lovingscience/chembl-v37-raw-activities huggingface dataset:
Compound (SMILES): O=[N+]([O-])c1ccc(CN2CCN(c3cc(N4CCCC4)nc(N4CCCC4)n3)CC2)cc1
InChIKey: KQLWSSDYPGXCNL-UHFFFAOYSA-N
Target: Caspase-4 (SINGLE PROTEIN), Homo sapiens
UniProt: P49662
Assay: Inhibition of human recombinant N-terminal His-tagged DTT-activated caspase-4 expressed in Escherichia coli using Ac-LEVD-AMC as substrate preincubated for 30 mins followed by substrate addition by fluorescence assay
Measurement: Ki = 215 nM (pChEMBL 6.670000076293945)
Descriptors: MW 437.55, ALogP 2.91, HBA 8, HBD 0, PSA 81.88, QED 0.5
Compound (SMILES): CN1CCN(Cc2ccc(-c3cn4c5nc(ncc35)NCCCCCCCCC(O)CCCCC4)cc2)CC1
InChIKey: SCPFYDCGZSWLOY-UHFFFAOYSA-N
Target: Tyrosine-protein kinase receptor UFO (SINGLE PROTEIN), Homo sapiens
UniProt: P30530
Assay: Inhibition of Axl (unknown origin) by microfluidic capillary electrophoresis assay
Measurement: IC50 = 17 nM (pChEMBL 7.769999980926514)
Descriptors: MW 532.78, ALogP 5.92, HBA 7, HBD 2, PSA 69.45, QED 0.44
Compound (SMILES): CC(C)c1cccc(NC(=O)c2cccc(N3CCc4c(cnc5ccccc45)C3)c2)c1
InChIKey: IZGSXTPUBXKDBJ-UHFFFAOYSA-N
Target: Platelet-derived growth factor receptor beta (SINGLE PROTEIN), Homo sapiens
UniProt: P09619
Assay: PDGFRbeta: Biochemical PDGFRβ kinase assays were performed in 96 well microtiter plates that were coated overnight with 75 ug of poly-Glu-Tyr (4:1) in 10 mM Phosphate Buffered Saline (PBS), pH 7.4. The coated plates were washed with 2 mls per well PBS+0.05% Tween-20 (PBS-T), blocked by incubation with PBS containing 1% BSA, then washed with 2 mls per well PBS-T prior to starting the reaction. Reactions were carried out in 100 uL reaction volumes containing 36 uM ATP in kinase buffer (50 mM Hepes buffer pH 7.4, 20 mM MgCl2, 0.1 mM MnCl2 and 0.2 mM Na3VO4). Test compounds were reconstituted in 100% DMSO and added to the reaction to give a final DMSO concentration of 5%. Reactions were initiated by the addition 20 ul per well of kinase buffer containing 200-300 ng purified cytoplasmic domain PDGFR-b protein (Millipore). Following a 60 minute incubation at 30° C., the reactions were washed 2 mls per well PBS-T. 100 ul of a monoclonal anti-phosphotyrosine antibody-peroxidase conjugate diluted 1:10,000 in PBS-T was added to the wells for 30 minutes. Following a 2 mls per well wash with PBS-Tween-20, 100 ul of 0-Phenylenediamine Dihydrochloride in phosphate-citrate buffer, containing urea hydrogen peroxide, was added to the wells for 7-10 minutes as a colorimetric substrate for the peroxidase.
Measurement: IC50 = 200 nM (pChEMBL 6.699999809265137)
Descriptors: MW 421.54, ALogP 6.17, HBA 3, HBD 1, PSA 45.23, QED 0.43
Compound (SMILES): O=C(c1cccc(C(F)(F)F)c1Cl)N1CCc2c(-c3ccccc3)n[nH]c2C1
InChIKey: GKXMHEVHFMPCFB-UHFFFAOYSA-N
Target: P2X purinoceptor 7 (SINGLE PROTEIN), Rattus norvegicus
UniProt: Q64663
Assay: FLIPR Assay: 1321 N1 cells expressing the recombinant human, rat or mouse P2X7 channel was cultured in HyQ DME/(HyClone/Dulbecco's Modified Eagle Medium) high glucose supplemented with 10% Fetal Bovine Serum (FBS) and appropriate selection marker. Cells were seeded at a density of 25000 cells/well (96-well clear bottom black walled plates) in 100 ul volume/well. On the day of the experiment, cell plates were washed with assay buffer, containing (in mM): 130 NaCl, 2 KCl, 1 CaCl2, 1 MgCl2, 10 HEPES, 5 glucose; pH 7.40 and 300 mOs. After the wash, cells were loaded with the Calcium-4 dye (Molecular Device) and incubated in the dark for 60 minutes. Test compounds were prepared at 250Ã¿ the test concentration in neat DMSO. Intermediate 96-well compound plates were prepared by transferring 1.2 uL of the compound into 300 uL of assay buffer. A further 3x dilution occurred when transferring 50 uL/well of the compound plate to 100 uL/well in the cell plate. Cells were incubateÂ  with test compounds and dye for 30 minutes. Calcium dye fluorescence was monitored in FLIPR as the cells were challenged by adding 50 uL/well of BzATP (final concentration is 250 uM BzATP (human and rat) or 600 (mouse)). The fluorescence change was measured 180 seconds after adding the agonist.
Measurement: IC50 = 194.8 nM (pChEMBL 6.710000038146973)
Descriptors: MW 405.81, ALogP 4.95, HBA 2, HBD 1, PSA 48.99, QED 0.66
Compound (SMILES): CCC(=O)NC1CCc2c(-c3ccc(C(F)(F)F)cc3F)cncc21
InChIKey: DBUUHHKKKNUIPG-UHFFFAOYSA-N
Target: Cytochrome P450 11B2, mitochondrial (SINGLE PROTEIN), Homo sapiens
UniProt: P19099
Assay: Cellular Enzyme Assay: G-402 cells expressing CYP11 constructs were established as described above and maintained in McCoy's 5a Medium Modified, ATCC Catalog No. 30-2007 containing 10% FCS and 400 ug/ml G418 (Geneticin) at 37° C. under an atmosphere of 5% CO2/95% air. Cellular enzyme assays were performed in DMEM/F12 medium containing 2.5% charcoal treated FCS and appropriate concentration of substrate (0.3-10 uM 11-Deoxycorticosterone, 11-Deoxycortisol or Corticosterone). For assaying enzymatic activity, cells were plated onto 96 well plates and incubated for 16 h. An aliquot of the supernatant is then transferred and analyzed for the concentration of the expected product (Aldosterone for CYP11B2; Cortisol for CYP11B1). The concentrations of these steroids can be determined using HTRF assays from CisBio analyzing either Aldosterone or Cortisol.
Measurement: EC50 = 1677 nM (pChEMBL 5.78000020980835)
Descriptors: MW 352.33, ALogP 4.42, HBA 2, HBD 1, PSA 41.99, QED 0.83
Compound (SMILES): Cn1c(SCCCN2CC[C@]3(C[C@@H]3c3ccc(C(F)(F)F)cc3)C2)nnc1-c1ccc(CC(N)=O)cc1
InChIKey: BCTUVZJFJIFLND-GJZUVCINSA-N
Target: Cytochrome P450 2C9 (SINGLE PROTEIN), Homo sapiens
UniProt: P11712
Assay: Inhibition of human CYP2C9 expressed in microsomes using FCA as substrate after 10 mins by P450 cypex assay
Measurement: IC50 > 7000 nM (pChEMBL 5.15500020980835)
Descriptors: MW 529.63, ALogP 4.89, HBA 6, HBD 1, PSA 77.04, QED 0.32
Compound (SMILES): COc1ccc(C(=O)N2CCC(N3CC(CC#N)(n4cc(-c5ncnc6[nH]ccc56)cn4)C3)CC2)cc1C#N
InChIKey: JHMOGMFDLJUAQS-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 521.59, ALogP 2.93, HBA 9, HBD 1, PSA 139.75, QED 0.41
Compound (SMILES): COCC(O)CN(c1cc(OC)cc(OC)c1)c1ccc2ncc(-c3cnn(C(C)C)c3)nc2c1.Cl
InChIKey: GJXMORWINPOZCG-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 477.57, ALogP 4.24, HBA 9, HBD 1, PSA 94.76, QED 0.36
Compound (SMILES): Nc1c(C(=O)c2cc3ccccc3o2)cnn1-c1cc(O)ccc1Cl
InChIKey: PHGFCPRSBHSCCN-UHFFFAOYSA-N
Target: Fibroblast growth factor receptor 2 (SINGLE PROTEIN), Homo sapiens
UniProt: P21802
Assay: Inhibition of human FGFR2 by time-resolved fluorescence or time-resolved fluorescence assay
Measurement: IC50 = 140 nM (pChEMBL 6.849999904632568)
Descriptors: MW 353.77, ALogP 3.79, HBA 6, HBD 2, PSA 94.28, QED 0.55
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3cccc(Cl)c3)CC2)C1
InChIKey: YAEMRFMASWMAIB-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 500.99, ALogP 3.7, HBA 7, HBD 1, PSA 106.73, QED 0.45
Compound (SMILES): COc1cc(CCN2CCN(C)CC2)ccc1Nc1nccc(-c2c(-c3cccc(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: IJHIXUNOBPCLFN-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 674.76, ALogP 6.53, HBA 9, HBD 2, PSA 99.92, QED 0.17
Compound (SMILES): Nc1ncnc2c1c(-c1ccc(Oc3ccccc3)cc1)nn2C1CCN(C(=O)/C=C/CN2CCOCC2)CC1
InChIKey: NIKYELXINWPOQX-QPJJXVBHSA-N
Target: Tyrosine-protein kinase JAK3 (SINGLE PROTEIN), Homo sapiens
UniProt: P52333
Assay: HotSpot kinase assay: IC50s were determined using the in vitro HotSpot kinase assay (purified enzymes, 33P-ATP, an appropriate substrate and 1 μM ATP.). For enzyme inhibition assays, compounds were tested in range of ten concentrations from 10 uM to 0.0005 uM using purified enzymes and the Hotspot kinase assay. Reaction conditions were 1 uM ATP, one hour incubation with inhibitor, and kinase activity detected using 33-ATP phosphorylation of an appropriately selected peptide substrate.
Measurement: IC50 > 10000 nM (pChEMBL 5)
Descriptors: MW 539.64, ALogP 3.92, HBA 9, HBD 1, PSA 111.63, QED 0.35
Compound (SMILES): CCOc1ccc(C[C@H]2C[C@H](C(=O)NO)C2)cc1-c1nc2c(CC)nn(C)c2c(=O)[nH]1
InChIKey: WFSWUBOROARLDR-HDJSIYSDSA-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 = 126 nM (pChEMBL 6.900000095367432)
Descriptors: MW 425.49, ALogP 2.36, HBA 7, HBD 3, PSA 122.13, QED 0.39
Compound (SMILES): COc1cn(C(CC2CC2(F)F)C(=O)Nc2ccc(C(=O)O)cc2)c(=O)cc1-c1cc(Cl)ccc1C#N
InChIKey: PPOMRFJZWPHFPA-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 = 39 nM (pChEMBL 7.409999847412109)
Descriptors: MW 527.91, ALogP 4.97, HBA 6, HBD 2, PSA 121.42, QED 0.43
Compound (SMILES): COc1cc(OC)cc(N(CCN2CCCNCC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.O=C(O)C(=O)O
InChIKey: XKKLEKLBWIRPBM-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 = 5623.41 nM (pChEMBL 5.25)
Descriptors: MW 487.61, ALogP 3.48, HBA 9, HBD 1, PSA 80.57, QED 0.4
Compound (SMILES): COc1cc2c(cc1OC)[C@@H]1Cc3c(OC)ccc(OC)c3CN1CC2
InChIKey: MLYZNZVURPVMPQ-KRWDZBQOSA-N
Target: D(2) dopamine receptor (SINGLE PROTEIN), Homo sapiens
UniProt: P14416
Assay: Affinity Assay: Each medicament was dissolved in serum-free F12 culture medium containing 100 μM of IBMX. CHO cells which can stably express D2 receptor were pre-incubated at 37° C. for 10 min, and then 10 μM Forskoline and 10 μM Dopanie were added at the same time to react for 10 min. 100 μL, of pre-cooled 1 M of HClO4 was added and the reaction was terminated at 4° C. for 1 hour. 20 μL of 2 M K2CO3 was added to neutralize the reaction. The resulting mixture was centrifugated at 3000 rpm for 15 min, and the precipitate KClO4 was discarded. A certain amount of the supernatant was taken for cAMP detection. Spiperone and Quinpirole were used as positive control.
Measurement: EC50 = 4030 nM (pChEMBL 5.389999866485596)
Descriptors: MW 355.43, ALogP 3.38, HBA 5, HBD 0, PSA 40.16, QED 0.84
Compound (SMILES): C=C(C)c1cc(N2CCOCC2)nc(-c2cc(NC(=O)c3cccc(C(F)(F)F)c3)ccc2C)n1
InChIKey: OJMHBRGTXHCAEY-UHFFFAOYSA-N
Target: RAF proto-oncogene serine/threonine-protein kinase (SINGLE PROTEIN), Homo sapiens
UniProt: P04049
Assay: In Vitro Enzyme Assay: Final assay conditions were 4 pM cRaf, 3 uM ATP, 10 nM biotin tagged MEK1 kinase dead protein substrate. Reactions were performed in Greiner384 well plates, catalog #784075. Reaction buffer was 50 mM Tris, pH 7.5, 50 mM NaCl, 10 mM MgCl2, 0.01% Tween-20, 0.05% BSA and 1 mM DTT. 5 ul of 2×cRaf plus MEK1 were dispensed into plates containing 0.25 ul of compound in 100% DMSO and incubated at room temperature for 30 minutes. Reactions were started by addition of 5 ul of 2×ATP. Reactions were run for two hours and terminated by addition of 10 ul of 2× antibody and Alphascreen bead mixture in Stop Buffer. Stop Buffer was 50 mM Tris, pH 7.5, 0.005% Tween-20, 25 mM EDTA.
Measurement: IC50 = 0.388 nM (pChEMBL 9.40999984741211)
Descriptors: MW 482.51, ALogP 5.59, HBA 5, HBD 1, PSA 67.35, QED 0.51
Compound (SMILES): COc1cc(OC)cc(N(CC(OCC(O)C(C)C)C(C)C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: AJDPVRCTXQVCTL-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 = 9549.93 nM (pChEMBL 5.019999980926514)
Descriptors: MW 533.67, ALogP 5.24, HBA 9, HBD 1, PSA 94.76, QED 0.26
Compound (SMILES): O=C([C@H]1CCCN1)N1CCN(c2nc(N3CCOCC3)nc(-n3c(C(F)F)nc4ccccc43)n2)CC1
InChIKey: RHXSBAVYCAXUKN-QGZVFWFLSA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of PI3Kgamma (unknown origin) expressed in baculovirus expression system by kinase-glo luminescence assay
Measurement: IC50 = 5859 nM (pChEMBL 5.230000019073486)
Descriptors: MW 513.55, ALogP 1.39, HBA 10, HBD 1, PSA 104.54, QED 0.54
Compound (SMILES): COc1cc(N2CCC(N3CCC[C@H](O)C3)CC2)ccc1Nc1nccc(-c2c(-c3cccc(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: JPRKDTOUWLIIBS-PMERELPUSA-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 730.82, ALogP 7.17, HBA 10, HBD 3, PSA 120.15, QED 0.14
Compound (SMILES): COc1cc(F)cc(N(CC2CC2)c2ccc3ncc(-c4cnn(CCO)c4)nc3c2)c1
InChIKey: VBCUYTZWMKPDOM-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 433.49, ALogP 4.18, HBA 7, HBD 1, PSA 76.3, QED 0.45
Compound (SMILES): COc1cc(OC)cc(N(C/C(=N\O)C(C)C)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: HRMKTZOBLPIBBW-XLVZBRSZSA-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 = 7585.78 nM (pChEMBL 5.119999885559082)
Descriptors: MW 460.54, ALogP 4.67, HBA 9, HBD 1, PSA 97.89, QED 0.23
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2cc(N)nc(C)n2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: NYBWRPLFCRQSSV-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 506.57, ALogP 3.92, HBA 10, HBD 1, PSA 117.1, QED 0.34
Compound (SMILES): CCOc1cc(N2CCC(CCS(C)(=O)=O)CC2)c(C)cc1Nc1nccc(-c2c(-c3ccc(OC)c(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: JHQYLHDWOAYSLZ-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 795.91, ALogP 8.1, HBA 11, HBD 2, PSA 140.05, QED 0.12
Compound (SMILES): COc1cc(N(CC2CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)cc(C(F)(F)F)c1
InChIKey: HJXFZYAQOJRGRY-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 453.47, ALogP 5.61, HBA 6, HBD 0, PSA 56.07, QED 0.38
Compound (SMILES): COC1=CC(N(CCO)c2ccc3ncc(-c4c(C(F)(F)F)nn(C)c4C(F)(F)F)nc3c2)CC(OC)=C1
InChIKey: KCZSJNIAKYVASC-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 543.47, ALogP 4.7, HBA 8, HBD 1, PSA 85.53, QED 0.43
Compound (SMILES): CN(C)CCOc1cccc(Nc2nccc(-c3c(-c4cccc(C(=O)Nc5cc(Cl)ccc5F)c4)nc4ccccn34)n2)c1
InChIKey: RHSLGSUTMGNNME-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 622.1, ALogP 7.19, HBA 8, HBD 2, PSA 96.68, QED 0.17
Compound (SMILES): CCOC(=O)N[C@H]1CC[C@H](CCN2CCN(c3nsc4ccccc34)CC2)CC1
InChIKey: BYJLEOXPONSXOY-IYARVYRRSA-N
Target: 5-hydroxytryptamine receptor 1A (SINGLE PROTEIN), Homo sapiens
UniProt: P08908
Assay: 5-HT1A Receptor Binding Test: 1. Experimental Materials:The isotopic ligand of 5-H1A receptor [3H]0.8-OH-DPAT (purchased from PE Corporation), (+)5-hydroxytryptamine (purchased from Sigma Corporation), GF/B glassfiber filter (purchased from Whatman Corporation), fat-soluble scintillation fluid: PPO and POPOP (purchased from Shanghai No. 1 Reagent Factory), toluene (purchased from Sinopharm Chemical Reagent Co., Ltd), and Tris (imported and subpackaged).Cells: HEK-293 cells stably expressing 5-HT1A receptors as obtained by gene recombination are cultured for 3-5 days in cell culture medium DMEM supplemented with 10% serum. The cells are collected with PBS and centrifuged at −4° C. and 3000 rpm for 10 min, the supernatant is then discarded, and the cell pellets are collected, preserved in refrigerator at −80° C., and resuspended with D1 Binding Buffer (pH 7.4) before use.2. Experimental Methods:Competitive inhibition ratio of each compound at the concentration of 10 μmol/L to inhibit the binding of [3H]8-OH-DPAT to 5-HT1A receptor is determined for primary screening.Compounds with an inhibition ratio of over 95% are subjected to the receptor binding test at a series of concentrations so as to determine half maximal inhibitory concentration (IC50, the concentration of the compound required for inhibiting 50% binding of [3H]8-OH-DPAT to 5-HT1A receptor). Each concentration is tested in duplicate, and tests are carried out independently twice for each compound. Total binding tube [3H].8-OH-DPAT 20 μL D1 Binding Buffer 20 μL Cells 160 μL  Non-specific tube [3H].8-OH-DPAT 20 μL 5-HT(10−4) 20 μL Cells 160 μL  Tube with the [3H].8-OH-DPAT 20 μL compound to be tested The compound to be tested 20 μL Cells 160 μL The components are mixed to homogeneity, and then the above tubes are transferred to water bath at 30° C. (1 h), removed into ice bath immediately, and suction filtered on Harvest (with ice cold Tris eluate for 5 times). The filter membrane is dried over medium heat for 8 min, removed into a centrifuge tube (0.5 mL), added with scintillation fluid, and left standed for 30 min before measurement.1%=(total binding CPM−the tested compound CPM)/(total binding CPM−non-specific CPM)×100%Ki=IC50/(1+[L]/KD) (Ki: the affinity of the drug to the receptor, L: the concentration of the radioligand, KD: the value of the affinity of the radioligand to the receptor)
Measurement: Ki = 8.03 nM (pChEMBL 8.100000381469727)
Descriptors: MW 416.59, ALogP 4.11, HBA 6, HBD 1, PSA 57.7, QED 0.77
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3cc(Cl)cc(C(F)(F)F)n3)CC2)C1
InChIKey: GPSJSZFVOZXEMY-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 569.98, ALogP 4.12, HBA 8, HBD 1, PSA 119.62, QED 0.38
Compound (SMILES): Nc1ncc(-c2cccc3[nH]ccc23)nc1C(=O)Nc1ncccc1N1CCC(N)CC1
InChIKey: CCFSCBCNTYCQQD-UHFFFAOYSA-N
Target: Receptor-type tyrosine-protein kinase FLT3 (SINGLE PROTEIN), Homo sapiens
UniProt: P36888
Assay: Inhibition of FLT3 (unknown origin)
Measurement: IC50 = 33 nM (pChEMBL 7.480000019073486)
Descriptors: MW 428.5, ALogP 2.78, HBA 7, HBD 4, PSA 138.84, QED 0.39
Compound (SMILES): CCn1nccc1NC(=O)N1CCC(N2CC(CC#N)(n3cc(-c4ncnc5[nH]ccc45)cn3)C2)CC1
InChIKey: YPNNZJJRSYBWMK-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 = 12.5 nM (pChEMBL 7.900000095367432)
Descriptors: MW 499.58, ALogP 2.66, HBA 9, HBD 2, PSA 136.58, QED 0.42
Compound (SMILES): COc1ccc(OC)c(N(CCCN2CCCC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: TXAUTICJVJOSJD-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 = 5623.41 nM (pChEMBL 5.25)
Descriptors: MW 472.59, ALogP 4.67, HBA 8, HBD 0, PSA 68.54, QED 0.35
Compound (SMILES): COc1cc(N2CCC(N3CCCCC3)CC2)c(C)cc1Nc1nccc(-c2c(-c3ccc(OC)c(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: GJIZZWWYNHHCFE-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 758.87, ALogP 8.51, HBA 10, HBD 2, PSA 109.15, QED 0.14
Compound (SMILES): C[C@H](Nc1nc(N)nc(N)c1C#N)c1nc2cccc(Cl)c2c(=O)n1-c1cncc(F)c1
InChIKey: FNFDELVCLWMEAC-VIFPVBQESA-N
Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (SINGLE PROTEIN), Homo sapiens
UniProt: P48736
Assay: Inhibition of human full length PI3K p110gamma using phosphatidylinositol 3,4,5-trisphosphate as substrate measured after 30 mins by TR-FRET assay
Measurement: IC50 = 150 nM (pChEMBL 6.820000171661377)
Descriptors: MW 451.85, ALogP 2.57, HBA 10, HBD 3, PSA 161.42, QED 0.42
Compound (SMILES): CC1(C)[C@@H]2CC[C@@]1(C)[C@@H](NC(=O)[C@H](CC1CCCCC1)NS(=O)(=O)N[C@@H](CCCCN)C(=O)O)C2.Cl
InChIKey: SXAUCWSUBICAAS-LZZNFXAASA-N
Target: Carboxypeptidase B2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96IY4
Assay: Inhibition of activated human plasma TAFI incubated for 15 mins in presence of 1% human serum albumin by chromogenic assay
Measurement: IC50 = 51 nM (pChEMBL 7.289999961853027)
Descriptors: MW 514.73, ALogP 2.66, HBA 5, HBD 5, PSA 150.62, QED 0.24
Compound (SMILES): CC1(C)C(=O)N(c2ccc(C#N)c(C(F)(F)F)c2)C(=S)N1c1ccc(C(=O)NCCCn2cccc(O)c2=O)c(F)c1
InChIKey: FHOQVZJRWRBYOV-UHFFFAOYSA-N
Target: Histone deacetylase 3 (SINGLE PROTEIN), Homo sapiens
UniProt: O15379
Assay: Inhibition of HDAC3 (unknown origin) assessed as inhibition of fluorogenic peptide deacetylation
Measurement: IC50 > 100000 nM (pChEMBL 4)
Descriptors: MW 601.58, ALogP 4.32, HBA 7, HBD 2, PSA 118.67, QED 0.24
Compound (SMILES): COc1cc(OC)cc(N(CCN2CCOCC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1.Cl
InChIKey: IOZOSZRZSAEJGK-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 474.57, ALogP 3.52, HBA 9, HBD 0, PSA 77.77, QED 0.38
Compound (SMILES): Cl.NC(N)=N/N=C/c1ccc(Cl)c(Cl)c1
InChIKey: XWTMACVBCUKXFY-GAYQJXMFSA-N
Target: Pyroglutamylated RF-amide peptide receptor (SINGLE PROTEIN), Homo sapiens
UniProt: Q96P65
Assay: Displacement of [125I]-43RFa from human QRFP receptor expressed in CHO cell membrane by TopCount scintillation counter method
Measurement: Ki > 5000 nM (pChEMBL 5.301000118255615)
Descriptors: MW 231.09, ALogP 1.81, HBA 2, HBD 3, PSA 74.26, QED 0.41
Compound (SMILES): N#CCC1(n2cc(-c3c(F)cnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3ccc(C#N)cc3F)CC2)C1
InChIKey: WIQUSYCVUZBNNO-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): COc1cc(OC)cc(N(CC#Cc2nccc(OC(C)C)n2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: QHWNOTNFJRKXDT-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 = 8511.38 nM (pChEMBL 5.070000171661377)
Descriptors: MW 535.61, ALogP 4.81, HBA 10, HBD 0, PSA 100.31, QED 0.26
Compound (SMILES): CC1(N)CCN(c2cccnc2NC(=O)c2nc(-c3ncccc3C(F)(F)F)cnc2N)CC1
InChIKey: XXJXHXJWQSCNPX-UHFFFAOYSA-N
Target: Protein kinase C alpha type (SINGLE PROTEIN), Homo sapiens
UniProt: P17252
Assay: Inhibition of PKCalpha (unknown origin) incubated for 15 mins in presence of 33P-ATP by Topcount scintillation counting method
Measurement: IC50 = 3 nM (pChEMBL 8.520000457763672)
Descriptors: MW 472.48, ALogP 3.1, HBA 8, HBD 3, PSA 135.94, QED 0.53
Compound (SMILES): COC(=O)[C@H](CO)NC(=O)[C@H](CCCCNC1C2CC3CC(C2)CC1C3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](Cc1ccccc1)NC(=O)CNC(=O)c1ccccc1
InChIKey: UCRSNRWWVDEHLO-JXGGDCLASA-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 874.09, ALogP 1.9, HBA 10, HBD 8, PSA 233.16, QED 0.06
Compound (SMILES): O=S(=O)(Nc1ccc(-c2nc3cc(NS(=O)(=O)c4ccccc4Br)ccc3o2)cc1)c1ccccc1Br
InChIKey: WSNOEJPHCWUVHH-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 = 28000 nM (pChEMBL 4.550000190734863)
Descriptors: MW 663.37, ALogP 6.62, HBA 6, HBD 2, PSA 118.37, QED 0.2
Compound (SMILES): c1cc2c(ncn3nnc(C4CCN(Cc5cncs5)CC4)c23)[nH]1
InChIKey: ZVWLKYCXNDODAP-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 = 14 nM (pChEMBL 7.849999904632568)
Descriptors: MW 339.43, ALogP 2.44, HBA 7, HBD 1, PSA 75, QED 0.62
Compound (SMILES): COCCNC(=O)Cn1cc(-c2cnc3ccc(N(CC4CC4)c4cc(OC)cc(OC)c4)cc3n2)cn1
InChIKey: RZKSYYNMHKFROG-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 516.6, ALogP 3.82, HBA 9, HBD 1, PSA 103.63, QED 0.28
Compound (SMILES): COc1cc(N2CCC(OC)CC2)ccc1Nc1nccc(-c2c(-c3ccc(OC)c(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: IHYLFEXVXXJEEG-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 691.74, ALogP 7.36, HBA 10, HBD 2, PSA 115.14, QED 0.15
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCC1CN(C)CCN1C
InChIKey: JHVXCKPKPWJTHM-UHFFFAOYSA-N
Target: Ephrin type-B receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P54760
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 462.38, ALogP 4.31, HBA 7, HBD 1, PSA 62.75, QED 0.59
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3)ncnc2cc1OCc1csc(-c2ccc(C(F)(F)F)cc2)n1
InChIKey: RSQKKUZJTBAHBG-UHFFFAOYSA-N
Target: Ephrin type-B receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: P54760
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 577.42, ALogP 8.41, HBA 7, HBD 1, PSA 69.16, QED 0.21
Compound (SMILES): Fc1ccc(NC2CCC(c3nnn4cnc5[nH]ccc5c34)CC2)cc1
InChIKey: WDSQTCWUUXVUNZ-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 = 560 nM (pChEMBL 6.25)
Descriptors: MW 350.4, ALogP 3.88, HBA 5, HBD 2, PSA 70.9, QED 0.59
Compound (SMILES): N#Cc1ccc(NC[C@H]2CC[C@H](c3nnn4cnc5[nH]ccc5c34)CC2)cc1
InChIKey: UPJACKSNPDNBCE-WKILWMFISA-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 371.45, ALogP 3.86, HBA 6, HBD 2, PSA 94.69, QED 0.57
Compound (SMILES): N#CCC1(n2cc(-c3ncnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3ccc(-c4cccc5ccncc45)c(F)c3)CC2)C1
InChIKey: KXEMJYMPUSGUCE-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 611.69, ALogP 5.41, HBA 8, HBD 1, PSA 119.62, QED 0.27
Compound (SMILES): COc1ccc(Cl)c(N(CCNC(C)C)c2ccc3ncc(-c4cn[nH]c4)nc3c2)c1.Cl
InChIKey: FZTNKJMQOBATKX-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 = 1174.9 nM (pChEMBL 5.929999828338623)
Descriptors: MW 436.95, ALogP 4.82, HBA 6, HBD 2, PSA 78.96, QED 0.41
Compound (SMILES): COc1ccn2c(-c3ccnc(Nc4ccc(N5CCC(N6CCCCC6)CC5)cc4OC)n3)c(-c3cccc(C(=O)Nc4c(F)cccc4F)c3)nc2c1
InChIKey: YJMRPORPEUGAKC-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 744.85, ALogP 8.2, HBA 10, HBD 2, PSA 109.15, QED 0.14
Compound (SMILES): COc1cc2c(Nc3ccc(Cl)c(Cl)c3F)ncnc2cc1OC[C@@H]1CN2CCC[C@H]2C(=O)N1C
InChIKey: RPLCLUCJTHAIOW-UGSOOPFHSA-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 520.39, ALogP 4.51, HBA 7, HBD 1, PSA 79.82, QED 0.48
Compound (SMILES): COc1nn2cc(-c3ccc(Cl)cc3)nc2s1
InChIKey: UKCLNFBWHOFDDT-UHFFFAOYSA-N
Target: Proteinase-activated receptor 4 (SINGLE PROTEIN), Homo sapiens
UniProt: Q96RI0
Assay: Antagonist activity at PAR4 in human platelets assessed as inhibition of activating peptide-induced P-selectin activation
Measurement: IC50 = 286 nM (pChEMBL 6.539999961853027)
Descriptors: MW 265.73, ALogP 3.12, HBA 5, HBD 0, PSA 39.42, QED 0.71
Compound (SMILES): O=C(C1CCCC1)N1CCC(c2ccc(C(O)(C(F)(F)F)C(F)(F)F)cc2)(S(=O)(=O)c2ccc(F)cc2)C1
InChIKey: AWOZLZVEQAYRHZ-UHFFFAOYSA-N
Target: Oxysterols receptor LXR-beta (SINGLE PROTEIN), Homo sapiens
UniProt: P55055
Assay: Agonist activity at LXRbeta (unknown origin) expressed in African green monkey CV1 cells
Measurement: EC50 > 7500 nM (pChEMBL 5.125)
Descriptors: MW 567.52, ALogP 5.23, HBA 4, HBD 1, PSA 74.68, QED 0.4
Compound (SMILES): COc1cc(OC)cc(N(CCN2CCN(CCO)CC2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: NIHYIKXINLALJA-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 517.63, ALogP 2.8, HBA 10, HBD 1, PSA 92.01, QED 0.34
Compound (SMILES): N#CCC1(n2cc(-c3ccnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)c3ccnc(C(F)(F)F)n3)CC2)C1
InChIKey: BVSSQCPOTRJYOO-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 > 20 nM (pChEMBL 7.698999881744385)
Descriptors: MW 535.53, ALogP 3.46, HBA 8, HBD 1, PSA 119.62, QED 0.42
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2ccnc(OC)c2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: RUNFHROXJGUGHE-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 506.57, ALogP 4.64, HBA 9, HBD 0, PSA 87.42, QED 0.3
Compound (SMILES): N#CCC1(n2ccc(-c3ncnc4[nH]ccc34)c2)CN(C2CCN(C(=O)c3cc(OC(F)(F)F)ccc3F)CC2)C1
InChIKey: IKCMYXRBLUAWAV-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 567.55, ALogP 4.69, HBA 7, HBD 1, PSA 103.07, QED 0.34
Compound (SMILES): Cc1nc2c(-c3cnc[nH]3)cc(N3CCOCC3)nn2c1Nc1cccc(C(F)(F)F)c1CN1CC(O)C1
InChIKey: MAEHEIXUINDDHE-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 = 1230 nM (pChEMBL 5.909999847412109)
Descriptors: MW 528.54, ALogP 3.2, HBA 9, HBD 3, PSA 106.84, QED 0.35
Compound (SMILES): CC1(C)C(=O)N(c2ccc(C#N)c(C(F)(F)F)c2)C(=S)N1c1ccc(C(=O)NCCCCCC(=O)NO)c(F)c1
InChIKey: IXWJWUHPBOISOI-UHFFFAOYSA-N
Target: Histone deacetylase 2 (SINGLE PROTEIN), Homo sapiens
UniProt: Q92769
Assay: Inhibition of HDAC2 (unknown origin) assessed as inhibition of fluorogenic peptide deacetylation
Measurement: IC50 = 2250 nM (pChEMBL 5.650000095367432)
Descriptors: MW 579.58, ALogP 4.43, HBA 6, HBD 3, PSA 125.77, QED 0.13
Compound (SMILES): COc1cc(OC)cc(N(CC#Cc2cc(C)ccn2)c2ccc3ncc(-c4cnn(C)c4)nc3c2)c1
InChIKey: NZCCKKOANLHWDZ-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 = 8912.51 nM (pChEMBL 5.050000190734863)
Descriptors: MW 490.57, ALogP 4.94, HBA 8, HBD 0, PSA 78.19, QED 0.31
Compound (SMILES): O=S(=O)(Nc1ccc(-c2nc3cc(NS(=O)(=O)c4ccccc4Cl)ccc3o2)cc1)c1ccccc1Cl
InChIKey: ONYXJGJFMZTBBX-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 = 22000 nM (pChEMBL 4.659999847412109)
Descriptors: MW 574.47, ALogP 6.4, HBA 6, HBD 2, PSA 118.37, QED 0.23
Compound (SMILES): N[C@H](C(=O)O)C(NS(=O)(=O)c1ccc(F)cc1)C(=O)O
InChIKey: SHOWNKVGAYTRRR-JAMMHHFISA-N
Target: Excitatory amino acid transporter 1 (SINGLE PROTEIN), Homo sapiens
UniProt: P43003
Assay: Inhibition of [3H]-D-Asp uptake at human EAAT1 expressed in HEK293 cells measured after 3 mins by TopCount method
Measurement: IC50 = 1621.81 nM (pChEMBL 5.789999961853027)
Descriptors: MW 306.27, ALogP -1.03, HBA 5, HBD 4, PSA 146.79, QED 0.53
Compound (SMILES): COc1cc(C(F)(F)F)ccc1N1CCOc2cc(S(=O)(=O)Nc3nccs3)ccc21
InChIKey: CFWANNDTQNLLHL-UHFFFAOYSA-N
Target: Sodium channel protein type 9 subunit alpha (SINGLE PROTEIN), Rattus norvegicus
UniProt: O08562
Assay: Inhibition of rat NaV1.7 by cell based whole cell voltage clamp method
Measurement: IC50 = 390 nM (pChEMBL 6.409999847412109)
Descriptors: MW 471.48, ALogP 4.5, HBA 7, HBD 1, PSA 80.76, QED 0.59
Compound (SMILES): CCOc1cc(N2CCN(C(C)C)CC2)ccc1Nc1nccc(-c2c(-c3cccc(C(=O)Nc4c(F)cccc4F)c3)nc3ccccn23)n1
InChIKey: KTINPNCRSQJINT-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 688.78, ALogP 7.66, HBA 9, HBD 2, PSA 99.92, QED 0.15
Compound (SMILES): CS(=O)(=O)N1CCN(c2ccc(OC[C@@H]3CO[C@@](Cn4ccnc4)(c4ccc(Cl)cc4Cl)O3)cc2)CC1
InChIKey: DJXJWGKDHLYIKQ-RCZVLFRGSA-N
Target: Cytochrome P450 3A4 (SINGLE PROTEIN), Homo sapiens
UniProt: P08684
Assay: Inhibition of human Cyp3A4 using testosterone as substrate by LC-MS/MS analysis
Measurement: IC50 = 158 nM (pChEMBL 6.800000190734863)
Descriptors: MW 567.5, ALogP 3.62, HBA 8, HBD 0, PSA 86.13, QED 0.41
Compound (SMILES): O=C(O)COC[C@H]1CC[C@H](COC(=O)N(c2ccc(F)cc2)c2cccc(F)c2)CC1
InChIKey: KOMJQCSEFACZRE-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 = 30 nM (pChEMBL 7.519999980926514)
Descriptors: MW 433.45, ALogP 5.15, HBA 4, HBD 1, PSA 76.07, QED 0.62
Compound (SMILES): N#CCC1(n2cc(-c3ccnc4[nH]ccc34)cn2)CN(C2CCN(C(=O)Nc3ccccc3F)CC2)C1
InChIKey: UHOQUEJDLFRPOL-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 498.57, ALogP 4.19, HBA 6, HBD 2, PSA 105.87, QED 0.43