115.71, QED 0.44
Compound (SMILES): Cc1ccc(C(Nc2c(Nc3cccc(C(=O)N(C)C)c3O)c(=O)c2=O)C2(C)CCCO2)o1
InChIKey: VWSXKWXISJLOQM-UHFFFAOYSA-N
Target: C-X-C chemokine receptor type 3 (SINGLE PROTEIN), Homo sapiens
UniProt: P49682
Assay: Antagonist activity at CXCR3 (unknown origin)
Measurement: IC50 = 1.259 nM (pChEMBL 8.899999618530273)
Descriptors: MW 453.5, ALogP 3.06, HBA 8, HBD 3, PSA 121.11, QED 0.37
Compound (SMILES): COc1ccc(OC)c(N(CCN)c2ccc3ncc(-c4cn[nH]c4)nc3c2)c1.Cl
InChIKey: UPLOKKOTKRYIAA-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 390.45, ALogP 3.13, HBA 7, HBD 2, PSA 102.18, QED 0.5
Compound (SMILES): COc1cc(OC)cc(N(CCN2CC=CCC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: LSKQQNXBSACZRH-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 470.58, ALogP 4.45, HBA 8, HBD 0, PSA 68.54, QED 0.35
Compound (SMILES): Cc1nc(F)ccc1NC(=O)N1CCC(N2CC(CC#N)(n3cc(-c4ncnc5[nH]ccc45)cn3)C2)CC1
InChIKey: SFGUZNYAVKBIGN-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
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 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 514.57, ALogP 3.29, HBA 8, HBD 2, PSA 131.65, QED 0.39
Compound (SMILES): COc1cccc(-c2ccnc3[nH]cc(C#N)c23)c1
InChIKey: ZZDGQQQSEKEUFO-UHFFFAOYSA-N
Target: Leucine-rich repeat serine/threonine-protein kinase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q5S007
Assay: LanthaScreen Kinase Activity Assay: In the assay, 1 nM LRRK2 WT or 250 pM LRRK2 G2019S kinase is incubated with the test compound (typically at 0 to 30 μM) for 30 minutes before the kinase reaction is initiated by addition of 1.3 mM ATP and 0.4 μM fluorescein-LRRKtide. The reaction mixture (20 μl total volume) is incubated for 2 hours at 30° C. before the reaction is terminated by addition of 10 mM EDTA and 1 nM terbium-labelled anti-phospho-LRRKtide antibody (final volume 20 μl). The mixture is further incubated for 30 minutes at RT. TR-FRET is measured by excitation of the terbium-donor with 340 nm light and subsequent (delay time 100 μs) measurement of terbium and fluorescein emission at 495 nm and 520 nm, respectively, over a time window of 1000 μs. The measurement is repeated 10 times for fluorescein and 10 times for terbium emission with a 2000 μs time window between repeats. TR-FRET measurements are performed on a Biomek Synergy plate. The TR-FRET signal is calculated as the emission-ratio at 520 nm over 495 nm.
Measurement: EC50 = 201 nM (pChEMBL 6.699999809265137)
Descriptors: MW 249.27, ALogP 3.11, HBA 3, HBD 1, PSA 61.7, QED 0.76
Compound (SMILES): C[C@H]1NC(=O)c2cc(-c3cccc4c(=O)n(C)c(NC(C)(C)C)nc34)[nH]c21
InChIKey: HLPARXMUJBJYFM-SNVBAGLBSA-N
Target: Serine/threonine-protein kinase pim-2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q9P1W9
Assay: Inhibition of full length recombinant Pim-2 (unknown origin) assessed as reduction in phosphorylation of biotinylated-BAD peptide at Serine 112 residue preincubated for 30 mins followed by substrate addition for 1 hr by HTRF assay
Measurement: IC50 = 0.2 nM (pChEMBL 9.699999809265137)
Descriptors: MW 365.44, ALogP 2.94, HBA 5, HBD 3, PSA 91.81, QED 0.65
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCCC1CCCCC1
InChIKey: WYZCWZRHCBLLRQ-UHFFFAOYSA-N
Target: Ephrin type-A receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P29317
Assay: AlphaScreen Assay: In AlphaScreen, when the donor and acceptor beads are close in proximity, a series of photochemical events will give rise to a fluorescent signal upon light activation. Here we use biotinylated poly-(Glu, Tyr) 4:1 as the kinase substrate, streptavidin-coated donor beads and anti-phosphortyrosine antibody PY100-coated acceptor beads. Upon phosphorylation, the peptide substrate can bind to both donor and acceptor beads, thus gives rise to fluorescence. Compounds, ATP, biotinylated poly-(Glu, Tyr) and kinases are mixed in a volume of 20 μL for 1 hr at ambient temperature using Greiner 384-well white clear bottom medium binding plates. Then 10 uL solution containing 15-30 mg/mL AlphaScreen beads, 75 mM Hepes, pH 7.4, 300 mM NaCl, 120 mM EDTA, 0.3% BSA and 0.03% Tween-20 is added to each well. After 2-16 hr incubation of the beads, plates are read in a Perkin Elmer AlphaQuest reader (available from PerkinElmer Life and Analytical Sciences, Inc., of Boston Mass.).
Measurement: IC50 = 525 nM (pChEMBL 6.28000020980835)
Descriptors: MW 446.38, ALogP 7.04, HBA 5, HBD 1, PSA 56.27, QED 0.42
Compound (SMILES): O=S(=O)(Nc1ccc(-c2nc3cc(NS(=O)(=O)c4ccc(Br)cc4)ccc3o2)cc1)c1ccc(Br)cc1
InChIKey: FKHDTZDCOPGXLO-UHFFFAOYSA-N
Target: Tyrosine-protein phosphatase non-receptor type 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P17706
Assay: Inhibition of human PTPN2 expressed in Escherichia coli Rosetta 2 (DE3) using pNPP as substrate after 45 mins by spectrophotometric method
Measurement: IC50 = 18000 nM (pChEMBL 4.75)
Descriptors: MW 663.37, ALogP 6.62, HBA 6, HBD 2, PSA 118.37, QED 0.2
Compound (SMILES): Cc1n[nH]c2ncc(-c3cccc(NC(=O)/C=C/N(C)C)c3)cc12
InChIKey: PLPHPNTWLARELL-BQYQJAHWSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: In Vitro Inhibition Assay: ITK and JAK3 Kinase assay procedures:Enzyme was incubated with substrate peptide in reaction buffer in the presence and absence of test compounds or Staurosporine. All additions were done on ice, followed by the addition of ATP mix. Wells were uniformly mixed using an Eppendorff plate shaker and incubated at 30° C. for 20 min, and stopped by the addition of 5 μL of 3% phosphoric acid. Volume was increased to 100 μL by adding 0.8% phosphoric acid which was then transferred to PC filter mats (Millipore), pre-equilibrated with 70% ethanol and water. Plates were washed thrice with 100 μL 0.8% phosphoric acid and dried for an hour at 60° C. 100 μL scintillation fluid was added into each well and reading taken in Perkin Elmer TOPCOUNT beta counter. The data analysis was performed by averaging the duplicate top count readings for each standard, negative, positive control (enzyme control) and samples and subtracting the average negative control from each reading which results in corrected values.
Measurement: IC50 > 100 nM (pChEMBL 7)
Descriptors: MW 321.38, ALogP 2.95, HBA 4, HBD 2, PSA 73.91, QED 0.72
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3ccc(-c4cc(F)cc(C#N)c4)c(F)c3)CC2)C1
InChIKey: HPXDUENAACWXMF-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
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 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 603.64, ALogP 4.87, HBA 8, HBD 1, PSA 130.52, QED 0.29
Compound (SMILES): CCC(CC(C(=O)Nc1ccc(C(=O)O)cc1)n1cc(OC)c(-c2cc(Cl)ccc2C#N)cc1=O)OC
InChIKey: NWTLKQWFPQKMLC-UHFFFAOYSA-N
Target: Plasma kallikrein (SINGLE PROTEIN), Homo sapiens
UniProt: P03952
Assay: Inhibition Assay: Test substances are dissolved in dimethyl sulphoxide and serially diluted in dimethyl sulphoxide (3000 μM to 0.0078 μM; resulting final concentrations in the test: 50 μM to 0.00013 μM). In each case 1 μl of the diluted substance solutions are placed into the wells of white microtitre plates from Greiner (384 wells). 20 μl of assay buffer (50 mM Tris/HCl pH 7.4; 100 mM sodium chloride solution; 5 mM of calcium chloride solution; 0.1% of bovine serum albumin) and 20 μl of plasma kallikrein from Kordia (0.6 nM in assay buffer) are then added successively. After 15 min of incubation, the enzyme reaction is started by addition of 20 μl of the substrate H-Pro-Phe-Arg-AMC dissolved in assay buffer (10 μl in assay buffer) from Bachem, the mixture is incubated at room temperature (22° C.) for 30 min and fluorescence is then measured (excitation: 360 nm, emission: 460 nm).
Measurement: IC50 = 23 nM (pChEMBL 7.639999866485596)
Descriptors: MW 523.97, ALogP 4.74, HBA 7, HBD 2, PSA 130.65, QED 0.39
Compound (SMILES): COc1cc(OC)cc(N(CCNC(=O)C2CCCN(C)C2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: KPQQBBDCGUBBFQ-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 529.65, ALogP 3.64, HBA 9, HBD 1, PSA 97.64, QED 0.35
Compound (SMILES): C=CCN(c1cc(F)cc(OC)c1)c1ccc2ncc(-c3cnn(C)c3)nc2c1
InChIKey: HLNPWTJAVUGIEO-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 389.43, ALogP 4.5, HBA 6, HBD 0, PSA 56.07, QED 0.45
Compound (SMILES): Cn1cc(-c2nc(N[C@@H]3CCCC[C@@H]3N)c(F)c3c2C(=O)NC3)cn1
InChIKey: MJHOMTRKVMKCNE-NWDGAFQWSA-N
Target: Tyrosine-protein kinase ZAP-70 (SINGLE PROTEIN), Homo sapiens
UniProt: P43403
Assay: Inhibition of human full length N-terminal GST-tagged ZAP-70 (1 to 619 residues) expressed in baculovirus expression system using ULight peptide as substrate after 1 hr in presence of ATP by TR-FRET assay
Measurement: IC50 = 75 nM (pChEMBL 7.119999885559082)
Descriptors: MW 344.39, ALogP 1.55, HBA 6, HBD 3, PSA 97.86, QED 0.78
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2ccncc2C#N)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: AGBXUKHUCRHKSZ-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 = 1230.27 nM (pChEMBL 5.909999847412109)
Descriptors: MW 501.55, ALogP 4.5, HBA 9, HBD 0, PSA 101.98, QED 0.31
Compound (SMILES): COc1cc(N2CCC(CCS(C)(=O)=O)CC2)c(C)cc1Nc1nccc(-c2c(-c3ccc(OC)c(C(=O)Nc4c(F)cccc4F)c3)nc3cc(F)ccn23)n1
InChIKey: OTMVHGFNBPEEJU-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 799.88, ALogP 7.85, HBA 11, HBD 2, PSA 140.05, QED 0.13
Compound (SMILES): COc1cc(C2OCCO2)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: XXGFUXOOCXYEEQ-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 457.53, ALogP 4.63, HBA 8, HBD 0, PSA 74.53, QED 0.4
Compound (SMILES): COc1cc(OC)cc(N(CCNC(C)C)c2ccc3ncc(-c4cnn(C5CCNCC5)c4)nc3c2)c1
InChIKey: SLEJFRIKJJZQKL-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 515.66, ALogP 4.57, HBA 9, HBD 2, PSA 89.36, QED 0.32
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)Nc3nc(-c4ccc(Cl)cc4)cs3)CC2)C1
InChIKey: HYXDCFGRMWSBTF-UHFFFAOYSA-N
Target: Tyrosine-protein kinase JAK2 (SINGLE PROTEIN), Homo sapiens
UniProt: O60674
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 = 75 nM (pChEMBL 7.119999885559082)
Descriptors: MW 599.12, ALogP 5.22, HBA 9, HBD 2, PSA 131.65, QED 0.27